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INTRODUCTION Fibromyalgia syndrome (FMS) is an entity with multiple concomitant disorders, rather than a single disorder. The common symptoms of FMS include sleep disorders, affective disorders, chronic generalized pain, and fatigue. The pathophysiology of FMS has yet to be elucidated, and no treatment is available for relieving all of the symptoms(1). Several studies in the literature have found a close correlation between FMS and sexual dysfunction. The main symptoms include decreased sexual drive, excitement, orgasm, and increased genital pain(2). From a psychological point of view, stress, chronic generalized pain, fatigue, and sleep disorder negatively affect the sexual life of patients with FMS. In addition, the medicines used for treating the disease are also known to negatively affect sexual function(2). Sleep problems are one of the most common symptoms in patients with FMS(3). This study reviews the relationship between disease progress, sleep problems, and sexual dysfunction.

al life of patients with FMS. In addition, the medicines used for treating the disease are also known to negatively affect sexual function(2). Sleep problems are one of the most common symptoms in patients with FMS(3). This study reviews the relationship between disease progress, sleep problems, and sexual dysfunction. MATERIALS AND METHODS A total of 140 sexually active, pre- or postmenopausal women who presented to our physical medicine and rehabilitation outpatient clinic between January 2016 and June 2016 who was diagnosed FMS in accordance with the American College of Rheumatology 1990(4) and 2010 criteria, were enrolled in the study. The exclusion criteria included pregnancy, breastfeeding, major depression, active infection or inflammation, and malignancies. The patients’ age, height, body weight, body mass index (BMI), and general pain score for the last 1 week were recorded. The patients were given three different sets of questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Fibromyalgia Impact Questionnaire (FIQ), and Female Sexual Function Index (FSFI) in order to evaluate sleep function, disease severity, and sexual function.

nd general pain score for the last 1 week were recorded. The patients were given three different sets of questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Fibromyalgia Impact Questionnaire (FIQ), and Female Sexual Function Index (FSFI) in order to evaluate sleep function, disease severity, and sexual function. The FIQ was developed by Burckhardt to evaluate the functional status, disease progression, and outcomes of patients with fibromyalgia. The Turkish version of the FIQ was validited by Sarmer et al.(5). The scale is used to follow up the conditions and outcomes of patients with FMS. The first item consists of 10 Likert-type questions. In the second and third items, the patient is asked to tick days to allow for the determination of “disease exposure” and “absence from work.” The scores obtained are adapted to 10. The remaining seven questions are based on marking the corresponding points in the equivalent visual scale. The scoring interval is 0-100.

In the second and third items, the patient is asked to tick days to allow for the determination of “disease exposure” and “absence from work.” The scores obtained are adapted to 10. The remaining seven questions are based on marking the corresponding points in the equivalent visual scale. The scoring interval is 0-100. The PSQI scale provides information about the type and severity of sleep disorder and sleep quality in the last 1 month. Out of a total of 24 questions, 19 questions are answered by the patient, and the remaining 5 are answered by the partner of the patient. Using the 19 questions answered by the patient, 7 subdimensions are evaluated, including the subjective sleep quality, sleep latency, sleep duration, routine sleep activity, sleep disorder, use of sleeping pills, and daytime dysfunction. Each item in the scale is graded from 0 (no problem at all) to 3 (severe problem). The total scores for the seven subdimensions give the total PSQI score. A total score of 5 and less indicates that the sleep quality is “good”(6). The Turkish validity of the scale was provided by Agargun et al.(7). The FSFI was developed by Rosen et al.(8) in 2000 as a multidimensional scale consisting of 6 parts and 19 items to assess sexual function in women. Six dimensions are involved in the scale: desire, excitement, lubrication, orgasm, satisfaction, and pain. The lowest score on the scale is 2.0, and the highest is 36.0. The coefficient is 0.6 for the first and second questions; 0.4 for questions 3-10; and 0.3 for questions 11-19. The study was approved by the local Ethics Committee (2015-58) and was performed in accordance with the ethics standards described in an appropriate version of the 1975 Declaration of Helsinki.

ghest is 36.0. The coefficient is 0.6 for the first and second questions; 0.4 for questions 3-10; and 0.3 for questions 11-19. The study was approved by the local Ethics Committee (2015-58) and was performed in accordance with the ethics standards described in an appropriate version of the 1975 Declaration of Helsinki. Statistical Analysis SPSS version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.) was used for data analysis. The normal distribution of data was checked using the Kolmogorov-Smirnov test. A comparison was made for each parameter. The t test was used for normally distributed groups, and the Mann-Whitney U test was used for abnormal distribution. Chi-square analyses were used for a detailed examination of differences across groups. We used the one-way ANOVA test to compare continuous variables. Regression analyses were run for comparing multiple variables. Pearson’s correlation analysis was used as the correlation analysis. The significance of these tests was defined as p≤0.05.

es were used for a detailed examination of differences across groups. We used the one-way ANOVA test to compare continuous variables. Regression analyses were run for comparing multiple variables. Pearson’s correlation analysis was used as the correlation analysis. The significance of these tests was defined as p≤0.05. RESULTS A total of 140 sexually active women aged 17-67 years who were diagnosed as having FMS were enrolled in this study. The mean age of the patients was 40.3±8.5 years, the mean BMI was 27.1±4.4, the general pain score [visual analogue scale, (VAS)] in the last 1 week was 6.9±2 cm, the mean PSQI was 24.8±10.8 (one patient with PSQI ≤5), the mean FIQ was 65.9±19.2, and the mean FSFI was 19.0±6.9. The descriptive data of the study are summarized in Table 1. Based on the results of the Kolmogorov-Smirnov test, it was observed that the FIQ, FSFI, and PSQI data did not have a normal distribution (p=0.032; p<0.001; p=0.002, respectively) (Table 2). All parameters were compared with each other using regression analysis and the Mann-Whitney U test. No significant relationship was observed between the mean PSQI and BMI values (p=0.401), whereas a significant relationship was found between the mean VAS values (last 1 week), FIQ, and FSFI (p=0.03; p=0.034; p<0.001; respectively) (Table 3).

mpared with each other using regression analysis and the Mann-Whitney U test. No significant relationship was observed between the mean PSQI and BMI values (p=0.401), whereas a significant relationship was found between the mean VAS values (last 1 week), FIQ, and FSFI (p=0.03; p=0.034; p<0.001; respectively) (Table 3). In the Pearson’s correlation analysis, a positive correlation was found between the PSQI and VAS (r=0.324; p=<0.001; p<0.001) and FIQ values (r=0.271; p=0.001). No correlation was found between the PSQI and FSFI values (p=0.645). The FSFI values were compared with all other parameters using regression analysis and the Mann-Whitney U test. No statistically significant relationship was observed between the FSFI, FIQ, and BMI values (p=0.183; p=0.682, respectively) (Table 3). A significant relationship was observed between the FSFI and PSQI values, age (in favor of younger ages) (p<0.001); no correlation was determined (r=0.27, p=0.325; r=0.57, p=0.251). A significant relationship was found between FIQ and VAS values (last 1 week) (p<0.001) (Table 3). A p value <0.005 was considered statistically significant. DISCUSSION Many functions of sex hormones may affect chronic pain syndromes such as migraine, headaches, FMS, inflammatory arthritis and back ache, and others(8). Scientific research has shown sex-specific differences in pain sensitivity and threshold. Although the underlying pathogenetic mechanism responsible for these differences has not yet been defined, the probability of a sex hormone effect on the nociceptive process has attracted attention(9).

nd back ache, and others(8). Scientific research has shown sex-specific differences in pain sensitivity and threshold. Although the underlying pathogenetic mechanism responsible for these differences has not yet been defined, the probability of a sex hormone effect on the nociceptive process has attracted attention(9). The pathophysiology of FMS includes alterations in ascending and descending central nervous and peripheral nerve pathways, which lead to increased pain and sensitivity. Research on the risk factors has focused on several genetic predispositions and the effects of stress and poor sleep(10). Recent human neuroimaging studies suggested that FMS, a chronic widespread pain disorder, exhibited altered thalamic (modulation of pain) structure and function(11). The exact etiology of FMS is unknown, and the pathogenesis involves psychology, environmental, genetics, hormonal (serotonin), and impaired sleep quality. Brooks et al.(12) found that gynecologic, endocrine, and autoimmune diagnoses were associated with a diagnosis of FMS. They also found a relationship between the timing of gynecologic surgery and pain onset in FMS. Patients with FMS commonly have various autoimmune, endocrine, gynecologic, or psychiatric disorders. Sexual dysfunction related to chronic fatigue syndrome has become an increased concern rceently; however, limited studies have analyzed this subject to date. FMS may cause sexual dysfunction as a result of impaired emotional state. Whether the partners of female patients with FMS also have impaired sexual life has been the subject of various investigations(13). Blazquez et al.(14) analyzed the sexual function of 615 patients with chronic fatigue syndrome, and remarked that frequency of sexual dysfunction with FMS, Sjögren syndrome, and Myofacial pain syndrome concerned cognitive, neurologic, and neurovegetative symptoms were higher.

the subject of various investigations(13). Blazquez et al.(14) analyzed the sexual function of 615 patients with chronic fatigue syndrome, and remarked that frequency of sexual dysfunction with FMS, Sjögren syndrome, and Myofacial pain syndrome concerned cognitive, neurologic, and neurovegetative symptoms were higher. Chronic generalized pain is the cardinal symptom of FMS, and results in decreased quality of life, along with physical and psychosocial impairments. Burri et al.(15). reported difficulty in lubrication, sexual pain, and increased sexual stress in female patients with FMS who presented with chronic generalized pain. Terzi et al.(16) determined a lower threshold of pain and a higher number of tender points in women with FMS who presented with dyspareunia compared with those without dyspareunia. The central pathophysiology in the development of dyspareunia in female patients with FMS still needs further investigation. Ghizzani et al.’s(17) results supported that coital pain develops with the severity of FMS symptoms depending on the cooperative effect of peripheral and central sensitization mechanisms in female patients with FMS.

siology in the development of dyspareunia in female patients with FMS still needs further investigation. Ghizzani et al.’s(17) results supported that coital pain develops with the severity of FMS symptoms depending on the cooperative effect of peripheral and central sensitization mechanisms in female patients with FMS. Palagini et al.(1) hypothesized that sleep disorders activate stress and inflammation systems, playing a central role in all other symptoms. This also accounts for the high frequency of togetherness with pain, sleep, and mental disorders. Starting from this point of view, it is suggested that the treatment of sleep disorders may help alleviate symptoms of FMS and mental disorders. In a study similar to the present study, which was performed by Amasyali et al.(18) in 54 patients, a positive correlation was observed between the patients with PSQI score >5 (poor sleep quality) and sexual dysfunction. Additionally, a marked link was found between the high FIQ scores and sexual dysfunction. The present study found poor sleep quality to be markedly associated with the pain score, severity of disease, and sexual dysfunction. No marked link was found between BMI and sleep disorder and sexual dysfunction. The rates of sexual dysfunction and poor sleep quality are higher at older ages. Hence, it is concluded that reductions in generalized pain, severity of disease, and sleep disorder may also reduce sexual problems in patients. In FMS, multiple symptoms are closely associated with each other, and sleep disorder appears to play a main function in the development of all other symptoms. FMS is a chronic pain syndrome characterized by subjective primary insomnia. It shows abnormalities in the continuity and architecture of sleep in polysomnographic findings. Reduced quality of sleep, increased awakening, reduced slow-wave sleep, and emergence of abnormal alpha waves (alpha-delta) in nonrapid eye movement sleep are seen in sleep recordings(19). FMS symptoms are considered to be related to nonrestorative sleep disorder associated with alpha-electroencephalogram sleep disorders. Additionally, patients with FMS may also report sleep disorders such as sleep apnea or periodic limb movements(19,20). Diaz-Piedra et al.(3) observed a lower sleep quality, a greater wake phase, and a higher number of awakenings in a one-night polysomnographic evaluation of patients with FMS compared with a control group. It was also seen that patients reported poor subjective sleep quality(3).

apnea or periodic limb movements(19,20). Diaz-Piedra et al.(3) observed a lower sleep quality, a greater wake phase, and a higher number of awakenings in a one-night polysomnographic evaluation of patients with FMS compared with a control group. It was also seen that patients reported poor subjective sleep quality(3). Stuifbergen et al.(20) evaluated the sleep disorders of 104 female patients with FMS and reported subjective sleep disorder in 44% of the patients and objective sleep disorder in 21%. In patients with objective sleep disorders, the pain score, tender point index, and FIQ scores were higher, and also more depressive symptoms were observed compared with the others.

sorders of 104 female patients with FMS and reported subjective sleep disorder in 44% of the patients and objective sleep disorder in 21%. In patients with objective sleep disorders, the pain score, tender point index, and FIQ scores were higher, and also more depressive symptoms were observed compared with the others. Miro et al.(21) studied whether patients with FMS had different cognitive alterations depending on their sex. According to the study, treatments aimed at decreasing emotional distress seemed to improve attention more in women than in men; those intended to improve sleep quality were likely to reduce alertness incompetency in women and executive problems in men. Similar to the literature, we found a statistically significant association with sleep disfunction, disease severity, pain, and sexual disfunction. In contrast to the literature, we found a positive correlation between sleep disfunction, disease severity, and pain. It has been estimated that pain is positively correlated with disease severity and poor sleep quality. According toour findings, BMI has no effect on sleep, disease severity, pain and sexual function. Our patient population was overweight and middle-aged to fit with FMS. We also found fewer sexual disfunction symptoms at younger ages.

mated that pain is positively correlated with disease severity and poor sleep quality. According toour findings, BMI has no effect on sleep, disease severity, pain and sexual function. Our patient population was overweight and middle-aged to fit with FMS. We also found fewer sexual disfunction symptoms at younger ages. The treatment of FMS involves pharmacologic (tricyclic antidepressants, antiepileptic agents, selective serotonin uptake inhibitors) and nonpharmacologic (massage, exercise, acupuncture) therapies(10). No drug is recuperative for all of the symptoms of FMS. When scheduling the treatment plan, it is necessary to take into consideration that FMS consists of multiple closely-associated symptoms(10). Therefore, behavioral programs should be included to increase (deep sleep) and improve poor sleep quality, which is the most common symptom. Therapeutic measures should be taken, the adverse effects of drugs should be minimized, and a multidisciplinary approach should be used to improve the patient’s quality of life.

. Therefore, behavioral programs should be included to increase (deep sleep) and improve poor sleep quality, which is the most common symptom. Therapeutic measures should be taken, the adverse effects of drugs should be minimized, and a multidisciplinary approach should be used to improve the patient’s quality of life. Study Limitations First, our patients’ age range was very wide (17 years up to 67 years old). Age has a major affect on both sleep quality and sexual life. The study includes both pre- and post-menopausal women. The status of menopause is another confounding factor that is in itself a cause for worse sexual domain scores compared with premenopausal women. In addition, related to menopause, some other sexual function questionnaires were developed for menopausal women. We did not consider the menopausal status of our patients with any questionnaire or laboratory examinations. Additionally, medication may have affected our study results; we did not ask about medicine use for menapause or FMS. The study is a single-centered study and our clinic is located at one of the eastern cities in Turkey. Literate patients filled out scales by themselves, but most illiterate patients did not want to complete the FSFI scale; therefore, we had to exclude them. It would be have been better if we had asked about the patients’ educational levels.

entered study and our clinic is located at one of the eastern cities in Turkey. Literate patients filled out scales by themselves, but most illiterate patients did not want to complete the FSFI scale; therefore, we had to exclude them. It would be have been better if we had asked about the patients’ educational levels. CONCLUSION Sleep disorder is regarded as the underlying cause for many signs and symptoms in FMS. Sexual dysfunction may develop in women with FMS due to the potency of the disease and poor sleep quality. We found that sleep dysfunction was significantly related with the severity of disease, pain and sexual disfunction. We also found a positive correlation between VAS and PSQI (when pain scor is higher, sleep disorder is seen more prevelant). Therefore, beyond others, the treatment of sleep disorder is of vital importance in the management of FMS. Ethics: Ethics Committee Approval: The study were approved by the İnönü University of Local Ethics Committee. Informed Consent: Consent form was filled out by all participants. Peer-review: Externally and Internally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Tuba Tülay Koca, Günseli Karaca Acet, Concept: Tuba Tülay Koca, Design: Tuba Tülay Koca, Data Collection or Processing: Tuba Tülay Koca, Günseli Karaca Acet, Analysis or Interpretation: Tuba Tülay Koca, Literature Search: Tuba Tülay Koca, Emrullah Tanrıkut, Burcu Talu, Writing: Tuba Tülay Koca. Conflict of Interest: No conflict of interest was declared by the authors.

Authorship Contributions: Surgical and Medical Practices: Tuba Tülay Koca, Günseli Karaca Acet, Concept: Tuba Tülay Koca, Design: Tuba Tülay Koca, Data Collection or Processing: Tuba Tülay Koca, Günseli Karaca Acet, Analysis or Interpretation: Tuba Tülay Koca, Literature Search: Tuba Tülay Koca, Emrullah Tanrıkut, Burcu Talu, Writing: Tuba Tülay Koca. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Descriptive data Table 2 Tests of normality Table 3 Multiple Comparisons of the parameters

INTRODUCTION The International Continence Association (ICS) described Urinary Incontinence (UI) as unintended urine continence that becomes a social and hygienic problem(1). Two hundred fifty million adult individuals are effected by UI around the world, between 7-37% of women aged between 20-39 years experience UI(2,3). In Turkey, it is known that the prevalence of UI in women ranges between 16.4% and 49.7%(4). Incontinence is a serious issue that results in loneliness, economic problems, and has a negative effect on an individual’s sexual life by causing shame, declining confidence, and a decrease in social activities(5). Although there are many risk factors that result in incontinence, the most apparent risk factors in women are old age and trauma experienced during delivery through pregnancy and higher parity numbers, and births with interventions and tears(6,7,8,9).

shame, declining confidence, and a decrease in social activities(5). Although there are many risk factors that result in incontinence, the most apparent risk factors in women are old age and trauma experienced during delivery through pregnancy and higher parity numbers, and births with interventions and tears(6,7,8,9). The most common type of incontinence experienced in women is stress urinary incontinence (SUI), which is seen commonly in middle aged and parous women, and experienced as a result of situations that increase the pressure on the abdomen such as coughing, laughing, and heavy lifting. Stress incontinence was described by the ICS as UI that occurs as a result of intravesical pressure overrunning urethra pressure without any increase in detrusor activity. Stress incontinence as an incontinence type, is the variety that patients can benefit the most from surgery among the treatment options. Although there are different techniques available in treatment, there is no agreement as to which surgical intervention is the most efficient and appropriate for which patient. We use the classic external to internal transobturator tape (TOT) technique for patients who present to our clinic with SUI or mixed urinary incontinence (MUI). In this study we aimed to compare the subjective and objective success of TOT surgery with other surgical techniques, to demonstrate the short- and long-term complications, and its effects on patients’ quality of life in light of the literature.

ts who present to our clinic with SUI or mixed urinary incontinence (MUI). In this study we aimed to compare the subjective and objective success of TOT surgery with other surgical techniques, to demonstrate the short- and long-term complications, and its effects on patients’ quality of life in light of the literature. MATERIALS AND METHODS Our study comprised 125 patients with MUI and SUI who were treated with TOT surgery between April 2010 and April 2012 in İstanbul Training and Research Hospital, Gynecology and Obstetrics clinic. In line with data integrity and patient compliance, 92 of the patients were included in our study. The study was conducted in İstanbul Training and Research Hospital, Perinatology and Delivery Unit, following receipt of approval from the Hospital Training and Planning Committee and Committee of Ethics. Within the indicated dates, patients considered within the scope of the study were informed and included in the study after receiving their signed form of approval. Patients who had urge incontinence, undergone surgery for incontinence, had a significant neurologic disorder, had undergone previous vaginal surgery, or used medication that created a tendency to bleed were excluded from the study. We retrospectively examined the patients urodynamics, ultrasonography, demographic characteristics, incontinence surveys, life quality scores [incontinence impact questionnaire, (IQ-7) and urinary distress inventory (UDI-6)], diagnostic findings, Q-type test, surgical records, and complications. Also, we reviewed the patients’ treatment adherence, life quality scores, urodynamics as evaluated per findings and complications following the discharge of the patients between 12 and 36 months. In the pre-operative period, the histories of the patients were collected and pelvic inspections, urinalysis, [(life quality tests: UDI-6 and incontinence impact questionnaire-7 (IIQ-7)], Q-type tests, urodynamics, and residual urine tests were conducted. The Baden-Walker classification was used to classify pelvic limb prolapsus in the pelvic inspection. Cough stress tests were positive for all the patients in our study. Cervix vesicae mobility was evaluated with Q-type test. If there was no reproduction in the urine culture taken prior to urodynamic testing, patients were proceeded to surgery; if reproduction was observed, patients were re-evaluated following appropriate antibiotic treatment.

ositive for all the patients in our study. Cervix vesicae mobility was evaluated with Q-type test. If there was no reproduction in the urine culture taken prior to urodynamic testing, patients were proceeded to surgery; if reproduction was observed, patients were re-evaluated following appropriate antibiotic treatment. For conducting multi-channel cystometry, 8 F micro-type transducers (2 transducers positioned on the tip and 6 cm behind, positioned in a 3 o’clock direction) were placed transurethrally in the patient. Pressure measurements were conducted by connecting the system to the patient who was laid on the patient examination couch as they drained their urine, and examined for residual urine. The bladder was filled with sterile physiologic serum at 50 cc/minute at room temperature. During the filling procedure, the time to first sensation of urine, and first urge to urinate, normal urge to urinate, strong urge to urinate, and maximal bladder capacity (maximum pressure level of the patient before urinary incontinence) were evaluated. During measurements following the 200 cc physiologic serum, UI was induced using the Valsalva maneuver in the lithotomy position. It was re-applied as 100 cc if no continence was observed. Valsalva leak point pressure values (VLPP) were considered for defining SUI sub types. Intrinsic sphincter insufficiency was diagnosed for the patients with VLPP below or equal to 60 cm H2O, and type 2 SUI was diagnosed for the patients with VLPP above or equal to 90 cm H2O. Detrusor dysfunction was diagnosed using urodynamics through an immediate increase in basal detrusor pressure as 15 cm H2O or more during the filling procedure.

ency was diagnosed for the patients with VLPP below or equal to 60 cm H2O, and type 2 SUI was diagnosed for the patients with VLPP above or equal to 90 cm H2O. Detrusor dysfunction was diagnosed using urodynamics through an immediate increase in basal detrusor pressure as 15 cm H2O or more during the filling procedure. For the decision of surgery, patient symptoms and urodynamic parameters were considered together. TOT procedures were conducted as external to internal as described by Delorme. All operations were performed using outside-in Obtryx (Boston Scientific, Natick, MA, USA) brand kits. All patients were administered intravenous 2 gr cefazolin sodium prior to surgery. A longitudinal incision of about 2 cm was made starting 0.5 cm from under the urethral meatus to the front wall of the vagina. Periurethral dissection was performed with blunt and sharp dissection until below the ischiopubic ramus. A bilateral 5-mm incision was made at the clitoris level, the lateral side of the labium majus, 15 mm lateral of the ischiopubic ramus. A hook-shaped TOT needle was advanced medially by palpating the posterior of the ischiopubic ramus and m. obturatorius internus with an index finger, which was on the paraurethral dissection point, and passed through the dermis, obturator membrane, and incision in the vagina, respectively. After this procedure, we checked whether vaginal fornix and urethra perforation had occurred. The mesh-attached needle was removed from the dermis from the reverse side. The same method was applied to the other side. The strain of the mesh was adjusted to leave an opening to allow for a scissor tip to enter between the urethra and band at the end of the procedure. At the end of the procedure, an 18 F foley catheter was placed. The duration of TOT and other additional surgical procedures (if applicable) was recorded.

the other side. The strain of the mesh was adjusted to leave an opening to allow for a scissor tip to enter between the urethra and band at the end of the procedure. At the end of the procedure, an 18 F foley catheter was placed. The duration of TOT and other additional surgical procedures (if applicable) was recorded. Additional pelvic floor interventions were performed on patients according to the indications. The patients’ catheter were removed on postoperative day 1 and we waited for spontaneous urination. As a result of the evaluations, 57 patients with SUI and 35 patients with MUI were included in the study. Statistical Analysis SPSS version 11.0 was used for the statistical analysis of this study (Statistical Package for the Social Sciences Inc; Chicago, IL, USA). Student’s t-test, the Mann-Whitney U, paired t-test, Wilcoxon rank test, Fisher’s exact test, and chi-square tests were used for comparisons. P<0.05 were accepted as statistically significant.

n 11.0 was used for the statistical analysis of this study (Statistical Package for the Social Sciences Inc; Chicago, IL, USA). Student’s t-test, the Mann-Whitney U, paired t-test, Wilcoxon rank test, Fisher’s exact test, and chi-square tests were used for comparisons. P<0.05 were accepted as statistically significant. RESULTS A total of patients 125 underwent TOT. In line with data integrity and patient compliance, 92 patients were included in our study. The average of the patients was 48.46 years (range, 29- 83 years). Fifty patients were premenopausal and 42 were postmenopausal patients. None of the postmenopausal patients were receiving hormone replacement treatment. The average menopause duration for patients who were postmenopausal was 10.12 years (range, 1-40 years). The mean follow-up duration was 22.17 months (range, 12-36 months). The average parity was 3.42 (range, 1-15); 4 patients had a history of cesarean section, and 2 patients had a history of vacuum-assisted birth. The average baby birth weight was 3708.26 gram (range, 2600-6000 g). The average duration of incontinence was 6.83 years (range, 1-40 years). The average body mass index (BMI) was calculated as 28.51± 4.3 kg/m2 (range, 23.3-39.5 kg/m2). According to BMI, 58.69% of the patients were overweight and 33.69% were obese. No patients were morbidly obese. Forty-one patients had systematic diseases: hypertension (n=16), diabetes (n=8), thyroid disease (n=5), chronic obstructive pulmonary disease (COPD) (n=6), hypertension + diabetes (n=4), and hypertension + COPD (n=2). Twenty (21.73%) patients had undergone previous gynecologic operations, none of which were in relation with incontinence; 6 (6%, 52) operations were hysterectomy. Thirty-five patients (38.05%) were diagnosed as having MUI and 57 patients (61.95%) were diagnosed as having SUI as a result of anamnesis, examinations, and urodynamic inspections. Patients with pure urge incontinence were excluded. All patients had symptoms of stress incontinence and cough stress test results were positive. Table 1 shows the demographic and clinical characteristics of the patients (Table 1).

gnosed as having SUI as a result of anamnesis, examinations, and urodynamic inspections. Patients with pure urge incontinence were excluded. All patients had symptoms of stress incontinence and cough stress test results were positive. Table 1 shows the demographic and clinical characteristics of the patients (Table 1). All patients underwent external to internal TOT procedures. Forty-five (48.91%) patients underwent additional procedures as per indication during the same surgical period: vaginal hysterectomy + anterior colporrhaphy (VAH + CAP) (n=5), anterior colporrhaphy (n=3), posterior colporrhaphy (n=23), manchester (n=3), anterior posterior colporrhaphy (n=4), abdominal hysterectomy + bilateral salpingo-ophorectomy (total abdominal hysterectomy + buthionine sulfoximine) (n=4), bilateral tube ligation, cyst extirpation (n=1). No intraoperative complications developed in the patients in the present study. No hematomas, wound site infections, or urinary system infections developed during the postoperative stage. Two (2.17%) patients developed a foreign body reaction. However, no interventions were conducted on the patients because the erosion in the vagina was less than 1 cm and asymptomatic. The patients were taken to follow-up. One (1.08%) patient developed incontinence and this patient was treated with anticholinergic agents.

o (2.17%) patients developed a foreign body reaction. However, no interventions were conducted on the patients because the erosion in the vagina was less than 1 cm and asymptomatic. The patients were taken to follow-up. One (1.08%) patient developed incontinence and this patient was treated with anticholinergic agents. The 35 patients with MUI were started on trospium chloride one week prior to operation and treatment continued following the operation. Patients were re-evaluated after an average of 22.17 months (range, 12-36 months). Patients were primarily evaluated at follow-up examinations as per their symptoms. Examinations, urodynamics, Q-type test, UDI-6, and IIQ surveys were conducted: one patient (1.1%) had worsened symptoms and 12 (13%) patients’ symptoms were improved, no significant changes were observed in 7 (7.6%) patients, and 72 (78.3%) were symptom free. The results were compared with the results obtained at the preoperative stage.

ynamics, Q-type test, UDI-6, and IIQ surveys were conducted: one patient (1.1%) had worsened symptoms and 12 (13%) patients’ symptoms were improved, no significant changes were observed in 7 (7.6%) patients, and 72 (78.3%) were symptom free. The results were compared with the results obtained at the preoperative stage. The first two questions of the UDI-6 survey are regarding symptoms of irritation and the 4th question is about stress symptoms, the 5th and 6th questions are related with obstruction; these questions are evaluated by grouping them individually. An average 1.02 score decrease was seen in the pre- and post-operative UDI-6 evaluations for the 1st and 2nd questions, an average 3.66 score decrease was seen for the 4th question, and a 4.57 score decrease was found for the 5th and 6th questions. All questions in UDI-6 and IIQ-7 saw an average score decrease of 10.86. The decrease in each evaluation was found statistically significant, which proved the positive effect on life quality (p<0.01). The 5th and 6th questions of UDI-6 had no statistically significant change (p>0.05) (Table 2). Seventy-two the patients (78.3%) were identified as having objective cure when the post-operative urodynamics were evaluated. Stress incontinence remained in 20 (21.7%) patients. Objective success was obtained in 65 out of 81 (80.2%) patients with anatomic incontinence, and 7 out of 11 (63.6%) patients with type 3 incontinence. There were no statistically significant differences between TOT success and stress anticontinence subtypes.

aluated. Stress incontinence remained in 20 (21.7%) patients. Objective success was obtained in 65 out of 81 (80.2%) patients with anatomic incontinence, and 7 out of 11 (63.6%) patients with type 3 incontinence. There were no statistically significant differences between TOT success and stress anticontinence subtypes. Regarding the patients with successful and unsuccessful operations, it was found that parity over 4 was an important reason for failure. Age, BMI, heavy baby birth weight, and duration of symptoms had no significance over the success of the operation (Table 3). Forty-five (48.91%) patients underwent additional operations as per the indication during the same operative period. There was no significant difference regarding TOT success between patients with without additional pelvic surgical operations. Six (6.5%) patients had a history of hysterectomy; no statistically significant difference was observed between patients with and without a history of hysterectomy. There was no statistically significant difference in the time to first sensation of urine and maximum bladder capacity regarding the pre-operative and post-operative cystometry values. There was a significant decline in the frequency of daytime and nighttime micturition among the patients (p<0.01). There were no significant difference between the residual urine quantity after an average of 22.17 months for the pre- and post-operative periods (p>0.05). According to the Q-type test results, there was no significant change in the mobility of the cervix vesicae (p>0.05) (Table 4).

urition among the patients (p<0.01). There were no significant difference between the residual urine quantity after an average of 22.17 months for the pre- and post-operative periods (p>0.05). According to the Q-type test results, there was no significant change in the mobility of the cervix vesicae (p>0.05) (Table 4). DISCUSSION The TOT procedure is commonly used in the treatment of UI. One of the most important characteristics that distinguishes TOT procedures from other sling operations is the low rate of complications. The most important complications of the burch procedure are difficulties with urination and an increase in prolapsus after the operation(10). For transvaginal tape procedures, complications include major limb injuries, bladder perforation, and bleeding(11). Although the low rate of complications were remarkable when the results of the TOT procedures were first published, an increase in general complication rates and different complications indigenous to TOT were reported as the follow-up durations and number of cases increased. Along with the possibility of experiencing extensive bleeding, wound site infections, obturatory abscess, urinary retention, and re-operation related with mesh erosion, leg and groin pains were also reported for TOT operations(12). Madjar et al.(13) suggested considering abdomen and pelvis tomography for patients with abdomen pain or urinary symptoms following sling procedures. The risk of vaginal erosion is between 0% and 2.7% following the TOT procedures(14). The most important complication observed in our study was vaginal erosion (n=2, 2.17%).

adjar et al.(13) suggested considering abdomen and pelvis tomography for patients with abdomen pain or urinary symptoms following sling procedures. The risk of vaginal erosion is between 0% and 2.7% following the TOT procedures(14). The most important complication observed in our study was vaginal erosion (n=2, 2.17%). Post-operative urinary retention can be connected to edema or pain but dysuria or urine retention that continues after one week must be considered seriously. If necessary, the tape must be loosened with traction and re-inserted properly using the same vaginal incision(15). In another study, bladder exit obstruction was identified in 3.8% of participants following TOT, and it was stated that removal or loosening of the tape as early as possible could be beneficial in the presence of a clinically significant obstruction(16). In our study 2 patients (2.17%) had temporary urine retention following the operation. For these patients catheters were left in the bladder for 1 week. Patients urinated comfortably after the removal of the catheters and no additional operations were required because the residual urine quantity was below 100 mL. One patient (1.08%) had novo urge incontinence in the post-operative period; this rate was 2% in the study conducted by Juma and Brito(17).

ladder for 1 week. Patients urinated comfortably after the removal of the catheters and no additional operations were required because the residual urine quantity was below 100 mL. One patient (1.08%) had novo urge incontinence in the post-operative period; this rate was 2% in the study conducted by Juma and Brito(17). For sling operations, it is not necessary to fix the urethral mobility. On the contrary, continuation of urethral mobility in the post-operative period provides dynamic bending for the urethra during stress(18). In our study, urethral mobility was observed as continuous in the Q-type test, and there were statistically significant changes in the pre- and post-operative values. In our study, UDI-6 and IIQ-7 forms, which were developed by Uebersax, were used to evaluate life quality before and after the TOT procedures. These forms have been used to evaluate life quality in most studies related with TOT(17,19). The patients’ survey answers were grouped, scored, and the pre- and post-operative scores were compared. When the UDI-6 stress (3rd and 4th questions) and urge (1st and 2nd questions) values were evaluated, the scores were found significantly decreased. No changes were noted in the obstructive (5th and 6th questions) scores. Similar results were reported in the studies conducted by Juma and Brito(17) and Grise et al.(20). The decline of both stress and urge symptoms reminded us of the integral theory of Petros and Ulmsten(21). Our data are in accordance with this theory.

changes were noted in the obstructive (5th and 6th questions) scores. Similar results were reported in the studies conducted by Juma and Brito(17) and Grise et al.(20). The decline of both stress and urge symptoms reminded us of the integral theory of Petros and Ulmsten(21). Our data are in accordance with this theory. There was a statistically significant increase in patients’ life quality scores in the post-operative period in IIQ-7 scores, which shows that the operations were successful. During the follow-up evaluations as per the symptoms, 12 (13.04%) patients reported a decline in incontinence symptoms, and 72 (78.03%) patients were considered cured. According to this result, 91.3% of patients achieved subjective success and this result is in accordance with the literature. Subjective success rates range between 78% and 91% in the literature(19,20). Seven patients (7.06%) reported no significant change and 1 (1.08%) patient described worsened symptoms and with urge incontinence being added to their stress incontinence. According to the general urodynamic results, 72 (78.3%) patients obtained objective cure. Objective success rates in the literature range between 75% and 89.3%(20,22).

%) reported no significant change and 1 (1.08%) patient described worsened symptoms and with urge incontinence being added to their stress incontinence. According to the general urodynamic results, 72 (78.3%) patients obtained objective cure. Objective success rates in the literature range between 75% and 89.3%(20,22). The number of pregnancies and parity, UI level, unsuccessful surgical operations in the past, VLPP ≤60 cm H20, and BMI <30 the operation observed in the study conducted by Rodriguez et al.(23) as not effecting the unwanted side effects and surgical success. In the same study, the effects of the urodynamic measures on SUI surgical treatment cure rates and VLPP were found not to affect the surgical treatment result. In our study, no significant effect for age, duration of symptoms, type of incontinence, heavy baby birth weight and BMI was found to affect treatment success. Parity over 4 was identified as a significant reason for failure. TOT is commonly conducted with other interventions. In a study that investigated whether the effects of the procedures on the pelvic floor affected TOT success rates, only 2 patient groups were compared; those who underwent TOT procedures, and patients with additional operations(24). In that study, the authors found that additional pelvic interventions had no effect on TOT success. Forty-five patients (50.6%) underwent additional pelvic operations besides TOT. No significant difference was found between patients with and without additional operations in terms of TOT operation success.

erations(24). In that study, the authors found that additional pelvic interventions had no effect on TOT success. Forty-five patients (50.6%) underwent additional pelvic operations besides TOT. No significant difference was found between patients with and without additional operations in terms of TOT operation success. CONCLUSION Stress incontinence continues to be an important health issue. TOT is a method that is easy to apply with low complication rates and a high rate of success. Our results show the high success rate and low complication rate of TOT procedures. In our study, TOT was considered an efficient and reliable method in accordance with the success rates obtained. However, there is a need for further random prospective studies with different methods and large populations in which long-term results are reported and compared. Ethic: Ethics Committee Approval: Ethics committee approval was received for this study from the Institutional Review Board, Informed Consent: Written informed consent was obtained from patients who participated in this study. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Cihan Aygül, Ramazan Özyurt, Concept: Serkan Kumbasar, Design: Bulay Aytek Şık, Data Collection or Processing: Cihan Aygül, Analysis or Interpretation: Serkan Kumbasar, Literature Search: Ramazan Özyurt, Writing: Bulat Aytek Şık. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Authorship Contributions: Surgical and Medical Practices: Cihan Aygül, Ramazan Özyurt, Concept: Serkan Kumbasar, Design: Bulay Aytek Şık, Data Collection or Processing: Cihan Aygül, Analysis or Interpretation: Serkan Kumbasar, Literature Search: Ramazan Özyurt, Writing: Bulat Aytek Şık. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Demographic and clinical characteristics of the patients Table 2 Evaluation of urinary distress inventory-6 and incontinence impact questionnaire-7 scores of the patients Table 3 Effects of various parameters on objective success Table 4 Changes in cystometry values

INTRODUCTION Abnormal uterine bleeding (AUB) is as any kind of uterine bleeding in terms of duration, frequency, and volume. In postmenopausal women, women without a menstrual cycle for one year, any bleeding is abnormal. Postmenopausal bleeding has different causes including endometrial atrophy, polyps, myomas, endometrial hyperplasia, and endometrial carcinoma. Endometrial carcinoma is the most common malignancy of genital organs in women in developed countries. About 80% of endometrial cancers in post-menopausal women occur at ages of 50 to 65 years(1). On the other hand 10% to 15% of women with post-menopausal bleeding have endometrial cancer(2,3). Therefore, it is important to evaluate AUB in postmenopausal women very carefully. Measurement of endometrial line thickness by transvaginal sonography (TVS) is the first step to determine the need for further evaluations to rule out malignancy in these patients(4). In case of endometrial thickness more than 4-5 mm in TVS of patients with postmenopausal bleeding, more evaluation is required to rule out cancer. Considering these values, the incidence of endometrial cancer with measurements thinner than this cut-off point is less than 1%(5,6). There is no agreement on the described threshold of endometrial thickness to differentiate between normal and abnormal endometrial pathologies in postmenopausal women without bleeding(7,8). Some guidelines and researchers have suggested that asymptomatic post-menopausal women with endometrial thickness of 4-5 mm or more do not need endometrial biopsy unless AUB occurs(9,10). However, some researchers believe that postmenopausal endometrial thickness represents an increased risk of malignancy or other underlying pathologies, such as hyperplasia, polyps or myomas, and should be evaluated(11). Hysteroscopy is a precise, easy, and quick method to assess and identify any intrauterine pathology with which we are able to observe the whole endometrial cavity and take adequate biopsies of any suspicious lesions. This procedure has recently been suggested as the best available method to evaluate the uterine cavity of women with endometrial line thickness with or without AUB(12,13).

tify any intrauterine pathology with which we are able to observe the whole endometrial cavity and take adequate biopsies of any suspicious lesions. This procedure has recently been suggested as the best available method to evaluate the uterine cavity of women with endometrial line thickness with or without AUB(12,13). Another advantage of hysteroscopy is the “see and treat” method in which simultaneous real-time macroscopic diagnosis of benign lesions and resection can be made(1,14). This study was designed to investigate and compare the histologic and hysteroscopic findings of post-menopausal women with AUB and asymptomatic women with increased endometrial thickness. MATERIALS AND METHODS This cross-sectional study was performed between May 2014 and June 2015 on post-menopausal women who were referred to a center in Tehran because of having endometrial thickness equal or more than 5 mm in TVS, with or without AUB. They were divided into two groups: women with AUB group and asymptomatic women with increased endometrial thickness (asymptomatic group). Menopause was defined as the absence of menstrual periods for more than 12 months. The study protocol was approved by our university’s ethics committee.

in TVS, with or without AUB. They were divided into two groups: women with AUB group and asymptomatic women with increased endometrial thickness (asymptomatic group). Menopause was defined as the absence of menstrual periods for more than 12 months. The study protocol was approved by our university’s ethics committee. The inclusion criteria were: (1) being menopausal; (2) aged 40-82 years; (3) having uterine bleeding; and (4) having increased endometrial thickness (≥5 mm). The exclusion criteria were: (1) using hormonal replacement therapy, anticoagulants or selective estrogen receptor modulators; (2) having vaginal bleeding with a known cause in the vagina or cervix; (3) having any adnexal abnormality in TVS; (4) having any kind of cancer; and (5) being menopausal because of ovarian surgery. All participants signed an informed consent form before participating in this study. Transvaginal ultrasound was done for all participants. Endometrial line thickness was measured at the thickest part in the longitudinal plan of TVS with 7.5 MHz vaginal probe. The cut-off value of endometrial thickness was 5 mm or more. Adnexal regions also were assessed by TVS. If any mass or abnormality was observed in the adnexa, the woman was excluded from the study(1,15). Of the 148 women who were referred to our center in the defined period, 110 women met the inclusion criteria. Among them, 67 women had AUB group and 47 women were asymptomatic with endometrial thickness (asymptomatic group).

ny mass or abnormality was observed in the adnexa, the woman was excluded from the study(1,15). Of the 148 women who were referred to our center in the defined period, 110 women met the inclusion criteria. Among them, 67 women had AUB group and 47 women were asymptomatic with endometrial thickness (asymptomatic group). Hysteroscopy was conducted in an outpatient setting with a 3.5-mm Storz hysteroscope and 30 degrees view by an operator with 8 years of experience in performing hysteroscopy. The media was normal saline and hysteroscopy was performed with or without complete or local anesthesia. The whole endometrial level and cavity were precisely and systematically evaluated using hysteroscopy. All findings were recorded accurately. Hysteroscopic findings were defined precisely based on the specific findings detected during the procedure. Normal hysteroscopic findings included a normal, non-vascular smooth level. Abnormal findings included polyps, submucosal myomas, endometrial hyperplasia, and endometrial cancer(16).

Hysteroscopy was conducted in an outpatient setting with a 3.5-mm Storz hysteroscope and 30 degrees view by an operator with 8 years of experience in performing hysteroscopy. The media was normal saline and hysteroscopy was performed with or without complete or local anesthesia. The whole endometrial level and cavity were precisely and systematically evaluated using hysteroscopy. All findings were recorded accurately. Hysteroscopic findings were defined precisely based on the specific findings detected during the procedure. Normal hysteroscopic findings included a normal, non-vascular smooth level. Abnormal findings included polyps, submucosal myomas, endometrial hyperplasia, and endometrial cancer(16). Hyperplasic endometrium was defined as endometrium that was highly vascular, thick, and polypoid in appearance. Endometrial grooves became visible whenever it was pressed by the hysteroscope. Presence of abnormal vascular pattern and irregular fragile polypoid tissue with bleeding necrosis was defined as a sign of endometrial carcinoma(17). Endometrial biopsy was performed for all participants with intrauterine lesions. Punch biopsies were conducted in women with atrophic endometrium who had no pathology in hysteroscopy. In women with pre-malignant or malignant lesions, targeted and random biopsies were performed. In women with polyps or myomas, the lesions were all resected using scissors or resectoscope, respectively. The biopsies were immediately placed in 10% formaldehyde and sent to the pathology laboratory. The pathologist knew nothing of the hysteroscopic findings. Histologic findings were defined as the final exact diagnosis standard of the endometrial pathology. The pathologic findings between the two groups and the percentages of each finding were analyzed. The hysteroscopy’s predictive value in endometrial lesions’ diagnosis was assessed based on the sensitivity, specificity, and positive and negative predictive values(18,19).

diagnosis standard of the endometrial pathology. The pathologic findings between the two groups and the percentages of each finding were analyzed. The hysteroscopy’s predictive value in endometrial lesions’ diagnosis was assessed based on the sensitivity, specificity, and positive and negative predictive values(18,19). Statistical Analysis Categorical and continuous variables are summarized as number (percentage) and mean, respectively. Hysteroscopy was considered as a screening test and endometrial biopsy as a standard. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 20 (Chicago, IL, USA) by calculating sensitivity, specificity, and positive and negative predictive values. RESULTS This study was conducted on post-menopausal women with a mean age of 57 years. Of the 110 participants with endometrial thickness equal or more than 5 mm, 67 (60.9%) had AUB. All 110 patients underwent hysteroscopy and endometrial biopsy. The hysteroscopic findings were categorized into five groups: normal, polyps, myomas, hyperplasia, and carcinoma (Table 1). We compared the hysteroscopy and pathology results of all participants. Among 17 women who had normal hysteroscopy in both groups, one woman in each group had simple hyperplasia in histopathology and the other had atrophy (atrophy in our classification was part of normal results) (Table 2).

RESULTS This study was conducted on post-menopausal women with a mean age of 57 years. Of the 110 participants with endometrial thickness equal or more than 5 mm, 67 (60.9%) had AUB. All 110 patients underwent hysteroscopy and endometrial biopsy. The hysteroscopic findings were categorized into five groups: normal, polyps, myomas, hyperplasia, and carcinoma (Table 1). We compared the hysteroscopy and pathology results of all participants. Among 17 women who had normal hysteroscopy in both groups, one woman in each group had simple hyperplasia in histopathology and the other had atrophy (atrophy in our classification was part of normal results) (Table 2). The most common finding on hysteroscopic evaluation was endometrial polyps in both groups (44.1% and 53.5% in AUB and asymptomatic groups, respectively). There were a total of 55 polyps and 20 myomas in both groups, which were confirmed by histopathology. Hyperplasia was found in 16 participants (11 and 5 in AUB and asymptomatic groups, respectively). This was confirmed with histology. Eleven cases were simple hyperplasia and five were complex or atypical hyperplasia. Three women in the AUB group and one in the asymptomatic group were suspected of having carcinoma in the hysteroscopy. Regarding the AUB group, the sensitivity, specificity, and positive and negative predictive values of the hysteroscopic view for finding normal results were 98%, 100%, 100% and 90%, respectively. In the asymptomatic group these parameters were 98%, 100%, 100% and 85%, respectively (Table 3). The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for polyps and myomas were 100%. The sensitivity, specificity, and positive and negative predictive values were 100% for detecting hyperplasia with hysteroscopy in both groups. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for detecting carcinoma in the AUB group were 100%, 97%, 33% and 100%, respectively (Table 3). All lesions occupying the uterus (53 polyps and 20 uterine myomas) were diagnosed using hysteroscopy.

with hysteroscopy in both groups. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for detecting carcinoma in the AUB group were 100%, 97%, 33% and 100%, respectively (Table 3). All lesions occupying the uterus (53 polyps and 20 uterine myomas) were diagnosed using hysteroscopy. DISCUSSION The average of life expectancy for women has increased in recent years because of improved quality of life. Also, the number of women older than 60 years is increasing. In spite of the absence of vaginal bleeding, these women may still have uterine pathologies such as endometrial hyperplasia, polyps, uterine fibroids, adenomiosis or even endometrial cancer, some of which can be malignant. Up to now, there is no common agreement regarding the clinical management of increased endometrial line thickness in post-menopausal women.

g, these women may still have uterine pathologies such as endometrial hyperplasia, polyps, uterine fibroids, adenomiosis or even endometrial cancer, some of which can be malignant. Up to now, there is no common agreement regarding the clinical management of increased endometrial line thickness in post-menopausal women. In our study, the common cause of endometrial thickening and AUB was endometrial polyp, which is consistent with other studies(1,20,21,22,23,24). Fortunately, polyps were not histologically malignant in our patients and this finding is in agreement with Loiacono et al.(24) study. Elfayomy et al.(2) showed that about 20% of polyps had malignant components hidden in their stem or center despite normal endometrial pathology in endometrial biopsy. Therefore, the authors suggested performing polypectomy via hysteroscopy in such women. On the other hand, 20 women of our study who only had increased endometrial thickness in TVS had submucosal myomas. Among them, 13 women had AUB and seven were asymptomatic. Therefore, we suggest that hysteroscopy be performed in all postmenopausal women with endometrial thickness ≥5 mm with or without AUB because of the successful resection of all polyps and sub-mucosal myomas without complications in these women(1,17,24,25). It seems that more evaluations are needed in such cases because 86% of asymptomatic women with increased endometrial line thickness had underlying pathologic findings. This is in agreement with the studies of Loiacono et al.(24) and Hartman et al.(15).

ub-mucosal myomas without complications in these women(1,17,24,25). It seems that more evaluations are needed in such cases because 86% of asymptomatic women with increased endometrial line thickness had underlying pathologic findings. This is in agreement with the studies of Loiacono et al.(24) and Hartman et al.(15). In a study by Korkmazer et al.(20) on post-menopausal women with increased endometrial thickness, all intra-uterine lesions including polyps and submucosal myomas were diagnosed only via hysteroscopy. Curettage was not able to detect all lesions in their study; 25 of 93 women with atrophic endometrium had endometrial polyp in hysteroscopy and direct biopsy. Also, Lee et al.(25) compared biopsies obtained by curettage and hysteroscopy in post-menopausal women with bleeding. The authors concluded that performing curettage may not be reliable enough for evaluating endometrial pathology and suggested that endometrial biopsy with hysteroscopy must become the standard of diagnosis in these women. If endometrial biopsy is performed blindly, the detection of endometrial polyps or submucosal myomas might be missed. This leads to under diagnosis of this pathology during menopause. Therefore, the possibility of missing the underlying pathology will be eliminated by doing hysteroscopy(20,26,27).

nosis in these women. If endometrial biopsy is performed blindly, the detection of endometrial polyps or submucosal myomas might be missed. This leads to under diagnosis of this pathology during menopause. Therefore, the possibility of missing the underlying pathology will be eliminated by doing hysteroscopy(20,26,27). In our study, there was more endometrial hyperplasia in the AUB group than in the asymptomatic group (16% vs. 11.6%, respectively). Hysteroscopy in these patients enabled us to take targeted biopsies under direct vision. According to some studies, hysteroscopy did not have the desirable sensitivity compared with endometrial biopsy in women with endometrial hyperplasia. Thus, it was suggested to take endometrial biopsy under direct visualization during hysteroscopy(2,28,29). The sensitivity, specificity, and positive and negative predictive values of hysteroscopy in diagnosing polyps, myomas, and endometrial hyperplasia were 100% in both groups. This finding is not in agreement with the diagnostic capability of hysteroscopy without biopsy in some studies(2,30,31). Loiacono et al.(24) diagnosed three women with endometrial carcinoma while studying women who had normal hysteroscopic findings. The sensitivity and positive predictive value of hysteroscopy decreased to 63% and 77% in their malignant cases. Our findings showed the same decrease in positive predictive value of hysteroscopy, which is consistent with their study. A limitation of our study was the small number of participants. Thus, the hysteroscopic values for endometrial malignancies’ diagnosis could not be assessed in the asymptomatic group. Of the women in AUB group, 1.5% had histologically confirmed endometrial cancer, and 5% had atypical or complex hyperplasia. However, the positive predictive value of hysteroscopy for diagnosing carcinoma was 35%. In some studies, the percentage of cancer in asymptomatic women with endometrial thickness more than 5 mm was 0.5-1.4%(32,33,34,35).

1.5% had histologically confirmed endometrial cancer, and 5% had atypical or complex hyperplasia. However, the positive predictive value of hysteroscopy for diagnosing carcinoma was 35%. In some studies, the percentage of cancer in asymptomatic women with endometrial thickness more than 5 mm was 0.5-1.4%(32,33,34,35). In a study by Elfayomy et al.(2) endometrial carcinoma was not reliably detected with hysteroscopy. In their study, 7 of 14 women (16.9%) with endometrial cancer had suspicious findings in hysteroscopy, and no abnormality was found in the other half. According to the authors, the specificity of hysteroscopy without biopsy was low in diagnosing endometrial cancer. This finding has been reported in other studies too(28,36). Therefore, it is recommended to perform a biopsy even if hysteroscopy finds no abnormality to increase the validity of hysteroscopy in diagnosing endometrial hyperplasia and cancer in post-menopausal women with bleeding or with endometrial line thickness of 5 mm or more in TVS. In our study, we compared the results of hysteroscopy with the results of histopathology in post-menopausal women with AUB or endometrial thickness of 5 mm or more. According to our findings and other studies, endometrial thickness is often due to the presence of benign lesions such as polyps and submucosal myomas(2,7,24). Our study showed that hysteroscopy is a safe and reliable method for evaluating benign endometrium lesions. In our study, all studied women had a histologic confirmation of their diagnosis, which makes our findings a desirable and optimal reference. Hysteroscopy is more accurate than transvaginal ultrasound or dilatation and curettage in the diagnosis of endometrial polyps and other space-occupying endometrial lesions in post-menopausal women(20,37). Considering the failure rate of ultrasound or dilatation and curettage in detecting some endometrial lesions, evaluation of the endometrial cavity by direct visualization is critical in diagnosing space-occupying lesions in post-menopausal women.

ther space-occupying endometrial lesions in post-menopausal women(20,37). Considering the failure rate of ultrasound or dilatation and curettage in detecting some endometrial lesions, evaluation of the endometrial cavity by direct visualization is critical in diagnosing space-occupying lesions in post-menopausal women. CONCLUSION In contrast to some studies that state that doing hysteroscopy in asymptomatic post-menopausal women with increased endometrial thickness is not cost-efficient(34,36,38) the present study showed that hysteroscopy is a safe and reliable procedure for evaluating benign lesions of endometrium such as polyps or submucosal myomas. In order to rule out endometrial hyperplasia and cancer in postmenopausal women with bleeding or asymptomatic women with endometrial thickness, performing hysteroscopy and taking endometrial biopsies is recommended even if no lesion has been found. Further long-term prospective studies with more participants are necessary to find the optimum endometrial thickness in asymptomatic postmenopausal women. The authors would like to thank Seyed Muhammed Hussein Mousavinasab for his sincere cooperation in editing this text. Ethics: Informed Consent: All participants signed an informed consent before participating in this study. Peer-review: Externally and Internally peer-reviewed.

In order to rule out endometrial hyperplasia and cancer in postmenopausal women with bleeding or asymptomatic women with endometrial thickness, performing hysteroscopy and taking endometrial biopsies is recommended even if no lesion has been found. Further long-term prospective studies with more participants are necessary to find the optimum endometrial thickness in asymptomatic postmenopausal women. The authors would like to thank Seyed Muhammed Hussein Mousavinasab for his sincere cooperation in editing this text. Ethics: Informed Consent: All participants signed an informed consent before participating in this study. Peer-review: Externally and Internally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Fatemeh Sarvi, Marzieh Aghahosseini, Concept: Ashraf Alleyassin, Design: Marzieh Ghasemi, Fatemeh Sarvi, Data Collection or Processing: Fatemeh Sarvi, Sima Gity, Analysis or Interpretation: Marzieh Ghasemi, Literature Search: Marzieh Ghasemi, Sima Gity, Fatemeh Sarvi, Writing: Marzieh Ghasemi, Sima Gity. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Hysteroscopic findings of our study groups Table 2 Comparison of the results of hysteroscopy and histopathologic findings of abnormal uterine bleeding and asymptomatic groups Table 3 Sensitivity, specificity, and positive and negative predictive values of hysteroscopy

gently removed. The vaginal septum was then dissected longitudinally using a unipolar needle electrode. After dissection, a 3-cm gap in the vaginal septum was obtained, which allowed drainage from the left uterine cavity (Figure 4). The patient tolerated the procedure well and was discharged from hospital the next day. The first follow-up visit was four weeks after the operation. She had no symptoms and no complications were observed. At the sixth month follow-up visit she reported regular and painless menstrual cycles. On ultrasound examination, no distension was observed in the uterine horns or vagina.

gently removed. The vaginal septum was then dissected longitudinally using a unipolar needle electrode. After dissection, a 3-cm gap in the vaginal septum was obtained, which allowed drainage from the left uterine cavity (Figure 4). The patient tolerated the procedure well and was discharged from hospital the next day. The first follow-up visit was four weeks after the operation. She had no symptoms and no complications were observed. At the sixth month follow-up visit she reported regular and painless menstrual cycles. On ultrasound examination, no distension was observed in the uterine horns or vagina. DISCUSSION The Müllerian duct develops craino-caudally and fuses between the 6th and 22nd gestational weeks. The prevalence of Müllerian anomalies is an issue that remains to be clarified. Discrepancies of diagnostic modalities, classification systems, terminologies, and population characteristics amongst available studies rendered this issue confounding. The estimated prevalence ranges from 0.1% to 3.8%(1). According to a largely accepted hypothesis, OHVIRA syndrome is caused by an embryonic arrest at about the 8th gestational week(2,3). It seems that an injury on the caudal portion of the mesonephric (Wolffian) duct subsequently leads to malformation and malfusion of Müllerian ducts. Injury on the mesonephric duct also results with renal anomalies. However, there are some reported cases with obstructed hemi-vagina, double uterus, and normal urinary systems, which seem to conflict with this hypothesis. Patients present with pelvic pain, dysmenorrhea, pelvic mass, and rarely with complications such as pyocolpos, endometriosis, and infertility(4). Most patients report a history of regular menses until the obstruction of the hemi-vagina resulted in distention and enlarged mass. Hence, physicians should suspect OHVIRA syndrome in young patients who present with these symptoms. Obstructed hemi-vagina and renal anomalies in OHVIRA syndrome are seen twice as frequently in the right side of the body compared with the left(5). The estimated mean age of diagnosis was defined as 14 years in the literature(2). This case had an unusual presentation considering the lateralization. These kinds of cases require a high amount of suspicion for diagnosis. Vaginal tissues are quite tense and the obstructed hemi-vagina may contain large amounts of blood. A sufficient enough absorption of blood between periods may prevent aggravation of the symptoms. Inability to perform vaginal examination on a virgin patient, lower accuracy of abdominal ultrasound, mild nature of symptoms, and lacking adequate amount of suspicion or experience may all contribute to delayed diagnosis and improper treatment, which may result in intra-abdominal infection and/or abscess.

he symptoms. Inability to perform vaginal examination on a virgin patient, lower accuracy of abdominal ultrasound, mild nature of symptoms, and lacking adequate amount of suspicion or experience may all contribute to delayed diagnosis and improper treatment, which may result in intra-abdominal infection and/or abscess. Early recognition is important in avoid complications.

INTRODUCTION Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders of women in the reproductive age group, affecting about 4 to 12% of women worldwide(1). It is characterized by a combination of hyperandrogenism (either clinical or biochemical), chronic anovulation and polycystic ovaries, and is frequently associated with insulin resistance and obesity. The underlying cause of PCOS is unknown. However, a genetic basis that is both multifactorial and polygenic is suspected, because there is well documented aggregation of the syndrome within families(2). Anti-mullerian hormone (AMH), also known as mullerian-inhibiting substance, was until recently, known mainly as a substance involved in male sexual differentiation. AMH is now considered as a marker that can estimate the quantity and activity of recruitable follicles in early stages of growth, thus being more reliable for the prediction of ovarian reserve. Women with PCOS have about 2-3 times elevated circulating and intrafollicular AMH levels. There are controversial data regarding whether the AMH excess in PCOS is related to the increment in the number of preantral follicles or due to an intrinsically increased production by granulosa cells. However, the increase may also be a consequence of other factors in PCOS such as hyperandrogenism and insulin resistance(3,4). This increased AMH is associated with retardation of follicular development.

ded metaphases were scored from each patient. Considering the criteria of the International System for Human Cytogenetic Nomenclature, three cells were karyotyped(20). In general, chromosome counts of 30 cells were undertaken; however, 50 or more cell counts were performed in the event that mosaicism was suspected(21). Statistical Analysis Statistical Package for the Social Science (SPSS 21) (IBM SPSS Version 8.5.0.0021 Licensed Materials Property of IBM Corp. Copyright IBM Corporation and others) was used for data analyses. Data analyses are expressed as mean and standard deviation. Student’s t-test and Mann-Whitney U test were used to compare clinical and biochemical data between the groups. Whether intra-group variables demonstrated normal distribution was determined using the Kolmogorov-Smirnov test. The investigation of correlation between the values was conducted using Spearman’s analysis. P values less than or equal to 0.05 were considered statistically significant.

e increment in the number of preantral follicles or due to an intrinsically increased production by granulosa cells. However, the increase may also be a consequence of other factors in PCOS such as hyperandrogenism and insulin resistance(3,4). This increased AMH is associated with retardation of follicular development. The principle behind laparoscopic ovarian drilling (LOD) in patients with PCOS is to destroy ovarian androgen-producing tissue and reduce peripheral conversion of androgens to estrogens. Specifically, a fall in serum levels of androgens and luteinizing hormone (LH) and an increase in the level of follicle-stimulating hormone (FSH) have been demonstrated after ovarian drilling(5,6). The endocrine changes following surgery are thought to convert the adverse androgen dominant intra-follicular environment to one that is estrogenic, and to restore the normal hormonal environment by correcting ovarian pituitary feedback(7). Identifying factors that determine the response of women with PCOS to LOD will help in selecting the patients who are likely to benefit from this treatment, thus avoiding fruitless treatment and improving success rate. The consistency of serum levels of AMH throughout the menstrual cycle, with very little inter cycle variability, makes it an attractive marker of response to treatment. With this background, we conducted a prospective cohort study to evaluate the effect of LOD on plasma levels of AMH in PCOS.

nd improving success rate. The consistency of serum levels of AMH throughout the menstrual cycle, with very little inter cycle variability, makes it an attractive marker of response to treatment. With this background, we conducted a prospective cohort study to evaluate the effect of LOD on plasma levels of AMH in PCOS. MATERIALS AND METHODS This is a prospective cohort study on clomiphene citrate (CC)-resistant women with anovulatory PCOS. The study was conducted in a 300-bed super specialty obstetrics and gynecology hospital and in vitro fertilization center. The women included in the study were aged between 18 to 35 years. This study was conducted over a period of one year (April 2013 to April 2014) and included 30 women who were infertile and anovulatory with CC resistant PCOS. Each woman underwent LOD. The primary outcomes were the effect of LOD on serum AMH levels and the difference between AMH levels in responders (women who ovulated) and non-responders (no ovulation). The secondary outcomes studies were the usefulness of AMH as a tool in evaluating the outcome of LOD and to assess the ovarian reserve after LOD. PCOS was diagnosed based on the 2003 Rotterdam European Society for Human Reproduction/American Society of Reproductive Medicine criteria(8). The women were followed up for a year after undergoing LOD and evaluated regarding the response to LOD in terms of ovulation and pregnancy, and also to determine whether there was any loss of ovarian function because of LOD.

European Society for Human Reproduction/American Society of Reproductive Medicine criteria(8). The women were followed up for a year after undergoing LOD and evaluated regarding the response to LOD in terms of ovulation and pregnancy, and also to determine whether there was any loss of ovarian function because of LOD. All women included in this study had normal hysteron-salpingogram and their partners had normal semen analysis according to the World Health Organization criteria(9). Blood samples were collected on day 2 of the cycle before and 1 week after LOD to measure plasma concentrations of AMH, luteinizan hormon (LH), follicle stimulating hormone (FSH), testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index {T/SHBG x 100}. Additional blood samples were collected 3 and 6 months after LOD for the measurement of AMH. Plasma samples were assayed for AMH in duplicate using a commercial enzyme-linked immunosorbent assay kit (Immunotech, Beckman-Coulter UK Ltd., High Wycombe, Buckinghamshire, United Kingdom) in accordance with the manufacturer’s protocol. The sensitivity of the assay was 0.24 ng/mL. The intraassay and interassay variabilities were 5% and 8%, respectively. Assays for LH and FSH were performed using an automated microparticle enzyme immunoassay (Abbott Axsymanalyser; Abbott Diagnostics). Assays for SHBG were performed using an automated chemiluminescent immunoassay (Immuliteanalyser; Diagnostic Products Corporation).

Additional blood samples were collected 3 and 6 months after LOD for the measurement of AMH. Plasma samples were assayed for AMH in duplicate using a commercial enzyme-linked immunosorbent assay kit (Immunotech, Beckman-Coulter UK Ltd., High Wycombe, Buckinghamshire, United Kingdom) in accordance with the manufacturer’s protocol. The sensitivity of the assay was 0.24 ng/mL. The intraassay and interassay variabilities were 5% and 8%, respectively. Assays for LH and FSH were performed using an automated microparticle enzyme immunoassay (Abbott Axsymanalyser; Abbott Diagnostics). Assays for SHBG were performed using an automated chemiluminescent immunoassay (Immuliteanalyser; Diagnostic Products Corporation). LOD was perfomed under general anesthesia using a monopolar electrocautery needle. Four punctures were made per ovary at a power setting of 40 W for 4-6 seconds at each point. If the patient did not ovulate after LOD, CC would be started 6-8 weeks after surgery on days 2-6 of the menstrual cycle. Ovulation was diagnosed by serial sonographic monitoring of follicular growth and follicular collapse with elevated serum progesterone levels 7 days later. The occurrence of ovulation or clinical pregnancy during a period of 6 months were noted. Pregnancy was diagnosed through a positive quantitative β-hCG and a definite gestational sac in an ultrasound examination.

nitoring of follicular growth and follicular collapse with elevated serum progesterone levels 7 days later. The occurrence of ovulation or clinical pregnancy during a period of 6 months were noted. Pregnancy was diagnosed through a positive quantitative β-hCG and a definite gestational sac in an ultrasound examination. Hormonal values were expressed as mean ± standard deviation. Comparison of values before and after LOD was performed using Student’s paired t-test. Comparison of values between responders and non-responders was made using Student’s independent t-test. All p-values less than 0.05 were considered significant. RESULTS The mean age of the participants was 28.3±3.5 years. The study cohort women were obese, as reflected by a high body mass index (BMI) and waist:hip ratio. Serum levels of AMH, LH, testosterone, and the LH:FSH ratio were higher in non-responders than responders before laparoscopy (Figure 1). About 80% (24/30) of women with PCOS responded to LOD as evidenced by spontaneous ovulation. The pregnancy rate was 41.66% (10/24). About 20.0% (6/30) women with PCOS were still resistant to LOD. About 58.33% (14/24) did not conceive despite the high ovulation rate (80%).

than responders before laparoscopy (Figure 1). About 80% (24/30) of women with PCOS responded to LOD as evidenced by spontaneous ovulation. The pregnancy rate was 41.66% (10/24). About 20.0% (6/30) women with PCOS were still resistant to LOD. About 58.33% (14/24) did not conceive despite the high ovulation rate (80%). Significant differences in AMH levels were observed between responders and non-responders before and after laparoscopy (p<0.001). Plasma levels of testosterone were significantly lower in responders when compared with non-responders (no ovulation). There was no significant difference in LH, LH:FSH between responders and non-responders both before and after LOD (Table 1 and 2). As a result of LOD, significant reductions in levels of AMH were observed in both responders and non-responders, but the magnitude of change was significantly higher in responders (p<0.001) when compared with non-responders (p<0.028) (Figure 2). There was no significant change in the levels of FSH in both responders and non-responders after LOD. No significant correlation was observed between plasma levels of AMH and age, BMI, LH or FSH. There was a significant positive correlation noted between plasma AMH and testosterone levels (any statistical test?). LOD led to reduced levels of AMH in patients with PCOS, but these changes were not statistically significant and only indicated the patient’s normality and had no negative impact on ovarian reserve.

H. There was a significant positive correlation noted between plasma AMH and testosterone levels (any statistical test?). LOD led to reduced levels of AMH in patients with PCOS, but these changes were not statistically significant and only indicated the patient’s normality and had no negative impact on ovarian reserve. A cut-off level of AMH was identified as 8.3 ng/mL, above which the chances of ovulation seemed to be significantly reduced. Women with AMH >8.3 ng/mL showed a significantly (p<0.001) lower ovulation rate (33.3%) than that of women with AMH <8.3 ng/mL (100%). Significant differences were observed in AMH levels before and after LOD, which may indicate a possible diminished ovarian reserve. Although the AMH values after LOD were found lower than those before LOD, the after values stayed higher than normal when compared with normal women without PCOS.

th AMH <8.3 ng/mL (100%). Significant differences were observed in AMH levels before and after LOD, which may indicate a possible diminished ovarian reserve. Although the AMH values after LOD were found lower than those before LOD, the after values stayed higher than normal when compared with normal women without PCOS. DISCUSSION The present study shows a positive correlation between plasma AMH and testosterone values in anovulatory women with PCOS. This agrees with the study conducted by Poujade O et al and many others(10). This positive association is explained by the stimulatory effect of androgens on the primodial follicular growth and granulosa cell proliferation that increases AMH secretion, or the inhibitory effect of AMH on aromatase activity, leading to an increase in androgens(10,11). Another cause for the increase in AMH and androgens in PCOS is secondary to hyperinsulinemia, because it enhances gonadotropin-stimulated steroid production in granulosa and theca cells. A possible explanation for the 58.33% of women with PCOS not conceiving, despite the high ovulation rate after LOD, is that the amount of ovarian tissue destroyed during LOD may not have been enough to induce favorable changes on reproductive parameters by reducing intraovarian AMH to a level consistent with resumption of ovulation. This study shows a significant decrease in serum testosterone, LH, and LH:FSH ratio, one week after LOD. These findings are in agreement with many previous studies(12,13). Although the after LOD values were found lower than the before LOD values with ovarian reserve markers, the after values remained higher in non-responders when compared with the responders. Previous studies have shown that the ovarian reserve in women with PCOS was found higher than in women with normal menstruation(13).

though the after LOD values were found lower than the before LOD values with ovarian reserve markers, the after values remained higher in non-responders when compared with the responders. Previous studies have shown that the ovarian reserve in women with PCOS was found higher than in women with normal menstruation(13). It can be deduced from earlier studies that LOD normalizes ovarian function, which is significant in follicular recruitment and maturation, and has no negative effect on ovarian reserve. It seems that the ovarian tissue damage occurs during and continues only for a short period after LOD, as evidenced by the fact that the AMH and FSH levels did not correlate with time since LOD(13,14). The reduction in AMH levels results from the bilateral diathermy technique where the androgen producing stroma is destroyed. There is a decrease in ovarian stromal blood flow and subsequently vascular endothelial growth factor and insulin-like growth factor 1, which are high in PCOS. In our study, LOD appeared not to be associated with an increased risk of diminished ovarian reserve. Most of the changes in ovarian reserve markers in the current work after LOD could be interpreted with the normalization of ovarian function in the enrolled women with PCOS rather than the reduction of ovarian reserve.

In our study, LOD appeared not to be associated with an increased risk of diminished ovarian reserve. Most of the changes in ovarian reserve markers in the current work after LOD could be interpreted with the normalization of ovarian function in the enrolled women with PCOS rather than the reduction of ovarian reserve. Similar to the study by Api(15), we found that the ovarian reserve of patients with PCOS did not change significantly after LOD, and the reduction of AMH after LOD may be referred to as the normalization of women with PCOS after LOD. Thus, the likelihood of traumatic injury to ovaries as because of LOD is negligible. Overall, it seems that although LOD leads to a reduction in AMH levels in women with PCOS, these are not statistically significant and only indicate the patient’s normality and has no negative impact on ovarian reserve(15).

after LOD. Thus, the likelihood of traumatic injury to ovaries as because of LOD is negligible. Overall, it seems that although LOD leads to a reduction in AMH levels in women with PCOS, these are not statistically significant and only indicate the patient’s normality and has no negative impact on ovarian reserve(15). CONCLUSION Based on the results of this study, LOD is recommended as an effective first-line treatment in women with PCOS who are anovulatory and clomiphene resistant. LOD has no negative effect on ovarian reserve, as shown by the markers of ovarian reserve such as FSH and AMH during the follow-up period. It is also recommended that women who are candidates for undergoing LOD may benefit from the measurement of serum AMH concentration to determine their likelihood of response to LOD. Women found to have high serum AMH levels (>8.3 ng/mL) can be counselled about the lower chances of responding to LOD. It is also recommended that using AMH as a reliable marker of ovarian reserve and measuring it in women with anovulatory PCOS undergoing LOD may provide a tool for predicting the outcome of LOD. Ethics: Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Peer-review: Internally peer-reviewed.

Ethics: Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Peer-review: Internally peer-reviewed. Table 1 Comparison of variables between responders and non-responders before laparoscopic ovarian drillin Table 2 Comparison of different variables between responders and non-responders after laparoscopic ovarian drilling Figure 1 Comparison of variables among responders and non-responders before and after laparoscopic ovarian drilling LH: Luteinizing hormone, FSH: Follicle-stimulating hormone, AMH: Anti-mullerian hormone, T: Testosterone, SHBG: Sex hormone-binding globülin, FAI: Free androgen index, LOD: Laparoscopic ovarian drilling Figure 2 Anti-mullerian hormone values before and after laparoscopic ovarian drilling among polycystic ovarian syndrome women AMH: Anti-mullerian hormone, LOD: Laparoscopic ovarian drilling

PRECIS: The management of a girl aged 13 years with obstructed hemivagina and ipsilateral renal anomaly syndrome is presented. INTRODUCTION Obstructed hemi-vagina and ipsilateral renal anomaly (OHVIRA) syndrome, traditionally known as Herlyn-Werner-Wunderlich syndrome, is a rare clinical entity of Müllerian anomalies, which has been reported as case reports since 1922. Obstructive mullerian anomalies are estimated to affect approximately 0.1-3.8% of the female population(1). It mainly presents with cyclical and or chronic pelvic pain and pelvic swelling while having regular cycles due to hematometrocolpos in the obstructed hemi-vagina. The classic presentation of OHVIRA syndrome is that of a postmenarchal girl with remittent pelvic pain, usually associated with menstruation, and a vaginal bulge on pelvic examination and/or foul discharge. The growing experience of OHVIRA syndrome in literature has familiarized physicians with this condition. However, delays in diagnosis are still a concern that may lead to complications such as chronic infection, endometriosis, and adhesions, which result in subfertility or infertility. Herein, we describe the evaluation and surgical management of a girl with OHVIRA syndrome who was diagnosed using magnetic resonance imaging (MRI) and pelvic ultrasound examination.

ncern that may lead to complications such as chronic infection, endometriosis, and adhesions, which result in subfertility or infertility. Herein, we describe the evaluation and surgical management of a girl with OHVIRA syndrome who was diagnosed using magnetic resonance imaging (MRI) and pelvic ultrasound examination. CASE REPORT A girl aged 13 years was referred to our hospital because of cyclical pain in the lower abdomen, which she had had for the last two months, hindering her daily activities. The patient denied having any recent abdominal trauma, vomiting or diarrhea, and menarche had occurred at age 12 years. She was not sexually active and under any medical treatment. The laboratory tests including complete blood count, tumor markers, and beta human chorionic gonadotropin were within normal ranges. An abdominal ultrasound examination revealed absence of the left kidney and a cystic mass adjacent to the uterus that filled the left half of the pelvis. The uterus was of normal size and shape with myometrium, cervix, and vagina. The abdominopelvic MRI scan demonstrated an enlarged mass consistent with hematometrocolpos, a uterus didelphys, along with left renal agenesis (Figures 1, 2). In the hospital where she was first admitted, a suprapubic catheter was placed into the left obstructed hemi-vagina under ultrasound guidance by the department of interventional radiology. Although the hematometrocolpos was drained, it was not a definitive treatment. On admission to our clinic, she had no pain but a suprapubic catheter that was sutured to skin. The external genitalia were normal. After the patient and her family were informed, vaginal examination was performed under general anesthesia. Vaginoscopy and hysteroscopy were performed in the lithotomy position without hymenotomy. The left hemi-vagina was blunt. After clear visualization of the right vagina, the vaginal septum was dissected using a hysteroscopic unipolar needle electrode. The left hemi-vaginal and uterine cavities were observed, along with the suprapubic drainage catheter (Figure 3). The supra-pubic catheter placed in the left obstructed hemi-vagina was gently removed. The vaginal septum was then dissected longitudinally using a unipolar needle electrode. After dissection, a 3-cm gap in the vaginal septum was obtained, which allowed drainage from the left uterine cavity (Figure 4). The patient tolerated the procedure well and was discharged from hospital the next day.

he symptoms. Inability to perform vaginal examination on a virgin patient, lower accuracy of abdominal ultrasound, mild nature of symptoms, and lacking adequate amount of suspicion or experience may all contribute to delayed diagnosis and improper treatment, which may result in intra-abdominal infection and/or abscess. Early recognition is important in avoid complications. In cases of OHVIRA, the vaginal septum is generally longitudinal and has variable thickness. Abdominal ultrasonography has been the preferred initial imaging modality; MRI should be considered for diagnosis and decision making if there is a suspicious morphology of the uterus and adnexa(2,3). The association between OHVIRA syndrome and other urogenital abnormalities can be better evaluated using MRI. MRI is far better than ultrasound for characterizing anatomic relationships owing to its multiplanar capabilities and larger field of view. However, the gold standard for diagnosis is laparoscopy, which has the added benefit of performing therapeutic drainage of hematometra/hematocolpos, vaginal septotomy, and marsupialization. Treatment usually involves surgery in the form of excision of the vaginal septum, which helps to relieve the obstruction. Previously, a two-step surgical approach including drainage and resection of the septum was performed. Also, hymenotomy was favored for better visualization. However, with improved surgical capabilities, it is possible to complete the surgery in one procedure without hymenotomy. Prognosis is good, with the major concern being preservation of fertility. However, symptom recurrence due to vaginal adhesions is possible. In such a condition, silicon dilators can be used following re-resection(6). Women with uterus didelphys have a high likelihood of becoming pregnant, with approximately 80% of patients able to conceive, but with elevated rates of premature delivery (22%) and abortion (74%); cesarean section is necessary in over 80% of patients(7). Understanding the imaging findings is critical for early diagnosis in an attempt to prevent complications such as endometriosis or adhesions from chronic infections with subsequent infertility.

with elevated rates of premature delivery (22%) and abortion (74%); cesarean section is necessary in over 80% of patients(7). Understanding the imaging findings is critical for early diagnosis in an attempt to prevent complications such as endometriosis or adhesions from chronic infections with subsequent infertility. CONCLUSION OHVIRA syndrome is a rare congenital anomaly with different clinical presentations. Ultrasound and MRI are the initial imaging modalities and laparoscopy is the gold standard for diagnosis. The main treatment modality is the resection of the vaginal septum through vaginoscopy without hymenotomy. Ethics: Informed Consent: Consent form was filled out by the patient. Peer-review: Externally and Internally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Cem Atabekoğlu, Yavuz Emre Şükür, Batuhan Turgay, Concept: Cem Atabekoğlu, Yavuz Emre Şükür, Design: Betül Yakıştıran, Cem Atabekoğlu, Data Collection or Processing: Betül Yakıştıran, Batuhan Turgay, Analysis or Interpretation: Cem Atabekoğlu, Yavuz Emre Şükür, Literature Search: Betül Yakıştıran, Writing: Betül Yakıştıran. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Authorship Contributions: Surgical and Medical Practices: Cem Atabekoğlu, Yavuz Emre Şükür, Batuhan Turgay, Concept: Cem Atabekoğlu, Yavuz Emre Şükür, Design: Betül Yakıştıran, Cem Atabekoğlu, Data Collection or Processing: Betül Yakıştıran, Batuhan Turgay, Analysis or Interpretation: Cem Atabekoğlu, Yavuz Emre Şükür, Literature Search: Betül Yakıştıran, Writing: Betül Yakıştıran. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 Magnetic resonance image demonstrating uterus didelphys with left hematometrocolpos Figure 2 Magnetic resonance image demonstrating left renal agenesis Figure 3 Suprapubic drainage catheter placed in the left obstructed hemi-vagina Figure 4 Vaginal septum and both vaginal spaces after dissection with a unipolar needle electrode

INTRODUCTION Aortic dissection is the separation of the aortic wall layers and formation of a true lumen and a false lumen. Acute aortic dissection in pregnant women is a rare but potentially life-threatening event. It is usually related to severe hypertension due to preeclampsia, coarctation of the aorta or connective tissue disorders such as Marfan’s syndrome. Aortic dissection may occur at any time during gestation (5% in the first trimester, 10% in the second trimester, 50% in the third trimester, and 20% postpartum)(1). Postpartum aortic dissection occurs between day 1 and day 42 after either vaginal or cesarean section delivery. We report a young woman without Marfan’s syndrome who developed postpartum ascending aortic dissection 5 days after she delivered a healthy female infant by cesarean section.

rimester, and 20% postpartum)(1). Postpartum aortic dissection occurs between day 1 and day 42 after either vaginal or cesarean section delivery. We report a young woman without Marfan’s syndrome who developed postpartum ascending aortic dissection 5 days after she delivered a healthy female infant by cesarean section. CASE REPORT A multiparous women aged 40 years who had an uneventful cesarean section 5 days previously was admitted to the emergency department with severe chest and back pain. According to information gained from the patient, she had regular antenatal checkups, she had no history of serious illness (chronic hypertension, cardiac disease, kidney disease, or connective tissue disorder), operations, or hospitalization. She had no family history of connective tissue diseases or signs of Marfan’s syndrome, and did not have preeclampsia or perinatal or prior heart disease. When she arrived at the hospital, her blood pressure was 160/60 mmHg, heart beat was 65 beats per minute, electrocardiography was normal, and D-dimer was high (2.860 ng/mL). The patient was referred to our hospital with a diagnosis of pulmonary embolism. Thoracal computed tomography angiography (CTA) showed type A aortic dissection (Figure 1). There was a dissection flap that started from the ascending aorta and extended into the iliac arteries. The diameter of ascending aorta was 43 mm. Transthoracic echocardiography revealed that her ejection fraction was 65%, and there was minimal regurgitation of the aortic valve. She was taken to the operating room.

1). There was a dissection flap that started from the ascending aorta and extended into the iliac arteries. The diameter of ascending aorta was 43 mm. Transthoracic echocardiography revealed that her ejection fraction was 65%, and there was minimal regurgitation of the aortic valve. She was taken to the operating room. Under deep hypothermic circulatory arrest, an ascending aortic replacement was performed. Four hours postoperatively, she was taken into surgery again due to major bleeding and hypotension. Surgery revealed that the dissection had progressed to the aortic root. Cardiopulmonary bypass was begun, and a Bentall operation was performed. Unfortunately, the patient could not tolerate this second operation and died of uncontrollable bleeding. DISCUSSION Aortic dissection can occur in pregnancy or during the postpartum period without pre-existing disease due to hormonal changes, regardless of whether delivery was vaginal or by cesarean section. After hypertension and Marfan’s syndrome, pregnancy is the most common risk associated with aortic dissection, a potentially deadly event.

ction can occur in pregnancy or during the postpartum period without pre-existing disease due to hormonal changes, regardless of whether delivery was vaginal or by cesarean section. After hypertension and Marfan’s syndrome, pregnancy is the most common risk associated with aortic dissection, a potentially deadly event. The increase of estrogen and progestogen in the third trimester of pregnancy may add additional risk because the aorta expresses oestrogen and progestogen receptors(2). Peripartum hormonal changes can cause fragmentation of reticular fibers, decreases in the amount of acid mucopolysaccharides, and damage to the normal shapes of elastic fibers, thereby increasing the risk of aortic dissection. These changes in the structure of the aorta during pregnancy have been reported to be similar to the medial degeneration pattern found in patients with aortic dissection. Cardiovascular stresses such as pressure, heart rate, stroke volume, cardiac output, left ventricular mass, and blood volume are increased by pregnancy, and may cause hemodynamic stress on the aortic wall(2). With the termination of puerperal uteroplacental circulation and uterine contraction, along with interstitial fluid absorption, the circulating volume could be increased by 15-25% within 72 h of delivery in a postpartum woman(3). Thus, the third trimester of pregnancy or immediate postpartum stage is the most common interval during which aortic dissection occurs.

tal circulation and uterine contraction, along with interstitial fluid absorption, the circulating volume could be increased by 15-25% within 72 h of delivery in a postpartum woman(3). Thus, the third trimester of pregnancy or immediate postpartum stage is the most common interval during which aortic dissection occurs. During pregnancy, the aorta and the vessel wall structures are generally weaker and more sensitive to hemodynamic forces. These pregnancy-related hemodynamic stresses and hormonal changes are the main factors for the development of aortic dissection(4). CTA and transesophageal echocardiogram are the gold standard for the diagnosis of aortic dissection. CTA provides important information about the extent of dissection, the relation between the true and false lumen, and aortic branch compromise. The complications of aortic dissection are aortic rupture, aortic regurgitation, acute myocardial infarction, tamponade, and end-organ ischemia. Back pain, chest pain, lower extremity ischemia and paraplegia are common symptoms of aortic dissection. If dissection involves the great vessels to the brain, loss of consciousness or signs of stroke may be seen. Survival is directly related to the timing of emergency intervention because the mortality rate increases 1 to 2% every hour during the first 24 to 48 hours after dissection(5). Open surgical repair of type A dissections is recommended.

e great vessels to the brain, loss of consciousness or signs of stroke may be seen. Survival is directly related to the timing of emergency intervention because the mortality rate increases 1 to 2% every hour during the first 24 to 48 hours after dissection(5). Open surgical repair of type A dissections is recommended. Yuan(3) evaluated 27 patients with postpartum aortic dissection. Pain was the most common symptom at onset, as it was in our petient. Sixteen (59.3%) patients had type A aortic dissections and four (14.8%) died(3). Yang et al.(6) reported 11 paients who had aortic dissection during the course of pregnancy or puerperium. They found 6 patients during the postpartum stage, 4 of whom had type A aortic dissections and 2 died. Immer et al.(7) reported 5 patients with postpartum type A aortic dissections, one patient died. Late presentation, delayed or misdiagnosis may be associated with postpartum aortic dissection because of its rarity(8). The differential diagnoses of severe chest pain include acute myocardial infarction, pulmonary embolism, and aortic dissection(8). Normal electrocardiogram cardiac enzymes are needed to exclude myocardial infarction. Normal coagulation test results and D-dimer level help rule out pulmonary embolism; the level of D-dimer was high in our case.

ses of severe chest pain include acute myocardial infarction, pulmonary embolism, and aortic dissection(8). Normal electrocardiogram cardiac enzymes are needed to exclude myocardial infarction. Normal coagulation test results and D-dimer level help rule out pulmonary embolism; the level of D-dimer was high in our case. In the present case, the cause of death was the progress of dissection and uncontrolled bleeding. The patient reported here was known to have had normal blood pressure throughout her pregnancy and had no risk factors such as trauma, smoking, drug or alcohol abuse. She also had no family history of Marfan’s syndrome. CONCLUSION This case suggests that acute aortic dissection can occur postpartum in young women who are normotensive and without Marfan’s syndrome. Therefore, it is important to consider aortic dissection as a possible diagnosis during pregnancy and also after delivery. Aortic dissection is easily misdiagnosed as other cardiac, muscular, neurologic, esophageal or renal diseases because it may present with different clinical symptoms, such as back, chest, epigastric and abdominal pain, and cardiac arrest, which could potentially lead to the death of a new mother. Thus, obstetricians should consider aortic dissection as a possible diagnosis when these symptoms present in a postpartum woman. We acknowledge the medical writing assistance provided by American Manuscript Editors (www.americanmanuscripteditors.com) for the final draft of the manuscript. The authors report no declarations of interest. Ethics: Informed Consent: It was taken.

CONCLUSION This case suggests that acute aortic dissection can occur postpartum in young women who are normotensive and without Marfan’s syndrome. Therefore, it is important to consider aortic dissection as a possible diagnosis during pregnancy and also after delivery. Aortic dissection is easily misdiagnosed as other cardiac, muscular, neurologic, esophageal or renal diseases because it may present with different clinical symptoms, such as back, chest, epigastric and abdominal pain, and cardiac arrest, which could potentially lead to the death of a new mother. Thus, obstetricians should consider aortic dissection as a possible diagnosis when these symptoms present in a postpartum woman. We acknowledge the medical writing assistance provided by American Manuscript Editors (www.americanmanuscripteditors.com) for the final draft of the manuscript. The authors report no declarations of interest. Ethics: Informed Consent: It was taken. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Mihriban Yalçın, Melih Ürkmez, Concept: Mihriban Yalçın, Design: Kaptanı Derya Tayfur, Data Collection or Processing: Serkan Yazman, Analysis or Interpretation: Mihriban Yalçın, Serkan Yazman, Literature Search: Mihriban Yalçın, Writing: Mihriban Yalçın. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 The computed tomography angiography showing the dissection

INTRODUCTION Cholangiocellular carcinomas are rare adenocarcinoma tumors of the bile ducts that may arise anywhere along the biliary tree. Cholangiocellular carcinomas involving the junction of the right and left bile ducts are called Klatskin tumors(1). Ovarian metastases of these tumors are very rare clinical presentations(2). We report bilateral ovarian metastases of a Klatskin tumor because of its rarity, aggressive structure, and difficulties in its management.

llular carcinomas involving the junction of the right and left bile ducts are called Klatskin tumors(1). Ovarian metastases of these tumors are very rare clinical presentations(2). We report bilateral ovarian metastases of a Klatskin tumor because of its rarity, aggressive structure, and difficulties in its management. CASE REPORT A gravida 4, parity two woman aged 54 years who was three years menopausal underwent surgery for cholangiocellular cancer, type B, one year ago (T3BN0, Stage 3B). She received gemcitabine and 5-fluorouracil infusion therapy every two weeks for 8 cycles and chemoradiation with 5-fluorouracil infusions after surgery. After one year, she was admitted to the emergency unit with the main symptoms of abdominal swelling and pain. An abdominal ultrasound scan revealed bilateral ovarian masses and she was referred to our gynecologic oncology section of the department of obstetrics and gynecology. The gynecologic examination of the external genitalia was compatibly normal regarding her age. Bimanual examination revealed a mass that filled the pelvis and extended to the umbilicus. Magnetic resonance imaging showed a cystic, hemorrhagic mass with polypoid protrusions from the cyst wall, measuring 105x95x65 mm, originating from the left ovary. There was also a tumor on the right ovary sized 3.5x4x5 cm, which shared the same properties. Hematologic and biochemical tests were normal. Serum tumor markers calcium (CA) 125 and CA 19-9 were 35.8 U/mL and 1782.7 U/mL, respectively. Upper and lower gastrointestinal system endoscopies were also found normal. She underwent a diagnostic laparotomy. A lobulated 18x20 cm mass that originated from the left ovary and filled the pelvis, and a 5x6-cm cystic septal lesion originating from the right ovary were observed in the lower abdomen (Figure 1). No tumor formation or implant was diagnosed in the pelvic peritoneum or in the upper abdomen. Peritoneal wash fluid and multiple peritoneal biopsies were taken from all quadrants. The left adnexal mass was excised and sent for frozen section examination. The result of frozen section examination was reported as a malignant tumor with mucinous features. Debulking surgery was performed. Microscopic examination of paraffin sections from bilateral ovaries and omentum revealed mucinous adenocarcinoma (Figure 2). Malignant cells were also observed in the peritoneal wash fluid.

he result of frozen section examination was reported as a malignant tumor with mucinous features. Debulking surgery was performed. Microscopic examination of paraffin sections from bilateral ovaries and omentum revealed mucinous adenocarcinoma (Figure 2). Malignant cells were also observed in the peritoneal wash fluid. A pathologic evaluation was also performed by comparing the findings of the previous material diagnosed as Klatskin tumor with the wash fluid sample and it was observed that both materials had similar characteristics of the same tumor. Immunohistochemical marker tests were performed to determine the tumor’s primary origin. There was positive staining for CDX2, cytokeratin 19, and cytokeratin 20 detected in the tumor cells. Cytokeratin 7, PAX8, estrogen, and progesterone receptors were found negative. The immunohistochemical findings supported pancreaticobiliary and gastrointestinal origin. The final result of the pathologic examination confirmed a metastatic adenocarcinoma of the hepatic ducts.

cytokeratin 20 detected in the tumor cells. Cytokeratin 7, PAX8, estrogen, and progesterone receptors were found negative. The immunohistochemical findings supported pancreaticobiliary and gastrointestinal origin. The final result of the pathologic examination confirmed a metastatic adenocarcinoma of the hepatic ducts. DISCUSSION Ovarian cancer remains an important place among gynecologic cancers because of the high mortality rate. The ovaries are also the target organs for metastasis from many malignancies. Metastatic cancers of the ovary constitute 5-10% of total ovarian tumors, and 10-30%’s of total malignant ovarian tumors(2). The incidence of metastatic ovarian tumors is increasing and the rates vary by countries. Frequency of metastatic ovarian cancer in Japan is reaching up to 40% because of high incidence of gastric cancers. However it is decreasing to 3% in Uganda(3). In addition, the immunohistochemical markers which are used to diagnose the primary origin also contribute to increasing incidence(2). The differential diagnosis of primary and metastatic tumors may be difficult. The pathological evaluation should be done with clinical evaluation in determining the primary origin. Metastatic ovarian cancer can mimic primary ovarian cancers, so imaging methods may be insufficient. The most common non-genital system tumors which metastasize to the ovary are from gastrointestinal system such as; breast, and hematopoietic systems(2).

e done with clinical evaluation in determining the primary origin. Metastatic ovarian cancer can mimic primary ovarian cancers, so imaging methods may be insufficient. The most common non-genital system tumors which metastasize to the ovary are from gastrointestinal system such as; breast, and hematopoietic systems(2). The structure of the ovary during the intraoperative observation may help for clinic differential diagnosis. The macroscopic presence of bilateral tumor, the implant on the ovarian surface, extra-ovarian mass and solid cystic components may be a predictor of metastatic ovarian tumors. All the bilateral tumors and unilateral tumors smaller than 10 cm are more likely to be metastatic cancer; and the unilateral tumors larger than 10 cm are more likely to have a primary ovarian origin(4).

the ovarian surface, extra-ovarian mass and solid cystic components may be a predictor of metastatic ovarian tumors. All the bilateral tumors and unilateral tumors smaller than 10 cm are more likely to be metastatic cancer; and the unilateral tumors larger than 10 cm are more likely to have a primary ovarian origin(4). A mucinous adenocarcinoma of the ovary can be the primary mucinous adenocarcinoma of the ovary or as in our case can originate from other organs or systems which can develop mucinous adenocarcinoma, including particularly the gastrointestinal tract. Histopathological features including infiltrative and nodular invasion pattern, lymphovascular invasion and the presence of signet ring cells can alert for the metastases(4). In addition, immunohistochemical markers can contribute to determining of the primary origin. However, in the presence of an ovarian tumor with mucinous adenocarcinoma morphology, the similarity in immunohistochemical findings of the primary and metastatic tumors should be kept in mind. Therefore; histopathological features, medical history, clinical and laboratory findings should be evaluated for the discrimination of primary or metastatic tumor. Although there are not any specific tumor markers for cholangiocellular carcinoma, increased levels of CA 19.9 (>100 U/mL) should be significant for pancreatic and cholangiocellular carcinomas(5). Despite the fact that the normal appearance of gastro intestinal system and pancreas, increased levels of CA 19.9 (1782.7 U/mL) is remarkable in our case and appropriate with isolated ovarian metastasis. Besides it has been reported that elevated levels of CA 19.9 is correlated with poor prognosis and advanced stage disease(6). The metastasis rate from the biliary tumors to the ovaries is very low in the current literature(1). The cases diagnosed with ovarian metastasis before the diagnosis of primary cholangiocellular carcinoma would show much worse prognosis(7). Whenever synchronous or metachronous metastases progress, identified surgical resection should be always recommended to these patients(8). In conclusion, metastatic ovarian tumors are a challenging condition for the gynecologists. The difficulties in the differential diagnosis of the metastatic and primary ovarian tumors required a detailed analysis.

nous metastases progress, identified surgical resection should be always recommended to these patients(8). In conclusion, metastatic ovarian tumors are a challenging condition for the gynecologists. The difficulties in the differential diagnosis of the metastatic and primary ovarian tumors required a detailed analysis. As many distant organs and tissues may metastasize to the ovaries the patients should be evaluated with medical history, examination of the genital and non-genital system, laboratory findings, as well as intraoperative observation. Prognosis of metastatic ovarian tumors is worse than the primary tumors. Multidisciplinary approach is important in the management of such tumors. Ethics: Informed Consent: Consent form was filled out by all participants. Peer-review: Internally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Sefa Kurt, İbrahim Astarcıoğlu, Concept: Sefa Kurt, Çağnur Ulukuş, Design: Sefa Kurt, Çağnur Ulukuş, Data Collection or Processing: Sefa Kurt, Seher Nazlı Kazaz, Analysis or Interpretation: Sefa Kurt, Seher Nazlı Kazaz, Literature Search: Sefa Kurt, Writing: Sefa Kurt. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Figure 1 A lobulated metastatic mass originated from the left adnexa, measuring 18x20 cm Figure 2 Mucinous adenocarcinoma. Atypical tumor cells containing mucin formed adenoid structures. Also, the stroma between tumor cells and the lumen of mucin formed adenoid structures is shown (hematoxylin&eosin, x100)

INTRODUCTION Angular pregnancy was first defined in 1898 by the American obstetrician Howard Kelly as implantation of the embryo just medial to the uterotubal junction, in the lateral angle of the uterine cavity(1,2). Angular pregnancy is distinguished from interstitial pregnancy by embryoposition where lateral uterine enlargement of an angular pregnancy displaces the round ligament upward and outward, whereas interstitial tubal pregnancy is located lateral to the round ligament(1). No absolute anatomic boundaries distinguish angular pregnancies from normal pregnancies, but the closer the location to the lateral angle of the uterus, the more it may cause visual asymmetry, symptoms, and adverse events when the pregnancy progresses(3). Angular pregnancy is potentially dangerous and may lead to complications during pregnancy and delivery, such as persistent pelvic pain and bleeding, spontaneous abortion, uterine rupture, retained placenta, placenta accreta, and severe bleeding leading to hysterectomy(1,4,5). Diagnosis is difficult, many cases may actually go undiagnosed. To the best of our knowledge, no reports have delineated the entire natural course of angular pregnancy from early diagnosis to delivery. We aimed to discuss the possible outcomes of an angular pregnancy and highlight the problems encounered during follow-up.

gnosis is difficult, many cases may actually go undiagnosed. To the best of our knowledge, no reports have delineated the entire natural course of angular pregnancy from early diagnosis to delivery. We aimed to discuss the possible outcomes of an angular pregnancy and highlight the problems encounered during follow-up. CASE REPORT A woman aged 34 years with a prior cesarean delivery, without symptoms, was admitted for a routine first antenatal examination in her 6th gestational week. Endovaginal sonography showed a gestational sac located in the right lateral angle of the uterine cavity. The gestational sac was covered by endometrium of the medial aspect of the uterotubal junction, and the endometrial thickness was continuous with central endometrial lining (Figure 1A, B, C). We informed the patient about possible the diagnoses, natural courses, and complications. After discussing the risks, the patient requested to continue the pregnancy and close follow-up was decided. She presented with slight but disturbing abdominal pain and intermittent vaginal bleeding at 9 weeks. Sonography revealed a gestational sac in the right uterine angle, which was continuing to grow towards the cavity (Figure 1D). However, the uterine growth was asymmetrical. Vaginal spotting resolved after 2 weeks. The pregnancy’s development towards the uterine cavity continued, the base of the placenta was located in the right uterine angle (Figure 2A). The patient was admitted to the hospital at 27 weeks’ gestation because of vaginal bleeding and mild uterine contractions. Sonography revealed a 9x4 cm subcorionic hematoma, anterior and next to the edge of the placenta (Figure 2B). There was no placental abruption. Tocolysis was initiated and antenatal corticosteroid was given because the fetus was immature. The hematoma areas were stabilized aboutfor 5 weeks.

d mild uterine contractions. Sonography revealed a 9x4 cm subcorionic hematoma, anterior and next to the edge of the placenta (Figure 2B). There was no placental abruption. Tocolysis was initiated and antenatal corticosteroid was given because the fetus was immature. The hematoma areas were stabilized aboutfor 5 weeks. Intermittent vaginal bleeding continued. Fetal biometry continued to progress appropriate to the gestational week. A cesarean section was performed at 32 weeks of gestation because of uterine contractions and dilatation of the cervix. A 1650-g female fetus was delivered. The uterus was seen asymetrically enlarged, the right uterine angle region was bulging. Upon exteriorizing the uterus, a 9x9 cm sacculation was seen (Figure 2C, D). The vessels were excessive and the area was bluishly discolored due to the placental location. The placenta was delivered manually and with difficulty. This area was very thin and lacking myometrial tissue, as confirmed by intrauterine and extrauterine palpation. Due to the continuation of bleeding, 3 square compression sutures with absorbable 0 poliglecaprone were placed passing anterior to the posterior uterine wall where the bleeding was intense. Myometrial contraction was accomplished. Obliteration of this saccular area was confirmed through intrauterine digital examination. The surgery was completed without any further complications. Bleeding was not observed, and the patient was discharged after 72 h.

he posterior uterine wall where the bleeding was intense. Myometrial contraction was accomplished. Obliteration of this saccular area was confirmed through intrauterine digital examination. The surgery was completed without any further complications. Bleeding was not observed, and the patient was discharged after 72 h. DISCUSSION Angular pregnancy is a rare and life-threatening obstetric complication in which the embryo is implanted in the lateral angle of the uterine cavity medial to the uterotubal junction and round ligament(1). Contrary to interstistial pregnancy, which locate in the muscular layer of the origin of tuba uterina and surrounded by myometrial layer, in angular pregnancy the embryo locates in the lateral wall endometrial thickness of the uterus(6,7). The surrounding endometrial tissue of embryo is continuous with the intracavitary endometrial line. A strict distinction between these three conditions is clinically important, because their findings, management, and outcomes are different(7). Interstitial pregnancy may progress without symptoms until inevitable rupture occurs at 12-16 weeks(6,7). Cornual pregnancy refers to a pregnancy in a rudimentary horn of a septate or bicornuate uterus(6). In angular pregnancy, the embryo may abort or develop in the uterine cavity(1). In contrast to interstitial pregnancy, angular pregnancy can progress to term(1,4). If a patient presents at an advanced gestational age, the physician should suspect angular pregnancy if thickened placenta is located in an asymmetrically confined area of the uterine angle(3). In the second and third trimester, the placenta may be seen limited to the uterine angle. Contrary to the normal placental growth pattern, the placenta of angular pregnancy must adopt a rigid uterine angle shape. In our opinion, the asymmetric appearance of the uterus, non-vertex fetal presentation, thickened placenta, placental adhesion anomalies, and muscular weakness of the area resulting from placental growth in the restricted, rather sharp edges of the uterine angle. This asymmetry can be seen and palpated in a thin patient in an abdominal examination. It is difficult to diagnose an angular pregnancy with certainty and to differentiate them from other abnormal implantations using ultrasound, because the main anatomic landmark (round ligament) is not visualized with this technique(6). However, angular pregnancy can be accurately diagnosed with endovaginal sonography, especially during early gestational weeks.

gnancy with certainty and to differentiate them from other abnormal implantations using ultrasound, because the main anatomic landmark (round ligament) is not visualized with this technique(6). However, angular pregnancy can be accurately diagnosed with endovaginal sonography, especially during early gestational weeks. Alternatively, 3-D ultrasound and magnetic resonance exams can facilitate diagnosis, reduce the possibility of diagnosis failure, evaluate placenta implantation anomalies, and predict the risk of uterine rupture(3,4,6,8). However, when magnetic resonance is not available, we believe that the most useful approach for an exact diagnosis is sequential ultrasound evaluations to determine whether the gestational growth is towards the uterine cavity. Angular pregnancies either terminate spontaneously or proceed to term. Even spontaneous termination might be complicated by improper separation of the placenta. A full-term delivery is likely if the gestational sac descends into the uterine cavity(1,4). Jansen and Elliott(1) reviewed 39 cases of suspected angular pregnancies and reported that 38.5% (10 of 26) had spontaneous or missed abortions, and 13.6% (3 of 22) had uterine ruptures. Recurrent bleeding can continue throughout pregnacy. The increased risk of preterm delivery, placental abruption, growth restriction, and postpartum endometritis is associated with angular pregnancy(3,8). Abnormal fetal position can be seen, as our case was always in the breech presentation. Potential disadvantages of expectant management may include catastrophic complications such as uterine rupture. This management can be chosen by patient decision. It is necessary to counsel patients about the possible complications and close monitoring and frequent ultrasound examination should be conducted. What complicates the decision for expectant management is that there are no early sonographic signs to establish prognostic factors, although the risk of adverse outcomes can be expected to be higher when the degree of asymmetry of the protrusion at the angle is high, and the myometrium of the uterine angle is thin. It may be safer to terminate these pregnancies during the early stages. However, an inaccessible position of implantation may cause difficult curettage. Hysteroscopy and/or laparoscopy guided curettage, and treatment with methotrexate in early angular pregnancies are the preferred methods of treatment(8).

ngle is thin. It may be safer to terminate these pregnancies during the early stages. However, an inaccessible position of implantation may cause difficult curettage. Hysteroscopy and/or laparoscopy guided curettage, and treatment with methotrexate in early angular pregnancies are the preferred methods of treatment(8). The site of angular pregnancy could cause uterine atony during delivery due to weakness or lack of myometrial tissue and inadequate contraction, and excessive vascular development. There may even be a need for hysterectomy if accompanied by a placental adhesion anomaly. In a case of suspected retained placenta, despite manual intervention, a coronal incision can be made into the myometrium overlying the placenta. In case of excessive bleeding due to atony, a few square sutures using long absorbable sutures from anterior to posterior through the uterus in order to obliterate the asymmetrical uterine sacculation can be peformed successfully as we did in our case. Ethics: Informed Consent: Consent form was filled out by all participants. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin, Müfit Cemal Yenen, Concept: İbrahim Alanbay, Mustafa Öztürk, Design: İbrahim Alanbay, Mustafa Öztürk, Data Collection or Processing: İbrahim Alanbay, Analysis or Interpretation: İbrahim Alanbay, Literature Search: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin, Writing: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin.

Yenen, Concept: İbrahim Alanbay, Mustafa Öztürk, Design: İbrahim Alanbay, Mustafa Öztürk, Data Collection or Processing: İbrahim Alanbay, Analysis or Interpretation: İbrahim Alanbay, Literature Search: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin, Writing: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.

Yenen, Concept: İbrahim Alanbay, Mustafa Öztürk, Design: İbrahim Alanbay, Mustafa Öztürk, Data Collection or Processing: İbrahim Alanbay, Analysis or Interpretation: İbrahim Alanbay, Literature Search: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin, Writing: İbrahim Alanbay, Mustafa Öztürk, Kazım Emre Karaşahin. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Figure 1 A) Transvaginal ultrasound view of the gestation sac at 6 weeks’ gestation. The sac is covered by the endometrium (*) and continuous with the intracavitary endometrial lining (**), B) Transabdominal ultrasound image of the angular pregnancy at 6 weeks’ gestation. The gestational sac is located in the right lateral side of the uterus. The myometrium surrounding the sac is thick and the uterus is asymmetric C) The gestastional sac growing towards the cavity at the 7th week, the ovary is seen lateral to the arrow. Note the thickness of the myometrium around the sac. D) Transabdominal ultrasound image of the angular pregnancy at 8+6 weeks’ gestation. The asymmetric uterine enlargement is distinct Figure 2 A) At 26 weeks’ gestational age, sonogram revealed a thickened and confined placenta at the right uterine angle B) Subchorionic hematoma at the placental edge C) Photograph of the angular pregnancy, anterior view of the uterus. The right cornual area protrudes as a sacculation. The uterus is distinctly asymetric D) The view of the posterior and right lateral side of the uterus. The area is discolored due to excessive vessel formation

INTRODUCTION Ectopic pregnancy is a serious condition in gynecologic practice. Treatment options for ectopic pregnancy include surgical treatment, expectant management, and medical treatment. Methotrexate (MTX) treatment is preferred for its fewer adverse effects and cost effectiveness(1).

INTRODUCTION Ectopic pregnancy is a serious condition in gynecologic practice. Treatment options for ectopic pregnancy include surgical treatment, expectant management, and medical treatment. Methotrexate (MTX) treatment is preferred for its fewer adverse effects and cost effectiveness(1). MTX is a folic acid antagonist and is generally used for the treatment of malignancies, autoimmune diseases, and ectopic pregnancies(2). The inhibitory effect on DNA synthesis of MTX is the rationale in the treatment of ectopic pregnancy in which the target is trophoblasts and fetal cells. Ninety percent of MTX given intravenously undergoes renal excretion without any change within 24 hours(3). Low-dose use of MTX gives freedom to a physician to use it frequently in the treatment of ectopic pregnancies. MTX treatment has two protocols; single dose and multiple dose regimens. The single injection of the drug, less follow-up time, lower cost, and no requirement for folinic acid use makes the single-dose protocol the most preferred. MTX is given 50 mg/m2 intramuscularly. Levels of beta-human chorionic gonadotropin (β-hCG) are measured on the 4th and 7th day of treatment. A second dose is not needed if the decrease in β-hCG levels is more than 15% between days 4 and 7. A second dose of MTX is needed in 15-20% of cases and only 1% of women who receive the single-dose protocol require a third dose(4,5,6). Adverse effects are generally mild and self-limited; the most common are stomatitis and conjunctivitis. Rare adverse effects include gastritis, enteritis, dermatitis, pneumonitis, alopecia, elevated liver enzymes, and bone marrow suppression. Approximately 30 percent of patients on the single-dose protocol have adverse effects; this rate is lower for patients on multi-dose regimens (40%)(7).

tomatitis and conjunctivitis. Rare adverse effects include gastritis, enteritis, dermatitis, pneumonitis, alopecia, elevated liver enzymes, and bone marrow suppression. Approximately 30 percent of patients on the single-dose protocol have adverse effects; this rate is lower for patients on multi-dose regimens (40%)(7). Renal and hepatic diseases, immunodeficiency, active pulmonary disease, and peptic ulcer disease are contraindications for MTX treatment(8,9,10). Herein, an otherwise healthy woman who had a severe adverse event with low-dose MTX treatment is presented.

tomatitis and conjunctivitis. Rare adverse effects include gastritis, enteritis, dermatitis, pneumonitis, alopecia, elevated liver enzymes, and bone marrow suppression. Approximately 30 percent of patients on the single-dose protocol have adverse effects; this rate is lower for patients on multi-dose regimens (40%)(7). Renal and hepatic diseases, immunodeficiency, active pulmonary disease, and peptic ulcer disease are contraindications for MTX treatment(8,9,10). Herein, an otherwise healthy woman who had a severe adverse event with low-dose MTX treatment is presented. CASE REPORT A gravida 3 woman aged 38 years was admitted to our hospital with symptoms of pelvic pain, diarrhea, and oral lesions. She had MTX (50 mg/m2) treatment when her β-hCG level was 2279 mIU/mL. Seven days after the first dose, a second dose of MTX treatment was given due to elevated β-hCG (2304 mIU/mL) and an ultrasound finding of a 2-cm gestational sac in the right fallopian tube. On day 4 of the second dose, emergency laparoscopic salpingectomy was performed for tubal rupture with hemorrhage. She was discharged from hospital on the first postoperative day and readmitted on the second day with bloody diarrhea (ten times a day), oral lesions, and macular rush on the scalp, neck, and chest regions. No remarkable details were noted in her medical history except MTX treatment. In the physical examination, she was pale and her vital signs and body temperature were in the normal range, and a macular rash on the chest, neck and scalp area (Figure 1) and mucositis in oral mucosa were detected (Figure 2). A blood count revealed hemoglobin (Hb) level of 6.4 gr/dL, the white blood cells number was 2000 /µL, creatinine was 1.76 mg/dL, β-hcg level was 91 mIu/mL. During the clinical follow-up, the general condition of the patient deteriorated. On the same day, her Hb level was 6.2 gr/dL and the white blood cell number was 1600/µL (Table 1). Lesions in the oral mucosa and skin increased and the diarrhea worsened. She was transferred to the intensive care unit. The serum level of MTX was high (more than 2 picograms/L). Calcium folinate infusion, and erythrocyte (4 units), thrombocyte (6 units) replacement and intravenous hydration and nutrition, and broad spectrum antibiotics were started. Sodium bicarbonate was administered via intravenous infusion to increase the excretion of the MTX alkalization of urine. Despite the supplementary treatment and folinic acid treatment, high levels of MTX continued and her cytopenic clinical state worsened. Plasmapheresis was considered for lowering MTX levels because glucarpidase (carboxypeptidase G2) is not available in Turkey. The level of MTX decreased after performing plasmapheresis.

Despite the supplementary treatment and folinic acid treatment, high levels of MTX continued and her cytopenic clinical state worsened. Plasmapheresis was considered for lowering MTX levels because glucarpidase (carboxypeptidase G2) is not available in Turkey. The level of MTX decreased after performing plasmapheresis. The patient’s symptoms and clinical findings regressed. After 18 days of hospitalization (one week intensive care unit) she was discharged from hospital with no symptoms.

Despite the supplementary treatment and folinic acid treatment, high levels of MTX continued and her cytopenic clinical state worsened. Plasmapheresis was considered for lowering MTX levels because glucarpidase (carboxypeptidase G2) is not available in Turkey. The level of MTX decreased after performing plasmapheresis. The patient’s symptoms and clinical findings regressed. After 18 days of hospitalization (one week intensive care unit) she was discharged from hospital with no symptoms. DISCUSSION MTX is a cheap and minimally toxic drug in low doses and is widely used in patients with non-ruptured ectopic pregnancy in suitable clinical conditions. Before treatment with MTX, a viable intrauterine pregnancy must be excluded; β-hCG levels, renal and liver function tests, and a complete blood count should be checked. MTX treatment has single-dose and multiple-dose protocols. Adverse effects can be seen more frequently in multi-dose protocols(7). The adverse effects of MTX are caused by irreversible inhibition of the enzyme dihydrofolate reductase in purine synthesis. Decreases in blood cells and hemorrhage from the gastrointestinal tract are due to the effect on rapidly dividing cells of the bone marrow and intestinal tract(11). Severe adverse effects are infrequent in MTX treatment for ectopic pregnancy. The potential severe adverse effects of MTX treatment are hepatotoxicity, pulmonary toxicity, risk of infection, myelosupression, and nephrotoxicity. Hepatotoxicity results from direct damage to hepatocytes or in patients with concomitant viral hepatitis. Minor aminotransferase elevations are common but hepatic steatosis, fibrosis, and cirrhosis are seen rarely. For this reason, screening for hepatitis B and hepatitis C virus infection and hepatic enzymes should be performed before initial therapy. MTX is an immunomodulatory but not significantly immunosuppressive agent. Myelosuppression is the major dose-limiting adverse effect of high- dose MTX, but it is infrequent in low-dose therapy. Hematologic toxicity associated with macrocytic red blood cells may be seen, but a more serious abnormality is the development of pancytopenia(12). Therefore, guidelines from the American College of Rheumatology recommend that a routine peripheral complete blood should be performed every four weeks in rheumatoid arthritis treatment(13). Nephrotoxicity due to MTX rarely occurs in treatment with high doses. A slight decrease in creatinine clearance can be seen even at low, weekly doses used in rheumatoid diseases(14).

eumatology recommend that a routine peripheral complete blood should be performed every four weeks in rheumatoid arthritis treatment(13). Nephrotoxicity due to MTX rarely occurs in treatment with high doses. A slight decrease in creatinine clearance can be seen even at low, weekly doses used in rheumatoid diseases(14). Development of myelosuppression and mucositis such as MTX- related toxicity risk, is highest in patients with prolonged exposure to high levels of plasma MTX concentrations. Glucarpidase, a bacterial enzyme, is used for a rapid decrease of plasma MTX levels, which hydrolyses MTX to its inactive metabolites. The greatest benefit is achieved with glucarpidase when plasma MTX concentrations are high(15). Low-dose MTX is used in the medical treatment of ectopic pregnancy. Severe toxicity is an unexpected condition. In the present case, two doses of MTX were given one week apart but severe toxicity occurred. Compared with other treatment indications of MTX, the dose was very low but the subsequent adverse effects were detrimental and life threatening. Although the patient had no renal insufficiency, a high serum level of MTX was detected. Intensive care unit treatment and folinic acid replacement failed. Fortunately, the patient’s signs and symptoms regressed with plasmapheresis. In review of the literature, severe toxicity due to MTX treatment for ectopic pregnancy was reported in a patient with renal insufficiency but severe toxicity in a healthy woman has not been reported(2). In conclusion, unexpected toxicity with MTX should be kept in mind during use of this simple treatment.

smapheresis. In review of the literature, severe toxicity due to MTX treatment for ectopic pregnancy was reported in a patient with renal insufficiency but severe toxicity in a healthy woman has not been reported(2). In conclusion, unexpected toxicity with MTX should be kept in mind during use of this simple treatment. Ethics: Informed Consent: Consent form was filled out by participant. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Mehmet Vural, Sunullah Soysal, Concept: Mehmet Vural, Sunullah Soysal, Design: Begüm Yıldızhan, Mehmet Vural, Data Collection or Processing: Sunullah Soysal, Gökçe Anık İlhan, Analysis or Interpretation: Begüm Yıldızhan, Gökçe Anık İlhan, Literature Search: Sunullah Soysal, Gökçe Anık İlhan, Writing: Sunullah Soysal. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Table 1 Complete blood count values Figure 1 Macular rash on the chest and neck area Figure 2 Oral lesions and mucositis detected

INTRODUCTION The age of normal menopause, which occurs as a result of the depletion of functional primordial follicles in ovaries, is 50±4 years(1). Loss of normal ovarian functions before the age of 40 years is referred to as primary ovarian insufficiency (POI)(2). In women under the age of 40 years who experience amenorrhea for longer than 4 months, and follicle-stimulating hormone (FSH) levels found at the menopausal range on two consecutive occasions with an interval of at least one month suggests POI(3). Ovaries do not cease all function in approximately 50% of affected women, and 5-10% of these women can get pregnant and give birth after the diagnosis of POI(3,4,5). POI is a common disorder that afflicts 1-2% of women younger than 40 years and 0.1% of women aged less than 30 years(6). It is a heterogeneous disorder that demonstrates great variations in causes and phenotypes. The focus of the present study was the etiology of POI, which affects one out of every 100 women under the age of 40 years. Follicle depletion is caused by insufficient formation of the primordial follicle pool in the intrauterine period, increased follicle consumption, and autoimmune or toxic follicle degradation. Follicle dysfunction, on the other hand, occurs when normal functions of ovarian follicles are blocked by a pathologic process, such as mutations of the FSH receptor(7) either mechanism results in functional insufficiency of the ovary.

eriod, increased follicle consumption, and autoimmune or toxic follicle degradation. Follicle dysfunction, on the other hand, occurs when normal functions of ovarian follicles are blocked by a pathologic process, such as mutations of the FSH receptor(7) either mechanism results in functional insufficiency of the ovary. POI comprises various diseases with a wide variety of pathogenesis such as genetic chromosomal, mitochondrial, enzymatic, iatrogenic, and immunologic aberrations, or infections(8). These causes may effect the ovary at each period of life, including prepubertal, pubertal, and reproductive periods(9). However, POI in patients is generally idiopathic, and the principal mechanisms are unknown. Oxidative stress (OS) causes lipid peroxidation, functionally and structurally. It changes protein and DNA, supports apoptosis, and conduces the risk of chronic diseases such as cancer and heart disease by the agency of effects on redox status and/or redox-sensitive signaling pathways and gene expression(10). Findings from in vitro, animal model, and clinical studies proposed that OS was implicated in the etiology of reverse reproductive cases in both women and men(11).

hronic diseases such as cancer and heart disease by the agency of effects on redox status and/or redox-sensitive signaling pathways and gene expression(10). Findings from in vitro, animal model, and clinical studies proposed that OS was implicated in the etiology of reverse reproductive cases in both women and men(11). The neutrophil to lymphocyte ratio (NLR), which is an indicator of systemic inflammation, demonstrates the balance between neutrophil and lymphocyte concentrations in the body. Inflammatory cytokines induce DNA damage and inhibit DNA repair(12). Studies showed that inflammatory mediators were increased in patients with premature ovarian failure (POF)(13). There are many rat studies in the literature regarding anti-inflammatory treatments in the treatment of POF(14). This is the first study in the literature to investigate NLR, total antioxidant status (TAS), and total oxidant status (TOS) in POI, which is of unknown cause in 95% of the cases. The purpose of this study was to elucidate the etiology and therapeutic approaches of POI.

lammatory treatments in the treatment of POF(14). This is the first study in the literature to investigate NLR, total antioxidant status (TAS), and total oxidant status (TOS) in POI, which is of unknown cause in 95% of the cases. The purpose of this study was to elucidate the etiology and therapeutic approaches of POI. MATERIALS AND METHODS A total of 30 patients aged 18-40 years of age (mean: 28.9±6.8 years) who presented to Dicle University Faculty of Medicine Clinic of Obstetrics and Gynecology between June 2012 and January 2014 and were diagnosed as having POI based on their clinical and endocrinologic data, and 30 healthy controls who were matched for ethnic background and age were included in the study. The features of 30 patients with presumptive primary ovarian insufficiency were investigated. The initial diagnosis was based on a serum FSH level higher than 40 mIU/mL in karyotypically normal women aged younger than 40 years who experienced menstrual irregularity or amenorrhea. Following the provision of written informed consent, FSH, luteinizing hormone (LH), estradiol (E2), thyroid-stimulating hormone (TSH), prolactin (PRL), triglyceride (TRG), total cholesterol (total-C), and glucose tests, as well as complete blood count were performed in the patients with POI and control subjects. Patients with thyroid diseases, hyperprolactinemia, Cushing’s disease, congenital adrenal hyperplasia or infectious diseases (pulmonary diseases, peritonsillar abscesses), cardiovascular diseases, endometrial lesions, malignant neoplasm), and patients that were administered such agents as hormonal agents, ovulation-inducing agents, glucocorticoids, anti-androgens, and anti-hypertensives over the six months prior to the study were excluded. The patients were enrolled if they were not on any drugs, had no history of recent infection or inflammation, were nonsmokers, and also had normal weight. Patients with secondary amenorrhea or pregnancy were also excluded.

ids, anti-androgens, and anti-hypertensives over the six months prior to the study were excluded. The patients were enrolled if they were not on any drugs, had no history of recent infection or inflammation, were nonsmokers, and also had normal weight. Patients with secondary amenorrhea or pregnancy were also excluded. In addition to family history of metabolic disorders, a detailed history including menstrual cycle pattern, temporal profile, severity of unwanted hair growth, and drug intake was taken at the time of enrollment. Weight and height measurements were made. Body mass index (BMI) was determined using the following formula: Weight (kg)/height (m2). One single observer performed transabdominal ultrasonography (USG) in all the participants to demonstrate ovarian morphology. To reveal possible gynecologic abnormalities, transvaginal USG was performed as appropriate using a Voluson 730 expert sonography 1.8 GHZ probe. The parameters examined in this study were as follows: Age, BMI, smoking, family history, co-existing conditions, complete blood count results, baseline hormone levels, NLR, TAS, and TOS values, and findings on sonography. This study, which was approved by the Local Ethics Committee of the university, was performed in the Obstetrics and Gynecology Clinic of Dicle University. Laboratory Tests

In addition to family history of metabolic disorders, a detailed history including menstrual cycle pattern, temporal profile, severity of unwanted hair growth, and drug intake was taken at the time of enrollment. Weight and height measurements were made. Body mass index (BMI) was determined using the following formula: Weight (kg)/height (m2). One single observer performed transabdominal ultrasonography (USG) in all the participants to demonstrate ovarian morphology. To reveal possible gynecologic abnormalities, transvaginal USG was performed as appropriate using a Voluson 730 expert sonography 1.8 GHZ probe. The parameters examined in this study were as follows: Age, BMI, smoking, family history, co-existing conditions, complete blood count results, baseline hormone levels, NLR, TAS, and TOS values, and findings on sonography. This study, which was approved by the Local Ethics Committee of the university, was performed in the Obstetrics and Gynecology Clinic of Dicle University. Laboratory Tests Participants gave blood samples between the third and the fifth days of the normal menstrual cycle, i.e. in the early follicular phase. Venous blood was taken from the forearm between 08:00-10:00 AM following a fast of eight hours. Blood samples were centrifuged without delay, and sera were kept at a temperature of -80 °C before laboratory testing. Levels of serum glucose, TRG, and total-C were determined using an Architect C 16000 autoanalyzer (Abbott Laboratories, Abbott Park, IL, USA).

Participants gave blood samples between the third and the fifth days of the normal menstrual cycle, i.e. in the early follicular phase. Venous blood was taken from the forearm between 08:00-10:00 AM following a fast of eight hours. Blood samples were centrifuged without delay, and sera were kept at a temperature of -80 °C before laboratory testing. Levels of serum glucose, TRG, and total-C were determined using an Architect C 16000 autoanalyzer (Abbott Laboratories, Abbott Park, IL, USA). FSH, LH, E2, PRL, TSH levels were determined using electrochemiluminescence immunoassay on a Cobas 601 analyzer (Roche Diagnostics, Mannheim, Germany). For the determination of NLR, complete blood counts of patients with POI and controls were studied using a CELL-DYN automated hematology analyzer (Ruby-Abbott Diagnostics, USA). TAS levels were measured using Erel’s(15) recently developed automated technique. In Erel’s(15) technique, a hydroxyl radical is generated, which is the most potent biologic radical. A solution of ferrous ion in Reagent 1 is combined with Reagent 2 that containing hydrogen peroxide in the assay. The radicals generated by the hydroxyl radical in this way are also potent radicals. As a result, the anti-oxidative action of the sample against the potent-free radical reaction is determined, which is triggered by the hydroxyl radical. The findings are reported in mmol Trolox Eq/L.

ing hydrogen peroxide in the assay. The radicals generated by the hydroxyl radical in this way are also potent radicals. As a result, the anti-oxidative action of the sample against the potent-free radical reaction is determined, which is triggered by the hydroxyl radical. The findings are reported in mmol Trolox Eq/L. TOS levels were measured using Erel’s(16) automated technique. In this technique, a ferrous ion-o-dianisidine complex is oxidized to ferric ion by oxidants found in the sample. Glycerol molecules, which are found in large amounts in the reaction medium, increase the oxidation reaction. In acidic material, the ferric ion creates a colored complex with xylenol orange. The intensity of color is measured spectrophotometrically and is related to the total amount of oxidant molecules in the sample. Calibration of the assay is performed using hydrogen peroxide. The findings are reported in µmol H2O2 Eq/L. The division of TOS by TAS yields the oxidative stress index (OSI) value. The following formula is used to calculate OSI: OSI (arbitrary unit)=TOS (µmol H2O2 Eq/L)/TAS (mmol Trolox Eq/L)(17).

TOS levels were measured using Erel’s(16) automated technique. In this technique, a ferrous ion-o-dianisidine complex is oxidized to ferric ion by oxidants found in the sample. Glycerol molecules, which are found in large amounts in the reaction medium, increase the oxidation reaction. In acidic material, the ferric ion creates a colored complex with xylenol orange. The intensity of color is measured spectrophotometrically and is related to the total amount of oxidant molecules in the sample. Calibration of the assay is performed using hydrogen peroxide. The findings are reported in µmol H2O2 Eq/L. The division of TOS by TAS yields the oxidative stress index (OSI) value. The following formula is used to calculate OSI: OSI (arbitrary unit)=TOS (µmol H2O2 Eq/L)/TAS (mmol Trolox Eq/L)(17). The analysis of chromosomes was conducted in the Department of Medical Biology-Genetics. Blood samples were taken into heparinized vacutainers for cytogenetic analysis, and the lymphocyte cultures were organized in duplicates(18). Two sets of slides were arranged from each culture. Karyotyping was conducted on routine peripheral blood lymphocyte cultures using G-banding following Trypsin and Giemsa staining (GTG)(19). A minimum of 30 GTG-banded metaphases were scored from each patient. Considering the criteria of the International System for Human Cytogenetic Nomenclature, three cells were karyotyped(20). In general, chromosome counts of 30 cells were undertaken; however, 50 or more cell counts were performed in the event that mosaicism was suspected(21).

iochemical data between the groups. Whether intra-group variables demonstrated normal distribution was determined using the Kolmogorov-Smirnov test. The investigation of correlation between the values was conducted using Spearman’s analysis. P values less than or equal to 0.05 were considered statistically significant. RESULTS No participants in this study had a pathologic presentation on pelvic ultrasound or a chromosomal abnormality. In addition, none of the participants had a family history of POI. No significant differences were found between the patients with POI and control subjects in age, marital status, gravidity, smoking and BMI (Table 1). No significant differences were found between the groups in lipid profile levels, TSH, PRL, or glucose. E2 levels were lower in patients with POI than in the control subjects p<0.001 (Table 2). However, NLR and levels of FSH, LH, TOS, and OSI were higher in patients with POI than in the control subjects (Table 3) (Figure 1). The levels of FSH were directly correlated with TOS, OSI, and NLR (r=0.573** p<0.001; r=0.584** p<0.001; r=0.541 p<0.001, respectively) and indirectly correlated with TAS (r=-0.437** p<0.001) (Figure 2). DISCUSSION In our study, we hypothesized that there would be increased OS, and investigated the presence of inflammation in patients with POF. Many studies have been conducted on ovarian reserve and OS. However, there are few studies in patients with POF. We determined increased OS and inflammation in patients with POF.

DISCUSSION In our study, we hypothesized that there would be increased OS, and investigated the presence of inflammation in patients with POF. Many studies have been conducted on ovarian reserve and OS. However, there are few studies in patients with POF. We determined increased OS and inflammation in patients with POF. Various etiologic factors are associated with POI: Autoimmune ovarian damage, genetic aberrations, infectious agents, toxins, iatrogenic factors, and environmental factors. Nevertheless, the majority of cases are idiopathic with no identifiable etiologic factors, even after a thorough examination(22). POI is usually sporadic; however, one of the first-degree relatives of 10-15% of patients also has this disorder(23). Therefore, patients should be asked about their family history. In addition, hypothyroidism, adrenal insufficiency, hypoparathyroidism, and other autoimmune diseases should be questioned. A family history of mental retardation, tremor-ataxia, and Parkinson-like symptoms might lead to consider Fragile X syndrome associated with FMR1 gene mutation(24). However, no patients with POI in the present study had a family history or an autoimmune disease.

dism, and other autoimmune diseases should be questioned. A family history of mental retardation, tremor-ataxia, and Parkinson-like symptoms might lead to consider Fragile X syndrome associated with FMR1 gene mutation(24). However, no patients with POI in the present study had a family history or an autoimmune disease. Chronic low-grade inflammation is a major contributor to the pathogenesis of POI. NLR, which is an indicator of systemic inflammation, demonstrates the balance between neutrophil and lymphocyte concentrations in the body. Compared with many other inflammatory markers, NLR adds no extra cost because it is inexpensive. It is widely available and routinely measured on admission. In the present study, NLR was found to be significantly elevated in patients with POI, which might indicate the potential role of increased inflammation in the etiology of POI. Previous studies reported that patients with POI had an increased risk of atherosclerosis and CVD(25) which might also be associated with increased inflammation in these patients.

to be significantly elevated in patients with POI, which might indicate the potential role of increased inflammation in the etiology of POI. Previous studies reported that patients with POI had an increased risk of atherosclerosis and CVD(25) which might also be associated with increased inflammation in these patients. The effect of OS in the etiopathogenesis of POF has not been widely studied. A recent study reported that administration of coenzyme Q in patients with POF who had high reactive oxygen species (ROS) levels improved the embryo quality(26). High superoxide ion amounts lead to a decline in the bioavailability of nitric oxide, an accrete in ROS levels, and OS. As compared with spermatozoa, female germ cells improve under hypoxic conditions in the ovarian cortex. However, exposure to supraphysiologic levels of ROS are deleterious to developing oogonia. Another study proposed that increased production of OS contributed to oophoritis associated with POF(27). High ROS levels stimulate mitochondrial DNA modifications. In addition, high ROS levels lead to mitochondria abnormality, which could lead to low adenosine triphosphate production due to disrupted oxidative phosphorylation and oogenesis, low oocyte number, and POF(28).

contributed to oophoritis associated with POF(27). High ROS levels stimulate mitochondrial DNA modifications. In addition, high ROS levels lead to mitochondria abnormality, which could lead to low adenosine triphosphate production due to disrupted oxidative phosphorylation and oogenesis, low oocyte number, and POF(28). OS is involved in the etiology of diverse degenerative conditions such as diabetes, atherosclerosis, arthritis, cancer, and aging(29). In addition, it was shown that ROS such as hydroxyl radicals, hydrogen peroxide, and superoxide anions are a part of the pathogenesis of bone loss caused by osteoclast differentiation and bone resorption(30). Furthermore, two previous studies suggested that ROS levels were elevated in POI, and OS may be a part of the etiology of idiopathic POI(31,32).

S such as hydroxyl radicals, hydrogen peroxide, and superoxide anions are a part of the pathogenesis of bone loss caused by osteoclast differentiation and bone resorption(30). Furthermore, two previous studies suggested that ROS levels were elevated in POI, and OS may be a part of the etiology of idiopathic POI(31,32). The role of OS in female fertility is an area worthy of sustained research. Preliminary research that analyzes the complete mitochondrial genome and OS should be tracked in different populations and in broader studies. This research should also investigate the ovary for mitochondrial nucleotide change because they develop in a different microenvironment in the ovary and are of different embryologic origin. However, owing to ethical constraints, such research is not feasible. In a study of male infertility from our laboratory, we found systemic blood ROS levels correlated with seminal ROS levels(33). Hence, the present study on blood TAS, TOS, and OSI in POI is significant, although it would be ideal to conduct further, similar studies on oocytes. The therapeutic tools currently available for the treatment of mitochondrial diseases due to mitochondrial deoxyribonucleic acid mutations are very few, and their efficacy is not yet well established(34). In a large series of 357 patients with POI, the median E2 level was only 10 pg/mL(35). In the present study, estrogen levels were found significantly lower in patients with POI compared with the control subjects.

The role of OS in female fertility is an area worthy of sustained research. Preliminary research that analyzes the complete mitochondrial genome and OS should be tracked in different populations and in broader studies. This research should also investigate the ovary for mitochondrial nucleotide change because they develop in a different microenvironment in the ovary and are of different embryologic origin. However, owing to ethical constraints, such research is not feasible. In a study of male infertility from our laboratory, we found systemic blood ROS levels correlated with seminal ROS levels(33). Hence, the present study on blood TAS, TOS, and OSI in POI is significant, although it would be ideal to conduct further, similar studies on oocytes. The therapeutic tools currently available for the treatment of mitochondrial diseases due to mitochondrial deoxyribonucleic acid mutations are very few, and their efficacy is not yet well established(34). In a large series of 357 patients with POI, the median E2 level was only 10 pg/mL(35). In the present study, estrogen levels were found significantly lower in patients with POI compared with the control subjects. There is no family history in the vast majority of women with POI. The chromosomes are normal, and there is no sign of auto-immunity in these women, which renders the mechanism of damage unknown. Therefore, hidden environmental damage from the past might be considered in these women. In men, it is known that viruses such as mumps might cause testicular inflammation and lead to permanent damage and lack of sperm. In addition, it is widely believed that sperm counts in men have reduced in recent years because of testicular exposure to environmental toxins and drugs. In this respect, it is probable that the ovaries are similarly affected by viruses and toxins. Viruses in particular are a potential cause of ovarian insufficiency in women with no identifiable cause. Anecdotal reports of virus infections that are rapidly followed by ovarian insufficiency provide support for this causal relationship(35). In the present study, NLR was found significantly elevated in patients with POI who had no history of inflammation or medication. As a result, idiopathic POI might be explained by inflammation caused by environmental toxins. Smoking is known to be detrimental to ovarian functions. On average, smokers experience menopause earlier than nonsmokers, which indicates a potential harmful effect of smoking on ovarian functions(36). Our study demonstrated no significant difference between patients with POI and healthy control subjects regarding smoking.

ng is known to be detrimental to ovarian functions. On average, smokers experience menopause earlier than nonsmokers, which indicates a potential harmful effect of smoking on ovarian functions(36). Our study demonstrated no significant difference between patients with POI and healthy control subjects regarding smoking. Previous studies reported that a diet rich in glucose and free fatty acid could trigger OS and an inflammatory response from mononuclear cells(37). The present study found no significant difference between patients with POI and controls in lipid profile and glucose levels. Therefore, increased OS observed in patients with POI might be associated with increased inflammation. Study Limitations A limitation of our study is that we did not measure anti-Müllerian hormone (AMH) levels. The AMH test is the best to evaluate the ovarian reserve, but it cannot be performed in our hospital; instead ovarian reserve was evaluated through FSH, LH, and E2 measurements. FSH and E2 are important markers of ovarian reserve, especially in the absence of known AMH levels. As far as we know, no other studies have investigated NLR, TAS, TOS, and OSI in patients with POI. The present study revealed elevated levels of NLR, TOS, and OSI in patients POI. Therefore, anti-oxidative and anti-inflammatory treatment might be administered to patients in the early stage of POI. However, larger studies are needed to clarify whether these elevated levels are a cause or a consequence of POI.

th POI. The present study revealed elevated levels of NLR, TOS, and OSI in patients POI. Therefore, anti-oxidative and anti-inflammatory treatment might be administered to patients in the early stage of POI. However, larger studies are needed to clarify whether these elevated levels are a cause or a consequence of POI. Ethics: Ethics Committee Approval: The study were approved by the Dicle University of Local Ethics Committee, Informed Consent: Consent form was filled out by all participants. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Elif Ağaçayak, Neval Yaman Görük, Concept: Hakan Küsen, Design: Elif Ağaçayak, Data Collection or Processing: Hakan Küsen, Ahmet Yıldızbakan, Analysis or Interpretation: Serdar Başaranoğlu, Mehmet Sait İçen, Hatice Yüksel, Sevgi Kalkanlı, Literature Search: Senem Yaman Tunç, Talip Gül, Writing: Elif Ağaçayak. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Demographic data of the groups Table 2 Levels of hormonal parameters in the groups Table 3 Levels of oxidative stress and inflammation markers in the groups Figure 1 Correlation analysis between follicle-stimulating hormone, total antioxidative capacity, total oxidative capacity, oxidative stress index, and neutrophil to lymphocyte ratio

the groups Table 2 Levels of hormonal parameters in the groups Table 3 Levels of oxidative stress and inflammation markers in the groups Figure 1 Correlation analysis between follicle-stimulating hormone, total antioxidative capacity, total oxidative capacity, oxidative stress index, and neutrophil to lymphocyte ratio NLR: Neutrophil to lymphocyte ratio, OSI: Oxidative stress index, FSH: Follicle-stimulating hormone, TOS: Total oxidant status Figure 2 Neutrophil to lymphocyte ratio, total antioxidative capacity, total oxidative capacity, oxidative stress index levels in patients with premature ovarian insufficiency and controls POF: Premature ovarian failure, TOS: Total oxidant status

INTRODUCTION Hyperemesis gravidarum (HG) is a common medical problem that affects nearly 1 percent of pregnant women, and causes morbidity both for the mother and fetus(1). The etiology is still unclear and until now, many theories have been introduced. Psychological factors, hormonal changes, gastrointestinal dysmotility, and immunologic dysregulation have been proposed as possible causes(2,3). In recent years, a close relationship was also recently found between HG and inflammation caused by helicobacter pylori infection(4,5). Vitamin D is a well-known immunomodulator and anti-inflammatory agent in the body. Vitamin D deficiency is shown as the one of the major causes of many diseases in the reproduction system(6,7). Sugito et al.(8) found that pregnant women with HG had increased cell-free DNA levels in blood, which was believed to emerge as a result of hyperactivity of the maternal immune system and destruction of trophoblasts. However, fasting, which is a feature of HG and pregnancy, are also known to weaken the human and cell-mediated immune system. Although both pregnancy and fasting are features of HG, in contrast to expectations, the immune system was activated in women with HG. It might be speculated that vitamin D has a key role in the etiopathogenesis of HG, and vitamin D deficiency might explain the immune theory of HG because vitamin D deficiency might lead to problems in immune regulation. Therefore, in the current study, our objective was to compare the 25-hydroxyvitamin D [25 (OH) D] and C reactive protein (CRP) levels between women with HG and controls.

Vitamin D is a well-known immunomodulator and anti-inflammatory agent in the body. Vitamin D deficiency is shown as the one of the major causes of many diseases in the reproduction system(6,7). Sugito et al.(8) found that pregnant women with HG had increased cell-free DNA levels in blood, which was believed to emerge as a result of hyperactivity of the maternal immune system and destruction of trophoblasts. However, fasting, which is a feature of HG and pregnancy, are also known to weaken the human and cell-mediated immune system. Although both pregnancy and fasting are features of HG, in contrast to expectations, the immune system was activated in women with HG. It might be speculated that vitamin D has a key role in the etiopathogenesis of HG, and vitamin D deficiency might explain the immune theory of HG because vitamin D deficiency might lead to problems in immune regulation. Therefore, in the current study, our objective was to compare the 25-hydroxyvitamin D [25 (OH) D] and C reactive protein (CRP) levels between women with HG and controls. MATERIALS AND METHODS A total of 30 women hospitalized with a diagnosis of HG as a study group and another 30 pregnant women who were matched to the HG group in terms of age, body mass index (BMI), and gestation period as a control group were enrolled into this prospective case-control study. The Institutional Review Board of the hospital (24.07.2013/, number 8) approved the current study and all patients gave written informed consent. This study was performed in accordance with the Declaration of Helsinki and patients were reviewed from a tertiary referral center between January 1st, 2013 to March 3rd, 2013. The inclusion criteria were as follows; age 18-35 years, between 6 and 12 gestational weeks, singleton pregnancy with healthy fetus, persistent nausea and vomiting (more than 4 times/day), presence of ketosis (>80 mg/dL in a urine specimen), and weight loss (more than 5% weight loss since pregnancy).

o March 3rd, 2013. The inclusion criteria were as follows; age 18-35 years, between 6 and 12 gestational weeks, singleton pregnancy with healthy fetus, persistent nausea and vomiting (more than 4 times/day), presence of ketosis (>80 mg/dL in a urine specimen), and weight loss (more than 5% weight loss since pregnancy). Patients who had multiple pregnancy; trophoblastic disease; habitual abortus; any systemic disease such as diabetes hypertension or thyroid disease; psychiatric disorder; any inflammatory disorder such as urinary tract infection; and those who used antiemetic medication or any kind of medication that could potentially affect hormones were excluded from the study. All participants underwent sonographic examination to confirm the gestational week, fetal heart rate, and the absence of placental pathology. When the difference between sonographic measurement and last menstrual date were more than 3 days, crown rump length measurement was used. Weight and height measurement were used to calculate BMI.

nderwent sonographic examination to confirm the gestational week, fetal heart rate, and the absence of placental pathology. When the difference between sonographic measurement and last menstrual date were more than 3 days, crown rump length measurement was used. Weight and height measurement were used to calculate BMI. Biochemical measurement of vitamin D and high sensitivity-C reactive protein Patients gave venous blood for biochemical tests following overnight fasting. Serum samples were centrifuged at 5000 revolutions/minute for 10 minutes within 20 minutes of blood sampling. Samples are stored at -80 °C. Total 25-OH-vitamin D levels in the plasma were measured using an ImmuChrom column (IC 3401 rp) kit with immune chromatographic methods. According to the instructions, the analytic detection limit of kit was 5.8 nmol/L and reference intervals were 10-60 μg/L in winter. High sensitivity-CRP (hs-CRP) levels were measured in serum using immunonephelometry (Cardio Phase hs-CRP, Siemens, Germany). In accordance with a statement for healthcare professionals from the American Heart Association/Centers for Disease Control and Prevention, hs-CRP levels were classified as follows: hs-CRP <1.0 mg/dL as low, hs-CRP between 1.0-3.0 mg/dL as intermediate, and hs-CRP >3.0 mg/dL as high levels(9).

s-CRP, Siemens, Germany). In accordance with a statement for healthcare professionals from the American Heart Association/Centers for Disease Control and Prevention, hs-CRP levels were classified as follows: hs-CRP <1.0 mg/dL as low, hs-CRP between 1.0-3.0 mg/dL as intermediate, and hs-CRP >3.0 mg/dL as high levels(9). Statistical Analysis The study data were analyzed using the Statistical Package for Social Sciences (SPSS) version 15.0 for Windows (SPSS, Chicago, IL). In order to see if the variables had normal distribution, histogram and Shapiro-Wilk tests were used. The mean plus/minus standard deviation, median (minimum-maximum), count and percentile are presented in accordance with the distribution of the data. Categorical variables were analyzed using Fisher’s exact test and chi-square tests. As a statistical method, Student’s t-test was performed for normally distributed variables and the Mann-Whitney U test was used to analyze non-normally distributed variables. Spearman’s correlation test was used to test the strength of correlation between the variables. A p value less than 0.05 was considered as statistical significance.

thod, Student’s t-test was performed for normally distributed variables and the Mann-Whitney U test was used to analyze non-normally distributed variables. Spearman’s correlation test was used to test the strength of correlation between the variables. A p value less than 0.05 was considered as statistical significance. RESULTS Age, gestational period, parity, and BMI were similar in the study and control groups (p>0.05) (Table 1). The was also no difference in hs-CRP and vitamin D concentrations between the study and control groups. Table 2 shows the comparison of hs-CRP levels and vitamin D levels in both groups. In the study group, 23 (76.7%) patients had low hs-CRP levels, 3 (10.0%) had intermediate, and 4 (13.3%) had high levels of hs-CRP. For the control group, 27 (90.0%) patients had low levels of CRP and 3 (10.0%) had intermediate levels of CRP; no significant difference was detected between the study and control groups regarding CRP levels (p=0.115). In the study group, 27 (90%) patients had low vitamin D levels, and 3 (10.0%) had high vitamin D levels. In control group, 22 (73.3%) patients had low levels of vitamin D, and 8 (26.7%) had high vitamin D levels; no significant differences were found between the study and control groups regarding vitamin D levels (p=0.181) (Table 2). No correlation was found between vitamin D and hs-CRP concentration in either the HG group or controls (p>0.05) (Table 3).

ents had low levels of vitamin D, and 8 (26.7%) had high vitamin D levels; no significant differences were found between the study and control groups regarding vitamin D levels (p=0.181) (Table 2). No correlation was found between vitamin D and hs-CRP concentration in either the HG group or controls (p>0.05) (Table 3). DISCUSSION Immune dysregulation and inflammation are suggested to have a critical role in the etiopathogenesis of HG(10,11). hs-CRP is a well-known inflammatory marker and vitamin D is an immune modulator and anti-inflammatory that plays a crucial role in the reproductive system. Therefore, we hypothesized that pregnant women with HG should have lower 25 (OH) D levels and higher hs-CRP levels compared with controls, and tested this hypothesis in this prospective case-control study. To our knowledge, the current study is the first trial in the existing literature to investigate the association between vitamin D concentrations and HG. Although it did not reach statistical significance, vitamin D levels were lower in the HG group compared with controls (p=0.090). In addition, no difference was found in hs-CRP concentrations between the two groups.

trial in the existing literature to investigate the association between vitamin D concentrations and HG. Although it did not reach statistical significance, vitamin D levels were lower in the HG group compared with controls (p=0.090). In addition, no difference was found in hs-CRP concentrations between the two groups. In a review that analyzed various factors that contribute to the diagnosis of HG, only helicobacter pylori was identified as having a definitive impact in the etiopathogenesis of the disease(4). Endoscopy conducted on women with HG proved that 90% had mucosal inflammation and helicobacter pylori activation in the stomach(12). However, not all pregnant women with helicobacter pylori exhibit the signs of HG and these women are possibly inclined to helicobacter pylori because of the problems in humoral and cell-mediated immunity(13). Leylek et al.(10) supported this hypothesis by showing an increase in immunoglobulin, complement, and lymphocyte counts in patients with HG, as a result of immunologic activation. Vitamin D has a pivotal role in many diseases of the reproductive system as an immune modulator and anti-inflammatory agent. Vitamin D receptors might be found on a large number of immune cells. Vitamin D helps fetal immune adaptation by inhibiting the secretion of cytokines from T-helper cells(14). In addition, it inhibits the secretion of pro-inflammatory cytokines from the placenta and suppresses the inflammatory response. Recent studies focused on the possibility that deficiency of vitamin D might be related with many maternal and fetal adverse outcomes such as spontaneous abortion, preterm labor, intrauterine growth restriction, and preeclampsia(15,16). The present study emphasizes the possibility that vitamin D, which is known to have numerous roles in the reproductive system, might also have an impact on HG CRP is an acute phase reactant and its synthesis is primarily stimulated by IL-6 and tumor necrosis factor as a reaction to infection and inflammation(17). Kuscu et al.(18) also reported that women with HG had increased levels of IL-6 levels and successful treatment of resistant cases with steroid treatment might be explained by the fact that steroids have anti-inflammatory effects. Therefore, hs-CRP levels might be speculated to increase in women with HG. To our knowledge, there is only one published study that investigated hs-CRP concentrations in women with HG(19).

ul treatment of resistant cases with steroid treatment might be explained by the fact that steroids have anti-inflammatory effects. Therefore, hs-CRP levels might be speculated to increase in women with HG. To our knowledge, there is only one published study that investigated hs-CRP concentrations in women with HG(19). In that case-control study, researchers evaluated 56 women and described an increase in hs-CRP levels in women with HG. However, in the current study, no difference was detected in hs-CRP levels between the study group and controls. Many factors such as socioeconomic status, dietary intake of carbohydrates, and smoking were also related to variations in CRP concentrations(20). The present study is a preliminary study and had a small number of patients; therefore, we might not have homogenized the two groups with these factors and thus failed to detect the difference in hs-CRP levels. CONCLUSION In the present study, vitamin D concentrations were lower in the HG group compared with controls, albeit the relation was not statistically significant. We might not have been able to reach definite results and clearly explain the role of vitamin D in the etiopathogenesis of HG because our study had a small number of patients. However, whether vitamin D has an impact on the etiopathogenesis of hyperemesis or inflammation underlies the disease that causes vitamin D levels to drop needs to be clarified. Therefore, further studies with higher numbers of patients are required to investigate the association between vitamin D and HG.

of patients. However, whether vitamin D has an impact on the etiopathogenesis of hyperemesis or inflammation underlies the disease that causes vitamin D levels to drop needs to be clarified. Therefore, further studies with higher numbers of patients are required to investigate the association between vitamin D and HG. Ethics: EEthics Committee Approval: The study were approved by the Local Ethics Committee of Zekai Tahir Burak Women’s Health Training and Research Hospital, Informed Consent: Consent form was filled out by all participants. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Saynur Yılmaz, Canan Demirtaş, Hakan Timur, Concept: Saynur Yılmaz, Dilek Uygur, Nuri Danışman, Design: Saynur Yılmaz, Dilek Uygur, Nuri Danışman, Data Collection or Processing: Saynur Yılmaz, Ayşe Şahin, Analysis or Interpretation: Saynur Yılmaz, Hakan Timur, Derya Akdağ Cırık, Literature Search: Derya Akdağ Cırık, Canan Demirtaş, Ayşe Şahin, Writing: Derya Akdağ Cırık, Saynur Yılmaz. Conflict of Interest: All authors declare no conflict of interest or competing interests. Financial Disclosure: The authors declared that this study has received no financial support. Table 1 Distribution of age, body mass index, and gestational age according to the study and control groups Table 2 Distribution of the high sensitivity-C reactive protein and vitamin D levels in the study and control groups Table 3 The correlation between high sensitivity-C reactive protein and vitamin D levels in the study and control groups

INTRODUCTION Pregnancy and birth are some of the most important physiologic processes in a woman’s life(1). The approach to birth varies in each society according to the sociologic structure. Pregnancy and the subsequent delivery are important events that should be evaluated biologically as well as physiologically and socially. Many views of pregnancy and especially the type of delivery are influenced by the characteristics of the society. The increase in the self-confidence of women as a result of their increased involvement in work life and relative financial independence in recent years has led to determination of their own delivery type. It is commonly believed that a history of a difficult birth experienced by the pregnant woman or her relatives has great influence on the issue(2). Requests by pregnant women for cesarean section delivery have increased despite the high risk of complications because of the fear of birth pains experienced during vaginal delivery and the knowledge that the risk of complications has decreased with current advanced technology(3). Concern that the infant and pelvic floor may be damaged is also a factor in vaginal delivery being preferred less. The fear of birth is the most important factor in preferring cesarean section delivery.

vaginal delivery and the knowledge that the risk of complications has decreased with current advanced technology(3). Concern that the infant and pelvic floor may be damaged is also a factor in vaginal delivery being preferred less. The fear of birth is the most important factor in preferring cesarean section delivery. Another factor in the increase of the cesarean section rate is malpractice, a serious concern for physicians. The number of legal cases due to complications during delivery is constantly increasing. The medical and legal responsibilities regarding both the mother and infant of a physician helping the delivery cannot be denied. However, the fear of litigation inevitably leads to self-protection attempts and a general avoidance of the scientific approach by the physician. In conclusion, the belief that cesarean section delivery with will be less painful and more reliable for the mother and less harmful for the infant directs women away from vaginal delivery. However, evidence-based medical practice has revealed that cesarean section delivery increases perinatal risk and morbidity and mortality, whereas vaginal delivery is more reliable(4). It is also self-evident that cesarean section delivery will have a negative effect on healthcare expenses, considering its cost and effect on returning to work. In this study, we administered a survey querying the delivery preferences of nulliparous pregnant women in the second trimester without an absolute indication for cesarean section with the aim of evaluating the relevant thoughts of the women.

In conclusion, the belief that cesarean section delivery with will be less painful and more reliable for the mother and less harmful for the infant directs women away from vaginal delivery. However, evidence-based medical practice has revealed that cesarean section delivery increases perinatal risk and morbidity and mortality, whereas vaginal delivery is more reliable(4). It is also self-evident that cesarean section delivery will have a negative effect on healthcare expenses, considering its cost and effect on returning to work. In this study, we administered a survey querying the delivery preferences of nulliparous pregnant women in the second trimester without an absolute indication for cesarean section with the aim of evaluating the relevant thoughts of the women. MATERIALS AND METHODS This study was conducted on pregnant women who presented to the Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology pregnant outpatients department for antenatal follow-up between May 2014 and February 2015. We used the survey completion method on nulliparous pregnant women in the 2nd trimester. None of the pregnant women included in the study had any contraindication in terms of vaginal delivery. The age, gestational week, educational level, information on birth methods, income level of the patient, and the delivery preference and reasons were questioned. A total of 237 nulliparous patients voluntarily completed the survey form and the data obtained were evaluated using various parameters. The pregnant women were divided into two groups as those requesting vaginal delivery and those requesting cesarean section. Data were evaluated using SPSS version 21. Parameters consistent with normal distribution were evaluated using the t-test, and non-normally distributed parameters were evaluated using the Mann-Whitney U test. Parameters with a p value <0.05 were considered significant. Ethics Committee Approval for the study was obtained from the Ankara University Faculty of Medicine Ethics Committee on 12 May 2014 (decision no; 08-348-14).

ing the t-test, and non-normally distributed parameters were evaluated using the Mann-Whitney U test. Parameters with a p value <0.05 were considered significant. Ethics Committee Approval for the study was obtained from the Ankara University Faculty of Medicine Ethics Committee on 12 May 2014 (decision no; 08-348-14). RESULTS We found that 221 (93.2%) of the 237 nulliparous pregnant women preferred vaginal delivery, and the remaining 16 (6.8%) preferred delivery by cesarean section. The reasons for the pregnant women’s choice of delivery are presented in detail in Tables 1 and 2. The pregnant women were queried on being informed on birth previously, educational levels, monthly income level, occupational status, and preference for delivery according to occupation (Table 3). When the delivery preferences were investigated according to the rates of being provided information, 54 (90%) of the 61 patients who were informed previously preferred vaginal delivery and 7 (10%) preferred cesarean section. Similarly, 167 (94.8%) of 176 patients who were not informed on the type of delivery preferred normal delivery and 9 (5.2%) preferred cesarean section (p=0.083). When educational levels were investigated, 65 (87.8%) of 74 patients who were university graduates preferred vaginal delivery, 99 (94.2%) of 105 patients who were high school graduates preferred vaginal birth, and 56 (98.2%) of 57 patients who were primary school graduates preferred vaginal delivery (p=0.016).

When the delivery preferences were investigated according to the rates of being provided information, 54 (90%) of the 61 patients who were informed previously preferred vaginal delivery and 7 (10%) preferred cesarean section. Similarly, 167 (94.8%) of 176 patients who were not informed on the type of delivery preferred normal delivery and 9 (5.2%) preferred cesarean section (p=0.083). When educational levels were investigated, 65 (87.8%) of 74 patients who were university graduates preferred vaginal delivery, 99 (94.2%) of 105 patients who were high school graduates preferred vaginal birth, and 56 (98.2%) of 57 patients who were primary school graduates preferred vaginal delivery (p=0.016). When occupational status was evaluated, 168 (94.9%) of 177 pregnant women who were not working preferred vaginal delivery and 53 (88.3%) of 60 pregnant women who were employed preferred vaginal delivery (p=0.077). According to the occupational groups, 135 of 143 pregnant women who had a specific occupation, the majority of which consisted of university graduates, preferred vaginal birth. The majority of the other professional groups also preferred vaginal delivery (p=0.50).

who were employed preferred vaginal delivery (p=0.077). According to the occupational groups, 135 of 143 pregnant women who had a specific occupation, the majority of which consisted of university graduates, preferred vaginal birth. The majority of the other professional groups also preferred vaginal delivery (p=0.50). DISCUSSION We found that 6.8% of the pregnant women included in our study preferred cesarean section delivery. Chong and Mongelli(5) reported that 3.7% of pregnant women requested elective cesarean section in their study. The World Health Organization (WHO) reported that the primary cesarean section ratio in all pregnant women should be less than 15%(6). Among the studies reported in Turkey, Yıldız et al.(7) conducted on nulliparous and multiparous (who had undergone vaginal delivery and cesarean section previously) pregnant women, 74% of nulliparous pregnant women preferred vaginal delivery but this rate was 97.3% in pregnant women who had experienced vaginal delivery previously. The same study reported a vaginal delivery request rate of 52.5% even in pregnant women who had undergone cesarean section in a previous delivery(7). Vaginal birth preference was reported to be due to early recovery (54.1%) and early return to routine activities (20.3%)(7). Vaginal delivery was similarly preferred by 84.1% in the study of Buyukbayrak et al.(8) Bektaş(9) also reported a vaginal delivery preference rate of 84%. The reasons offered by the women for preferring vaginal delivery in these studies were similar to our findings and those reported in other studies in the literature(8,10,11,12).

very was similarly preferred by 84.1% in the study of Buyukbayrak et al.(8) Bektaş(9) also reported a vaginal delivery preference rate of 84%. The reasons offered by the women for preferring vaginal delivery in these studies were similar to our findings and those reported in other studies in the literature(8,10,11,12). A sociological review of delivery preference showed that it varied according to the society. This preference was affected by many factors such as the physiological status of the woman, as well as the social environment, experiences of others, economic status, and customs and traditions(10). Vaginal birth has been considered a normal human physiologic stage since mankind first appeared and is the basic delivery form. The preferred type of birth was vaginal delivery in our study as in many other studies.

A sociological review of delivery preference showed that it varied according to the society. This preference was affected by many factors such as the physiological status of the woman, as well as the social environment, experiences of others, economic status, and customs and traditions(10). Vaginal birth has been considered a normal human physiologic stage since mankind first appeared and is the basic delivery form. The preferred type of birth was vaginal delivery in our study as in many other studies. Although the request rate for cesarean section delivery was higher in university graduate women, no statistically significant difference was found. Similarly, it has been reported that the cesarean section request rates increased as the age and educational level of women increased by Koc(13), and as the income level and educational level increased by Behaque et al.(14). Women are becoming more actively involved in work life with their changing role in society, and their resultant increasing financial power has increased the age of pregnancy. This in turn has led to a concern regarding putting the infant at risk with pregnancies becoming more and more important. The request for cesarean section is therefore increased at advanced ages. However, various rates have been reported in studies on populations with different socio-economic levels(14). This demonstrates that the approach to birth has a sociocultural background.

at risk with pregnancies becoming more and more important. The request for cesarean section is therefore increased at advanced ages. However, various rates have been reported in studies on populations with different socio-economic levels(14). This demonstrates that the approach to birth has a sociocultural background. The basic reason why the majority of our patients preferred vaginal delivery is that pregnancy is accepted as a natural and normal process in our society as in most other societies. Pregnant women who preferred vaginal delivery expressed that they find vaginal birth healthier additional comments section of the survey.

at risk with pregnancies becoming more and more important. The request for cesarean section is therefore increased at advanced ages. However, various rates have been reported in studies on populations with different socio-economic levels(14). This demonstrates that the approach to birth has a sociocultural background. The basic reason why the majority of our patients preferred vaginal delivery is that pregnancy is accepted as a natural and normal process in our society as in most other societies. Pregnant women who preferred vaginal delivery expressed that they find vaginal birth healthier additional comments section of the survey. Although vaginal delivery is preferred in studies, the cesarean section delivery rate was found as 48% in the latest statistical study conducted in Turkey(15). However, we know that delivery with cesarean section should be used as an alternative in cases where vaginal delivery is not possible or constitutes a danger for the infant and/or the mother. It was reported that cesarean sections should be performed with medical indications at the American Congress of Obstetricians and Gynecologists 2006(16). It was also emphasized in 1999 by International Federation of Gynecologists and Obstetricians that performing cesarean section for non-medical reasons was not ethical(17). The Turkish Ministry of Health aims for pregnant women with a medical indication to give birth with cesarean section under the best possible conditions while minimizing cesarean section delivery with non-medical indications. The cesarean section rates reported in Turkey are much higher than the 15% recommended in “Health for Everybody in 2000” as publicized by the WHO(6). A legislation released in 2012 stated that cesarean section could be preferred if the situation mandates it for the safety of the either mother or baby.

ical indications. The cesarean section rates reported in Turkey are much higher than the 15% recommended in “Health for Everybody in 2000” as publicized by the WHO(6). A legislation released in 2012 stated that cesarean section could be preferred if the situation mandates it for the safety of the either mother or baby. We think that if pregnant women receive detailed information from physicians regarding the forms of delivery during follow-up this will decrease cesarean section delivery rates. The low cesarean section rate, short hospitalization duration, lower birth induction requirement, and lower analgesia requirement in a study conducted on pregnant women who had been provided information by midwives demonstrated the importance of informing these women(18). The Turkey Population Health Research 2013 data revealed that physicians undertake the follow-up and delivery for most pregnant women. High cesarean section rates may stem from physicians seeing too many patients and not having time to inform pregnant women due to time constraints. The fear of malpractice also plays a role(15).

y Population Health Research 2013 data revealed that physicians undertake the follow-up and delivery for most pregnant women. High cesarean section rates may stem from physicians seeing too many patients and not having time to inform pregnant women due to time constraints. The fear of malpractice also plays a role(15). The reasons for preferring cesarean section in our study were mainly fear of birth, avoiding putting the infant at risk, avoiding pain, and fear of prolapse. Seventy-two percent of the women preferred optional cesarean section due to normal fear of birth in a study that evaluated the opinions on cesarean section in Turkey(19). The majority of patients preferred delivery with cesarean section due to stress and fear at similar rates in the study of Yıldız et al.(7) Fear of birth was found to be the most common (59%) among the reasons for requesting cesarean section in a study conducted in Iran(20). The rate of preferring cesarean section delivery for the same reason was found as 36% in Sweden(21). Half of the women who preferred delivery with cesarean section due to fear of birth in Sweden and Finland changed their preferences to vaginal delivery after effective anxiety training(22). Decreasing the fear of normal delivery with training in pregnant women who request delivery with cesarean section may increase the request rate for vaginal delivery.

ivery with cesarean section due to fear of birth in Sweden and Finland changed their preferences to vaginal delivery after effective anxiety training(22). Decreasing the fear of normal delivery with training in pregnant women who request delivery with cesarean section may increase the request rate for vaginal delivery. Patients should be informed on the types of birth during pregnancy and healthcare staff should be supportive during the birth process considering the psychological dimension of pregnancy. This would help decrease the cesarean section rates and the related mortality and morbidity while encouraging vaginal birth.

ivery with cesarean section due to fear of birth in Sweden and Finland changed their preferences to vaginal delivery after effective anxiety training(22). Decreasing the fear of normal delivery with training in pregnant women who request delivery with cesarean section may increase the request rate for vaginal delivery. Patients should be informed on the types of birth during pregnancy and healthcare staff should be supportive during the birth process considering the psychological dimension of pregnancy. This would help decrease the cesarean section rates and the related mortality and morbidity while encouraging vaginal birth. Although most women in our society are aware that birth is a normal process, there has been a significant increase in the cesarean section rate. The pregnancy process should be evaluated biologically, physiologically, and socially, and pregnant women should be encouraged regarding vaginal delivery in this period. Physicians who emphasize cesarean section delivery because of time pressure and increasing malpractice cases also affects these rates. The Ministry of Health should therefore consider increasing support for physicians and increasing the number of healthcare staff when evaluating birth-related policies. A retrospective evaluation of our results shows that the cesarean section rate was 48.1% (114 pregnant women). One hundred thirty-one of the women in our study comprised patients who presented to the clinic when active delivery had started, 106 women presented due to reasons such as a delay in delivery, request for a cesarean section or cesarean section requirement. Cesarean section became necessary in 29% (38 women) of the 131 pregnant women who presented during active delivery. Delivery with cesarean section was realized in 71.6% (79 women) of the remaining 106 pregnant women. This indicates that most of the women who gave birth by cesarean section were women in whom active delivery had not started and they underwent elective cesarean section. We believe that most of these women were directed to cesarean section with reasons such as environmental pressure, patient request, fear of birth, or physician guidance. The current proliferation of private hospitals has had a great effect on the increasing cesarean section rates. Cesarean section rates up to 90% have been reported when the data of private hospitals are evaluated. This creates an impression that healthcare policies implemented in state and private hospitals are different.

current proliferation of private hospitals has had a great effect on the increasing cesarean section rates. Cesarean section rates up to 90% have been reported when the data of private hospitals are evaluated. This creates an impression that healthcare policies implemented in state and private hospitals are different. CONCLUSION In conclusion, women should be informed on the type of birth and both methods should be explained in a realistic and scientific manner in terms of benefit and risk. An effort is being made to increase vaginal birth rates worldwide and the same effort should be made in Turkey. Physicians feel a serious threat of malpractice and this should be decreased through regulations by the Ministry of Health and informing society. Physicians need to monitor the health of the mother and baby in the best way during pregnancy and birth, and they should support pregnant women in choosing vaginal delivery if there is no contraindication. Ethics: Ethics Committee Approval: The study were approved by the Ankara University Ankara University Medical Faculty Ethics Committee on 12 May 2014 with decision no. 08-348-14, Informed Consent: Consent form was filled out by all participants. Peer-review: External and Internal peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Dilek Yüksel, Tuncay Yüce, Acar Koç, Concept: Tuncay Yüce, Acar Koç, Design: Tuncay Yüce, Acar Koç, Data Collection or Processing: Dilek Yüksel, Erkan Kalafat, Seda Şahin Aker, Analysis or Interpretation: Tuncay Yüce, Literature Search: Dilek Yüksel, Writing: Dilek Yüksel.

Contributions: Surgical and Medical Practices: Dilek Yüksel, Tuncay Yüce, Acar Koç, Concept: Tuncay Yüce, Acar Koç, Design: Tuncay Yüce, Acar Koç, Data Collection or Processing: Dilek Yüksel, Erkan Kalafat, Seda Şahin Aker, Analysis or Interpretation: Tuncay Yüce, Literature Search: Dilek Yüksel, Writing: Dilek Yüksel. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Reasons of the pregnant women for preferring vaginal delivery Table 2 Reasons of the pregnant women for preferring cesarean delivery Table 3 Characteristics of pregnant women according to vaginal or cesarean section delivery preference

INTRODUCTION Endometrial cancer (EC) is the sixth most common cancer in women worldwide and the twelfth most common cancer overall(1). Bokhman(2) first suggested that there were 2 types of ECs that had different microscopic, clinical, epidemiologic, and genetic properties in 1983. Type I ECs, represented by endometrioid carcinomas, constitute 80% of all ECs. Type II tumors are composed of other cell types of ECs that are less frequently observed. Most common cell types included in type II ECs are serous carcinoma (SC) and clear cell carcinoma (CCC). Type II tumors are estrogen independent, seen in older and thinner patients, diagnosed at more advanced stages, and the likelihood of recurrence and death of the disease is much higher with type II compared with type I tumors(3).

ll types included in type II ECs are serous carcinoma (SC) and clear cell carcinoma (CCC). Type II tumors are estrogen independent, seen in older and thinner patients, diagnosed at more advanced stages, and the likelihood of recurrence and death of the disease is much higher with type II compared with type I tumors(3). SC and CCCs account for 10% and 3% of ECs but are responsible for 39% and 8% of cancer deaths, respectively(4). Therefore, it is important to approach these tumors differently and to separate them from endometrioid tumors in studies that analyze patients with ECs. They are usually analyzed together in studies that investigate characteristic features, management, and survival of patients with these tumors they are rare are more aggressive than endometrioid ECs. This may also explain the disparate results obtained in the literature, because these two tumors are also different with distinct clinical behavior and pathogenetic properties. They have different molecular alterations and separate ways of spreading. Most serous tumors have p53 mutation because only 14% of clear cell tumors have this mutation. Serous tumors have a tendency to spread intraperitoneally just like its ovarian counterparts, whereas clear cell tumors show a propensity for distant metastasis(5). Many studies have compared these tumors with type I or poorly-differentiated ECs. However, there is little data in the literature with regard to the differences between these 2 tumors.

to spread intraperitoneally just like its ovarian counterparts, whereas clear cell tumors show a propensity for distant metastasis(5). Many studies have compared these tumors with type I or poorly-differentiated ECs. However, there is little data in the literature with regard to the differences between these 2 tumors. In this study, we aimed to present a comparison of SC and CCC in terms of surgico-pathologic and clinical features, and survival, and to determine factors that affect recurrence and survival. MATERIALS AND METHODS Patients with clear cell and serous EC who underwent surgery in our clinic between January 1993 and December 2013 were retrospectively analyzed. The data related to demographic characteristics, intraoperative findings, surgico-pathologic results, patients’ treatments, recurrence and the site of recurrence, and survival were collected from the electronic gynecologic oncology clinic database system, pathology reports, and surgical records. Patients were staged according to the 2009 International Federation of Gynecology and Obstetrics criteria. Institutional review board approval was obtained.

e and the site of recurrence, and survival were collected from the electronic gynecologic oncology clinic database system, pathology reports, and surgical records. Patients were staged according to the 2009 International Federation of Gynecology and Obstetrics criteria. Institutional review board approval was obtained. In our clinic, patients with a preoperative or intraoperative pathologic diagnosis of clear cell or serous tumor undergo staging surgery directly. Staging surgery involves total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic and paraaortic lymphadenectomy, abdominal cytology, and omentectomy as standard. Omentectomy was performed as total, infracolic or omental biopsy according to the cell type, intraoperative examination, and decision of the surgeon. Cytoreductive surgery was performed in addition to staging surgery in case there was macroscopic disease intraoperatively. In terms of adjuvant therapy, only radiotherapy or sandwich therapy (3 cycles of chemotherapy followed by radiotherapy, and then 3 cycles of chemotherapy) or only chemotherapy or radiotherapy followed by chemotherapy were applied at the discretion of the surgeon and according to the stage of the disease.

In our clinic, patients with a preoperative or intraoperative pathologic diagnosis of clear cell or serous tumor undergo staging surgery directly. Staging surgery involves total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic and paraaortic lymphadenectomy, abdominal cytology, and omentectomy as standard. Omentectomy was performed as total, infracolic or omental biopsy according to the cell type, intraoperative examination, and decision of the surgeon. Cytoreductive surgery was performed in addition to staging surgery in case there was macroscopic disease intraoperatively. In terms of adjuvant therapy, only radiotherapy or sandwich therapy (3 cycles of chemotherapy followed by radiotherapy, and then 3 cycles of chemotherapy) or only chemotherapy or radiotherapy followed by chemotherapy were applied at the discretion of the surgeon and according to the stage of the disease. Patients were followed-up every 3 months in the first 2 years after adjuvant therapy, within every six months until the fifth year, and yearly thereafter. Pelvic examination, complete blood count and blood chemistry, and abdominal ultrasonography were performed at every follow-up. Chest X-ray was performed yearly or in the event of clinical suspicion. Thoracic and/or abdominal computerized tomography was used when needed. In the follow-up, a Papanicolaou smear and cancer antigen-125 (Ca) level tests were used, even though we did not use them routinely.

nography were performed at every follow-up. Chest X-ray was performed yearly or in the event of clinical suspicion. Thoracic and/or abdominal computerized tomography was used when needed. In the follow-up, a Papanicolaou smear and cancer antigen-125 (Ca) level tests were used, even though we did not use them routinely. Pelvic recurrence was defined as recurrence distal to the pelvic inlet (true pelvis), upper abdominal recurrence as recurrence between the pelvic inlet and the diaphragm, and extraabdominal recurrence as all other recurrences. Ascites and peritonitis carcinomatosa were included in the upper abdominal recurrences, whereas recurrence in the liver parenchyma and bone were included in the extraabdominal recurrences. The period from surgery to recurrence or last visit was defined as progression-free survival (PFS), and the period from surgery to death or last visit was defined as overall survival (OS). Follow-up time was evaluated as the time between surgery and the time of the patient’s last examination (death or last visit).

ces. The period from surgery to recurrence or last visit was defined as progression-free survival (PFS), and the period from surgery to death or last visit was defined as overall survival (OS). Follow-up time was evaluated as the time between surgery and the time of the patient’s last examination (death or last visit). Statistical Analysis Statistical data were analyzed using Statistical Package for Social Sciences (SPSS) version 17 (SPSS Inc., Chicago IL, USA). Descriptive statistics are presented using median and range or mean and standard deviation where appropriate. Student’s t-test and the Mann-Whitney U test were used to compare means and medians, respectively, in different groups. The chi-square test or Fisher’s exact test were used where appropriate to compare proportions and percentages in different groups. Kaplan-Meier estimation was used for the analysis of survival. The logrank test and univariate Cox regression analysis were used for analysis of categorical and continuous variables that affect survival, respectively. The possible factors identified with univariate analysis were entered into multivariate Cox regression analysis. Statistical significance was considered as p<0.05.

. The logrank test and univariate Cox regression analysis were used for analysis of categorical and continuous variables that affect survival, respectively. The possible factors identified with univariate analysis were entered into multivariate Cox regression analysis. Statistical significance was considered as p<0.05. RESULTS Surgico-pathologic factors In our clinic, 1640 patients with EC underwent surgery between January 1993 and December 2013. In the defined time period, 100 (6.1%) patients were diagnosed as having either clear cell or serous uterine tumor. Among these, 49 patients had clear cell and 51 patients had serous uterine carcinoma. The mean age at diagnosis was 63±8.2 years. All but seven patients were staged surgically. Forty-two patients had stage 1 disease, five patients had stage 2, 32 patients had stage 3 and 19 patients had stage 4 disease. Forty-two percent of patients had advanced stage (stage III and IV) disease in the clear cell group, and 62% had advanced stage disease in the serous group (p=0.044).

s were staged surgically. Forty-two patients had stage 1 disease, five patients had stage 2, 32 patients had stage 3 and 19 patients had stage 4 disease. Forty-two percent of patients had advanced stage (stage III and IV) disease in the clear cell group, and 62% had advanced stage disease in the serous group (p=0.044). The median number of harvested lymph nodes was 50 (range, 2-118), and these numbers were 16 (range, 1-55) and 37 (range, 2-69) for paraaortic and pelvic regions, respectively. Among the patients with lymphadenectomy, 41 (44%) patients had lymph node metastasis. Of these patients, 16 patients had only pelvic involvement, 8 patients had only paraaortic involvement, and 16 patients had both pelvic and paraaortic involvement. In one patient the region of involvement was not defined. Thirty-seven percent of patients with CCC and 51% of patients with SC had lymph node metastasis (p=0.17). Lymphovascular space invasion (LVSI) was positive in 40 patients; it was positive in 40% and 61% of patients with CCC and serous tumor, respectively (p=0.07). Abdominal cytology was positive in 23 patients. Omental metastasis was observed in 21 patients. Twenty-one (22%) patients had ovarian involvement. The median Ca-125 level was 28 (range, 1-915). There was no difference between the 2 tumor types in terms of number of harvested lymph nodes, myometrial invasion, cervical involvement, cytologic positivity, tumor size, ovarian involvement, omental metastasis, preoperative Ca-125 level, and the site of recurrence (abdominal vs. extraabdominal) (Table 1).

The median number of harvested lymph nodes was 50 (range, 2-118), and these numbers were 16 (range, 1-55) and 37 (range, 2-69) for paraaortic and pelvic regions, respectively. Among the patients with lymphadenectomy, 41 (44%) patients had lymph node metastasis. Of these patients, 16 patients had only pelvic involvement, 8 patients had only paraaortic involvement, and 16 patients had both pelvic and paraaortic involvement. In one patient the region of involvement was not defined. Thirty-seven percent of patients with CCC and 51% of patients with SC had lymph node metastasis (p=0.17). Lymphovascular space invasion (LVSI) was positive in 40 patients; it was positive in 40% and 61% of patients with CCC and serous tumor, respectively (p=0.07). Abdominal cytology was positive in 23 patients. Omental metastasis was observed in 21 patients. Twenty-one (22%) patients had ovarian involvement. The median Ca-125 level was 28 (range, 1-915). There was no difference between the 2 tumor types in terms of number of harvested lymph nodes, myometrial invasion, cervical involvement, cytologic positivity, tumor size, ovarian involvement, omental metastasis, preoperative Ca-125 level, and the site of recurrence (abdominal vs. extraabdominal) (Table 1). Adjuvant therapy Nine patients had no adjuvant therapy, and 71 patients completed adjuvant therapy. Twenty-one patients had radiotherapy only, 34 patients had chemotherapy only, 11 patients received sandwich therapy, and 5 patients had radiotherapy followed by chemotherapy. Platin- based chemotherapy was used (paclitaxel + carboplatin, n=31; paclitaxel + cisplatin, n=9; cisplatin, n=3; paclitaxel, n=1, doxorubicin + cisplatin, n=5; paclitaxel + carboplatin + epirubicin, n=1). Thirty-five patients completed six cycles of chemotherapy. Eighteen were lost to follow-up following surgery. Eighty percent of patients with CCC and 65% of patients with serous tumor received adjuvant therapy (p=0.08). Details of the adjuvant therapy in patients with CCC and serous tumor are defined separately in Table 2. Radiotherapy seemed to be used more commonly in patients with CCC; however, there was no statistical difference between the groups regarding the type of adjuvant therapies used (p=0.192).

adjuvant therapy (p=0.08). Details of the adjuvant therapy in patients with CCC and serous tumor are defined separately in Table 2. Radiotherapy seemed to be used more commonly in patients with CCC; however, there was no statistical difference between the groups regarding the type of adjuvant therapies used (p=0.192). Recurrence Recurrence was observed in 22 patients (27.5%). This number was 9 (24%) and 13 (31%) for patients with CCC and SC, respectively (p=0.47). The mean time to recurrence was 12 months (range, 1-45 months). The time to recurrence and site of recurrence were similar in the two tumor types. Recurrence was only in the upper abdomen in nine patients, only extraabdominal in four patients, only in the pelvis in two patients, in the upper abdomen and extraabdominal in three patients, in the pelvis and extraabdominal in two patients, in the pelvis and upper abdomen in one patient, and in the pelvis, upper abdomen, and extraabdominal in one patient. The recurrence pattern of the 2 tumor types is defined in detail in Table 3. In the subgroup analysis of patients with clear cell tumors, only lymph node involvement was associated with recurrence (p=0.04). Depth of myometrial invasion, LVSI, ovarian involvement, omental metastasis, cervical invasion, age, number of lymph nodes harvested, tumor size, and taking adjuvant therapy were not associated with recurrence. The patients who had recurrence had higher preoperative Ca-125 levels (p=0.014).

ed with recurrence (p=0.04). Depth of myometrial invasion, LVSI, ovarian involvement, omental metastasis, cervical invasion, age, number of lymph nodes harvested, tumor size, and taking adjuvant therapy were not associated with recurrence. The patients who had recurrence had higher preoperative Ca-125 levels (p=0.014). In the group with serous tumor, paraaortic lymph node metastasis, presence of LVSI, ovarian and omental metastasis, and higher preoperative Ca-125 level were associated with a higher risk of recurrence (p=0.017, p=0.004, p=0.007, p=0.001 and p=0.007, respectively). On the other hand, pelvic lymph node metastasis, myometrial invasion, positivity of peritoneal cytology, cervical invasion, age, number of lymph nodes harvested, tumor size, and taking adjuvant therapy were not associated with recurrence. Survival Analysis The median follow-up time was 18.5 months (range 1-156 months), and was 39 months (range, 1-156 months) and 28 months (1-96 months) for patients with CCC and SC ECs, respectively (p=0.035). Five patients with CCC and eight patients with SC ECs died in the follow-up period; one patient with CCC died during adjuvant therapy and the other who had SC died before the adjuvant therapy (1 following 3 cycles of chemotherapy and 1 before adjuvant therapy-renal insufficiency). Five-year PFS was 53.6%; 60.6% and 45.5% for CCC and serous tumor, respectively (p=0.465) (Figure 1). Five-year OS was 77.1%; 85.8% and 67.8% for CCC and serous tumors, respectively (p=0.565) (Figure 2).

Survival Analysis The median follow-up time was 18.5 months (range 1-156 months), and was 39 months (range, 1-156 months) and 28 months (1-96 months) for patients with CCC and SC ECs, respectively (p=0.035). Five patients with CCC and eight patients with SC ECs died in the follow-up period; one patient with CCC died during adjuvant therapy and the other who had SC died before the adjuvant therapy (1 following 3 cycles of chemotherapy and 1 before adjuvant therapy-renal insufficiency). Five-year PFS was 53.6%; 60.6% and 45.5% for CCC and serous tumor, respectively (p=0.465) (Figure 1). Five-year OS was 77.1%; 85.8% and 67.8% for CCC and serous tumors, respectively (p=0.565) (Figure 2). In the univariate analysis of the clear cell subgroup, omental metastasis, paraaortic involvement, peritoneal cytology positivity, and taking no adjuvant therapy were associated with worse 5-year OS (p=0.002, p=0.003, p<0.001, p=0.035 respectively), and omental metastasis, paraaortic involvement, pelvic involvement, positivity of peritoneal cytology, preoperative Ca-125 level and ovarian metastasis were associated with 5-year PFS (p<0.001, p=0.014, p=0.044, p<0.001, p=0.016 and p=0.006, respectively) (Tables 4 and 5). Multivariate analysis could not be performed in this subgroup.

stasis, paraaortic involvement, pelvic involvement, positivity of peritoneal cytology, preoperative Ca-125 level and ovarian metastasis were associated with 5-year PFS (p<0.001, p=0.014, p=0.044, p<0.001, p=0.016 and p=0.006, respectively) (Tables 4 and 5). Multivariate analysis could not be performed in this subgroup. In the univariate analysis of the serous subgroup, lower number of harvested lymph nodes, paraaortic metastasis, and LVSI were associated with worse 5-year OS (p=0.017, p<0.001, p=0.041 respectively), and paraaortic metastasis, omental metastasis, and LVSI were associated with worse 5-year PFS (p<0.001, p=0.004, p=0.006, respectively) (Tables 4 and 5). Multivariate analysis could not be performed for OS and it could not detect any independent prognostic factor for 5-year PFS. DISCUSSION Type II ECs differ from endometrioid tumors with their less favorable characteristics. They have a tendency to present at more advanced stages and to recur earlier(6,7). In the present study, 42% of patients had advanced stage (stage III and IV) disease in the clear cell group, and 62% had advanced stage disease in the serous group (p=0.044). The rate of advanced stage disease is reported between 40% to 56% in the literature for both serous and clear cell tumors(3,4,6,7). The different rates may be explained by the different rates of comprehensive surgical staging in these studies. SC, ECs seem to present at more advanced stages than CCCs according to our results.

e of advanced stage disease is reported between 40% to 56% in the literature for both serous and clear cell tumors(3,4,6,7). The different rates may be explained by the different rates of comprehensive surgical staging in these studies. SC, ECs seem to present at more advanced stages than CCCs according to our results. There was no difference between the 2 tumor types in terms of number of harvested lymph nodes, myometrial invasion, cervical involvement, cytologic positivity, tumor size, ovarian involvement, omental metastasis, preoperative Ca-125 level, and the site of recurrence (abdominal vs. extraabdominal). LVSI was positive in 40% and 61% of patients with CCC and serous tumor, respectively (p=0.07). This difference seems clinically significant. However, it did not reach statistical significance. Omental metastasis was observed in 24% of the patients. Although omentectomy is controversial in the staging surgery of type II ECs, omental metastasis was reported as 13% and up to 25% for CCC and SC, respectively, in different studies(8,9).

s clinically significant. However, it did not reach statistical significance. Omental metastasis was observed in 24% of the patients. Although omentectomy is controversial in the staging surgery of type II ECs, omental metastasis was reported as 13% and up to 25% for CCC and SC, respectively, in different studies(8,9). There is no consensus regarding adjuvant therapy for type II ECs. Adjuvant chemotherapy is usually suggested for patients with type II ECs for all stages, because even patients with uterine SC without myometrial invasion treated with observation alone were shown to have a risk of recurrence, which varied from 0 to 30%(10) and clear cell tumors were reported to have a tendency for distant recurrence(5). Although there are different results in the literature, adjuvant radiotherapy is usually accepted to decrease local recurrence, but an exact effect on survival has not been shown(3,6). In our study, 80% of patients with CCC and 65% of patients with serous tumor received adjuvant therapy (p=0.08).

distant recurrence(5). Although there are different results in the literature, adjuvant radiotherapy is usually accepted to decrease local recurrence, but an exact effect on survival has not been shown(3,6). In our study, 80% of patients with CCC and 65% of patients with serous tumor received adjuvant therapy (p=0.08). Recurrence was observed in 22 (27.5%) patients; the recurrence pattern was similar between the 2 groups. Twenty-two percent to 38% of patients were reported to have recurrence in the literature(11,12,13). In the subgroup analysis of patients with CCC, only lymph node involvement was associated with recurrence. In the group with serous tumor, paraaortic lymph node metastasis, presence of LVSI, and ovarian and omental metastasis were associated with a higher risk of recurrence. Additionally, the patients who had recurrence in both groups had higher preoperative Ca-125 levels. Preoperative Ca-125 was also associated with 5-year PFS in patients with CCC in our study (p=0.016). There are no data in the literature on the relation between Ca-125 level and uterine clear cell tumors. On the other hand, the association of uterine SC and Ca-125 level has been studied in several trials. In a study that analyzed the relation between preoperative Ca-125 level and uterine SCs in 41 patients, Olawaiye et al.(14) showed that preoperative Ca-125 was associated with disease stage at diagnosis and with the likelihood of death. In addition, Abramovich et al.(15) reported that a rising Ca-125 was associated with relapse.

that analyzed the relation between preoperative Ca-125 level and uterine SCs in 41 patients, Olawaiye et al.(14) showed that preoperative Ca-125 was associated with disease stage at diagnosis and with the likelihood of death. In addition, Abramovich et al.(15) reported that a rising Ca-125 was associated with relapse. In the present study, 5-year PFS was 60.6% and 45.5% for CCC and serous tumor, respectively (p=0.465). These rates were 85.8% and 67.8% for 5-year OS (p=0.565). In the study by Scarfone et al.(13) these rates were reported as 67% and 55% for 5 year PFS, and 77% and 71% for 5-year OS, respectively. Thomas et al.(16) found that 5-year PFS and OS were 46% and 55% in 99 patients with CCC. There is a wide range of survival rates reported in the literature. Different complete staging and cytoreduction rates, and different adjuvant therapies may account for this situation. Complete surgical staging including lymphadenectomy and cytoreduction are recommended to be performed for all patients with these tumors, because more than half of these patients are upstaged during these procedures and residual disease was shown to be associated with worse survival(6,7). Ninety-three percent of our patients underwent complete surgical staging and cytoreductive surgery and the numbers of lymph nodes removed were quite high. These may be the reasons for the high survival rates in our study.

during these procedures and residual disease was shown to be associated with worse survival(6,7). Ninety-three percent of our patients underwent complete surgical staging and cytoreductive surgery and the numbers of lymph nodes removed were quite high. These may be the reasons for the high survival rates in our study. In the current study, in the univariate analysis of the clear cell subgroup, omental metastasis, paraaortic involvement, peritoneal cytology positivity, and receiving no adjuvant therapy were associated with worse 5-year OS, and omental metastasis, paraaortic involvement, pelvic involvement, peritoneal cytology positivity, preoperative Ca-125 level, and ovarian metastasis were associated with 5-year PFS. However, in the study by Thomas et al.(16) age more than 60 years, LVSI, and myometrial invasion equal to or greater than half were reported associated with both 5-year PFS and OS in the univariate analysis that included 99 patients with uterine CCC. In the same study, a multivariate analysis revealed that stage and adjuvant radiotherapy were independent prognostic factors for both PFS and OS, and systemic lymphadenectomy was an independent prognostic factor for OS only. Abeler and Kjørstad(17) showed in a study of 97 patients with uterine CCC that 17% of patients with LVSI survived 5 years, in contrast to 49% of patients without this finding. In the univariate analysis of the serous subgroup of our study population, lower number of harvested lymph nodes, paraaortic metastasis, and LVSI were associated with worse 5-year OS, and paraaortic metastasis, omental metastasis, and LVSI were associated with worse 5-year PFS. Similar findings were shown in a study that analyzed 129 patients with uterine SC. In that study, worse 5-year OS was reported associated with LVSI and positive lymph nodes in the univariate analysis. Different to other studies, the same study also showed that myometrial invasion was related to OS(18). Myometrial invasion was also reported associated with PFS in 83 women with stage I uterine SC. The authors could not show a relation between LVSI, number of harvested lymph nodes, age, and survival(11). Similarly, Fader et al.(19) were unable to demonstrate an association between LVSI and PFS.

on was related to OS(18). Myometrial invasion was also reported associated with PFS in 83 women with stage I uterine SC. The authors could not show a relation between LVSI, number of harvested lymph nodes, age, and survival(11). Similarly, Fader et al.(19) were unable to demonstrate an association between LVSI and PFS. Study Limitations The retrospective nature of the study was one of our limitations. Additionally, the adjuvant chemotherapy and radiotherapy protocols could not be standardized during the study period. However, this study included 100 patients with CCC and SC ECs from a single institution and the clinico-pathologic features of the patients could be obtained in detail. Most patients in this study underwent complete staging and cytoreductive surgery including comprehensive lymphadenectomy. These are considered to be the advantages of our study. CONCLUSION In this study, with the exception that SC ECs presented at more advanced stages, we could not show a statistically significant difference between patients with CCC and SC ECs regarding surgico-pathologic features, recurrence rates and patterns, and survival rates. However, patients with SC ECs had a tendency to have less favorable characteristics compared with CCC. We also demonstrated factors that affected recurrence and survival. Ethics: Ethics Committee Approval: Institutional review board approval was obtained, Informed Consent: None, retrospective. Peer-review: External and Internal peer-reviewed.

CONCLUSION In this study, with the exception that SC ECs presented at more advanced stages, we could not show a statistically significant difference between patients with CCC and SC ECs regarding surgico-pathologic features, recurrence rates and patterns, and survival rates. However, patients with SC ECs had a tendency to have less favorable characteristics compared with CCC. We also demonstrated factors that affected recurrence and survival. Ethics: Ethics Committee Approval: Institutional review board approval was obtained, Informed Consent: None, retrospective. Peer-review: External and Internal peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Nurettin Boran, Gökhan Tulunay, Taner Turan, Concept: Nurettin Boran, Gökhan Tulunay, Taner Turan, Design: Taner Turan, Data Collection or Processing: Derya Akdağ Cırık, Tolga Taşçı, Analysis or Interpretation: Taner Turan, Işın Üreyen, Literature Search: Günsu Kimyon Cömert, Tolga Taşçı, Osman Türkmen, Writing: Işın Üreyen, Alper Karalok. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Comparison of clinico-pathologic characteristics of patients Table 2 Comparison of adjuvant therapies between the tumor types Table 3 Pattern of recurrence Table 4 Five-year overall survival Table 5 Five-year progression-free survival Figure 1 Five-year progression-free survival Figure 2 Five-year overall survival

PRECIS: The long-term influences of episiotomy on urinary and/or fecal incontinence, pelvic floor dysfunction, sexual function, and dyspareunea are still not clear and studies on these issues are necessary. INTRODUCTION For a succesful vaginal birth, vaginal and cervical expansion should occur slowly and the tissue should be allowed to stretch in a proper manner. At this time, spontaneous tears may ensue in rapid descent, particularly during the fetal head descent and the formation of vaginal dilatation. Even if these tears, as described by Fernando who divided them into four degrees, most frequently involve perineal skin and mucosa (1st degree), they may extend to perineal muscle (2nd degree), anal sphinchter complex (3rd degree), and anal mucosa (4th degree). Another reason for vaginal tears at birth is controlled and properly made perineal incisions performed at the end of the second stage of labor to ease parturition by increasing the vaginal diameter, known as episiotomy(1). Two types have been described; median (from the posterior fourchette to the anus) and mediolateral (from hymenal ring downwards with at least a 45-degree angle). However, standardization in the method of application and repair of episiotomy is still lacking today. Additionally, in the majority of studies conducted on this issue to date, the parameters likely to influence the healing process and long-term outcomes are not clear.

l ring downwards with at least a 45-degree angle). However, standardization in the method of application and repair of episiotomy is still lacking today. Additionally, in the majority of studies conducted on this issue to date, the parameters likely to influence the healing process and long-term outcomes are not clear. EARLY STUDIES AND SHORT-TERM EFFECTS After being described by Ould(2) in 1741, episiotomy was first recommended to be applied in a mediolateral fashion in all births of nulliparous women in order to protect the fetal head from trauma and the pelvic floor from extreme lacerations in 1921(3). For years, episiotomy was believed to be repaired more easily and to reduce the risk of severe lacerations in the short term, and to protect against pelvic floor relaxation, sexual dysfunction, and long-term urinary and/or fecal incontinence, as compared with spontaneous vaginal or perineal tears. It was also considered associated with neonatal benefits such as lower incidences of asphyxia, cranial trauma, cerebral hemorrhage, mental retardation, and shoulder dystocia. Consequently, episiotomy was used extensively until the first half of the nineteenth century and the frequency of application gradually increased. However, in the second half of the twentieth century, increasing evidence that episiotomy did not actually provide these benefits began to be published(4). Thereupon, Thacker and Banta(4) reviewed the related studies conducted between 1860 and 1980 and analyzed the results to investigate whether episiotomy provided any benefits. As a result, they reported that the number of studies available was insufficient and that the studies were not reliable enough to substantiate their hypotheses; thus, the results did not support the routine use of episiotomy. Moreover, it was indicated that postpartum pain and discomfort became evident and serious complications, and maternal death might even occur after episiotomy(4). During the defined period and the following 10 years, publications mostly originated from the United States and were of minor scale, in addition, as almost all dealt with midline episiotomy. There is a very limited number of publications on mediolateral episiotomy and the most comprehensive study was from Argentina, a randomized controlled trial that included 2.606 women from 8 centers(5).

y originated from the United States and were of minor scale, in addition, as almost all dealt with midline episiotomy. There is a very limited number of publications on mediolateral episiotomy and the most comprehensive study was from Argentina, a randomized controlled trial that included 2.606 women from 8 centers(5). In that study, routine, restrictive or selective episitotomies were compared and episiotomy rates were reported to be 82.6% and 30.1% in the restrictive and routine groups, respectively. Perineal lacerations of 3rd or 4th degree were reported lower in the restrictive group than in the routine group (1.2% vs. 1.5%). Subsequently, the review by Homsi et al.(6) indicated the possible drawbacks of routine episiotomy to be the extension of the episiotomy incision, unsuitable anatomic outcomes, increased blood loss and hematoma formation, pain, inflammation, infection and dehiscence within the episiotomy region, sexual dysfunction, and increased costs (Table 1).

Homsi et al.(6) indicated the possible drawbacks of routine episiotomy to be the extension of the episiotomy incision, unsuitable anatomic outcomes, increased blood loss and hematoma formation, pain, inflammation, infection and dehiscence within the episiotomy region, sexual dysfunction, and increased costs (Table 1). EPISIOTOMY AND LONG-TERM EFFECTS A significant proportion of the studies relevant to episiotomy actually assessed short- and medium-term period outcomes; long-term complications associated with episiotomies were not explicit. In a systematic review published in 2005 in the Journal of the American Medical Association that included only 26 prospective randomized controlled trials even though 986 publications had been published between 1950 and 2004, data beyond the postpartum first year was only provided in two studies,(7) one of which was conducted by Sleep and Grant(8) in 1987 who compared routine versus restrictive episiotomy during spontaneous vaginal delivery within a single center. That study, which was initiated with 1.000 women in 1984, was terminated with 674 women in the 3rd postpartum year and reported that there was no significant difference between the two groups in terms of dyspareunia and urinary incontinence. The other study was conducted by Rockner(9) in 1990 and reported no statistically significant difference in the incidence of urinary incontinence between groups with and without episiotomy at the postpartum 4th year. However, no study has provided data on anal incontinence beyond the 1st postpartum year. As a result, there is no evidence to support the maternal benefits of routine episiotomy.

ically significant difference in the incidence of urinary incontinence between groups with and without episiotomy at the postpartum 4th year. However, no study has provided data on anal incontinence beyond the 1st postpartum year. As a result, there is no evidence to support the maternal benefits of routine episiotomy. One of the largest studies on the long-term complications of episiotomy was conducted in France with the participation of two hospitals that adopted diverse policies regarding episiotomy(10). Long-term outcomes of restrictive and routine episiotomy were compared in this study, including deliveries of 774 nulliparous women with singleton and cephalic presentation pregnancies between 37 and 41 gestational weeks. Four postpartum years later, 627 women responded with a 81% return rate and the patient distribution was 320 versus 307 women; the episiotomy rates were 49% and 88% in the restrictive and routine episiotomy groups, respectively. The rates of urinary incontinence, perineal pain, and dyspareuneu were lower in the restrictive group than in the routine episiotomy group with rates of 26% vs. 32%, 6% vs. 8%, and 18% vs. 21%, respectively, but not there was no significant difference. Similarly, fecal and flatus incontinences were lower in the restrictive group than in the routine episiotomy group with rates of 11% vs. 16%, and 8% and 13%, respectively; statistical significance was reached only for flatus incontinence. Consequently, the authors stressed that routine episiotomy did not protect against anal and urinary incontinence, there was even a increased risk of anal incontinence in the long term, and that restrictive episiotomy should be preferred to routine episiotomy.

tical significance was reached only for flatus incontinence. Consequently, the authors stressed that routine episiotomy did not protect against anal and urinary incontinence, there was even a increased risk of anal incontinence in the long term, and that restrictive episiotomy should be preferred to routine episiotomy. In the early 2000s, publications reporting the increasing incidence of severe obstetric lacerations began to emerge and in the United Kingdom, and the incidence of perineal lacerations of grade 3 or 4, with a reported incidence of 1.8% in 2000, was reported to rise to 5.9% in 2011, which exhibited a 3-fold increase(11). An increased risk for severe perineal lacerations were indicated associate with increased maternal age, instrumental delivery, Asian race, higher socio-economic status, birth weight of 4.000 g or above, and shoulder dystocia. Some publications reported that selective episiotomy decreased the likelihood of 3rd or 4th degree perineal lacerations;(12) whereas, in a large observational study that included approximately 3.000 births, risk of perineal lacerations was reported associated with a set of factors, mainly including median episiotomy(13). Today, there are two remarkable retrospective studies regarding mediolateral episiotomy. The first is a retrospective population-based study conducted in 2001, which comprised 284.000 vaginal births(14). In that study, risk factors for 3rd degree perineal tears were investigated and episiotomy rate was reported as 35.1%, the rate of 3rd degree perineal tears was presented much lower than those in previous reports (1.94% vs. 4-5%). The authors concluded that forceps delivery was the most remarkable risk factor for 3rd degree perineal laerations [odds rate (OR), 3.33; 95% confidence Interval (CI): (2.97-3.74)] and that mediolateral episiotomy should be performed as a primary measure in case of fetal macrosomia to prevent 3rd degree perineal lacerations. The latter was a retrospective study conducted by Baumann et al.(15) in 2006 that included 40.000 vaginal births. In contrast to the previous study, the rate of anal sphincter laceration in primiparous women was reported as high as 5.2% and 17 obstetric risk factors, which may result in sphincter injury. Moreover, it was emphasized that anal sphincter laceration was most strongly associated with episiotomy [OR, 3.23; 95% CI: (2.73-3.80)] and forceps delivery [OR, 2.68; 95% CI: (2.17-3.33)].

laceration in primiparous women was reported as high as 5.2% and 17 obstetric risk factors, which may result in sphincter injury. Moreover, it was emphasized that anal sphincter laceration was most strongly associated with episiotomy [OR, 3.23; 95% CI: (2.73-3.80)] and forceps delivery [OR, 2.68; 95% CI: (2.17-3.33)]. Beyond the causes of severe obstetric lacerations, there were no concrete data on repair and long-term outcomes. In a retrospective case-control survey study, 171 women who underwent anal sphincter rupture surgery between 1971 and 1990 were matched with 171 control women for time and number of deliveries and all women were interrogated twice in both 1996 and 2005 as to whether there had been any increase in sexual and anorectal symptoms, regardless of the menopausal state; a statistically significant increase was determined in study group(16). In particular, the rates of anorectal symptoms in 1996, when questioned for the first time, were 16% and 38% in control and study groups, respectively, whereas in 2005, they were 22% and 61%, respectively, which revealed that the increase in the variation of rates, as the years advanced, was statistically significant in the study group (p<0.0001). Additionally, in the questionnaire in 2005, dyspareunia and fecal incontinence during intercourse were investigated and found significantly different between the controls and study patients (13% vs. 29%, p=0.01 and 1% vs. 13%, p=0.05, respectively). Similar results were reported in another study conducted in 1988; the anal incontinence rate in women with complete perineal rupture occuring at vaginal delivery, as declared after a mean of 78 months was 22%, whereas it was 0% in the control women (p<0.01)(17). Even though perineal laceration was succesfully repaired, Poen et al.(18) also affirmed the anal incontinence rate after 5 years to be 40%.

nence rate in women with complete perineal rupture occuring at vaginal delivery, as declared after a mean of 78 months was 22%, whereas it was 0% in the control women (p<0.01)(17). Even though perineal laceration was succesfully repaired, Poen et al.(18) also affirmed the anal incontinence rate after 5 years to be 40%. RESTRICTED INSTEAD OF ROUTINE EPISIOTOMY? The first Cochrane review available in the literature, in the context of benefits and possible risks of routine episiotomy, which aimed to compare routine versus restricted episiotomy as well as midline versus mediolateral episiotomy, was published in 1999, and revised in 2004 and 2009(19). The authors included only 8 randomized controlled trials, comprising a total of 5.541 women, because most of the studies were of low-quality(5,20,21,22,23,24,25,26). The frequency episiotomy was 75.15% in the routine group, and 28.40% in restrictive group. The limitations of the review were the limited data for episiotomy technique and lack of high-quality studies included in the review, although there were 3 studies available comparing midline and mediolateral episiotomies. Based on the results of the review, the incidence of any anterior trauma was significantly higher in the restrictive group than in the routine group [relative risk (RR), 1.84; 95% CI: (1.61-2.10)]. However, the only data on long-term episiotomy complications available was dyspareunia at 3 postpartum years and there was no significant difference between the groups [RR, 1.21; 95% CI: [0.84-1.75)]. Consequently, it was reported that routine episiotomy did not reduce the rates of urinary incontinence, pain, and sexual dysfunction, and that it has no benefit to the newborn. The recommendations of both National Institute of Clinical Excellence and Royal College of Obstetricians and Gynaecologists are similar and compatible with each other. In 2006, the American College of Obstetricians and Gynecologists stated that the frequency of anal sphincter and rectal mucosa injury in vaginal deliveries with median episiotomy was higher than in those with mediolateral episiotomy and they recommended restrictive mediolateral episiotomy, if necessary (Level A), and also expressed that routine episiotomy did not prevent pelvic floor damage (Level B)(27).

cy of anal sphincter and rectal mucosa injury in vaginal deliveries with median episiotomy was higher than in those with mediolateral episiotomy and they recommended restrictive mediolateral episiotomy, if necessary (Level A), and also expressed that routine episiotomy did not prevent pelvic floor damage (Level B)(27). Prophylactic episiotomy still continues to be widely used today, although the number of publications that recommend against its routine use is higher. Obstetricians’ perception that episiotomy decreases the risk of perineal trauma as compared with spontaneous tears, apparently without having any basis of scientific evidence, constitutes the most substantial justification for this practice(28). The implementation of episiotomy is likely to be influenced by the physician’s working environment, conditions and individual diversities as well as mother and fetal factors. One study reported that midwives were more prone to perform episiotomies than physicians,(29) and another indicated that faculty providers performed episiotomies at a lower rate than private providers(30). The study by Gossett and Dunsmoor Su(31) revealed individual differences more clearly.

s mother and fetal factors. One study reported that midwives were more prone to perform episiotomies than physicians,(29) and another indicated that faculty providers performed episiotomies at a lower rate than private providers(30). The study by Gossett and Dunsmoor Su(31) revealed individual differences more clearly. EPISIOTOMY AND SEXUAL DYSFUNCTION Postpartum sexual life has recently been a subject of research. Studies have also demonstrated that postpartum sexual problems are common in the short term. Although perineal pain and dyspareunia that occur in the postpartum period are considered the main issues that prevent normal sexual activity, our knowledge on this issue is lacking because there are insufficient studies comparing ante- and postpartum sexual activity. According to the results of the study conducted by Abdool et al.(32) in 2009, perineal pain and dyspareunia results from perineal trauma, lacerations, episiotomy and forceps or vacuum use at delivery. Moreover, the authors also reported that perineal pain develops in 42% of patients in the early postpartum period and declines to 22% and 8% in the postpartum 8th and 12th weeks, respectively. Another study that included 921 primiparous women stated that 25% of women had lower sexual desire and functioning at the postpartum 6th month and 42% and 22% of women had dyspareunia at the 3rd and 6th postpartum months, respectively(33). In the same investigation, it was reported that women with a second degree perineal trauma had 80% more dyspareunia symptoms, and those who had third degree perineal trauma had 270%, as compared with women who had no perineal trauma. However, there is very limited high-level evidence regarding long-term postpartum sexual dysfunctions. A limited number of studies that compared routine and restrictive episiotomy outcomes reported that the frequency of dyspareunia at the 3rd and 4th postpartum years did not differ between the groups(8,10,19). A study from the Netherlands stressed that dyspareunia was significantly more common in women who underwent repair surgery for anal sphincter rupture than in those who did not, when the patients were questioned 15 years after their delivery (dyspareunia 13% vs. 29%, respectively, p=0.01)(16).

tween the groups(8,10,19). A study from the Netherlands stressed that dyspareunia was significantly more common in women who underwent repair surgery for anal sphincter rupture than in those who did not, when the patients were questioned 15 years after their delivery (dyspareunia 13% vs. 29%, respectively, p=0.01)(16). CONCLUSION Even though a substantial number of publications do not recommend the implementation of routine prophylactic episiotomy, it still continues to be widely performed. It is not clear as to which approach should be adopted in operative delivery; however, the hitherto gathered data supports restrictive rather than routine episiotomy. Moreover, data as to whether routine episiotomy reduces the incidence of severe obstetric lacerations is lacking, as well as whether episiotomy improves the long-term risks of pelvic floor relaxation, pelvic organ prolapse, urinary incontinence, and dyspareunia remains unclear, and further studies on this issue are still warranted. Ethics: Peer-rewiev: External and Internal peer-reviewed. Authorship Contributions: Surgical and Medical Practices: İsmet Gün, Bülent Doğan, Özkan Özdamar, Concept: İsmet Gün, Özkan Özdamar, Design: İsmet Gün, Data Collection or Processing: İsmet Gün, Bülent Doğan, Özkan Özdamar, Analysis or Interpretation: İsmet Gün, Bülent Doğan, Literature Search: Bülent Doğan, Özkan Özdamar, Writing: İsmet Gün, Özkan Özdamar. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.

Authorship Contributions: Surgical and Medical Practices: İsmet Gün, Bülent Doğan, Özkan Özdamar, Concept: İsmet Gün, Özkan Özdamar, Design: İsmet Gün, Data Collection or Processing: İsmet Gün, Bülent Doğan, Özkan Özdamar, Analysis or Interpretation: İsmet Gün, Bülent Doğan, Literature Search: Bülent Doğan, Özkan Özdamar, Writing: İsmet Gün, Özkan Özdamar. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Table 1 Short and long-term consequences of performing an episiotomy

INTRODUCTION Female genital mutilation/cutting (FGM/C) is the medically unnecessary modification of the female external genitalia for cultural reasons, which leads to dysfunction(1). Historically, there have been references to its existence in Ancient Egypt; no one actually knows when, how or why FGM/C began. It is important to note that there have been no medically documented justifications that show the benefits of this practice for the purpose of enhancing woman’s health. The procedure is named “female circumcision” in countries where it is practiced, but the term “FGM” is used in medical literature because of its harmful physical and psychological consequences(2). It is often performed before adolescence. FGM/C is still known to be practiced in approximately 30 countries in Africa, in a few countries on the Arab Peninsula, among some communities in Asia, and among immigrants from these areas who have settled in Europe, Australia, and North America(2). It affects approximately 100 million women worldwide and another 2 million procedures are performed each year(2,3). Although the practice may show variations from one country to another, it is performed secretly because it is an illegal practice. Typically, the procedure is undertaken by a traditional circumciser using a sharp blade or razor, which is not sterilized, and without any anesthesia(4,5,6). The World Health Organization (WHO) has categorized FGM/C into four main groups: Type 1: Amputation of the prepuce, sometimes along with partial or total removal of the clitoris (sunna).

Although the practice may show variations from one country to another, it is performed secretly because it is an illegal practice. Typically, the procedure is undertaken by a traditional circumciser using a sharp blade or razor, which is not sterilized, and without any anesthesia(4,5,6). The World Health Organization (WHO) has categorized FGM/C into four main groups: Type 1: Amputation of the prepuce, sometimes along with partial or total removal of the clitoris (sunna). Type 2: Amputation of the clitoris and part or all of the labia minora (excision). Type 3: Amputation of the clitoris and labium minora. Cutting of the labium majora and sutured wound edges. A small opening is created to allow the flow of urine and menstrual blood (infibulation). Type 4: A new category that encompasses a group of other operations on the external genitalia including piercing or incising the clitoris and/or labia, stretching the clitoris and/or labia, cauterization, scraping and/or cutting of the vagina, introduction of corrosive substances and herbs into the vagina, and similar practices(7).

category that encompasses a group of other operations on the external genitalia including piercing or incising the clitoris and/or labia, stretching the clitoris and/or labia, cauterization, scraping and/or cutting of the vagina, introduction of corrosive substances and herbs into the vagina, and similar practices(7). Pain, hemorrhage, and infections are the three most important early complications. The long-term complications, especially as related to type 3 (infibulation) and these are infertility, vulvar mass-keloids, vesicovaginal fistula, and vesicourethral fistula, menstrual irregularities, chronic cystitis and dysuria, chronic pelvic pain, and dyspareunia. Maternal and fetal mortality and morbidity is also increased due to dystocia(8,9). A number of studies also concluded that FGM/C had adverse effects on circumcised women’s sexual life, leaving them feeling inadequate at intercourse(10,11). This study describes the presentation of long- term complications of FGM/C and the surgical management of clitoral keloids. CASE REPORT This was a retrospective study of the case notes on 27 patients with FGM/C who had clitoral masses and were referred to Sudan Nyala Turkish Hospital between May 2014 and September 2015. Gynecologic history, long-term complications of FGM/C, size of masses, and short-term complications after surgery were recorded. Surgical excision was performed for all patients by the same surgeon and all specimens were evaluated by the same pathologist.

udan Nyala Turkish Hospital between May 2014 and September 2015. Gynecologic history, long-term complications of FGM/C, size of masses, and short-term complications after surgery were recorded. Surgical excision was performed for all patients by the same surgeon and all specimens were evaluated by the same pathologist. Twenty-seven patients with clitoral mass were admitted to our gynecology outpatient clinic. All of the patients had a history of undergoing FGM/C. All masses were pre-diagnosed as clitoral keloid before surgery. The demographics and gynecologic history of the patients are shown in Table 1. The mean age of the patients were 18.07±7.16 years. FGM/C had been performed on all patients when they were aged between 7 to 9 years. The mean time between the procedure and notification of vulvar mass was 4.37±1.96 years. The sizes of the masses varied between 3 to 10 centimeters. The mean time between notification of the mass and referral to a gynecologist was 6.15±5.76 years. The percentages of FGM/C types and symptoms are shown in Table 2. Most of the patients had type 3 FGM/C (n=20), which is the most destructive procedure and has the worst prognosis. The most common symptoms were dysuria with chronic cystitis and dyspareunia. All patients had at least two long-term health problems. Surgical excision was performed for all patients. There were no early complications recorded in any of the patients. Pathologically all masses were reported as keloid. Pictures of one patient before and after the surgery are shown in Figures 1 and 2.

The percentages of FGM/C types and symptoms are shown in Table 2. Most of the patients had type 3 FGM/C (n=20), which is the most destructive procedure and has the worst prognosis. The most common symptoms were dysuria with chronic cystitis and dyspareunia. All patients had at least two long-term health problems. Surgical excision was performed for all patients. There were no early complications recorded in any of the patients. Pathologically all masses were reported as keloid. Pictures of one patient before and after the surgery are shown in Figures 1 and 2. DISCUSSION Currently, over 100 million women throughout the world have been subjected to the practice of FGM/C. Likewise, 66.000 women in the United Kingdom and 50.000 women in France have been reported(12). The age at which girls undergo FGM/C is mostly before 12 years(1,2,7). In our study, all patients underwent FGM/C between the ages of 7 and 9 years.

on women throughout the world have been subjected to the practice of FGM/C. Likewise, 66.000 women in the United Kingdom and 50.000 women in France have been reported(12). The age at which girls undergo FGM/C is mostly before 12 years(1,2,7). In our study, all patients underwent FGM/C between the ages of 7 and 9 years. FGM/C is accepted as an assault on the human rights of women by the WHO because the practice deprives women of their rights to experience their sexuality. Its detrimental psychological and psychosexual lifelong effects on women’s sexual life have been examined in many studies. The psychotherapist and social activist Leila Hussein’s case can be given to show the seriousness of this non-medical practice. In her report to the Guardian, she stated that she recalled every single detail: She was cut when she was seven years old, four women held her down, she felt every single cut, and she screamed so much that she fainted(13). Girls who have not been circumcised are considered sexually active and labeled as “ghalfa,” which is used for a woman who is sexually free and not respectful, who has the potential not to show fidelity to her family; as such these girls would be a target for abuse in their schools and social environments(12). In order to protect their daughters from this kind of abuse, families choose to have their daughters circumcised for concerns of virginity when their daughters marry.

, who has the potential not to show fidelity to her family; as such these girls would be a target for abuse in their schools and social environments(12). In order to protect their daughters from this kind of abuse, families choose to have their daughters circumcised for concerns of virginity when their daughters marry. A significant number of children undergo FGM/C when under 1 year of age, which concurs with the global trend of FGM/C occurring at an increasingly younger age. This reduces the chance of the child remembering or being aware that the practice has taken place, thus reducing the chances of presenting to a physician(14). In our study, all patients were aged between 7 to 9 years when FGM/C was performed. The dermatologic findings of FGM/C have been extensively reported in case reports and include keloids, epidermoid cysts, clitoral neuromas, and scarification. Women may delay treatment of keloids in the genital region for years because of embarrassment or fear of surgical options. Large keloids can contribute to obstetric complications(15). We found that the mean time between notification of keloid and referral to a gynecologist was 6.15±5.76 years; this delay was more than ten years in six patients.

of keloids in the genital region for years because of embarrassment or fear of surgical options. Large keloids can contribute to obstetric complications(15). We found that the mean time between notification of keloid and referral to a gynecologist was 6.15±5.76 years; this delay was more than ten years in six patients. Allah et al.(16) performed surgical excision for 149 patients with keloids. The recurrence rate was 100%. The authors concluded that keloids were not homogeneous biologic entities and were related with increased immunologic factors. The best prevention is to avoid the scar itself(16). Gurunluoglu et al.(17) reported a case of clitoral keloid that developed after a traumatic laceration. The keloid was treated with surgical excision, followed by silastic sheet application for six months. The sizes of keloid lesions were between 3 to 10 centimeters in our study. We performed surgical excision for all patients. There were no early complications recorded in any patients, but we did not have results for long-term follow-up.

ated with surgical excision, followed by silastic sheet application for six months. The sizes of keloid lesions were between 3 to 10 centimeters in our study. We performed surgical excision for all patients. There were no early complications recorded in any patients, but we did not have results for long-term follow-up. Women with FGM/C have a significantly higher prevalence of long-term health problems such as dysmenorrhea, vulvar or vaginal pain, problems related to anomalous healing (e.g., fibrosis, keloid, synechia), and sexual dysfunction. They are also much more likely to suffer complications during delivery (perineal tear, obstructed labor, episiotomy, cesarean, stillbirth), and complications associated with anomalous healing. Similarly, newborns were found more likely to suffer complications such as fetal distress and caput of the fetal head(18). In our study, the patients’ most common symptoms were dysuria, dyspareunia, and pruritus. All case notes were obtained from the gynecology clinic; therefore, we had no data about obstetric complications. Despite prohibition, FGM/C is performed on girls illegally. These women have significantly higher prevalence of long-term health problems related to the genitourinary system. In cases of vulvar mass, keloid development secondary to FGM/C should be considered for immigrant patients. Keloids can be removed by surgical excision and this procedure can alleviate some long-term morbidities of FGM/C. Ethics: Informed Consent: Consent form was filled out by all participants. Peer-review: External and Internal peer-reviewed.

Despite prohibition, FGM/C is performed on girls illegally. These women have significantly higher prevalence of long-term health problems related to the genitourinary system. In cases of vulvar mass, keloid development secondary to FGM/C should be considered for immigrant patients. Keloids can be removed by surgical excision and this procedure can alleviate some long-term morbidities of FGM/C. Ethics: Informed Consent: Consent form was filled out by all participants. Peer-review: External and Internal peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Ertuğrul Gazi Özbey, Özer Birge, Concept: Murat Akbaş, Özer Birge, Design: Murat Akbaş, Özer Birge, Data Collection or Processing: Ertuğrul Gazi Özbey, Özer Birge, Analysis or Interpretation: Murat Akbaş, Mehmet Adıyeke, Literature Search: Murat Akbaş, Özer Birge, Writing: Murat Akbaş. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Table 1 The demographics and gynecologic history of the patients Table 2 Percentages and numbers of female genital mutilation/cutting types and symptoms Figure 1 Vulvar mass before surgery Figure 2 After surgery

INTRODUCTION Pectus excavatum (PE) is the depression of the lower part of manubrium sterni and xiphoid process. It is the most common anterior chest wall deformity. It’s incidence is 1 in 400 to 1.000 live births and it is three to five times more common in males(1). PE is usually sporadic but can also be associated with connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome, neuromuscular disease, and a variety of other genetic conditions, including Noonan syndrome and Turner syndrome. The main problem of PE depends on the cardiopulmonary morbidity caused by the narrowing of the thoracic space. The severity of the chest wall deformity determines the morbidity. Another problem with PE is the psychosocial problems caused by the cosmetic concerns. One third of PE patients present during infancy(2). Spontaneous regression is rare and progression may continue until the end of adolescence(3). The main symptoms of these patients are exertional intolerance, chest pain, and shortness of breath. Respiratory problems may even begin during infancy. Until now, prenatal diagnosis of this deformity has been reported only once by Salamanca et al.(4) in two patients who postnatally diagnosed as having Down syndrome. In this report, we present another case which we diagnosed as PE during a second-trimester fetal anatomic scan.

One third of PE patients present during infancy(2). Spontaneous regression is rare and progression may continue until the end of adolescence(3). The main symptoms of these patients are exertional intolerance, chest pain, and shortness of breath. Respiratory problems may even begin during infancy. Until now, prenatal diagnosis of this deformity has been reported only once by Salamanca et al.(4) in two patients who postnatally diagnosed as having Down syndrome. In this report, we present another case which we diagnosed as PE during a second-trimester fetal anatomic scan. CASE REPORT A pregnant woman aged 35 years presented during her 23rd week of gestation for a routine fetal anatomic scan. Her medical history was not significant for any clinical condition. She had a healthy boy aged 11 years delivered by cesarean section. The ultrasound examination was performed using a Voluson 730 Pro with RAB2-5L 3D abdominal transducer (2-5 MHz) probe. Fetal biometric measures were compatible with the gestational age. The fetus had a normal anatomic scan except for the depression at the lower part of the sternum. The depression at this level was seen in both the transverse and sagittal sections of the lower thorax (Figure 1). The defect did not deteriorate the cardiac functions of the fetus. Pectus severity index (PSI) as adopted from postnatal method was calculated as 1.44 (Figure 1). There was no family history for any anterior chest wall deformity. The patient delivered a 3.100 g male baby during the 39th week of gestation by cesarean section with an Apgar score of 9/10. Postnatal examination confirmed the diagnosis of PE and he had no cardiopulmonary complications during the two-year follow-up period (Figure 2). The child was otherwise healthy. Therefore, surgical correction of the deformity was postponed until after the end of adolescence.

esarean section with an Apgar score of 9/10. Postnatal examination confirmed the diagnosis of PE and he had no cardiopulmonary complications during the two-year follow-up period (Figure 2). The child was otherwise healthy. Therefore, surgical correction of the deformity was postponed until after the end of adolescence. DISCUSSION PE is an anterior chest wall deformity that primarily compromises cardiopulmonary functions in severe cases. However, cosmetic problems are the major problem for most patients. Currently, surgery is the only treatment approach for these patients. Severe chest wall restriction could initiate symptoms during infancy and may require surgical treatment during this period. For other patients, surgery is usually postponed until the end of adolescence, because the deformity may worsen during the growth spurt of adolescence. Severity of PE is defined by PSI, which is measured using a computerized tomography scan of the thorax(5). PSI is the ratio of the lateral diameter of the chest to the distance between the sternum and spine at the point of maximal depression(5). Surgery is offered to patients with a PSI of >3.25(5). Prenatal adaption of this index is reported for the first time in our case. The PSI of our fetus (1.44) was consistent with good prognosis (PSI<3.25), which can be defined as deferability of surgery at least until the end of adolescence. Other tests needed for these patients are electrocardiography, echocardiography, and exercise tests in order to establish preoperative cardiopulmonary functions.

PSI of our fetus (1.44) was consistent with good prognosis (PSI<3.25), which can be defined as deferability of surgery at least until the end of adolescence. Other tests needed for these patients are electrocardiography, echocardiography, and exercise tests in order to establish preoperative cardiopulmonary functions. To the best of our knowledge, prenatal diagnosis of PE has been reported only once in the literature, in 1992(4). In that report, two cases were described and both were later diagnosed as having Down syndrome, even though children with Down syndrome rarely have PE. In our case, PE was not associated with any genetic syndrome like Down, Turner or Noonan. Routine karyotyping may not be necessary for prenatally-diagnosed cases. Congenital cardiac anomalies (atrial/ventricular septal defects, partial atrioventricular septal defects), cardiac malpositioning or pericardial effusion are associated with PE(6). Therefore, these fetuses should be examined thoroughly for any cardiac anomaly. Consequently, chest wall examination should be incorporated into the routine fetal anatomic scan during the second trimester. Accompanying abnormal findings may require karyotyping. Patients should be counseled that this is rarely associated with genetic syndromes and prognosis depends mainly on the severity of the defect and cardiopulmonary complications it causes. PSI might be a promising marker for determining the prognosis of such fetuses if it can be supported by other studies. Ethics: Informed Consent: It was taken from the patient. Peer-review: Externally peer-reviewed.

Consequently, chest wall examination should be incorporated into the routine fetal anatomic scan during the second trimester. Accompanying abnormal findings may require karyotyping. Patients should be counseled that this is rarely associated with genetic syndromes and prognosis depends mainly on the severity of the defect and cardiopulmonary complications it causes. PSI might be a promising marker for determining the prognosis of such fetuses if it can be supported by other studies. Ethics: Informed Consent: It was taken from the patient. Peer-review: Externally peer-reviewed. Authorship Contributions: Surgical and Medical Practices: Cihan Çetin, Concept: Cihan Çetin, Selim Büyükkurt, Cansun Demir, Design: Cihan Çetin, Mete Sucu, Mehmet Özsürmeli, Cansun Demir, Data Collection or Processing: Cihan Çetin, Analysis or Interpretation: Cihan Çetin, Selim Büyükkurt, Mete Sucu, Literature Search: Cihan Çetin, Mete Sucu, Mehmet Özsürmeli, Cansun Demir, Writing: Cihan Çetin, Selim Büyükkurt, Mehmet Özsürmeli. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 Ultrasonographic images of pectus excavatum, a) Axial thoracic section, pectus severity index is calculated by the ratio of the lateral diameter of the chest to the distance between the sternum and spine at the point of maximal depression (pectus severity index: 4.24 cm/2.94 cm=1.44), b) Sagittal thoracic section (arrows indicate the defect) Figure 2 Postnatal photograph of the child with pectus excavatum

INTRODUCTION The recommendation of the World Health Organization (WHO) is exclusive breastfeeding (EBF) of infants during the first six months of life, and breastfeeding (BF) for two years or beyond with complementary foods for achieving optimal growth and health(1). In addition to providing essential nutrients to infants, breastmilk has been shown to be related to decreased sudden infant death syndrome, respiratory-gastrointestinal tract infections, and allergic diseases, as well as a lower risk of developing obesity, cardiovascular disease, diabetes, and hematologic malignancies in future life(2,3,4). Reduction in postpartum blood loss due to increased uterine activity and greater weight loss compared with mothers who bottle feed are the reported benefits of BF for mothers(2,3). Despite all recommendations of the WHO, the rates of initiation and duration of BF are still far from expectations worldwide. According to the United Nations Children’s Fund (UNICEF), EBF rates for the first 6 months have not changed significantly since 1990 and are around 36%(5).

INTRODUCTION The recommendation of the World Health Organization (WHO) is exclusive breastfeeding (EBF) of infants during the first six months of life, and breastfeeding (BF) for two years or beyond with complementary foods for achieving optimal growth and health(1). In addition to providing essential nutrients to infants, breastmilk has been shown to be related to decreased sudden infant death syndrome, respiratory-gastrointestinal tract infections, and allergic diseases, as well as a lower risk of developing obesity, cardiovascular disease, diabetes, and hematologic malignancies in future life(2,3,4). Reduction in postpartum blood loss due to increased uterine activity and greater weight loss compared with mothers who bottle feed are the reported benefits of BF for mothers(2,3). Despite all recommendations of the WHO, the rates of initiation and duration of BF are still far from expectations worldwide. According to the United Nations Children’s Fund (UNICEF), EBF rates for the first 6 months have not changed significantly since 1990 and are around 36%(5). Various factors have been shown associated with both the initiation and duration of BF. It has been shown that advanced age, higher maternal educational level, higher socioeconomic status, BF education, social support, and an infant with birthweight over 3 kg and >38 weeks gestation have a positive affect on BF(6,7,8,9,10,11). The belief of mothers that their milk is inadequate, the failure to provide adequate information and support from healthcare workers, breast problems due to incorrect BF, and the increased use of bottle-feeding/pacifiers are important causes for early discontinuation of BF(7,12,13,14).

tive affect on BF(6,7,8,9,10,11). The belief of mothers that their milk is inadequate, the failure to provide adequate information and support from healthcare workers, breast problems due to incorrect BF, and the increased use of bottle-feeding/pacifiers are important causes for early discontinuation of BF(7,12,13,14). According to the Turkish Population and Health Survey (TPHS) 2013 report, BF is very common in Turkey, with 96% of children breastfed for some period. However, despite many encouraging studies condected in our country, both early initiation and exclusive BF rates are still far below the desired levels. Only 50% of childen are breastfed within the first hour and the median duration of EBF is only 1.2 months. The rate of EBF during the first six months fell to 30.1% in 2013, which was 41.6% in 2008(15,16). The main objective of the present study was to determine the initation time of BF and complementary feeding practices during the first six months of life among Turkish mothers who gave birth in a baby-friendly hospital, risk factors associated with lack of early initiation, and EBF.

According to the Turkish Population and Health Survey (TPHS) 2013 report, BF is very common in Turkey, with 96% of children breastfed for some period. However, despite many encouraging studies condected in our country, both early initiation and exclusive BF rates are still far below the desired levels. Only 50% of childen are breastfed within the first hour and the median duration of EBF is only 1.2 months. The rate of EBF during the first six months fell to 30.1% in 2013, which was 41.6% in 2008(15,16). The main objective of the present study was to determine the initation time of BF and complementary feeding practices during the first six months of life among Turkish mothers who gave birth in a baby-friendly hospital, risk factors associated with lack of early initiation, and EBF. MATERIALS AND METHODS A cross-sectional study was performed in the maternity ward of a tertiary hospital, one of the major maternity centers in Ankara, the capital of Turkey, between March and October 2015. A total of 350 mothers aged ≥20 years who gave birth in the hospital participated in the study on a voluntary basis. The exclusion criteria were multiple pregnancies, preterm births (<37 weeks), foreign patients, women with health problems, babies with health problems, and those who required the neonatal intensive care unit or intubation. The study was approved by the Keçiören Training and Research Hospital Local Ethics Committee (approval no: 2012-KAEK-15/1073) and was performed in accordance with the ethical standards described in an appropriate version of the 1975 Declaration of Helsinki, as revised in 2000.

eonatal intensive care unit or intubation. The study was approved by the Keçiören Training and Research Hospital Local Ethics Committee (approval no: 2012-KAEK-15/1073) and was performed in accordance with the ethical standards described in an appropriate version of the 1975 Declaration of Helsinki, as revised in 2000. Our hospital is a certificated baby-friendly institution and all mothers are explained the benefits of breastmilk and given BF education after delivery by lactation consultants. After being informed about the study, informed written consent was obtained from the mothers. A questionnaire consisting of questions about demographic characteristics, obstetric history, and BF history was completed by two research assistants 12-24 hours after birth. The survey also investigated whether the infant received prelacteal feeds and their nature. Information about gestational age, birth weight, sex of the infant, and type of birth were obtained from hospital records. When discharging from the hospital, all patients were informed that they would be called by the research assistant at the end of the sixth month postpartum in order to get the infant’s nutritional information and feeding practices. During this call, information about BF, factors affecting BF and its duration, and feeding practices of the infant were obtained. Initiation time and related factors were assessed for over 350 patients. Assessments related to BF duration and EBF were peformed with 329 patients, excluding the 21 patients that could not be reached at the end of six months.

After being informed about the study, informed written consent was obtained from the mothers. A questionnaire consisting of questions about demographic characteristics, obstetric history, and BF history was completed by two research assistants 12-24 hours after birth. The survey also investigated whether the infant received prelacteal feeds and their nature. Information about gestational age, birth weight, sex of the infant, and type of birth were obtained from hospital records. When discharging from the hospital, all patients were informed that they would be called by the research assistant at the end of the sixth month postpartum in order to get the infant’s nutritional information and feeding practices. During this call, information about BF, factors affecting BF and its duration, and feeding practices of the infant were obtained. Initiation time and related factors were assessed for over 350 patients. Assessments related to BF duration and EBF were peformed with 329 patients, excluding the 21 patients that could not be reached at the end of six months. Definitions Definitions included in the study: -Early breasfeeding was defined as BF within one hour postpartum. -Initiation time of first breastfeed was the time at which the baby was first breastfed after delivery. -Exclusive breastfeeding was defined as BF only since birth and no other supplemental fluids. -Partial breastfeeding was defined as mainly BF combined with supplemental foods. -Bottle-feeding was defined as only feeding with formula or non-human milk without BF.

-Initiation time of first breastfeed was the time at which the baby was first breastfed after delivery. -Exclusive breastfeeding was defined as BF only since birth and no other supplemental fluids. -Partial breastfeeding was defined as mainly BF combined with supplemental foods. -Bottle-feeding was defined as only feeding with formula or non-human milk without BF. -Complementary feeding was defined as transition from EBF to family foods. Statistical Analysis The analyses were performed using Statistical Package for the Social Sciences software version 15.0 (SPSS Inc., Chicago, IL, USA). Results are presented as mean ± standard deviation and n (%). The suitability of continuous variables to normal distribution was analyzed using the Kolmogorov-Smirnov test. Nominal data were expressed using cross tables depending on initiation times before or after one hour, and EBF more or less than six months. Differences between groups were assessed using χ2, Fisher or Yates tests for categorical variables. Multivariate logistic regression analysis was used to determine which factor best predicted BF within one hour postpartum, and which factor predicted EBF for six months. The Hosmer-Lemeshow test was used to determine the goodness of fit of the logistic regression model. A p value of <0.05 was considered statistically significant.

e logistic regression analysis was used to determine which factor best predicted BF within one hour postpartum, and which factor predicted EBF for six months. The Hosmer-Lemeshow test was used to determine the goodness of fit of the logistic regression model. A p value of <0.05 was considered statistically significant. RESULTS Socio-demographic and obstetric characteristics The mean age of the study group at birth was 27.58±5.4 years (range, 20-42 years), and the mean gestational age was 38.7±1.2 weeks (range, 37-41 weeks). The majority of the mothers were housewives, 11.7% were working mothers, and 68.4% were with their babies at home during the first six months. Regarding education, 64% of the mothers were educated at primary school or illiterate. Just under half (47.7%) of the women experienced a vaginal delivery and 4% of the babies weighed <2500 gr. The mean birthweight of babies was 3234.34±436.1 g (range, 2080-4800 g), and 55.1% of the babies were girls. Breastfeeding initiation and influencing factors In total, 97.4% of the mothers in this study initiated BF. Of the 341 patients, 60.1% initiated BF within the first hour, and 22.6% within the second hour after birth. Of the mothers who gave vaginal birth, 76.8% initiated BF within the first hour, whereas this ratio was 44.6% in the cesarean group. The mean first BF time was 1.67±1.0 hours postpartum (range, 1-6 hours), 1.33±0.7 hours for vaginal delivery, and 1.97±1.1 hours in the cesarean group.

within the second hour after birth. Of the mothers who gave vaginal birth, 76.8% initiated BF within the first hour, whereas this ratio was 44.6% in the cesarean group. The mean first BF time was 1.67±1.0 hours postpartum (range, 1-6 hours), 1.33±0.7 hours for vaginal delivery, and 1.97±1.1 hours in the cesarean group. Table 1 shows the characteristics of the study group according to the BF initiation time. Planned pregnancy and vaginal delivery were found as factors that had an affect on the initiation time of BF. Planned pregnancy and vaginal delivery were found as significant factors for early BF in the logistic regression analysis (Table 2). Early BF was significantly higher in the vaginal delivery group. Breastfeeding patterns, rates and infant feeding practices of the study group Bottle feeding from birth was reported in 2.7% of the mothers, 88.3% of the mothers stated that breast milk was the first food taken by the newborns, the rest of the newborns were fed with other fluids before breast milk and then breastfed. The number of mothers who stated that they stopped BF from the first to fifth months were 12, 15, 29, 30, and 54 mothers, respectively. Partial bottle feeding was disclosed by 61.1% of the mothers, and 38.9% exclusively breastfed until six months from birth (Table 3).

Breastfeeding patterns, rates and infant feeding practices of the study group Bottle feeding from birth was reported in 2.7% of the mothers, 88.3% of the mothers stated that breast milk was the first food taken by the newborns, the rest of the newborns were fed with other fluids before breast milk and then breastfed. The number of mothers who stated that they stopped BF from the first to fifth months were 12, 15, 29, 30, and 54 mothers, respectively. Partial bottle feeding was disclosed by 61.1% of the mothers, and 38.9% exclusively breastfed until six months from birth (Table 3). When the partial feeding group was asked why they were giving formula/other drinks, the most common responses were concerning the insufficiency of breastmilk (39.6%), a family belief that the baby’s weight gain was inadequate (25.5%), supplementing BF (21.9%), and convenience of the mother (13%). EBF rates fell whereas partial/bottle feeding rates increased as babies grew older (Table 4). Some 39.8% of the infants in the study group were introduced to solid foods before 6 months, which is the recommended age by the WHO. Solid foods were more commonly initiated around 4-6 months (6.9% at 4 months, 12.8% at 5 months, 20.1% at 6 months, and 60.2% at the end of six months). The mean infant age at which solid foods were introduced was 5.33±0.9 months and for formula milk it was 2.23±1.8 months.

ths, which is the recommended age by the WHO. Solid foods were more commonly initiated around 4-6 months (6.9% at 4 months, 12.8% at 5 months, 20.1% at 6 months, and 60.2% at the end of six months). The mean infant age at which solid foods were introduced was 5.33±0.9 months and for formula milk it was 2.23±1.8 months. Exclusive breastfeeding duration and influencing factors EBF for 6 months was maintained by 38.9% of the mothers. The mean duration of BF was 4.86±1.6 months, and the mean duration of EBF was 3.66±2.3. Table 5 summarizes the maternal and infant characteristics of the EBF group compared with the early cessation groups. Low education levels of mother and father, not receiving antepartum BF education, random BF, rare BF at night, nipple problems, bottle/pacifier use, and lack of social support were found as variables associated with early cessation of BF. In the multivarite analysis, antepartum BF education was found as the most significant factor in EBF duration (Table 2).

er, not receiving antepartum BF education, random BF, rare BF at night, nipple problems, bottle/pacifier use, and lack of social support were found as variables associated with early cessation of BF. In the multivarite analysis, antepartum BF education was found as the most significant factor in EBF duration (Table 2). DISCUSSION This study presents the BF and complementary feeding practices of Turkish mothers, with a focus on risk factors associated with lack of early initiation and EBF. Planned pregnancy and vaginal delivery were found as the most important factors in early initiation, whereas antepartum BF education was the most important factor for EBF duration in logistic analysis. Education level of mother and father, frequency of BF, number of BFs at night, nipple problems, bottle/pacifier use, and social support were found as other factors that had statistically significant effects on the duration times of EBF.

m BF education was the most important factor for EBF duration in logistic analysis. Education level of mother and father, frequency of BF, number of BFs at night, nipple problems, bottle/pacifier use, and social support were found as other factors that had statistically significant effects on the duration times of EBF. In our study, the percentage of early initiation was 60.1%. This ratio can be considered in the good group according to the classification of WHO [poor (0-29%), fair (30-49%), good (50-89%), and very good (90-100%)](17). Although this result is not at the desired level, it is better than the initiation times found in other studies conducted in our country, which determined rates between 9.9%-50%(16,18,19). Being a baby-friendly hospital and providing all mothers with lactation consultancy after birth may have had an effect on these results. Despite the efforts on BF education all over the country, the premature introduction of other fluids before BF (11.2%) is still common because of a superstition among people.

,18,19). Being a baby-friendly hospital and providing all mothers with lactation consultancy after birth may have had an effect on these results. Despite the efforts on BF education all over the country, the premature introduction of other fluids before BF (11.2%) is still common because of a superstition among people. One of the most important factors found to affect early initiation in our study was delivery type, consistent with the literature. Mothers who gave birth vaginally were significantly more likely to initiate early BF compared with cesarean deliveries. As was shown by several studies, cesarean birth is one of the most important obstacles that causes a delay in the initiation times of BF(18,20,21). Pain after surgery, significant discomfort in holding and positioning the baby, delayed skin-to-skin contact, delay in the production of breastmilk, limited mobility, and needing extra help for BF could account for this delay. Women who undergo cesarean delivery may need additional help to attain comfortable and correct positioning of their infant for BF. In recent years, cesarean section rates are above the expected levels around the world. According to Turkey Health Statistics, 50% of all births were performed by cesarean section in 2013, similar to our results (52.3%)(22). Developing policies to reduce cesarean rates is essential, but it should also be noted that providing special lactation consultancy and emphasizing skin-to-skin contact in patients where cesarean is mandatory is necessary.

50% of all births were performed by cesarean section in 2013, similar to our results (52.3%)(22). Developing policies to reduce cesarean rates is essential, but it should also be noted that providing special lactation consultancy and emphasizing skin-to-skin contact in patients where cesarean is mandatory is necessary. In the study group, the initiation times of BF in women who gave birth after a planned pregnancy were significantly less than for women with unplanned pregnancies. Consistent with our results, Taylor and Cabral(23) found a stronge inverse association between unwanted pregnancies and BF in their study of 6733 first singleton live births. Kost et al.(24) reported that women with unwanted pregnancies were less likely to breastfeed their babies than those who intended to conceive. Therefore, as a woman’s attitude toward her baby can affect her likelihood of baby-care and consequently her decision to breastfeed, the importance of lactation consultancy should be kept in mind for women with unplanned pregnancies.

ncies were less likely to breastfeed their babies than those who intended to conceive. Therefore, as a woman’s attitude toward her baby can affect her likelihood of baby-care and consequently her decision to breastfeed, the importance of lactation consultancy should be kept in mind for women with unplanned pregnancies. The majority of mothers in the study group initiated BF, but only 38.9% of them exclusively breastfed their infants for six months. Although this result is better than the 30.1% detected in the TPHS 2013 report, it is still far behind the desired levels. According to UNICEF, global rates of BF have remained stagnant since 1990, with only 36% of children aged less than six months were exclusively breastfed in 2012, worldwide(5). The higher results of our study compared with the TPHS and UNICEF may be explained by the fact that our hospital is in a semi-urban region that serves a relatively better income group who have higher antepartum follow-up and BF education rates compared with other regions of our country. Also, our hospital is a baby-friendly hospital that aims to promote and support BF, and this might have had an influence on the results. It should be kept in mind that there still exists a need for encouraging mothers to exclusively feed their babies with breast milk for up to six months. Mothers should be informed about the benefits of breast milk, BF techniques, and how to avoid circumstances that would negatively affect this.

nfluence on the results. It should be kept in mind that there still exists a need for encouraging mothers to exclusively feed their babies with breast milk for up to six months. Mothers should be informed about the benefits of breast milk, BF techniques, and how to avoid circumstances that would negatively affect this. Both maternal and paternal education were found as effective factors for BF duration in our study. Similar to our results, low maternal and paternal education were found as risk factors for early weaning of BF in the literature(6,10). Maternal working status has been previously negatively linked to BF, EBF in housewives was reported more than in working mothers(12,20). Interestingly, this finding is in contrast with our results. The higher EBF rates in the working mothers in our study group may be associated with their late return to work and being at home, especially during the first six months. In our study group, mothers who breastfed more frequently during the day and the night, as suggested by our health staff, breastfed their infants significantly longer than did mothers who breastfed their infants upon demand. It is known that maternal milk production is positively correlated with the demand of the infant and frequent feeding maintains breast milk supply(1,25). The findings of our study also support this information.

staff, breastfed their infants significantly longer than did mothers who breastfed their infants upon demand. It is known that maternal milk production is positively correlated with the demand of the infant and frequent feeding maintains breast milk supply(1,25). The findings of our study also support this information. Bottle/pacifier use and nipple problems were reported as negative influencing variables of BF duration(26). It is known that the use of bottle/pacifier possibly changes the baby’s oral dynamics and sucking pattern and may lead to both a reduction in BF frequency and breast demand. For improving EBF, effective strategies to reduce bottle/pacifier should be developed for use among infants, especially those younger than 6 months. Nipple problems are common among BF mothers. Lack of information about BF positions and poor latch of the baby are the most frequent cause of damage to nipples(27). As these problems are the common causes of early weaning of BF, health staff should pay special attention to mother’s breasts in the early postpartum period. Proper BF education by a lactation consultant is essential in the prevention of these problems and ensuring the continuity of BF.

cause of damage to nipples(27). As these problems are the common causes of early weaning of BF, health staff should pay special attention to mother’s breasts in the early postpartum period. Proper BF education by a lactation consultant is essential in the prevention of these problems and ensuring the continuity of BF. Regression analysis indicated that antepartum BF education was the most significant predictor for the duration of BF. One of the top reasons for the early cessation of BF is mothers’ inadequate knowledge about the importance of breast milk and BF techniques. Successful BF starts when the mother thinks she is going to breastfeed her baby and believes that she can accomplish it. The affect of antepartum BF education on increasing EBF rates has been shown in several studies(28,29). In a study performed in Israel to explore the effect of BF education given in the perinatal period, it was found that both the initiation and the duration rates of BF were increased(30). Therefore, antepartum education should be considered by health staff to increase the self-confidence of mothers.

eral studies(28,29). In a study performed in Israel to explore the effect of BF education given in the perinatal period, it was found that both the initiation and the duration rates of BF were increased(30). Therefore, antepartum education should be considered by health staff to increase the self-confidence of mothers. In the present study, the most commonly reported reason for starting supplementary drinks was the belief of breastmilk insufficiency. The concern about milk insufficiency among mothers is still very common and stems from having insufficient information on the proper techniques to increase breast milk. Mothers should be relaxed so that they are able to produce enough breastmilk for the proper growth of their infants, and informed about the importance of frequent feeding with the correct technique for stimulating optimal milk production(1,25). Similar to our study, results of early introduction of complementary foods, contrary to WHO recommendations are of great concern, especially in developing countries. Mothers should be warned about the impact of premature introduction of complementary foods on early termination of EBF, without conferring any growth advantage over EBF(20).

y, results of early introduction of complementary foods, contrary to WHO recommendations are of great concern, especially in developing countries. Mothers should be warned about the impact of premature introduction of complementary foods on early termination of EBF, without conferring any growth advantage over EBF(20). Study Limitations There are several limitations to our study. The nature of data collection was retrospective and the responses were self-limited, which may have led to over or under estimation of BF practices and duration. To minimize these errors, all the questionnaires were completed by the same author to ensure consistent technique. Enough time was allocated to all patients to avoid rushing and insufficient thinking time of the patients for the questions. Also, the cross-sectional nature of the study prevented determining causal relationships of knowledge, attitudes, or interest with the rates of BF. However, the hospital where the study was conducted is a large women’s health center located in a semi-urban region, which exhibits a close profile to the entire country. At the same time, the study is important in indicating the effectiveness of baby-friendly hospital practices, especially postpartum BF education. Larger prospective studies are needed to clarify BF duration rates, factors that affect these practices, and practical things that should be done to increase these rates in our country.

time, the study is important in indicating the effectiveness of baby-friendly hospital practices, especially postpartum BF education. Larger prospective studies are needed to clarify BF duration rates, factors that affect these practices, and practical things that should be done to increase these rates in our country. CONCLUSION In conclusion, this study reported important factors that affect the initiation and the duration of BF. Despite all the efforts spent on this subject, both the initiation and duration of BF rates are still below the desired levels in our country. The results of our study indicate the importance of awareness of both mothers and their family members regarding the significance and benefits of BF. Efforts should therefore be made to ensure both professional and social support to mothers to prevent early cessation of BF. We are grateful to all mothers for participating the study and sharing their time. We also thank P. LeMotte who made the English corrections of the study. Ethics Ethics Committee Approval: The study was approved by the Keçiören Training and Research Hospital Local Ethics Committee (Approval number: 2012-KAEK-15/1073), Informed Consent: Consent form was filled out by all participants. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: M.C., F.D.Ö., Concept: E.Y., O.F.K., Design: E.Y., T.K., Data Collection or Processing: E.Y., Z.V.Y., Analysis or Interpretation: E.Y., F.D.Ö., Literature Search: Z.V.Y., Writing: E.Y. Conflict of Interest: No conflict of interest was declared by the authors.

Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: M.C., F.D.Ö., Concept: E.Y., O.F.K., Design: E.Y., T.K., Data Collection or Processing: E.Y., Z.V.Y., Analysis or Interpretation: E.Y., F.D.Ö., Literature Search: Z.V.Y., Writing: E.Y. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 General characteristics of the study group according to the initiation time Table 2 Logistic regression analyses for factors associated with initiation time of breastfeeding (a) and with exclusive/predominantly breastfeeding (b) Table 3 Breastfeeding, feeding patterns, and breastfeeding rates of the study group Table 4 Infant feeding patterns during the first six months Table 5 General characteristics of the study group according to breastfeeding type

PRECIS: Using the Bologna score, we evaluated the content and quality of the intrapartum care offered in vaginal births in Turkey, based on the example of a state hospital. INTRODUCTION The high birth rate and percentages of maternal and infant deaths in Turkey continue to occupy a priority as major health issues. The World Health Organization (WHO)(1) calls attention to the fact that the number of midwives, midwifery care outcomes, and quality are essential in reducing maternal and infant mortality rates and in reaching related global goals. Monk et al.(2) reported that spontaneous vaginal birth rates are higher among women who give birth in maternity units that are under the direction of midwives and that newborn health indicators exhibit similar or even better outcomes when this is practiced. On the other hand, because statistics on maternal and infant mortality do not reflect the quality of maternal healthcare services, the process of caregiving must be evaluated separately(3). In this context, the content and quality of intrapartum care is of vital importance in putting an end to mother and infant mortality and morbidity rates that are a consequence of preventable causes(4). Researches in recent years and evidence-based practices have led to important changes in intrapartum care. With the rise in the use of technological methods such as electronic fetal monitorization and induced labor, length of stay in the hospital has been reduced and the scope of midwifery, nursing, and medical care has changed(5).

recent years and evidence-based practices have led to important changes in intrapartum care. With the rise in the use of technological methods such as electronic fetal monitorization and induced labor, length of stay in the hospital has been reduced and the scope of midwifery, nursing, and medical care has changed(5). The strategies of the WHO(6) designed to end preventable maternity mortality have pointed to the need to prioritize the basic care and follow-ups of women and newborns throughout the process of labor and birth. In addition, in the effort to end preventable maternal and infant mortality and morbidity, it is stressed that every pregnant woman and newborn needs to receive evidence-based basic care from well-trained healthcare professionals and to have this in a supportive environment(4). From another perspective, research points to the probable association between intrapartum care practices and the rise in cesarean rates, so it is important to avoid elective induction practices and to maintain professional teamwork if cesarean rates are to be reduced(7).

and to have this in a supportive environment(4). From another perspective, research points to the probable association between intrapartum care practices and the rise in cesarean rates, so it is important to avoid elective induction practices and to maintain professional teamwork if cesarean rates are to be reduced(7). Intrapartum care constitutes an important part of healthcare directed toward women in Turkey. The technological developments of recent years have significantly affected the scope of intrapartum care. Elective cesarean and general cesarean section birth rates have steadily increased, rising to 48.1%(8). Despite reports that epidural anesthesia raises the risk with cesareans(9), there has been a rising trend toward the use of epidural anesthesia. At the same time, there has also been an increasing trend toward interventions with which restricted use is recommended, such as episiotomy (20%) and induction (10%)(10,11). It is known that practices such as the lithotomy position (used in almost all births), unnecessary palpation, shaving of the perineum, enema, use of catheters, establishing vascular access, restriction of eating and drinking water, amniotomy (60%), and fetal monitorization are widespread(11,12). Moreover, there are serious issues with providing emotional and physical support during labor and with practicing nonpharmaceutic pain management methods. These are matters about which adequate assistance is not provided. From a different perspective, however, there are some positive developments in Turkey in the context of intrapartum care. Almost all births (97.2%) take place in the hospital and with the assistance of healthcare professionals (97.4%)(8). Rates of early bonding between mother and child and starting breastfeeding are considerably high (70.2%)(13).

, however, there are some positive developments in Turkey in the context of intrapartum care. Almost all births (97.2%) take place in the hospital and with the assistance of healthcare professionals (97.4%)(8). Rates of early bonding between mother and child and starting breastfeeding are considerably high (70.2%)(13). There are no studies in the national literature that address the content and quality of intrapartum care. There are certain criteria used in evaluating the quality of intrapartum care(14). This study employed the standard measurement instrument, the Bologna score, which is based on the WHO recommendations for evaluating the quality of care in vaginal deliveries, which was drawn up by Chalmers and Porter(15) and used by Sandin-Bojö and Kvist(16,17,18). The purpose of this research was to assess the content and quality of intrapartum care offered in vaginal births in Turkey, based on the example of a state hospital and using the Bologna score.

lity of care in vaginal deliveries, which was drawn up by Chalmers and Porter(15) and used by Sandin-Bojö and Kvist(16,17,18). The purpose of this research was to assess the content and quality of intrapartum care offered in vaginal births in Turkey, based on the example of a state hospital and using the Bologna score. MATERIALS AND METHODS The research was of cross-sectional design. The study was conducted between January 1st, 2013 and December 31st, 2014 at Aydın Maternity and Children’s Hospital with 303 women giving birth by vaginal delivery who were recruited on the basis of a convenience sampling. The number of vaginal births at this hospital in 2013 was 3051. The number of women recruited into the study was determined as 341 at a confidence level of 95% (s=0.05), with p=0.50 and n=3051. A total of 360 women who expected a vaginal delivery were invited into the study. Of these women, 48 were taken in for emergency cesarean section and data could not be collected for 9, resulting in the final analysis being performed with a total of 303 women. The study protocol was approved by the Adnan Menderes University Faculty of Medicine Ethics Committee (approval number: 2012/111).

the study. Of these women, 48 were taken in for emergency cesarean section and data could not be collected for 9, resulting in the final analysis being performed with a total of 303 women. The study protocol was approved by the Adnan Menderes University Faculty of Medicine Ethics Committee (approval number: 2012/111). In the 150-bed Aydın Maternity and Children’s Hospital where the research was conducted, midwives provide care for women going into vaginal delivery. At this hospital, women are generally placed in the lithotomy position, with their back slightly raised, their legs in stirrups and mediolateral episiotomy is performed, particularly on primigravidae. Moreover, the practice in this hospital proscribes vaginal delivery after cesarean section has been performed once. In the two-year period in which this research took in the hospital (2013-2014), the rate of primary cesarean births was 15.63% (n=1397/8937), the total cesarean rate was 31.08% (n=2778/8937), and the rate of operative delivery (vacuum) was 1.18% (n=73/6191).

inal delivery after cesarean section has been performed once. In the two-year period in which this research took in the hospital (2013-2014), the rate of primary cesarean births was 15.63% (n=1397/8937), the total cesarean rate was 31.08% (n=2778/8937), and the rate of operative delivery (vacuum) was 1.18% (n=73/6191). The researchers collected data for the research using a questionnaire that was developed based on the pertinent literature(19,20), and assessed using the Bologna score. The questionnaire’s 36 items probed the women’s sociodemographic and obstetric characteristics; whether their pregnancies had been planned and wanted; whether they had received antenatal care; their height and weight; smoking status; cervical dilation upon admittance to hospital; whether an enema, epidural anesthesia, vacuum or episiotomy had been performed during labor; and the baby’s Apgar score in the fifth minute. Bologna score: This is an instrument that was developed by Chalmers and Porter(15) for the purpose of assessing the quality of care given to women during the process of labor, based on the intrapartum care recommendations of the WHO(21). The researchers first translated the Bologna score into the Turkish language. To verify the comprehensibility and the applicability of both the questionnaire and the Bologna score, a pilot study was conducted with 10 individuals, after which sections that were difficult to understand or apply were revised.

the WHO(21). The researchers first translated the Bologna score into the Turkish language. To verify the comprehensibility and the applicability of both the questionnaire and the Bologna score, a pilot study was conducted with 10 individuals, after which sections that were difficult to understand or apply were revised. Women who were admitted to the maternity unit and were expected to have a vaginal delivery were invited into the study. The women were first informed about the study and their verbal and written consent was obtained. Later, the researchers completed the questionnaires based on the results obtained from face-to-face interviews held with the mothers. Other parts of the research data were obtained from patient files and through observations. All of the questions in the data collection instrument contained concrete data and therefore no differences stemming from observations existed. Statistical Analysis The Statistical Package for the Social Sciences Version 18 (PASW Inc, Chicago, IL, USA) was used in the data analysis. All of the variables in the study were analyzed using descriptive statistics. RESULTS The study was conducted with 303 women giving vaginal birth whose mean age was 25.14±5.37 years (range, 14-41 years). Data on the women’s age groups, their educational level and employment status, perceived income level, social security status, civil status, obstetric characteristics, body mass index (BMI) before pregnancy, and weight gained during pregnancy can be found in Table 1.

mean age was 25.14±5.37 years (range, 14-41 years). Data on the women’s age groups, their educational level and employment status, perceived income level, social security status, civil status, obstetric characteristics, body mass index (BMI) before pregnancy, and weight gained during pregnancy can be found in Table 1. Of the women in the study, 35.7% (n=108) had experienced one, 29.1% (n=88) two, 20.1% (n=61) three, and 15.1% (n=61) had experienced 4-13 pregnancies; 40.5% (n=123) had gone through one live birth and had one living child. Some 17.5% (n=53) of the women had experienced one and 3.9% (n=12) 2-4 spontaneous abortions, and 3.3% (n=10) had experienced one and 1.3% (n=4) 2-3 curettages. It was found that 24.4% (n=74) of the women had not planned the pregnancy and 8.3% (n=25) had not wanted the pregnancy, 1.3% (n=4) had not received prenatal care, and 7.2% (n=22) received prenatal care after the 13th week of pregnancy. It was observed that the women’s pre-pregnancy mean BMI score was 23.14±3.41 kg/m2 (range, 15.99-34.67 kg/m2) and their average weight gain over the course of the pregnancy was 10±21 kg (range, 0-33 kg). Smoking prior to pregnancy was reported by 20.8% of the women and 13.2% said they smoked during pregnancy (Table 1).

It was observed that the women’s pre-pregnancy mean BMI score was 23.14±3.41 kg/m2 (range, 15.99-34.67 kg/m2) and their average weight gain over the course of the pregnancy was 10±21 kg (range, 0-33 kg). Smoking prior to pregnancy was reported by 20.8% of the women and 13.2% said they smoked during pregnancy (Table 1). Table 2 reveals data on the women’s deliveries and their status of being at high risk. Four percent (n=12) of the women had not reached term when they were admitted to the maternity unit, the babies were not in the vertex presentation in 3.3% (n=10), and 7.3% (n=22) did not undergo a spontaneous onset of labor. The fetal heart rate of two fetuses (0.7%) were not within normal boundaries (120-160 bpm). There was some kind of obstetric complication in previous births in 5.0% (n=15) of the women, and 11.2% (n=34) had complications in the present birth; 1.7% (n=5) had a medical condition that needed special care. The following risk factors were observed in some women in the study: preterm labor (n=16), presentation anomaly (n=10), induced labor (n=22), fetal distress (n=2), meconium amniotic fluid (n=5), oligohydramnios (n=2), intrauterine exitus (n=1), placenta previa (n=1), gestational diabetes (n=1), and gestational hypertension (n=1). Furthermore, bleeding occurred in 4 women after birth and 1 woman developed a deep vaginal tear, and 2 women’s infants had Apgar scores below 7 in the fifth minute.

iotic fluid (n=5), oligohydramnios (n=2), intrauterine exitus (n=1), placenta previa (n=1), gestational diabetes (n=1), and gestational hypertension (n=1). Furthermore, bleeding occurred in 4 women after birth and 1 woman developed a deep vaginal tear, and 2 women’s infants had Apgar scores below 7 in the fifth minute. Some 45.2% (n=137) of the women were admitted to hospital with a cervical dilation of 1-3 cm, 76.6% (n=232) were administered enemas, 3.3% (n=10) had epidural anesthesia, vacuum extraction was performed on 2.6% (n=8), and an episiotomy was performed on 54.1% (n=164). Spontaneous lacerations that needed suturing were experienced by 23.8% (n=72) women. Twelve (4.0%) women gave birth to babies who had Apgar scores below 7 in the first minute, and two women’s babies (0.6%) had Apgar scores below 7 in the fifth minute (Table 2). When the quality of the care given to the women was evaluated using the Bologna score, it was found that 92.7% (n=281) went into spontaneous labor and all of the births were assisted by midwives or doctors. Only 7 (2.3%) women had a supporting individual by her side and only 1 (0.3%) gave birth in a nonsupine position. A partogram was used to follow up on the birth process in 72.6% (n=220) women, and 82.5% (n=250) achieved contact with their babies within the first hour after birth. Induction was used in 76.6% (n=232) of women and fundal pressure was applied to 27.4% (n=83) (Table 3).

only 1 (0.3%) gave birth in a nonsupine position. A partogram was used to follow up on the birth process in 72.6% (n=220) women, and 82.5% (n=250) achieved contact with their babies within the first hour after birth. Induction was used in 76.6% (n=232) of women and fundal pressure was applied to 27.4% (n=83) (Table 3). DISCUSSION This study examined the content and quality of intrapartum care provided at a state hospital in Turkey using the Bologna score. From the observations of current practices of intrapartum care at the hospital, it could be seen that the use of a partogram, fundal pressure, and the nonsupine position, as well as having a supporting person present at the birth were not in compliance with the international standards recommended by the WHO nor with evidence-based practices. The data obtained are important in that they reveal the current status through the example of a hospital in Turkey. It was seen that high-risk factors were at play in the case of some of the women in the study. This may have increased the probability that certain interventions such as induction would be performed. A small percentage of the women (4.0%) were not at term (37+0-41+6 weeks) when they were admitted to the maternity unit for vaginal labor. A study conducted in Switzerland similarly noted that only 6.0% of pregnant women were admitted for delivery before their 37th gestational week(18). These outcomes may be associated with early delivery risk or with early membrane rupture.

37+0-41+6 weeks) when they were admitted to the maternity unit for vaginal labor. A study conducted in Switzerland similarly noted that only 6.0% of pregnant women were admitted for delivery before their 37th gestational week(18). These outcomes may be associated with early delivery risk or with early membrane rupture. A significant percentage woman (45.2%) was admitted to hospital in the latent phase. It is reported, however, that women should be admitted to the maternity unit at a later stage, that is, in the active phase of labor (when cervical dilation is 4 cm or more)(22). It has also been asserted that early admittance to the maternity unit may be associated with increased rates of oxytocin and analgesic use(22).

is reported, however, that women should be admitted to the maternity unit at a later stage, that is, in the active phase of labor (when cervical dilation is 4 cm or more)(22). It has also been asserted that early admittance to the maternity unit may be associated with increased rates of oxytocin and analgesic use(22). Our results could be associated with the traditional approach adopted by healthcare professionals and the general public in Turkey. Women are unable to distinguish between real and false labor, are unaware of the course of labor, and rush to the hospital as soon as they feel the first contractions because of the current inadequacy of prenatal education in Turkey. When this happens, healthcare professionals admit them to the hospital against the probability of risk, which occurred with most women (76.6%) in the present study. This rate is considerably higher than what was reported in Switzerland(17) and Canada(23), where rates were 39% and 5.4%, respectively. This might be a consequence of the country’s prevailing general health practices related to this matter. This is the case even though it is known in Turkey, however, that evidence-based research has shown that enemas and other applications that are not mother-friendly should be avoided under all circumstances.

ctively. This might be a consequence of the country’s prevailing general health practices related to this matter. This is the case even though it is known in Turkey, however, that evidence-based research has shown that enemas and other applications that are not mother-friendly should be avoided under all circumstances. It was observed in this study that epidural anesthesia was administered to only a few women (3.3%). This rate is much lower than reported by Sandin-Bojö et al.(17,18), Chalmers et al.(24), and Li et al.(25) (57%, 48.7%, 57.3%, and 18.3%, respectively). This finding may be connected to the fact that techniques of coping with labor pains are not widely used in Turkey. The vacuum technique is generally used as a birthing instrument in Turkey. The use of vacuum extraction in this study was 2.6%, lower than reported by Li et al.(25) and Sandin-Bojö and Kvist(18) (10.5% and 8.1%, respectively). In a study conducted in Canada, Chalmers et al.(23) reported a vacuum extraction utilization rate of 10.0% and a rate of 14.3% for all instrumental deliveries. In another study performed at the same location as the present study, the vacuum extraction rate was similar (3.74%), significantly lower than reported in studies conducted in other countries(11). Although the low rate of births with intervention reported in the literature in Turkey is a positive finding, this may be associated with the high rate of cesarean deliveries.

he present study, the vacuum extraction rate was similar (3.74%), significantly lower than reported in studies conducted in other countries(11). Although the low rate of births with intervention reported in the literature in Turkey is a positive finding, this may be associated with the high rate of cesarean deliveries. It was observed in the study that episiotomies are still widely implemented (54.1%). Similar results were reported in studies previously conducted in Aydın (59.21%) and Ankara (64.0%)(11,12). These rates are much higher than reported in the United Kingdom (UK)(25) and Canada(24) (11.2% and 20.7%, respectively). This finding is important because it reflects the traditional approach of clinical personnel to performing episiotomies. A significant percentage of women (23.8%) experienced spontaneous lacerations that needed suturing. In another study that was carried out previously at the same hospital, spontaneous lacerations requiring repair with sutures were reported as 8.98%(11). This rate was reported as 64% in a study in Canada(24) and 15.7% in the UK(25). The differences in these results may be associated with birth assistance techniques used by health professionals (e.g., birth position, perineal massage, management of the second phase).

iring repair with sutures were reported as 8.98%(11). This rate was reported as 64% in a study in Canada(24) and 15.7% in the UK(25). The differences in these results may be associated with birth assistance techniques used by health professionals (e.g., birth position, perineal massage, management of the second phase). When intrapartum care was evaluated in this study using the Bologna score, it was found that most women (92.7%) experienced spontaneous onset of labor. The study encompassed all births in the hospital and all of these births were attended to by midwives or doctors. On the other hand, the Turkish Ministry of Health encourages hospital births in the presence of health professionals. The Turkish Population Health Research Survey results of the last five years show that 97% of the births taking place in the country occurred under the supervision of health professionals(8). Similarly, studies conducted in Brazil(26) and Switzerland(18) reported that all births occurred with the help of health professionals. These findings are positive and gratifying when considered in terms of maternal and infant health.

aking place in the country occurred under the supervision of health professionals(8). Similarly, studies conducted in Brazil(26) and Switzerland(18) reported that all births occurred with the help of health professionals. These findings are positive and gratifying when considered in terms of maternal and infant health. Studies on the provision support during childbirth in Turkey are still controversial and all intrapartum care is handled by midwives. The results of the present study confirmed that only 7 women were able to receive supportive intrapartum care. The WHO(1), on the other hand, strongly recommends in its “Coalition for Improving Maternity Services”(10) that among the mother-friendly care that can be provided, mothers in childbirth should have, besides midwives, nurses, and doctors on hand, a doula (a woman assisting the mother in labor) or other individuals (spouse, partner, family member, friend) to provide support during labor. In their study in Switzerland, Sandin-Bojö and Kvist(18) reported that 98.7% of mothers in labor received this kind of support. This brings the matter of intrapartum care services in Turkey to the forefront and points to the need for reviewing and developing the system.

member, friend) to provide support during labor. In their study in Switzerland, Sandin-Bojö and Kvist(18) reported that 98.7% of mothers in labor received this kind of support. This brings the matter of intrapartum care services in Turkey to the forefront and points to the need for reviewing and developing the system. Similar to other Turkish studies(11,12), the present study observed that almost all births occurred with women in the supine position and her legs in stirrups. This high percentage is pronounced when compared with the rate of 35% reported in Switzerland(18) and the rate of 57% reported in Canada for placing women’s legs in stirrups and the rate of 48% for the use of the supine position(24). In other studies, it is reported that even though placing the mother in vertical positions during labor and childbirth positively affects the mother’s control and satisfaction in terms of the length of the second stage, the performance of an episiotomy, instrumental birth, severe pain, and the fetal heartbeat(27), it is the attitudes of health professions that play a decisive role in choosing a position for the mother(28). Nieuwenhuijze et al.(29) stressed that making a joint decision is important in terms of increasing women’s sense of control and satisfaction.

tomy, instrumental birth, severe pain, and the fetal heartbeat(27), it is the attitudes of health professions that play a decisive role in choosing a position for the mother(28). Nieuwenhuijze et al.(29) stressed that making a joint decision is important in terms of increasing women’s sense of control and satisfaction. In this study, most births (73%) were monitored using a partogram. Rani et al.(30) and Sandin-Bojö and Kvist(18) reported similar findings (72% and 93%, respectively). Giglio et al.(26), however, reported a considerably lower percentage (29%). According to these results, it may be said that the use of the partogram varies depending upon the individual working protocols of institutions. In most births (83%), contact between mother and child took place in the first hour after birth. Similar results were reported in other studies conducted in Turkey(13,31). This rate was 92% in a study conducted in Switzerland(18). These findings show that healthcare practices are satisfactory in terms of ensuring early contact between mother and child.

een mother and child took place in the first hour after birth. Similar results were reported in other studies conducted in Turkey(13,31). This rate was 92% in a study conducted in Switzerland(18). These findings show that healthcare practices are satisfactory in terms of ensuring early contact between mother and child. In this study, the rate of inducing labor was significantly high (76.6%). Similar results have been reported in other studies conducted in Turkey(11). In studies carried out in many other countries, lower rates for using oxytocin or labor augmentation were reported(17,18,23,24,25,26). Moreover, the WHO(1) suggests as part of its description of mother-friendly hospital applications that the practice of induced labor must be used to a limited extent and not for more than 10% of births. These findings indicate that there is a need to carry out studies that will help to reduce the use of induction methods in Turkey.

WHO(1) suggests as part of its description of mother-friendly hospital applications that the practice of induced labor must be used to a limited extent and not for more than 10% of births. These findings indicate that there is a need to carry out studies that will help to reduce the use of induction methods in Turkey. The WHO(32) reports a very low quality of evidence regarding the routine use of amniotomy and induction and offers a weak recommendation regarding these procedures. Smyth et al.(33) also asserted that amniotomy was not recommended as a standard part of intrapartum care and management. In the present study, however, and similar to the results of other studies conducted in Turkey(11), it was observed that amniotomy (67%) and induction (60%) were widely used. Matsuo et al.(34) and Sartore et al.(35) reported lower rates of induction in their studies (49% and 22%, respectively). These findings are important in that they show that amniotomies and induction are in fact routine in Turkey. It was seen in the study that fundal pressure was applied to a significant percentage (27.4%) of women. This rate is lower than previously reported in other studies conducted in Turkey(11,36). On the other hand, it is higher than reported in other countries(18,23). This finding is significant because it points to the dimension of the wide use of fundal pressure in intrapartum care in Turkey despite the recommendation that this is not made a routine part of care given in this period.

nducted in Turkey(11,36). On the other hand, it is higher than reported in other countries(18,23). This finding is significant because it points to the dimension of the wide use of fundal pressure in intrapartum care in Turkey despite the recommendation that this is not made a routine part of care given in this period. Study Limitations There are some limitations to this study. The first is that the study was based on a nonrandom sampling. Accordingly, the results obtained represent the women taken into the study and cannot be generalized. Secondly, the study data were collected through face-to-face interviews and observations from patient files. The different sources may have affected the reliability of the data obtained. Only concrete and uncomplicated data may increase the reliability of research. Thirdly, at the hospital where the study was carried out, all cases of spontaneous lacerations were sutured. This may have explained the higher percentage of sutured lacerations compared with that reported in the international literature. Fourthly, the difficulty in collecting data in the study for cases of emergency and planned cesareans made it necessary to include only women who were having their babies through vaginal delivery. Accordingly, there is a need for studies that include emergency and planned cesarean births. This study does, however, include the ratios of primary and total cesarean deliveries that took place over the period the research was conducted.

sary to include only women who were having their babies through vaginal delivery. Accordingly, there is a need for studies that include emergency and planned cesarean births. This study does, however, include the ratios of primary and total cesarean deliveries that took place over the period the research was conducted. CONCLUSION This study revealed that the intrapartum care provided at a state hospital in Turkey was in compliance with international standards and evidence-based practices recommended by the WHO in terms of the presence of trained health professionals during labor and that early bonding was achieved between mother and child. However, the care was not in compliance in terms of factors related with admittance to hospital, performing episiotomies, enema, the use of partograms, induction, fundal pressure, and the nonsupine position, or in terms of receiving the assistance of a supportive individual during labor. According to the findings, recommendations might be: (1) Administrators should reformulate intrapartum care services to comply with the recommendations of the WHO, international standards and evidence-based practices. (2) The curriculums of programs of formal and widespread education should be reviewed and adjusted in concordance with standards and health professionals should thus be encouraged to update their knowledge and practices in this context. (3) Health administrators should create institutional and national policies that will raise the quality of current healthcare services and bring them up to par with international standards. (4) Studies on this matter should be conducted at different hospitals, with the inclusion of emergency and planned cesarean cases and with different sample groups. (5) More experimental, qualitative and quantitative research should be undertaken to explore specific problems at different hospitals to reveal the attitudes and experiences of healthcare professionals, and to suggest solutions.

ith the inclusion of emergency and planned cesarean cases and with different sample groups. (5) More experimental, qualitative and quantitative research should be undertaken to explore specific problems at different hospitals to reveal the attitudes and experiences of healthcare professionals, and to suggest solutions. Ethics Ethics Committee Approval: Regulatory permission for the collection of data for the research was obtained from the Turkish Ministry of Health Aydın State Hospitals Association General Secretariat. The study protocol was approved by the Adnan Menderes University, Faculty of Medicine Ethics Committee (Approval number: 2012/111), Informed Consent: The women recruited into the research were informed about the study and their verbal consent was obtained. Peer-review: External and internal peer-reviewed. Authorship Contributions Obstetrics and Gynaecology Practice: Z.K., D.A.K., G.G., Concept: Z.K., D.A.K., G.G., Design: Z.K., D.A.K., G.G., Data Collection or Processing: D.A.K., G.G., Analysis or Interpretation: Z.K., D.A.K., G.G., Literature Search: Z.K., G.G., Writing: Z.K., G.G. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support. Table 1 Sociodemographic characteristics of the women and variables related to pregnancy (n=303) Table 2 Risk status related to childbirth (n=303) Table 3 The items in the Bologna score (indicators of the effectiveness of care during labor) (n=303)

INTRODUCTION Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. GDM is defined as glucose intolerance with onset or first recognition during pregnancy and is a well-established risk factor for adverse infant health outcomes, including fetal macrosomia, birth trauma, neonatal hypoglycemia, and fetal death(1,2). The initial criteria for GDM were established by O’Sullivan and Mahan in 1964. In this criteria, two or more abnormal glucose values in the 3-h, 100-g oral glucose tolerance test (OGTT) were considered pathological(3). In 1979 and 1982, the National Diabetes Data Group (NDDG) and Carpenter and Coustan (C&C), respectively, recommended new diagnostic thresholds for the 100-g OGTT. These approaches are still used for pregnant women who have a high glucose challenge test (GCT) result(4,5). More recently, after an extensive analyses of the Hyperglycemia and Adverse Pregnancy Outcomes study, the International Association of Diabetes and Pregnancy Study Group (IADPSG) recommended a single-step approach and new diagnostic criteria for GDM that was based on a 2-h, 75-g OGTT(6,7). However, in general practice, this approach is still controversial. The American Diabetes Association and World Health Organization have adopted the IADPSG recommendation, whereas the American College of Obstetricians and Gynecologists advises continuing with the two-step screening strategy(8,9,10).

-h, 75-g OGTT(6,7). However, in general practice, this approach is still controversial. The American Diabetes Association and World Health Organization have adopted the IADPSG recommendation, whereas the American College of Obstetricians and Gynecologists advises continuing with the two-step screening strategy(8,9,10). GDM prevalence varies widely depending on the population studied, age, and the diagnostic test employed. In Turkey, the prevalence ranges from 1.2% to 4.48% according to the criteria of NDDG and C&C. However, there are no data on GDM prevalence using the new, single-step approach. Our aim was to determine GDM prevalence and to compare the two-step approach with the single-step approach among a population from the southeastern region of Turkey. MATERIALS AND METHODS This study was approved by the Ethics Committee of Selçuk University Faculty of Medicine on September 8th, 2015 (approval number: 2015/267).

Our aim was to determine GDM prevalence and to compare the two-step approach with the single-step approach among a population from the southeastern region of Turkey. MATERIALS AND METHODS This study was approved by the Ethics Committee of Selçuk University Faculty of Medicine on September 8th, 2015 (approval number: 2015/267). This retrospective study was conducted between January 2008 and December 2014 in the Birecik State Hospital, Şanlıurfa, which is located in the southeastern region of Turkey and provides service to approximately 150000 people. All women who were non-diabetic, between 24 and 28 weeks’ pregnancy, and aged between 15 and 49 years were screened for GDM using a two-step approach between January 2008 and December 2011, and the single-step approach between January 2012 and December 2014. During the two-step approach, all pregnant women were screened for GDM with the 50-g, 1-h GCT. A positive GCT result was defined as a serum glucose level of ≥140 mg/dL. Patients with a positive GCT underwent a 3-h, 100-g diagnostic OGTT. Patients with two or more elevated glucose results from the diagnostic OGTT were diagnosed as having GDM according to the criteria of O’Sullivan [i.e. fasting plasma glucose (FPG) level: ≥90 mg/dL, 1 h: ≥165 mg/dL, 2 h: ≥145 mg/dL, and 3 h: ≥125 mg/dL], NDDG (FPG: ≥105 mg/dL, 1 h: ≥190 mg/dL, 2 h: ≥165 mg/dL, and 3 h: ≥145 mg/dL), and C&C (FPG: ≥95 mg/dL, 1 h: ≥180 mg/dL, 2 h: ≥155 mg/dL, and 3 h: ≥140 mg/dL). In the single step approach, patients were screened for GDM with a 2-h, 75-g OGTT. GDM was diagnosed by a single elevated 2-h, 75-g glucose tolerance test (FPG: ≥92 mg/dL, 1 h: ≥180 mg/dL and 2 h: ≥153 mg/dL) as defined by the IADPSG.

dL), and C&C (FPG: ≥95 mg/dL, 1 h: ≥180 mg/dL, 2 h: ≥155 mg/dL, and 3 h: ≥140 mg/dL). In the single step approach, patients were screened for GDM with a 2-h, 75-g OGTT. GDM was diagnosed by a single elevated 2-h, 75-g glucose tolerance test (FPG: ≥92 mg/dL, 1 h: ≥180 mg/dL and 2 h: ≥153 mg/dL) as defined by the IADPSG. Statistical Analysis The records of pregnant women screened for GDM were extracted from the laboratory information system. All glucose measurements in patient samples were performed using the hexokinase method. Demographic variables were compared using student’s t-test. Linear trends with age and GDM prevalence were calculated using logistic regression. Statistical analyses were performed using SPSS v16. A p-value <0.05 was considered significant.

ose measurements in patient samples were performed using the hexokinase method. Demographic variables were compared using student’s t-test. Linear trends with age and GDM prevalence were calculated using logistic regression. Statistical analyses were performed using SPSS v16. A p-value <0.05 was considered significant. RESULTS A total of 1385 pregnant women were screened for GDM with a two-step approach between January 2008 and December 2011. Of these women, 501 (36.2%) were found at risk for GDM during GCT and were included in the 3-h, 100-g diagnostic OGTT. During the diagnostic OGTT, 66 of the 501 patients were diagnosed as having GDM according to the criteria of NDDG and 111 and 185 of 501 patients were diagnosed as having GDM according to the criteria of C&C and O’Sullivan, respectively. GDM prevalence was found as 4.8%, 8%, and 13.4% based on the criteria of NDDG, C&C, and O’Sullivan, respectively, during the two-step approach. GDM prevalence for each year is presented in Table 1. A total of 1663 pregnant women were screened for GDM using the single-step approach between January 2012 and December 2014, and 371 were diagnosed as having GDM. The GDM prevalence rate was found as 22.3% according to the criteria of IADPSG. The prevalence rates for each year are presented in Table 2. In our study, patients who were diagnosed as having GDM were significantly older than healthy patients (Table 3). GDM prevalence increased with increasing age with both approaches (Table 4).

RESULTS A total of 1385 pregnant women were screened for GDM with a two-step approach between January 2008 and December 2011. Of these women, 501 (36.2%) were found at risk for GDM during GCT and were included in the 3-h, 100-g diagnostic OGTT. During the diagnostic OGTT, 66 of the 501 patients were diagnosed as having GDM according to the criteria of NDDG and 111 and 185 of 501 patients were diagnosed as having GDM according to the criteria of C&C and O’Sullivan, respectively. GDM prevalence was found as 4.8%, 8%, and 13.4% based on the criteria of NDDG, C&C, and O’Sullivan, respectively, during the two-step approach. GDM prevalence for each year is presented in Table 1. A total of 1663 pregnant women were screened for GDM using the single-step approach between January 2012 and December 2014, and 371 were diagnosed as having GDM. The GDM prevalence rate was found as 22.3% according to the criteria of IADPSG. The prevalence rates for each year are presented in Table 2. In our study, patients who were diagnosed as having GDM were significantly older than healthy patients (Table 3). GDM prevalence increased with increasing age with both approaches (Table 4). DISCUSSION GDM prevalence may differ depending on the population being screened and the diagnostic test being performed. GDM prevalence was reported as 8.8% using the NDDG criteria and 10.6% using the C&C criteria in Spain(11,12). GDM prevalence was also determined as 5.5% in the United States of America (USA), 8.4% in China, and 7.7% in Morocco according to the C&C criteria(13,14,15).

ng screened and the diagnostic test being performed. GDM prevalence was reported as 8.8% using the NDDG criteria and 10.6% using the C&C criteria in Spain(11,12). GDM prevalence was also determined as 5.5% in the United States of America (USA), 8.4% in China, and 7.7% in Morocco according to the C&C criteria(13,14,15). In studies conducted in different regions of Turkey, GDM prevalence was found between 1.23% and 4.2% according to the criteria of the NDDG, and between 2% and 4.48% according to the C&C criteria(16,17,18,19,20). In our study, GDM prevalence was found as 4.8% and 8% using the NDDG and C&C criteria, respectively, which is higher than that those reported in previous Turkish studies. The higher GDM prevalence is probably due to regional dietary habits. GDM was higher using the criteria of C&C than with the NDDG criteria. This increase may result from the increased sensitivity of the test when using the C&C criteria because its glucose value for a diagnosis of GDM is lower than in the NDDG criteria. After IADPSG issued a consensus statement on the new criteria for the diagnosis of GDM, GDM prevalence significantly increased when the new criteria were adopted(12,21,22). GDM prevalence increased 3.3 times in Spain (10.6% to 35.5%), 2.8 times in the USA (5.5% to 15.6%) and 2.25 times in China (8.4% to 18.9%) using the new IADPSG criteria(12,13,14).

statement on the new criteria for the diagnosis of GDM, GDM prevalence significantly increased when the new criteria were adopted(12,21,22). GDM prevalence increased 3.3 times in Spain (10.6% to 35.5%), 2.8 times in the USA (5.5% to 15.6%) and 2.25 times in China (8.4% to 18.9%) using the new IADPSG criteria(12,13,14). In Turkey, our study is the first to determine GDM prevalence using the new, single-step approach. Similar to other studies, we found that GDM prevalence using the IADPSG single-step approach increased the positivity rate as much as 4.5 times than that of the two-step NDDG approach, 3 times more than the two-step C&C approach, and 1.7 times more than the two-step O’Sullivan approach. This significant increase results from the fact that only one elevated result is sufficient to make the diagnosis, not two. In our study, the increase in GDM prevalence with IADPSG was 2 times higher in a subgroup of women aged <30 years. In our study, GDM prevalence increased significantly with increasing age, regardless of the criteria used. A similar association has been observed in various studies(16,23,24). GDM prevalence in women aged >30 years was 4.2 times greater than that of women aged ≤30 years using the C&C and NDDG criteria, 2.5 times greater using the criteria of O’Sullivan, and 2 times greater using the IADPSG criteria. This means that the criteria of O’Sullivan and IADPSG diagnose more younger women (i.e. women <30 years) as having GDM.

ed >30 years was 4.2 times greater than that of women aged ≤30 years using the C&C and NDDG criteria, 2.5 times greater using the criteria of O’Sullivan, and 2 times greater using the IADPSG criteria. This means that the criteria of O’Sullivan and IADPSG diagnose more younger women (i.e. women <30 years) as having GDM. CONCLUSION Therefore, the new IADPSG criteria provide a higher GDM prevalence and diagnose more young women. This may also be effective in decreasing the medical disbursement for the treatment of the disease; however, the benefits of these findings are still unclear. New prospective studies may highlight the outcomes of new approaches by the criteria of IADPSG. Ethics Ethics Committee Approval: This study was approved by the Ethics Committee of Selçuk University Faculty of Medicine on 08.09.2015 (Approval number: 2015/267), Informed Consent: Retrospective study. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: E.A., F.D.G., Concept: E.A., A.Ü., Design: E.A., S.A., Data Collection or Processing: E.A., F.D.G., Analysis or Interpretation: E.A., S.A., Literature Search: E.A., Writing: E.A., S.A. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: E.A., F.D.G., Concept: E.A., A.Ü., Design: E.A., S.A., Data Collection or Processing: E.A., F.D.G., Analysis or Interpretation: E.A., S.A., Literature Search: E.A., Writing: E.A., S.A. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Gestational diabetes mellitus prevalence according to the two-step approaches by year Table 2 Gestational diabetes mellitus prevalence according to the single-step approach by year Table 3 Age characteristics of healthy patients and patients with gestational diabetes mellitus Table 4 The trends in the prevalence of gestational diabetes mellitus with age

INTRODUCTION The primary purpose of prenatal aneuploidy screening tests is early detection of pregnancies at high risk for Down syndrome, which is the most common autosomal trisomy among live births(1). First trimester combined screening tests can detect approximately 84% of trisomy cases with a false positive rate (FPR) of 5 percent(2). Incorporation of assessment of nasal bone, tricuspid blood flow, and ductus venosus (DV) waveform to the combined test increases the detection rate to approximately 93-96% with a FPR of 2.5 percent. In the second trimester, by combining classic ultrasonographic markers for Down syndrome (hyperechogenic intestines, an echogenic cardiac focus, pyelectasis, and short femur or humerus) with maternal age can diagnose 70% of trisomy 21 cases, but it may also record a false positive diagnosis in 10-15% of cases(3). DV is a special shunt that directs oxygen rich blood from the umbilical vein to the heart(4). The characteristic properties of ductal blood flow include a high flow rate during ventricular systole (S wave) and diastole (D wave), and a continuous forward flow during atrial systole (A wave). A-wave negativity is regarded as a reflection of fetal cardiac dysfunction(5).

ood from the umbilical vein to the heart(4). The characteristic properties of ductal blood flow include a high flow rate during ventricular systole (S wave) and diastole (D wave), and a continuous forward flow during atrial systole (A wave). A-wave negativity is regarded as a reflection of fetal cardiac dysfunction(5). Abnormal DV waveforms between 10 to 13+6 weeks have shown a relationship with chromosomal defects, cardiac anomalies, and poor gestational prognosis(5). Following the demonstration of a correlation between abnormal ductal flow and nuchal translucency (NT), it has been proposed that a combined assessment of DV and NT thickness may increase the efficacy of early sonographic screening of trisomy 21. Ultrasonographic evaluations in the first trimester have shown that this abnormality is present in 66.3% to 80% of trisomy 21 cases(6). Additionally, DV flow abnormality is a common finding in the presence of a cardiac defect in fetal Doppler examination in the first trimester(7,8). Furthermore, some abnormalities have been found in DVD ultrasonography during pregnancies with gestational hypertension (GHT), preeclampsia, and gestational diabetes mellitus (GDM)(9,10,11).

low abnormality is a common finding in the presence of a cardiac defect in fetal Doppler examination in the first trimester(7,8). Furthermore, some abnormalities have been found in DVD ultrasonography during pregnancies with gestational hypertension (GHT), preeclampsia, and gestational diabetes mellitus (GDM)(9,10,11). Although analysis of free fetal DNA in maternal blood flow for screening is a promising method, its widespread use is still restricted due to high costs. Thus, parameters that aid increased detection rates of routine screening tests are still substantial. The aim of our study was to determine whether DV waveform abnormality in Doppler ultrasonography would aid in second trimester screening when the detection rate is relatively low, and whether it was correlated with maternal complications.

t aid increased detection rates of routine screening tests are still substantial. The aim of our study was to determine whether DV waveform abnormality in Doppler ultrasonography would aid in second trimester screening when the detection rate is relatively low, and whether it was correlated with maternal complications. MATERIALS AND METHODS Our study included 174 pregnant women aged 20 to 45 years who were followed up at Zekai Tahir Burak Women’s Health Training and Research Hospital between May 2010 and September 2010. The study design was approved by the local institutional ethics committee and review board (approval number: 04/2009-16). Written consent for participation was obtained prior to recruitment into the study. The subjects were referred for high risk for Down syndrome and scheduled for amniocentesis as a result of a risk assessment based on maternal age and/or the results of double test [NT, nasal bone hypoplasia, and beta human chorionic gonadotropin (βhCG) and pregnancy-associated plasma protein A measurements between 11 and 13+6 gestational weeks] or triple test (βhCG, unconjugated estriol, and alpha-fetoprotein measurements between 16 and 19 gestational weeks). All pregnancies were between 16 and 20 gestational weeks. High-risk pregnancies including multiple pregnancies, maternal diabetes, and hypertension were excluded.

s between 11 and 13+6 gestational weeks] or triple test (βhCG, unconjugated estriol, and alpha-fetoprotein measurements between 16 and 19 gestational weeks). All pregnancies were between 16 and 20 gestational weeks. High-risk pregnancies including multiple pregnancies, maternal diabetes, and hypertension were excluded. DVD was performed to all subjects prior to the amniocentesis procedure. Ultrasonographic examination and measurements were conducted by two sonographers (G.K. and A.Y.) using a Voluson 730 Expert color Doppler ultrasonography device. A 4 MHz convex transducer was used in all examinations. Doppler ultrasonography was performed in the right ventral part of the fetal body on the mid-sagittal plane. Pulsed Doppler was used for measurements from the mid-section of ductus venosus. After adjustment of the insonation angle to <30 °C, DV was easily visualized using the aliasing phenomenon. Abnormal DV blood flow was defined as reversed velocities during atrial contraction (A-wave). The demographic data of the patients, and results of amniocentesis and detailed ultrasonography were recorded. The women were followed up throughout pregnancy and gestational complications were investigated. Neonatal records were inspected after birth. All study data were digitally recorded and analyzed using Statistical Packages for the Social Science (SPSS) version 11.5. All variables are expressed as mean ± standard deviation, frequency, and percentage. All comparisons were performed using the Mann-Whitney U test. Nominal and ordinal variables were analyzed using one of the chi-square tests suitable for expected values and frequencies of the variables (Fisher’s exact, and Yates’s chi-square tests). Statistical significance was set at p<0.05.

frequency, and percentage. All comparisons were performed using the Mann-Whitney U test. Nominal and ordinal variables were analyzed using one of the chi-square tests suitable for expected values and frequencies of the variables (Fisher’s exact, and Yates’s chi-square tests). Statistical significance was set at p<0.05. RESULTS One hundred seventy-four women were enrolled in the study. The mean maternal age was 32.15 years; the mean number of previous pregnancies was 3.06; the mean number of previous deliveries was 2.24; and the mean number of previous abortions was 0.75. The demographic data of patients are shown in Table 1. Amniocentesis was scheduled according to the results of first trimester screening in 66 patients and the results of second trimester screening in 98 patients. Twenty-four (13.8%) subjects were aged more than 35 years. Of these, six women had detected risk in the first screening test and eight had risk in the second trimester screening test. The remaining 10 women were offered amniocentesis due to maternal anxiety. In the later stages of pregnancy, 6 (3.4%) women developed GDM, 4 (2.3%) developed GHT, 4 (2.3%) developed preeclampsia, and 2 (1.1%) developed abortus. Eleven (68.8%) of 16 pregnancies with maternal complications had normal DVD and 5 (31.2%) had abnormal DVD. Three (50%) of these women had GDM and 2 (50%) had preeclampsia. The presence of reversed a-wave in DV was a significant predictor of maternal complications in later weeks of pregnancy (p=0.003, Fisher’s exact test) (Table 2).

of 16 pregnancies with maternal complications had normal DVD and 5 (31.2%) had abnormal DVD. Three (50%) of these women had GDM and 2 (50%) had preeclampsia. The presence of reversed a-wave in DV was a significant predictor of maternal complications in later weeks of pregnancy (p=0.003, Fisher’s exact test) (Table 2). Among the pregnant women without fetal problems (spontaneous abortus, trisomy, cardiac defect), 157 (95.7%) had normal DVD and 7 (4.3%) had reversed a-wave in DV. A total of 10 fetuses had problems, 2 of which were lost to spontaneous abortion (post-amniocentesis abortus), 4 had cardiac anomalies, and 5 had trisomy 21 (1 fetus had both trisomy 21 and ventricular septal defect). In 13 of 174 cases, Doppler studies indicated a reversed a-wave in the ductus venosus. Of those, 3 fetuses had trisomy 21, which related to 60% (3 of 5 fetuses) of all fetuses with trisomy 21. In the euploid group, reversed flow in the DV was observed in 5.9% of the cases. The rate of reversed a-wave in DV was significantly higher than in normal DVD in fetuses with trisomy 21 (p=0.003, Fisher’s exact test) (Table 3). DISCUSSION The diagnostic accuracy and false positivity rates of the available screening methods for trisomy 21 have not reached an ideal level(12,13). Recently, a novel screening method called non-invasive prenatal test based on free fetal DNA analysis in maternal blood was developed(14,15). However, such tests cannot be included in routine screening tests owing to their high costs in developing countries.

ethods for trisomy 21 have not reached an ideal level(12,13). Recently, a novel screening method called non-invasive prenatal test based on free fetal DNA analysis in maternal blood was developed(14,15). However, such tests cannot be included in routine screening tests owing to their high costs in developing countries. Based on fetal ultrasonographic examinations of cases of trisomy 21, former studies reported that DV showed an abnormal flow pattern in these cases(16,17,18). In a study on over 5000 pregnant women, 281 cases of trisomy 21 were diagnosed. An abnormal flow pattern in DVD was observed in 80% of trisomy 21 cases and 5% of euploid fetuses(12). Another study detected a DV flow pattern abnormality in the first trimester in 66.3% of trisomy 21 cases(6). In most studies where DV was assessed with Doppler ultrasonography, the assessment was made in the first trimester. Geipel et al.(16) evaluated women with 808 euploid fetuses and 37 fetuses with Down syndrome between the 14th and 18th weeks of gestation. These women were investigated for the presence of abnormal DV waveform, tricuspid regurgitation, and nasal bone hypoplasia/aplasia. The trisomy 21 group had reversed a-wave in DVD at a rate of 23.3%, tricuspid regurgitation 27%, and nasal bone hypoplasia/aplasia 45.9%, and the euploid group had a rate of 1.6% for reversed a-wave in DVD, 4.6% for tricuspid regurgitation, and 3.2% for nasal bone hypoplasia/aplasia. The authors concluded that the presence of these ultrasonographic markers in the second trimester increased the risk of Down syndrome by 6-15-fold. Combining maternal age, nuchal fold, nasal bone, tricuspid regurgitation with DVD, they accurately diagnosed 90% of all trisomy 21 cases(16). A large-scale study conducted in 2011 that involved 20,000 euploid fetuses and 20,000 cases of trisomy 21 showed that tests including DV, tricuspid blood flow, and nasal bone at 15-18 gestational weeks improved trisomy 21 screening performance when used in conjunction with maternal age. That study revealed rates of 1.7% and 14.3% for abnormal DV flow in the euploid and trisomy 21 groups, respectively(17).

ses of trisomy 21 showed that tests including DV, tricuspid blood flow, and nasal bone at 15-18 gestational weeks improved trisomy 21 screening performance when used in conjunction with maternal age. That study revealed rates of 1.7% and 14.3% for abnormal DV flow in the euploid and trisomy 21 groups, respectively(17). We detected DV waveform abnormalities in 3 (60%) of 5 cases of trisomy 21. Our study indicated that DVD evaluation at 16-20 gestational weeks was significantly beneficial for predicting trisomy 21, in accordance with the above-mentioned studies. The strengths of our study over other studies include its prospective design and the more homogenous nature of its sample. Study Limitations Our limitation is the small sample size. It has been shown previously that among cases proven to be free of chromosomal anomalies in first trimester fetal Doppler ultrasonography examination, abnormal DV flow pattern was present in 0-40% of those without cardiac defects, but 75-100% of those with cardiac defects(7,8). We found that 3 of 4 fetuses with cardiac problems had abnormal DV waveform. This rate appears to be in accordance with previously reported studies.

fetal Doppler ultrasonography examination, abnormal DV flow pattern was present in 0-40% of those without cardiac defects, but 75-100% of those with cardiac defects(7,8). We found that 3 of 4 fetuses with cardiac problems had abnormal DV waveform. This rate appears to be in accordance with previously reported studies. It has been reported that women with GHT and preeclampsia had altered DV waveforms in fetal Doppler ultrasonographic examination performed after the index of disorder due to placental dysfunction(9). A recent study that aimed to determine the performance of maternal characteristics, Doppler, and a set of biochemical markers for preeclampsia screening in the first and second trimester demonstrated that inclusion of pulsatility index of DV to other parameters could potentially aid patient counseling with regard to early screening for preeclampsia(10). We demonstrated abnormal DV flow in all 4 cases of preeclampsia. Some studies indicated that the pulsatility index of DV was higher in women with GDM compared with control subjects(11,18). We found an abnormal DV flow pattern in 3 of 6 women with gestational diabetes. Our results concerning GDM were in agreement with literature reports. In our study, the ratio of DVD abnormality was significantly greater in pregnancies that would later develop maternal complications.

ompared with control subjects(11,18). We found an abnormal DV flow pattern in 3 of 6 women with gestational diabetes. Our results concerning GDM were in agreement with literature reports. In our study, the ratio of DVD abnormality was significantly greater in pregnancies that would later develop maternal complications. CONCLUSION Despite limited safety data due to the small number of fetuses with Down syndrome, we are of the opinion that the addition of DVD to second trimester screening tests will be an inexpensive and beneficial method to increase the rate of Down syndrome detection in women who cannot undergo DVD examinations in the first trimester. DVD examination in the second trimester may also provide information to predict adverse pregnancy outcomes such as preeclampsia and GDM. However, this hypothesis needs to be supported by further research with large sample sizes. Ethics Ethics Committee Approval: The study was approved by the Zekai Tahir Burak Women’s Health Training and Research Hospital Local Ethics Committee (Approval number: 04/2009-16), Informed Consent: Consent form was filled out by all participants. Peer-review: External and internal peer-reviewed. Authorship Contributions Surgical and Medical Practices: G.K., A.Y., Concept: G.K., N.D., Design: S.E.Y., M.Ö.A., Data Collection or Processing: G.K., A.Y., Analysis or Interpretation: S.E.Y., M.Ö.A., N.D., Literature Search: G.K., A.Y., S.E.Y., Writing: G.K., A.Y., S.E.Y. Conflict of Interest: No conflict of interest was declared by the authors.

Surgical and Medical Practices: G.K., A.Y., Concept: G.K., N.D., Design: S.E.Y., M.Ö.A., Data Collection or Processing: G.K., A.Y., Analysis or Interpretation: S.E.Y., M.Ö.A., N.D., Literature Search: G.K., A.Y., S.E.Y., Writing: G.K., A.Y., S.E.Y. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 The demographic data of the patients Table 2 Correlation between maternal complications and ductus venosus Doppler Table 3 Distribution of normal and abnormal ductus venosus flow rate waveforms based on the presence of Down syndrome

PRECIS: The neonatal mortality rate was 30 times higher in preterm neonates than in term neonates, which indicates a survival gap between the two groups. INTRODUCTION Prematurity presents a significant challenge to the global community due to the rapid increase in its incidence and its disproportionate contribution to increased infant mortality rates. In 2010, approximately 15 million babies were born preterm, and more than 1 million died due to complications during the first month of life(1). Globally, among all neonatal deaths in 2013, 35% were caused by preterm birth complications alone(2). Research that expands our understanding of the causes and risk factors of preterm birth and how to identify women and adolescents at risk is particularly needed to decrease the global neonatal mortality rate(1). Without accurate, comprehensive background information describing the existing state of preterm neonatal births, risk factors, and national mortality, an international improvement in preterm neonatal care would be extremely challenging to achieve. Population-based studies reporting the outcomes of preterm birth using standardized mortality definitions are highly recommended in low- and middle resource settings(3).

eonatal births, risk factors, and national mortality, an international improvement in preterm neonatal care would be extremely challenging to achieve. Population-based studies reporting the outcomes of preterm birth using standardized mortality definitions are highly recommended in low- and middle resource settings(3). Jordan has a total fertility rate of 3.5 per woman, and a birth rate of 27 per 1000 people (2010-2012)(4). Corresponding to the global picture, during 2013, half of the 4000 children in Jordan who died under the age of five years were neonates(2). Jordan ranked 97th globally in under-five mortality rates in 2012(5). Despite a progressive decline in neonatal mortality rates between 1990 and 2013, the national neonatal mortality rate remains high, at 11 neonatal deaths per 1000 live births in 2013(2). However, evidence regarding the incidence, geographic distribution, associated factors, and mortality risks of preterm births in Jordan is limited; these are mostly deduced from single settings or confined to data from limited geographic areas(6,7,8,9,10,11,12,13,14). This study is part of a larger nation-wide study, conducted in 2012 and 2013, to examine perinatal mortality in Jordan(15). The purpose of this paper was to report the incidence of preterm birth, its risk factors, and its contribution to neonatal mortality. MATERIALS AND METHODS Study design This was a national, prospective, hospital-based study.

Jordan has a total fertility rate of 3.5 per woman, and a birth rate of 27 per 1000 people (2010-2012)(4). Corresponding to the global picture, during 2013, half of the 4000 children in Jordan who died under the age of five years were neonates(2). Jordan ranked 97th globally in under-five mortality rates in 2012(5). Despite a progressive decline in neonatal mortality rates between 1990 and 2013, the national neonatal mortality rate remains high, at 11 neonatal deaths per 1000 live births in 2013(2). However, evidence regarding the incidence, geographic distribution, associated factors, and mortality risks of preterm births in Jordan is limited; these are mostly deduced from single settings or confined to data from limited geographic areas(6,7,8,9,10,11,12,13,14). This study is part of a larger nation-wide study, conducted in 2012 and 2013, to examine perinatal mortality in Jordan(15). The purpose of this paper was to report the incidence of preterm birth, its risk factors, and its contribution to neonatal mortality. MATERIALS AND METHODS Study design This was a national, prospective, hospital-based study. Setting The study was conducted at 18 maternity hospitals that were carefully selected based on criteria determined by the study’s technical committee, which consisted of representatives from the United Nations International Children’s Emergency Fund (UNICEF), the World Health Organization (WHO), and the Jordanian health sectors. These criteria reflected the diverse socioeconomic status of the participants and the quality levels of services provided to them. The hospital selection criteria also considered the workload of the hospitals in terms of the number of deliveries.

), the World Health Organization (WHO), and the Jordanian health sectors. These criteria reflected the diverse socioeconomic status of the participants and the quality levels of services provided to them. The hospital selection criteria also considered the workload of the hospitals in terms of the number of deliveries. Accordingly, the 18 hospitals were distributed over the three regions of the country: seven hospitals in the middle, six in the north, and five in the south. The hospitals represented all health care delivery sectors in the three geographic regions of Jordan, including urban and rural areas. The number of births selected from each hospital was proportional to the number of births in each health sector and region. The Institutional Review Boards at the Ministry of Health and selected hospitals approved the study (approval number: 2012/035). Participants All women who gave birth to dead or live neonates at 20 or more weeks of gestation in each of the selected hospitals were eligible for inclusion and were interviewed before discharge from the hospital. The sampling criteria and size of the larger study are described in detail elsewhere(15). In the current analysis, the sample was limited to singleton women who gave birth to live neonates. Women who gave birth to stillborn babies were excluded. Written informed consent was obtained for each participant prior to commencing the interviews.

a and size of the larger study are described in detail elsewhere(15). In the current analysis, the sample was limited to singleton women who gave birth to live neonates. Women who gave birth to stillborn babies were excluded. Written informed consent was obtained for each participant prior to commencing the interviews. Data source and measurements A number of questionnaires and forms were developed, revised, and finalized by the study team to facilitate the gathering and recording of research data. The questionnaires had specific instructions, and the content was organized to increase clarity and enhance the accuracy of the obtained data. A team of 3-6 midwives/nurses, led by an obstetrician and a neonatologist or pediatrician, was assigned to collect data at each selected hospital. Qualified local trainers conducted a two-day training workshop for researchers working in each region. The study questionnaires and forms were pre-tested in the field on a sample of women similar to those who were actually included in the study. The pre-discharge interview questionnaire contained information about the socio-demographic, maternal, and clinical characteristics of the women; information about pregnancy, labor, and delivery; relevant information about the neonates; and perinatal and neonatal deaths. Information was also gathered from the participating women’s medical records pre-discharge. Woman whose neonates died before discharge were asked further questions about the circumstances and causes of death.

out pregnancy, labor, and delivery; relevant information about the neonates; and perinatal and neonatal deaths. Information was also gathered from the participating women’s medical records pre-discharge. Woman whose neonates died before discharge were asked further questions about the circumstances and causes of death. For those women who did not experience perinatal or neonatal death before discharge, consent to follow-up with them postpartum was obtained, and their phone number was noted. The women who agreed to be contacted were called 30 days postpartum to participate in a phone interview; questions were asked about whether the neonate was alive, the health of the neonate, and details of visits to health facilities for both the mother and her neonate. If, through this screening call, it was discovered that a neonate had died, plans were made for a follow-up interview at the woman’s home for a “verbal autopsy”.

ons were asked about whether the neonate was alive, the health of the neonate, and details of visits to health facilities for both the mother and her neonate. If, through this screening call, it was discovered that a neonate had died, plans were made for a follow-up interview at the woman’s home for a “verbal autopsy”. Neonatal gestational ages were recorded in the women’s medical records by practicing physicians. The gestational age was based on both ultrasound and the last menstrual period (the interval between the first day of the mother’s last normal menstrual period and the date of delivery of the fetus or newborn). A preterm neonate was defined as a neonate that was born before 37 completed weeks of pregnancy. Based on the gestational age, preterm babies were further classified as born between 32-36 weeks of gestation and born at <32 weeks. A birth weight less than 2500 grams (5 pounds, 8 ounces) was considered as low birth weight and a birth weight of 2500 grams and above was considered as normal weight. The neonatal mortality rate was defined as the number of deaths during the first 28 completed days of life per 1000 live births that occurred during the study period. Neonatal deaths were subdivided according to the time of death into early neonatal deaths at 0-6 days after live birth and late neonatal deaths at 7-27 days after live birth. Both were expressed as per 1000 live births.

ring the first 28 completed days of life per 1000 live births that occurred during the study period. Neonatal deaths were subdivided according to the time of death into early neonatal deaths at 0-6 days after live birth and late neonatal deaths at 7-27 days after live birth. Both were expressed as per 1000 live births. The hospital diagnosis of the causes of neonatal deaths was based on standard obstetric and neonatal guidelines. The deaths were classified according to the National Institute for Heath and Care Excellence (NICE) system, a standard classification system that is based on the modified Wigglesworth classification(16), together with information on the calculation of birth weight in relation to gestational length. The NICE classification program classifies neonatal death into one of a range of specific, mutually exclusive, cause-of-death subgroups. The order of the subgroups is strictly hierarchical.

d Wigglesworth classification(16), together with information on the calculation of birth weight in relation to gestational length. The NICE classification program classifies neonatal death into one of a range of specific, mutually exclusive, cause-of-death subgroups. The order of the subgroups is strictly hierarchical. Statistical Analysis Data were described using means (standard deviation) for continuous variables, and frequencies and percentages were used for categorical variables. The differences between proportions were tested using chi-square tests. Risk factors were analyzed using generalized, linear-mixed multilevel models, and traditional logistic regression analysis was used to measure the hierarchical complexity of predictor variables. The Akaike information criterion (AIC) and the Bayesian information criterion were used to select and compare models based on the -2 log likelihood. Based on the information criteria, we preferred the final binary logistic regression model predicting prematurity over the final generalized linear mixed model with one random intercept, because it had smaller AIC values. Based on a likelihood ratio test, the binary logistic regression (no random effect) was still preferred. The variables were included in the model systematically, and those with p<0.10 in the univariate analysis were included in the model. The possible associated factors were examined for evidence of multicollinearity, which was reflected by either the changes in the direction of effect between the univariate and multivariable analysis or implausible standard errors for a particular variable. A p-value of <0.05 was considered statistically significant. Traditional and multilevel analyses were performed using IBM SPSS 20 (SPSS Inc., Chicago, IL, USA).

ed by either the changes in the direction of effect between the univariate and multivariable analysis or implausible standard errors for a particular variable. A p-value of <0.05 was considered statistically significant. Traditional and multilevel analyses were performed using IBM SPSS 20 (SPSS Inc., Chicago, IL, USA). RESULTS Participants’ characteristics During the study period, 21 075 women gave birth in the selected hospitals. Approximately one third of deliveries (34.2%) occurred in the northern region, 55.0% in the middle region, and 10.8% in the southern region. About 30.5% of women gave birth in private hospitals, 46.9% in public hospitals, 18.7% in military hospitals, and 3.8% in teaching hospitals. Almost all women (99%) sought antennal care, with 70.1% seeking antennal care >8 times. Less than one-third (32%) of women had an education level that was lower than high school, and 41.5% had an income of >350 Jordanian dinar (JD) per month (1 $= 0.71 JD). About 8.0% of women had a history of preterm or low-birth-weight delivery, 3.2% were smokers, 1.2% had preeclampsia, 1.2% had gestational diabetes, 0.5% had pre-gestational diabetes, and 4.8% had pre-gestational high blood pressure.

school, and 41.5% had an income of >350 Jordanian dinar (JD) per month (1 $= 0.71 JD). About 8.0% of women had a history of preterm or low-birth-weight delivery, 3.2% were smokers, 1.2% had preeclampsia, 1.2% had gestational diabetes, 0.5% had pre-gestational diabetes, and 4.8% had pre-gestational high blood pressure. Incidence of preterm birth Among the participants, 5.8% delivered before 37 completed weeks of gestation. The majority of preterm deliveries (85%) occurred between 32 and 36 weeks, and 15% reached <32 weeks of gestation. The preterm birth rate, according to the socio-demographic and clinical characteristics of the mothers and their babies, is shown in Table 1. The preterm birth rate was the lowest among women aged 20-35 years (7.8% for women aged <20 years, 5.4% for women aged 20-35 years, and 7.7% for women aged >35 years). The rate was extremely high among women who did not use antenatal care services (13.8%). The rate was also higher among women who had a history of preterm/low-birth-weight delivery (14.4%), hypertension (12.6%), preeclampsia (24.7%), gestational diabetes (10.3%), pre-gestational diabetes (25.7%), and women who were hospitalized between 24 and 34 gestational weeks. The rate of cesarean section births (46.4%), both planned and emergency, among the preterm neonates was almost equal to that by vaginal delivery (50.7%).

on (12.6%), preeclampsia (24.7%), gestational diabetes (10.3%), pre-gestational diabetes (25.7%), and women who were hospitalized between 24 and 34 gestational weeks. The rate of cesarean section births (46.4%), both planned and emergency, among the preterm neonates was almost equal to that by vaginal delivery (50.7%). The main characteristics of the full-term and preterm deliveries are shown in Table 2. Presentation at delivery was cephalic in 95.4% of full-term deliveries and 86.9% of preterm deliveries. About 27% of full-term deliveries and 46.4% of preterm deliveries were performed via cesarean section. Neonatal resuscitation was necessary for 9.6% of full-term babies and 29.2% of preterm babies. Preterm babies were more likely to have poor Apgar scores at 1 and 5 minutes compared with full-term babies. Risk factors of preterm delivery In multivariable analysis (Table 3), male sex [odds ratio (OR)=1.2], primigravid (OR=1.6), hypertension (OR=1.5), preeclampsia (OR=3.1), and diabetes (OR=1.6) were significantly associated with an increased risk of preterm delivery. Women aged between 20 and 35 years had the lowest risk of giving birth to a preterm neonate compared with older or younger women. A mother’s weight <50 kg, hospitalization at 24-34 gestational weeks, no antenatal care visits or <8 visits during pregnancy, and a history of preterm or low-birth-weight delivery or stillbirth/neonatal death were all associated with an increased risk of preterm delivery.

m neonate compared with older or younger women. A mother’s weight <50 kg, hospitalization at 24-34 gestational weeks, no antenatal care visits or <8 visits during pregnancy, and a history of preterm or low-birth-weight delivery or stillbirth/neonatal death were all associated with an increased risk of preterm delivery. Rates and causes of neonatal mortality among preterm and full-term babies The neonatal mortality rate was four per 1000 live births among full-term (early neonatal death=three per 1000 live births, and late neonatal death=one per 1000 live births). The neonatal mortality rate was 123 per 1000 live births among preterm babies (early neonatal death=99 per 1000 live births, and late neonatal death=24 per 1000 live births). Among normal birth weight babies, the neonatal mortality rate was 3 per 1000 live births for full-term and 22 per 1000 live births for preterm babies. Among low-birth-weight babies, the rate was 32 per 1000 live births for full-term, and 116 per 1000 live births for preterm babies. The causes of death for full-term and preterm babies are shown in Table 4.

neonatal mortality rate was 3 per 1000 live births for full-term and 22 per 1000 live births for preterm babies. Among low-birth-weight babies, the rate was 32 per 1000 live births for full-term, and 116 per 1000 live births for preterm babies. The causes of death for full-term and preterm babies are shown in Table 4. DISCUSSION The incidence of preterm births in the current study was 5.8%, comparable to that reported in developed countries such as Finland, Ireland, and Sweden(17). The preterm birth rate in this study compares positively with that observed in the United States and in most low- and middle-income countries(17,18,19,20). The relatively lower incidence rate in this study may be due to the larger number of participants aged 20-35 years and educated participants. Evidence from previous studies indicated that young (<20 years) and advanced (≥40 years) maternal ages are strong risk factors of preterm births(9,21,22). Similarly, increased risks of mothers having a preterm birth were associated with low or no education levels(21).

cipants aged 20-35 years and educated participants. Evidence from previous studies indicated that young (<20 years) and advanced (≥40 years) maternal ages are strong risk factors of preterm births(9,21,22). Similarly, increased risks of mothers having a preterm birth were associated with low or no education levels(21). The incidence rate of preterm birth noted in this study was also lower than that reported in earlier studies in Jordan(7,9,10). The proportion of preterm births, as reported by single-setting studies conducted in Jordan, ranged between 10.7%(7) and 12.8%(10) out of the total births in each setting, and the highest mortality in the neonatal intensive care unit was among preterm and low-birth-weight admissions(12). The discrepancy in the incidence of preterm births between the current study and previous studies in Jordan could be due to the small samples and geographic areas studied previously. The lower preterm birth rate in our study could indicate the positive progress that has been made recently in the quality of maternal-fetal health care in Jordan. The high number of women in the current study who attended antenatal clinics supports this supposition.

mall samples and geographic areas studied previously. The lower preterm birth rate in our study could indicate the positive progress that has been made recently in the quality of maternal-fetal health care in Jordan. The high number of women in the current study who attended antenatal clinics supports this supposition. However, the high attendance rate of antenatal care in this study did not reflect positively on the preterm neonatal mortality rate. The mortality rate of 123/1000 was relatively high. The neonatal mortality rate was 30 times higher among preterm neonates than among full-term neonates, indicating a survival gap between the groups; this disparity may be perceived as an urgent call for the systematic improvement of postnatal and neonatal intensive health care in Jordan. The best intervention for prevention of spontaneous preterm birth in women with risk factors is still unclear(23). However, simple cost-effective and research-supported interventions are available to reduce deaths among premature babies; for example, the promotion of early and exclusive breastfeeding, handwashing, and innovative skin-to-skin care(24,25). The prevention of hypothermia and management of respiratory distress syndrome, neonatal pneumonia, sepsis, and hyperbilirubinemia are evidence-based interventions that can greatly increase the survival of small and sick neonates(24).

rly and exclusive breastfeeding, handwashing, and innovative skin-to-skin care(24,25). The prevention of hypothermia and management of respiratory distress syndrome, neonatal pneumonia, sepsis, and hyperbilirubinemia are evidence-based interventions that can greatly increase the survival of small and sick neonates(24). Globally, 4 out of 5 newborn deaths result from three preventable and treatable conditions, primarily prematurity(25,26). Prematurity alone was the direct cause of almost 50% of neonatal deaths in the current study, followed by congenital anomalies and maternal medical conditions. Prematurity is often complicated by infections and respiratory complications, which commonly leads to the death of preterm infants(19,27). These complications can be prevented and treated by skilful and high-quality postnatal care of preterm neonates, especially during the first week of life. Our findings indicate that preterm neonates were four times more likely to die postnatally during the first week of life, compared with later times after birth. Nevertheless, high-quality antenatal screening and care are still key components in efforts to identify preterm birth risk factors early, prevent preterm births, and reduce infant mortality.

erm neonates were four times more likely to die postnatally during the first week of life, compared with later times after birth. Nevertheless, high-quality antenatal screening and care are still key components in efforts to identify preterm birth risk factors early, prevent preterm births, and reduce infant mortality. This research showed that the incidence of preterm birth was significantly reduced when mothers received health care in antenatal clinics during pregnancy. The more antenatal visits mothers attended during pregnancy, the lower was the risk of preterm births. Previous studies have shown that preterm births were significantly more common among women who had no or only occasional visits to antenatal care(27,28,29,30). In this study, the risk of preterm birth was almost four times greater in women who did not attend antenatal care, a risk ratio that is consistent with a study in Thailand(29). Globally, the proportion of women receiving antenatal care at least once during pregnancy was 83% between 2007 and 2014. However, only 64% of pregnant women attended the WHO-recommended minimum of four or more antenatal care visits(31). Correspondingly, in this study, almost all of the women had received antenatal care at least once. However, nationally, this is not sufficient, because more than one quarter of the sample received less than the national goal of a minimum of eight visits; this indicates a need to improve women’s access to and compliance with antenatal health services. These results may influence health policies in Jordan and globally.

owever, nationally, this is not sufficient, because more than one quarter of the sample received less than the national goal of a minimum of eight visits; this indicates a need to improve women’s access to and compliance with antenatal health services. These results may influence health policies in Jordan and globally. The identification of warning signs during pregnancy is an important goal of antenatal care(31). Preeclampsia, diabetes, and hypertension, whether pre-existing or gestational, are maternal medical conditions that commonly predict preterm birth(20,32), a finding that is similar to those of this study. For women with preeclampsia, the risk of preterm delivery was three times greater than it was for women who were not affected. This highlights that screening and medical management during antenatal care are clinically important to decrease the risk of preterm birth. Madan et al.(33) found that the risk of preterm birth was augmented for obese and overweight mothers if they experienced one or more of the conditions listed above. Their conclusion highlights the importance of including weight indices in the assessment of preterm birth risk factors. The evidence suggests an increase in the likelihood of preterm birth when body mass index (BMI) decreases below or increases above normal(29,33). Due to too many missing data, the researchers were unable to include BMI in the statistical analysis of their study; however, their results provide additional evidence of the role of underweight mothers on the increased risk of preterm birth.

when body mass index (BMI) decreases below or increases above normal(29,33). Due to too many missing data, the researchers were unable to include BMI in the statistical analysis of their study; however, their results provide additional evidence of the role of underweight mothers on the increased risk of preterm birth. Multiparous women with a history of preterm birth are also at risk for further preterm birth(21,29,33). In the current study, the likelihood of having a preterm birth at least doubled when there was a history of preterm or low-birth-weight delivery in previous pregnancies; a rate similar to that reported in a Canadian study(21). Likewise, primigravida was associated with a 1.6 increase in the likelihood of giving birth to a preterm neonate, which is approximate to the findings of similar studies(21,29). The rate of caesarian section births, both planned and emergency, among the preterm neonates was remarkably high (46.4%) and is worth further investigation.

igravida was associated with a 1.6 increase in the likelihood of giving birth to a preterm neonate, which is approximate to the findings of similar studies(21,29). The rate of caesarian section births, both planned and emergency, among the preterm neonates was remarkably high (46.4%) and is worth further investigation. Maternal hospitalization during 24-34 weeks of gestation was associated with a very high likelihood of preterm delivery. This finding is understandable because early maternal hospitalization during pregnancy indicates the existence of maternal or fetal health problems or early identification of a potential problem. The reasons for hospitalization and types of care provided need more investigation because these factors could lead to a better understanding of preterm birth risk factors and hence prevent prematurity complications and preterm neonate mortality. Interventional studies that incorporate the results of this study in preterm delivery risk assessment in maternal and child health centers are also encouraged.

ause these factors could lead to a better understanding of preterm birth risk factors and hence prevent prematurity complications and preterm neonate mortality. Interventional studies that incorporate the results of this study in preterm delivery risk assessment in maternal and child health centers are also encouraged. Study Limitations Although this study had several strengths compared with previous studies, it also had several limitations. Among the strengths of the current research were that it was nation-wide, covered a wide geographic area, and included information from all birth records in all sectors and types of hospital settings. It was not feasible, however, to include information on deliveries that occurred outside formal birth settings, such as private homes, which do occur in Jordan, albeit rarely. Although not all of the results of this study can be generalized to other countries, efforts were made to follow the WHO’s recommended definitions of prematurity and international standards of reporting mortality to allow for international comparisons and to enhance generalizing the data. In addition, this study was conducted over a specific period; therefore, replicating this study is highly recommended in future years to compare trends over time and identify changes in preterm birth estimates. Moreover, a longitudinal cohort study is strongly encouraged to follow preterm neonates because it would be highly beneficial to identify the long-term outcomes of preterm births, and the health needs of babies who survive prematurity.

e years to compare trends over time and identify changes in preterm birth estimates. Moreover, a longitudinal cohort study is strongly encouraged to follow preterm neonates because it would be highly beneficial to identify the long-term outcomes of preterm births, and the health needs of babies who survive prematurity. CONCLUSION Addressing the major risks associated with the incidence and the mortality of preterm neonates is a priority to reduce the global burden of preterm birth, along with identifying areas that are crucial to improve the health care systems across countries. Regarding risk factors, the limited research carried out in Jordan shows that the rate of preterm and low-birth-weight infants was highest for males and first-born neonates(10) among teenage women(8,13) and women aged 35 years or above(9,10), as well as for women in consanguineous marriages(11). By adding relevant information from Jordan, this study has contributed evidence to international comparison tables, and to the national as well as the international picture about prematurity.

ates(10) among teenage women(8,13) and women aged 35 years or above(9,10), as well as for women in consanguineous marriages(11). By adding relevant information from Jordan, this study has contributed evidence to international comparison tables, and to the national as well as the international picture about prematurity. The authors would like to thank UNICEF for funding the study and for providing the needed administrative and technical help. In particular, appreciation is forwarded to Ms. Maha Al Homsi and Buthainah Al Khateeb from UNICEF for their invaluable support for the study. Gratitude is also forwarded to John Snow Inc. for implementing the study and to field researchers of neonatologists, pediatricians, and nurses for their marvelous effort in collecting the data. Special thanks go to all participating mothers for their cooperativeness, without which the study could not have come to a successful conclusion. Finally, we would like to thank Editage (www.editage.com) for English language editing. Ethics Ethics Committee Approval: The study was approved by the Institutional Review Boards at the Ministry of Health, Jordan (Approval number: 2012/035), Informed Consent: A written informed consent was obtained from each participating woman. Peer-review: External and internal peer-reviewed. Authorship Contributions Concept: Y.S.K., A.M.B., Design: Y.S.K., A.M.B., Data Collection or Processing: Y.S.K., A.M.B., Analysis or Interpretation: N.M.A.R., Y.S.K., A.M.B., Literature Search: N.M.A.R., Y.S.K., A.M.B., Writing: N.M.A.R., Y.S.K., A.M.B.

Ethics Committee Approval: The study was approved by the Institutional Review Boards at the Ministry of Health, Jordan (Approval number: 2012/035), Informed Consent: A written informed consent was obtained from each participating woman. Peer-review: External and internal peer-reviewed. Authorship Contributions Concept: Y.S.K., A.M.B., Design: Y.S.K., A.M.B., Data Collection or Processing: Y.S.K., A.M.B., Analysis or Interpretation: N.M.A.R., Y.S.K., A.M.B., Literature Search: N.M.A.R., Y.S.K., A.M.B., Writing: N.M.A.R., Y.S.K., A.M.B. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received financial support by the United Nations International Children’s Emergency Fund (UNICEF). Table 1 The rate of preterm birth according to socio-demographic and clinical characteristics of mothers and their babies Table 2 The main characteristics of full and preterm deliveries Table 3 Multivariable analysis of factors associated with preterm delivery Table 4 The leading causes of neonatal deaths among full term and preterm babies, based on the National Institute for Heath and Care Excellence classification

INTRODUCTION Obstetric anal sphincter injuries (OASIS) account for a significant complication of vaginal deliveries and cause fecal incontinence (FI), which is defined as the involuntary leakage of gas, fluid or solid stool(1). They are seen in 0.5-9% of all deliveries(2). Post-delivery FI incidence, however, is about 3%(3). Only 30% of patients with OASIS were observed to have FI symptoms a year after delivery(4). It has also been reported that rates of fecal emergency and FI in the geriatric population reaches up to 53-80%(5). As endosonography became more common, occult anal sphincter injuries were detected in most of women with FI. Moreover, it has been shown that 20-41% of women who had normal deliveries but were without FI symptoms had ongoing occult anal sphincter injuries(6). Although there have been ample studies on occult anal sphincter injuries within the last decade, its clinical significance and natural history are still unclear(7). Further, it has also been argued that these injuries might become symptomatic at later ages(8). The reason for the increase seen in FI prevalence in women at later ages is controversial. It has been suggested that the existence of estrogen and progesterone receptors in women led to an increase in FI in the postmenopausal stage because of their hormonal effects on sphincters and pelvic floor muscles(9) but this correlation still proves to be controversial(10,11).

in women at later ages is controversial. It has been suggested that the existence of estrogen and progesterone receptors in women led to an increase in FI in the postmenopausal stage because of their hormonal effects on sphincters and pelvic floor muscles(9) but this correlation still proves to be controversial(10,11). We believe that occult anal sphincter injuries following delivery become symptomatic with changes seen in the postmenopausal stage. Therefore, our aim in this study was to investigate whether occult anal sphincter injuries are among the causes of postmenopausal FIs.

in women at later ages is controversial. It has been suggested that the existence of estrogen and progesterone receptors in women led to an increase in FI in the postmenopausal stage because of their hormonal effects on sphincters and pelvic floor muscles(9) but this correlation still proves to be controversial(10,11). We believe that occult anal sphincter injuries following delivery become symptomatic with changes seen in the postmenopausal stage. Therefore, our aim in this study was to investigate whether occult anal sphincter injuries are among the causes of postmenopausal FIs. MATERIALS AND METHODS Before the study was initiated, the consent of Necmettin Erbakan University, Meram Faculty of Medicine’s Board of Ethics for Clinical Trials was obtained (approval number: 2013/79). Healthy women who presented to the gynecology outpatient clinics of Necmettin Erbakan University Meram Faculty of Medicine between May 2013 and November 2013 with a history of delivery but with no previous history of anal sphincter injury were included in the study. Women aged between 18 and 70 years with at least one delivery and a 6-month interval after their latest delivery were covered by the study. Patients who had been clinically diagnosed as having sphincter injuries and subsequently received treatment for these injuries, and women aged over 70 years were excluded from the study because they were thought to be unsuitable for the tests required. All participants who had vaginal deliveries had a mediolateral episiotomy story at the first birth. Participants who underwent multiple episiotomies or did not have episiotomy were not included in the study. The criteria for inclusion and exclusion in the study are shown in Table 1.

e unsuitable for the tests required. All participants who had vaginal deliveries had a mediolateral episiotomy story at the first birth. Participants who underwent multiple episiotomies or did not have episiotomy were not included in the study. The criteria for inclusion and exclusion in the study are shown in Table 1. Informed consents were obtained from all participants and they were allocated into 4 groups according to their mode of delivery and menopausal status. Each group had 50 participants, a total of 200 for the whole study. Sample size was set at a minimum of 46 participants for each group with a margin of error of α=0.05 and β=0.20 as revealed by the power analysis performed based on study data presented by Donnelly et al.(12). Groups Group 1: Premenopausal women with a history of vaginal delivery, Group 2: Postmenopausal women with a history of vaginal delivery, Group 3: Premenopausal women with a history of c-section (premenopausal control group), Group 4: Postmenopausal women with a history of c-section (postmenopausal control group). Premenopausal period: Women aged between 18 and 49 years with at least one delivery and who menstruated at least once in the last 12 months. Postmenopausal period: Women aged between 49 and 70 years who had no history of menstruation in the last 12 months.

Group 4: Postmenopausal women with a history of c-section (postmenopausal control group). Premenopausal period: Women aged between 18 and 49 years with at least one delivery and who menstruated at least once in the last 12 months. Postmenopausal period: Women aged between 49 and 70 years who had no history of menstruation in the last 12 months. Evaluation of participants The age, mode of delivery, number of deliveries, history of postpartum clinical anal sphincter, history of anal sphincter repair, and whether the patients had had symptoms of postpartum FI were questioned. FI scoring was conducted according to the 20-point Wexner incontinence scale (WIS), which is based on patients’ gas, fluid, solid incontinence status and designed to determine changes in lifestyle and the frequency of the need to use pads. Anorectal manometric measurement All subjects received rectum cleansing with a fleet enema before the examination. The subjects were evaluated in the left lateral decubitus position. A Peritron precision perineometer 9300AV (Cardio Design Pty Ltd, Oakleigh, Victoria, Australia) perineometer and 3010 (Cardio Design Pty Ltd, Oakleigh, Victoria, Australia) type anal sensor were used.

leansing with a fleet enema before the examination. The subjects were evaluated in the left lateral decubitus position. A Peritron precision perineometer 9300AV (Cardio Design Pty Ltd, Oakleigh, Victoria, Australia) perineometer and 3010 (Cardio Design Pty Ltd, Oakleigh, Victoria, Australia) type anal sensor were used. The anal probe was 80 mm in length and was produced to have a pressure-sensitive part of 30 mm in the middle. The average figure for serial measurements of 1 minute anal channel resting pressure of the subjects was recorded. The subjects were then told to contract the anal sensor as powerfully as they could and to hold it in contraction. This procedure was repeated 3 times with 10 second intervals and the data were recorded. The values with the most successful contraction were determined to be the manometric values of the subject(13). Maximum contraction pressure values were taken into consideration in the evaluation of the subjects’ external anal sphincter (EAS) contractions. The pressure unit was taken in cm H20 values in measurements conducted with the perineometer.

ssful contraction were determined to be the manometric values of the subject(13). Maximum contraction pressure values were taken into consideration in the evaluation of the subjects’ external anal sphincter (EAS) contractions. The pressure unit was taken in cm H20 values in measurements conducted with the perineometer. Endoanal ultrasonography The anal endosonography procedure was performed at the imaging laboratory of our hospital’s gastroenterology clinic. Imaging was conducted using a Fujinon ITD-01 EUS and a P2612M model flexible radial ultrasonic sonoprobe with 12 MHz frequency. All endoanal ultrasonography (EAUSG) procedures were performed by two physicians experienced in gastroenterology and proctology. The participants’ information about their mode of delivery was not shared with the physician performing EAUSG. The locations of all defects [OASIS and/or internal anal sphincter (IAS)] were located. Statistical Analysis The mean, standard deviation, lowest, highest median, frequency, and percentage rates were used in the descriptive statistics of the collected data. The distribution of variables was measured using the Kolmogorov-Smirnov test. The Mann-Whitney U test was used for the analysis of quantitative data, and the chi-square test was used for the analysis of qualitative data. The effect level was investigated by univariate and multivariate logistic regression. SPSS 22.0 was used for all analyses.

iables was measured using the Kolmogorov-Smirnov test. The Mann-Whitney U test was used for the analysis of quantitative data, and the chi-square test was used for the analysis of qualitative data. The effect level was investigated by univariate and multivariate logistic regression. SPSS 22.0 was used for all analyses. RESULTS The demographic data of the premenopausal (group 1 + group 3) and postmenopausal (group 2 + group 4) groups are shown in Table 2. The episiotomies in vaginal deliveries were all mediolateral. There were no statistical differences between the groups regarding the participants’ body mass index (BMI), high birth weight, and instrument use (p>0.51). The mean age and the number of deliveries of the patients in group 1 were similar to those of group 3. The endoanal ultrasonography imaging revealed that 20 (40%) and 2 (4%) patients in groups 1 and 3 had occult anal sphincter defects, respectively. Although sphincter defects were mostly seen in the EAS (24%) in group 1, only 2 patients were detected as having IAS defects in group 3 (Table 3). Anorectal manometric measurements showed that the maximum extrusion pressure, mean extrusion duration, and mean extrusion pressure values of group 1 were significantly lower than group 3 [odds ratio (OR): 1.02, 95% confidence interval (CI): 1.01-1.039; OR: 1.04, 95% CI: 1.02-1.05; OR: 1.03, 95% CI: 1.02-1.05; p<0.01, respectively). There was no significant difference (p>0.05) between group 1 and group 3 regarding WIS and the mean resting pressure values (Table 4).

were significantly lower than group 3 [odds ratio (OR): 1.02, 95% confidence interval (CI): 1.01-1.039; OR: 1.04, 95% CI: 1.02-1.05; OR: 1.03, 95% CI: 1.02-1.05; p<0.01, respectively). There was no significant difference (p>0.05) between group 1 and group 3 regarding WIS and the mean resting pressure values (Table 4). There was no difference between group 2 and group 4 with regards to the mean age of the patients and the number of deliveries. Twenty-two (44%) patients in group 2 were detected to have occult anal sphincter defects according to endoanal ultrasonography data, and 2 (4%) patients in group 4 had sphincter defects (p<0.001). The most common sphincter defect seen in group 2 was EAS (24%). Anorectal manometric measurements showed that the maximum extrusion pressure, mean extrusion duration, mean extrusion pressure values of group 2 were significantly lower than group 4 (1.025 OR, 95% CI:0,46-0,78; p<0.001). There was, however, no significant difference between the groups regarding the mean resting pressure. The Wexner score of group 2 was significantly higher than group 4 (0.64 OR, 95% CI:[0.48-0.86]; p=0.003). Although 8 (16%) of patients had distinctive FI and 14 (28%) had incontinence symptoms in group 2, 10 (20%) patients had started to have fecal complaints in group 4 (Table 5).

s regarding the mean resting pressure. The Wexner score of group 2 was significantly higher than group 4 (0.64 OR, 95% CI:[0.48-0.86]; p=0.003). Although 8 (16%) of patients had distinctive FI and 14 (28%) had incontinence symptoms in group 2, 10 (20%) patients had started to have fecal complaints in group 4 (Table 5). When the patients who had had vaginal delivery were compared with regards to their menopausal status, there were no statistical differences between the groups according to EAUSG data with regards to the existence of sphincter defects and the location of defects (p=0.68). Anorectal manometric measurements showed that the maximum extrusion pressure, mean extrusion duration, mean extrusion pressure values of group 2 were significantly lower than group 1 (p<0.05). The Wexner scores of the groups were not significantly different (Table 6). Although no obvious FI was observed in group 1, 7 (14%) patients in group 2 had obvious FI. Figure 1 graphically demonstrates maximum contrusion pressures, WIS, mean contrusion durations, and mean contrusion pressure values of all groups.

.05). The Wexner scores of the groups were not significantly different (Table 6). Although no obvious FI was observed in group 1, 7 (14%) patients in group 2 had obvious FI. Figure 1 graphically demonstrates maximum contrusion pressures, WIS, mean contrusion durations, and mean contrusion pressure values of all groups. DISCUSSION One of the most significant causes of FI in women is vaginal deliveries that result in anal sphincter injuries. Although OASIS is seen in 0.5-9% of all deliveries, it has been reported that 35-44% of women who had vaginal deliveries also had occult anal sphincter injuries when EAUSG began to be used by physicians(6). However, FI symptoms are observed in only 20% of these women. Therefore, the natural history and significance of occult anal sphincter injuries still proves to be controversial(14). In our study, we investigated the effects of occult anal sphincter injuries formed after vaginal deliveries on FI seen in the postmenopausal stage. Factors such as the number of deliveries, which increase the risk of FI after vaginal delivery, use of vacuum and forceps during delivery, BMI, existence and type of episiotomy, and birthweight were regarded as similar to those of the co-control groups. The premenopausal and postmenopausal anorectal manometric measurement data of women with vaginal deliveries were worse than women with c-sections (Table 6). During the course of our study, we observed that anal sphincter functions in post-vaginal delivery life were negatively affected regardless of the existence of FI symptoms. Furthermore, we ascertained that c-section had a protective effect both on OASIS and anal sphincter functions. Similarly, Hannah et al.(15) also reported that c-section proved to be protective for postpartum FI symptoms.

in post-vaginal delivery life were negatively affected regardless of the existence of FI symptoms. Furthermore, we ascertained that c-section had a protective effect both on OASIS and anal sphincter functions. Similarly, Hannah et al.(15) also reported that c-section proved to be protective for postpartum FI symptoms. When we compared the results of the premenopausal groups, we saw that 20 (40%) among the patients with vaginal delivery had occult anal sphincter injuries. When patients with vaginal deliveries were compared with the control group, there was no difference between FI symptoms and Wexner incontinence scores, although the former’s mean maximum extrusion pressure was lower (p>0.05). Studies in literature have reported that as EAUSG went into effect in medical practice, the rate of sphincter injuries reached 35% in primiparous women and 40% in multiparous women(16). Moreover, FI symptoms in these patients were observed less than sphincter injuries (13% and 23%, respectively)(17). Thus, some sphincter injuries formed during vaginal delivery do not result in FI. It is highly likely that remnant sphincter tissue is exposed to hypertrophy and enables the continuation of continence by increasing the amount of collagen in spite of the sphincter injury.

incter injuries (13% and 23%, respectively)(17). Thus, some sphincter injuries formed during vaginal delivery do not result in FI. It is highly likely that remnant sphincter tissue is exposed to hypertrophy and enables the continuation of continence by increasing the amount of collagen in spite of the sphincter injury. When the postmenopausal groups were compared, 44%(22) of the vaginal delivery group had sphincter injuries. When the vaginal delivery group was compared with the control group, however, it was ascertained that the former had both worse manometric measurement results and significantly higher WIS (p=0.03; Table 5). Based on these data, it can be suggested that anal sphincter injuries that formed after vaginal delivery in the premenopausal stage remained occult but they proved to be a factor, which give way to an increase in FI symptoms in the postmenopausal stage. In contradiction to our results, Mous et al.(18) stated that the increase in FIs in the postmenopausal stage was related to postmenopausal disorders seen in the pelvic floor rather than sphincter injuries formed during vaginal delivery. With increasing age, and especially during the postmenopausal stage when estrogen in the body decreases, type 1 collagen tissue, which has thicker and stronger fibers, is replaced by type 3 collagen tissue, which has thinner, weaker, and isolated fibers. Moreover, IAS sclerosis develops with increasing age and atrophic changes take place in the EAS and pelvic floor muscles with the decrease in estrogen as menopause begins(19). Furthermore, vaginal deliveries cause the pelvic diaphragm to move downward and give way to weakness in the pelvic floor(20). When all these mechanisms are taken into consideration, it is clear that bodily changes in the postmenopausal stage increase FI. The results of our study revealed that patients with vaginal deliveries had worse results in all anorectal manometric measurements and higher WIS compared with those in the co-control groups when we compared the results of postmenopausal patients with vaginal deliveries and c-sections. Therefore, we believe that occult anal sphincter injuries become symptomatic with pelvic floor disorders formed in the postmenopausal stage, and they bring about a further increase in the incidence of FI.

e co-control groups when we compared the results of postmenopausal patients with vaginal deliveries and c-sections. Therefore, we believe that occult anal sphincter injuries become symptomatic with pelvic floor disorders formed in the postmenopausal stage, and they bring about a further increase in the incidence of FI. Our results are in parallel with former studies; however, two previous studies that compared more than 15-year follow-up results of patients with FI with or without anal sphincter injury reported contradictory results(21,22). Nygaard et al.(21) found no significant difference pertaining to FI between women with c-section delivery and those who had OASIS during normal delivery, and Faltin et al.(22) conducted a study with similar groups and the authors reported that OASIS had little contribution to FI. The results of our study revealed that women with vaginal deliveries had a higher rate of anal sphincter injury and had higher WIS and FI symptoms in the postmenopausal stage compared with women with c-section deliveries in the same stage. Previous studies in the literature stated that FI symptoms increased depending on many factors in the postmenopausal stage(20). The results of our study demonstrated that occult sphincter injury proved to be a significant factor that exacerbated these symptoms.

ed with women with c-section deliveries in the same stage. Previous studies in the literature stated that FI symptoms increased depending on many factors in the postmenopausal stage(20). The results of our study demonstrated that occult sphincter injury proved to be a significant factor that exacerbated these symptoms. Study Limitations One of the limitations of our study is that we did not conduct research on pudendal nerve damage. There is, however, controversy over the effect of pudendal nerve damage formed during vaginal delivery on FI formation(23). In a study by Sultan et al.(6) the authors found that 16% of primiparous women and 15% of multiparous women had long-term pudendal nerve terminal motor latency (PNTML) 6 weeks after vaginal delivery, but there was no relationship between PNTML change and the development of FI symptoms. Further, abnormal PNTML prolongation had a statistically significant relationship with anal sphincter injuries. The results of another study showed that only one third of prolonged PNTMLs 6 months after delivery remained pathological(24). Thus, we neglected to investigate the effects of pudendal nerve damage on FI in our study.

abnormal PNTML prolongation had a statistically significant relationship with anal sphincter injuries. The results of another study showed that only one third of prolonged PNTMLs 6 months after delivery remained pathological(24). Thus, we neglected to investigate the effects of pudendal nerve damage on FI in our study. The other limitation of our study is that the participants in the pre- and postmenopausal groups were composed of different individuals. Pre- and postmenopausal data of participants in the same group could have rendered this study more significant. Instead, we selected participants with FI predisposing factors such as age, number of deliveries, BMI, birthweight, and instrument use to ensure similarity between the groups. This method of selection, in turn, contributed to the reliability of our study. CONCLUSION Vaginal deliveries prove to be one of the most significant causes that increase the rate of anal sphincter injuries. Anal sphincter injury formed subsequent to vaginal delivery can be an important factor which gives way to an increase in the incidence of postmenopausal FIs and the formation of FI symptoms in women. Ethics Ethics Committee Approval: The study was approved by the Necmettin Erbakan University, Meram Faculty of Medicine Local Ethics Committee (Approval number: 2013/79), Informed Consent: Consent form was filled out by all participants. Peer-review: External and internal peer-reviewed. Authorship Contributions

CONCLUSION Vaginal deliveries prove to be one of the most significant causes that increase the rate of anal sphincter injuries. Anal sphincter injury formed subsequent to vaginal delivery can be an important factor which gives way to an increase in the incidence of postmenopausal FIs and the formation of FI symptoms in women. Ethics Ethics Committee Approval: The study was approved by the Necmettin Erbakan University, Meram Faculty of Medicine Local Ethics Committee (Approval number: 2013/79), Informed Consent: Consent form was filled out by all participants. Peer-review: External and internal peer-reviewed. Authorship Contributions Surgical and Medical Practices: S.K., S.Ç., A.K., Concept: S.K., H.A., C.K., Design: S.K., M.Ç., Data Collection or Processing: S.K., S.Ç., A.K., Analysis or Interpretation: C.K., Literature Search: A.K., S.Ç., Writing: S.K. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: S.K., S.Ç., A.K., Concept: S.K., H.A., C.K., Design: S.K., M.Ç., Data Collection or Processing: S.K., S.Ç., A.K., Analysis or Interpretation: C.K., Literature Search: A.K., S.Ç., Writing: S.K. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 The study inclusion and exclusion criteria Table 2 Demographic data of the participants according to premenopausal and postmenopausal stages Table 3 Endoanal ultrasound data of participants that location and size of defect at all groups Table 4 The comparison of demographic data, endoanal ultrasonography, and manometric measurement results of groups 1 and 3 Table 5 The comparison of demographic data, endoanal ultrasonography, and manometric measurement results of groups 2 and 4 Table 6 Comparison of vaginal delivery groups’ demographic, endoanal ultrasonography, and anorectal manometric data according to menopausal status Figure 1 The distribution of maximum contrusion pressure, Wexner incontinence scale, mean contraction duration, and mean contraction pressure values of the participants according to the groups

INTRODUCTION Genitourinary fistulas represent significant morbidity, especially in developing nations where obstetric trauma is the major etiologic cause. The true incidence is unknown, and lack of seeking care is a major contribution for this uncertainty(1). Vesicovaginal fistulas (VVFs) are the most commonly acquired fistulae of the urinary tract. In developed nations, surgery, especially gynecologic procedures, is the major cause(2,3,4). The most common symptom in patients with VVF is constant urine leakage from the vagina. Predisposing factors such as chronic illnesses, previous surgery, chemotherapy, infections for postoperative fistulae are blamed, but the majority occur without any of these factors(5). Diagnosis of genitourinary fistula requires a thorough medical history and careful physical examination. Timing for presentation of symptoms may differ due to the cause and location of the fistula. Most present with leakage of urine from the vagina, immediately following injury. However, fistulae resulting from hysterectomy or cesarean delivery often present later than one or two weeks from the inciting surgery. Radiation-induced fistulas generally occur years after treatment. The diagnosis can be established based on symptoms and physical examination alone (methylene blue is frequently utilized) or using imaging techniques such as cystoscopy, magnetic resonance imaging, computerized tomography (Figure 1) or ultrasound. Cystoscopy may clarify the exact anatomic origin and it is used frequently.

The diagnosis can be established based on symptoms and physical examination alone (methylene blue is frequently utilized) or using imaging techniques such as cystoscopy, magnetic resonance imaging, computerized tomography (Figure 1) or ultrasound. Cystoscopy may clarify the exact anatomic origin and it is used frequently. The type of surgical technique chosen (transvesical, transvaginal, laparoscopic or robotic), depends on surgeon experience, whether the fistula is simple or complex, and patient characteristics. Complex or high fistulas are better treated abdominally with meticulous dissection, and simple ones can be treated easily vaginally by simple excision of the devascularized tissue and multi-layer approximation of healthy tissues. Vaginal operations can be performed according to the Latzko technique as denuding vaginal epithelium and tension free re-suturing, without excision of the entire fistula tract. In this study, we retrospectively evaluated our treatment modalities for primary VVF repair after a gynecologic surgery, and discussed the feasibility and outcomes of the surgical techniques used in our institution over a 10-year period. The aim of this single-center study was to contribute evidence to the Turkish literature by describing the surgical management of VVF treatment in one university hospital in Turkey. This may aid physicians in the selection of appropriate surgery for their patients.

hniques used in our institution over a 10-year period. The aim of this single-center study was to contribute evidence to the Turkish literature by describing the surgical management of VVF treatment in one university hospital in Turkey. This may aid physicians in the selection of appropriate surgery for their patients. MATERIALS AND METHODS Patient selection Between 2006 and 2015, a total of 20 patients were admitted to Süleyman Demirel University Hospital, Isparta, for VVF management after an inciting gynecologic surgery. Patient characteristics are outlined in Table 1. The Süleyman Demirel University Ethics Committee and Review Board approved the study (approval number: 01.06.2016/02). The study was performed in accordance with the ethical standards described in an appropriate version of the 1975 Declaration of Helsinki, as revised in 2000. METHODS Surgical techniques Transvaginal repair After positioning the patient in low-lithotomy, we usually start with cystoscopy, especially if there is an uncertainty about involvement of the ureters. A Foley catheter is routinely placed to mark the fistula tract. A cystoscopic identification of the tract is made and ureteral catheterization is performed if the ureteric orifices show close proximity to the fistula.

usually start with cystoscopy, especially if there is an uncertainty about involvement of the ureters. A Foley catheter is routinely placed to mark the fistula tract. A cystoscopic identification of the tract is made and ureteral catheterization is performed if the ureteric orifices show close proximity to the fistula. For transvaginal repair, we prefer excision of the fistula tract and multi-layer closure with or without a Martius flap or fat pad. The excision is accomplished by taking margins with healthy tissue, approximately 1-1.5 cm in diameter. After excising the fistulous tract, the first layer sutured is the bladder mucosa, followed by the detrusor and/or prevesical or endopelvic fascia, and the third or fourth layer incorporates vaginal epithelium. Before the repair of the vaginal epithelium, a leak test is performed using diluted methylene blue. The vaginal epithelium is sutured in a perpendicular fashion with 2-0 Vicryl. For inner layers, 3-0 Vicryl is preferred. A Martius flap is used especially for larger or devascularized tissues managed with the vaginal route. The Martius flap procedure involves the use of a 2-cm wide fat pad dissected along the labium majus and tunneled as a vascular barrier under the vagina in the location of the excised fistula.

3-0 Vicryl is preferred. A Martius flap is used especially for larger or devascularized tissues managed with the vaginal route. The Martius flap procedure involves the use of a 2-cm wide fat pad dissected along the labium majus and tunneled as a vascular barrier under the vagina in the location of the excised fistula. Transabdominal repair For the abdominal approach, after a Pfannenstiel or midline incision and exploration of the pelvis, a cystotomy is made on the dome of the bladder, and if the fistula opening is located near the ureteral orifices, ureteral stents are placed. The fistulous tract is marked by placing a 14-F Foley catheter. The fistulous tract is excised with the catheter inside. An omental or peritoneal flap is attached between the vaginal wall and bladder if necessary. The vagina is closed with 2-0 Vicryl, and the bladder is closed in 2 layers using 3-0 Vicryl. Laparoscopic repair Laparoscopic surgery is performed in our institution using one umbilical port for the camera, one suprapubic 10-mm port, and two 5-mm ports bilaterally located medial to the anterior superior iliac spines. We use a 30-degree angled camera for the repair. The vesicovaginal plane is dissected until reaching the fistula tract without making a prior cystotomy. The tract is totally excised and the vagina and bladder are separately sutured using 3-0 Vicryl. A leak test is performed using diluted methylene blue.

r iliac spines. We use a 30-degree angled camera for the repair. The vesicovaginal plane is dissected until reaching the fistula tract without making a prior cystotomy. The tract is totally excised and the vagina and bladder are separately sutured using 3-0 Vicryl. A leak test is performed using diluted methylene blue. Urinary diversion Urinary diversion is achieved as a part of the pelvic exenteration procedure. The ileal conduit technique is chosen for these patients. A 15-cm ileal segment is isolated using GIA staplers, and a side-to-side anastomosis is performed for the remaining bowel segments using GIA staplers. The left ureter is passed under a tunnel created in the mesentery of the sigmoid colon. A Wallace type 1 anastomosis is performed, as conjoining the distal ends of the ureters together we perform the anastomosis to the proximal end of the ileal segment. Using a Foley catheter to drain the conduit, feeding tubes are passed into each ureter and secured to the distal end of the ileal loop, and a Foley catheter is used to drain the conduit. The stoma is matured to the right side of the patient between the umbilicus and the superior anterior iliac spine. Statistical Analysis Statistical analysis of the data was performed using SPSS 15.0 (SPSS Inc. Chicago, IL, USA) and p<0.05 was determined as significant. Non-parametric data were compared using Mann-Whitney U test and Pearson’s chi-square test. The effect of age on the preference of the surgical route was calculated using the Mann-Whitney U test.

Statistical Analysis Statistical analysis of the data was performed using SPSS 15.0 (SPSS Inc. Chicago, IL, USA) and p<0.05 was determined as significant. Non-parametric data were compared using Mann-Whitney U test and Pearson’s chi-square test. The effect of age on the preference of the surgical route was calculated using the Mann-Whitney U test. RESULTS Abdominal repair was chosen for 11 (55%) patients, vaginal repair for 5 (25%), laparoscopic repair for 2 (10%), and 2 patients underwent ileal conduit urinary diversion (10%). Patient characteristics for each repair type are shown in Table 2. Of the surgeries performed by urologists, 75% were via the abdominal route and 8.3% were vaginal. Laparoscopic repairs were only performed by urologists. All patients treated by gynecologists were operated using the transvaginal route. It is clear that urologists preferred the abdominal or laparoscopic route, whereas gynecologists preferred the vaginal route, and this difference was statistically significant (p<0.05). Eighty percent of operations performed both by gynecologists and urologists were performed abdominally. The most common single symptom was urinary incontinence (80%), followed by constant leakage of urine through the vagina (20%). Cystoscopy was performed for 85% of the patients for confirmation of the diagnosis and to evaluate the exact location of the fistula, and physical examination only sufficed for 15% of the patients.

most common single symptom was urinary incontinence (80%), followed by constant leakage of urine through the vagina (20%). Cystoscopy was performed for 85% of the patients for confirmation of the diagnosis and to evaluate the exact location of the fistula, and physical examination only sufficed for 15% of the patients. For patients managed through the vaginal route, 20% were treated with a Martius flap, and 80% with a simple excision and repair. For patients operated via the abdominal route, 18% needed an omental flap; no tissue interposition was used for the remainder. Ureteral catheterization was performed for 5 patients, all of whom were managed via the transabdominal route. Their fistulas had proximity to ureteral orifices, 3 needed bilateral catheterization, and two needed unilateral catheterization (Table 2). Two VVFs with obstetric etiologies were managed using abdominal excision and repair. The first patient was nulliparous and she had preterm labor at 35 weeks. The second patient had 3 prior vaginal births and had an obstructed labor due to macrosomia. A cesarean section was performed for both obstructed labors and fistulas developed thereafter.

tiologies were managed using abdominal excision and repair. The first patient was nulliparous and she had preterm labor at 35 weeks. The second patient had 3 prior vaginal births and had an obstructed labor due to macrosomia. A cesarean section was performed for both obstructed labors and fistulas developed thereafter. For the patients with malignancies, both had prior history of radiotherapy. The first patient had recurrent endometrial cancer and the other had a cervical cancer and had undergone primary radiotherapy. Both had central recurrence with vesicovaginal fistulas with no evidence of extra-pelvic metastasis. Ileal conduits were performed for both patients as part of a total pelvic exenteration procedure. An infra-levator pelvic exenteration was performed for the patient with cervical cancer, whereas a supralevator procedure sufficed for the patient with endometrial cancer. Excluding the patients with malignancies who underwent ileal conduit procedures, the mean hospitalization time was less in patients managed with transvaginal repair group (3.4 days) compared with transabdominal repair (7.9 days), and the difference was statistically significant (p<0.05). We expected a tendency of more older patients to have undergone surgery through the vaginal route, but we found no difference between the groups, even when we classified the groups by age as 25-45 years, 46-55 years, and >55 years (p>0.05). The mean parity number of the patients who underwent abdominal repair was 1.9, for vaginal repairs 3.8, and for laparoscopic repairs 2 (p<0.05).

urgery through the vaginal route, but we found no difference between the groups, even when we classified the groups by age as 25-45 years, 46-55 years, and >55 years (p>0.05). The mean parity number of the patients who underwent abdominal repair was 1.9, for vaginal repairs 3.8, and for laparoscopic repairs 2 (p<0.05). One case was started vaginally and converted to laparotomy, after excision of the fistulous tract. For this patient, the multi-layer closure of tissues was impossible through the vaginal route due to the high location of the fistula. The patient had a recent history of a concomitant abdominal hysterectomy for myoma uteri and Burch colposuspension procedure for urinary incontinence. One patient developed stress urinary incontinence after the repair. The patient was initially managed via the abdominal route. She was offered various treatment modalities including sub-urethral slings and bulking agents, but she refused treatment. The only recurrence was noted in a patient who had undergone laparoscopic surgery. A transabdominal repair was successfully performed 4 weeks after the first surgery. No flap was used due to the well-vascularized appearance of the tissues. The etiology of the fistula was abdominal hysterectomy for myoma uteri, which performed 6 weeks earlier than the first repair attempt. No recurrence occurred during her 1-year follow-up.

was successfully performed 4 weeks after the first surgery. No flap was used due to the well-vascularized appearance of the tissues. The etiology of the fistula was abdominal hysterectomy for myoma uteri, which performed 6 weeks earlier than the first repair attempt. No recurrence occurred during her 1-year follow-up. DISCUSSION In this retrospective study, we evaluated only the surgical approach for the management of VVFs; therefore, patients who were conservatively treated were out of the scope of this study. There are controversies as to whether the treatment should be conservative or surgical. In the minority of cases, the fistula may close spontaneously after 2-4 weeks of urethral catheterization, especially if the fistula is detected early (no epithelization on the fistula tract) and the diameter is small(6). Timing of the repair is also important. When identified before 72 hours after iatrogenic cystotomy, VVF can be repaired immediately. If the diagnosis of a small fistula is established late and the fistula is epithelized, electrocoagulation of the mucosal layer and catheterization may lead to closure in up to 75% of cases(7).

of the repair is also important. When identified before 72 hours after iatrogenic cystotomy, VVF can be repaired immediately. If the diagnosis of a small fistula is established late and the fistula is epithelized, electrocoagulation of the mucosal layer and catheterization may lead to closure in up to 75% of cases(7). In a recent report from Turkey, outcomes of 53 cases with VVFs were discussed and none of the fistula closed with conservative management(8). The use of fibrin sealants for closure of small fistulae has also been reported(9,10). Fibrin glue has also been successfully used instead of Martius flap in cases when tissue interposition was needed(11). However, in our clinic, we do not have such experience. As reported in the study of 52 cases by Kapoor et al.(12), the mean blood loss and postoperative pain may be less, and the mean hospital stay may be shorter for transvaginal repair compared with transabdominal repair, especially in non-complicated cases.

eded(11). However, in our clinic, we do not have such experience. As reported in the study of 52 cases by Kapoor et al.(12), the mean blood loss and postoperative pain may be less, and the mean hospital stay may be shorter for transvaginal repair compared with transabdominal repair, especially in non-complicated cases. For vaginal approach, our clinic prefers simple excision and repair, and the long-term success of this approach seems excellent, because none of the fistula recurred. In the literature, the success of transvaginal repair ranges from 70% to 100%(13,14,15). A large prospective cohort study from Africa that compared 1273 abdominal and vaginal genitourinary fistula repairs found that vaginal route repairs were associated with increased risk of failure in closing the fistula compared with the abdominal route. However, the follow-up was 84 to 99 days, nearly 20% of the patients had a degree of genital mutilation; there was extensive scarring in 7.7% of patients operated via vaginal route versus 3.5% of patients operated via the abdominal route, only 3.69% of the patients underwent abdominal surgery, and finally the population comprised VVFs and all types of genitourinary fistulas(16). Martius flap is used only for 20% of patients, and is chosen for tissues that appear as devascularized. The success of this technique seems more than 90%(2). The vaginal approach may also be possible for supra-trigonal fistulas, depending on the experience of the surgeon(17).

For vaginal approach, our clinic prefers simple excision and repair, and the long-term success of this approach seems excellent, because none of the fistula recurred. In the literature, the success of transvaginal repair ranges from 70% to 100%(13,14,15). A large prospective cohort study from Africa that compared 1273 abdominal and vaginal genitourinary fistula repairs found that vaginal route repairs were associated with increased risk of failure in closing the fistula compared with the abdominal route. However, the follow-up was 84 to 99 days, nearly 20% of the patients had a degree of genital mutilation; there was extensive scarring in 7.7% of patients operated via vaginal route versus 3.5% of patients operated via the abdominal route, only 3.69% of the patients underwent abdominal surgery, and finally the population comprised VVFs and all types of genitourinary fistulas(16). Martius flap is used only for 20% of patients, and is chosen for tissues that appear as devascularized. The success of this technique seems more than 90%(2). The vaginal approach may also be possible for supra-trigonal fistulas, depending on the experience of the surgeon(17). The abdominal route should be considered for larger, more complex or recurrent fistulas. Large fistulas (>2 cm) and those close to ureteric orifices may be considered as “complicated” or “complex” and there is no consensus as to which fistulas are considered as complicated. The success abdominal repair ranges between 90-100%(14). Despite the proven long-term results of the vaginal approach for VVFs, there is a tendency in our clinic to perform abdominal repairs, especially for cases that urologists perform. However, that difference may be according to a selection bias; urologists generally deal with more complicated cases. Both patients who received prior radiotherapy underwent surgery with urologists and gynecologists together, and the laparoscopic failure of closure was performed by the urologists. The mean number of births was higher in transvaginal repair group compared with the transabdominal group, and this may be one of the factors for surgeons to consider when choosing either route.

t surgery with urologists and gynecologists together, and the laparoscopic failure of closure was performed by the urologists. The mean number of births was higher in transvaginal repair group compared with the transabdominal group, and this may be one of the factors for surgeons to consider when choosing either route. The laparoscopic approach, as an alternative, results in less morbidity and recovery is faster than the transabdominal route. The success of this approach is comparable with open procedures(18). However, it requires advanced skills such as suturing in non-ergonomic angles. There are no randomized controlled studies to evaluate whether abdominal, laparoscopic or vaginal approach is superior. We found that the mean hospitalization time was less for vaginal repairs, and avoiding a laparotomy may also reduce the rate of complications, although we did not encounter any. It would be appropriate to repeat classic teaching that if the fistula is large, complex, ureteral involvement is suspected, an abdominal approach may be preferred over a vaginal approach.

s less for vaginal repairs, and avoiding a laparotomy may also reduce the rate of complications, although we did not encounter any. It would be appropriate to repeat classic teaching that if the fistula is large, complex, ureteral involvement is suspected, an abdominal approach may be preferred over a vaginal approach. No de-novo stress urinary incontinence was reported in the vaginal or laparoscopically managed groups, but there was one in the trans-abdominally managed group. After excluding patients with urinary diversion, the rate was 11%. After fistula surgery, most residual incontinence is thought to be stress urinary incontinence(19). Nevertheless, there are some data in favor of detrusor instability as a major contributing factor. A report from the United Kingdom mentioned a post-repair stress urinary incontinence rate of about 11%, whereas detrusor instability was documented as 50% in this population(15). In another report, it was indicated that both stress and urge symptoms occurred in similar numbers in patients after a repaired fistula(20). A report from Australia indicated a 23.9% rate of urinary incontinence after repair. In developing countries where obstetric fistulas are major contributors, this rate seems much higher(21,22). A series of 318 consecutive patients from Addis Ababa, where the main inciting factor was obstetric trauma for the fistula, reported an immediate post-operative incontinence rate of 33%(14). Bladder neck involvement and proximal urethral contribution to fistula can be considered as risk factors for post-closure incontinence(23).

f 318 consecutive patients from Addis Ababa, where the main inciting factor was obstetric trauma for the fistula, reported an immediate post-operative incontinence rate of 33%(14). Bladder neck involvement and proximal urethral contribution to fistula can be considered as risk factors for post-closure incontinence(23). In the current study, abdominal hysterectomies alone contributed to 65% of the fistulas and hysterectomy with Burch colposuspensions caused 10% of the fistulas. These rates are closer to the rates of developed nations as gynecologic surgeries, mainly abdominal hysterectomies, rather than obstetric traumas, are causes of the fistulas(4,12,24). The effect of colposuspension as a contributing factor could not be analyzed because of concomitant hysterectomies. It is crucial to meticulously dissect the bladder from the cervix and proximal vagina, suturing only vagina without incorporating the detrusor fibers and avoiding excessive use of electrocautery while working in close proximity to the bladder, because usually no cystostomy or urinary tract injury is encountered during hysterectomies causing fistulas.

ssect the bladder from the cervix and proximal vagina, suturing only vagina without incorporating the detrusor fibers and avoiding excessive use of electrocautery while working in close proximity to the bladder, because usually no cystostomy or urinary tract injury is encountered during hysterectomies causing fistulas. The incidence of fistulas caused by radiotherapy for malignant conditions such as cervical cancer and endometrial cancer is about 5%(25). For these circumstances, urinary diversion may be chosen. Simple repair is generally not suitable for these patients because of fibrosis, unhealthy tissue and distorted anatomy may not be amenable to re-approximation. If a repair is to be attempted, an intervening well-vascularized flap is strongly recommended. Successful fistula repair is reported as between 70 and 100% in non-irradiated patients, and between 40% and 100% for patients who had prior radiotherapy(14). Urinary diversions are much preferred for patients with cancer who have previously been irradiated. Both ileal conduits performed at our institution were as part of pelvic exenteration procedures for central recurrence of tumors. Study Limitations

The incidence of fistulas caused by radiotherapy for malignant conditions such as cervical cancer and endometrial cancer is about 5%(25). For these circumstances, urinary diversion may be chosen. Simple repair is generally not suitable for these patients because of fibrosis, unhealthy tissue and distorted anatomy may not be amenable to re-approximation. If a repair is to be attempted, an intervening well-vascularized flap is strongly recommended. Successful fistula repair is reported as between 70 and 100% in non-irradiated patients, and between 40% and 100% for patients who had prior radiotherapy(14). Urinary diversions are much preferred for patients with cancer who have previously been irradiated. Both ileal conduits performed at our institution were as part of pelvic exenteration procedures for central recurrence of tumors. Study Limitations One of the major limitations of the study is that the number of the patients was small for each group to be compared; for example, there were only two cases managed laparoscopically among twenty patients. Also, the retrospective design of our study may be a drawback, but a prospective trial for management of vesicovaginal fistulas is hard due to its rarity. In our opinion, a multi-center trial design is more appropriate for prospective trials related with this problem.

ses managed laparoscopically among twenty patients. Also, the retrospective design of our study may be a drawback, but a prospective trial for management of vesicovaginal fistulas is hard due to its rarity. In our opinion, a multi-center trial design is more appropriate for prospective trials related with this problem. CONCLUSION Nearly all VVFs in this series resolved with primary surgery, regardless of the approach. No flap is needed for tissues that appear well vascularized. The mean hospitalization time is less in patients managed with transvaginal repair compared with transabdominal repair, and this difference emphasizes the vaginal route as the first choice without compromising the success rate. Ethics Ethics Committee Approval: The study was approved by the Süleyman Demirel University Local Ethics Committee (Approval number: 01.06.2016/02), Informed Consent: Consent form was filled out by all participants. Peer-review: External and internal peer-reviewed. Authorship Contributions Surgical and Medical Practices: T.O., S.S., E.E., Concept: E.E., B.T., Design: F.S.C., B.T., Data Collection or Processing: F.S.C., B.T., Analysis or Interpretation: B.T., Literature Search: B.T., Writing: B.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: T.O., S.S., E.E., Concept: E.E., B.T., Design: F.S.C., B.T., Data Collection or Processing: F.S.C., B.T., Analysis or Interpretation: B.T., Literature Search: B.T., Writing: B.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Patients’ characteristics Table 2 Vesicovaginal fistula characteristics stratified by repair type Figure 1 Computerized tomography urogram of a patient who underwent laparoscopic fistula repair in the delayed phase. Arrows indicate the fistula tract a) Axial image b) Sagittal image

INTRODUCTION Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Its age-adjusted incidence is increasing, probably due to increased life expectancy and obesity. However, the mortality rate has increased more rapidly than the incidence over the past three decades(1). One explanation for this discrepancy is that patients are being diagnosed at an older age, which leads to an increased rate of high-risk histologies and advanced-stage cancers. EC is staged surgically based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system(2). Lymph node (LN) metastasis is one of the most important prognostic factors for EC(3). Although a systematic lymphadenectomy is an essential part of staging surgery, FIGO did not define the optimal limits for lymphadenectomies, nor the adequate number of LNs required for the comprehensiveness of the procedure. On the other hand, it is well known that lymphadenectomy may be associated with increased complications, mainly including lymphedema, vascular, ureteral and visceral injuries, deep vein thrombosis, chylous ascites, and ileus(4). In the current study, we aimed to analyze variables affecting LN involvement and to assess the need for systematic lymphadenectomy in patients with EC.

EC is staged surgically based on the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system(2). Lymph node (LN) metastasis is one of the most important prognostic factors for EC(3). Although a systematic lymphadenectomy is an essential part of staging surgery, FIGO did not define the optimal limits for lymphadenectomies, nor the adequate number of LNs required for the comprehensiveness of the procedure. On the other hand, it is well known that lymphadenectomy may be associated with increased complications, mainly including lymphedema, vascular, ureteral and visceral injuries, deep vein thrombosis, chylous ascites, and ileus(4). In the current study, we aimed to analyze variables affecting LN involvement and to assess the need for systematic lymphadenectomy in patients with EC. MATERIALS AND METHODS A single centre retrospective analysis was conducted in a total of 128 consecutive patients with EC who underwent systematic pelvic or combined pelvic and paraaortic lymphadenectomy between 2009 and 2012. Patients were excluded if they had primary synchronous malignancy or if they had no LN dissection. Clinicopathologic data including age, type of surgical procedure, tumor histotype, tumor size, grade, depth of myometrial invasion, lymphovascular space involvement (LVSI), cervical involvement, adnexal involvement, positive peritoneal cytology, number of LNs, and LN involvement were extracted from patient charts and the institutional database following approval of institutional review board of Akdeniz University. Written informed consent was not required for this type of retrospective study. This study has been approved by the Local Ethics Committee of the Akdeniz University (date and approval number: 2012/1205). The study was performed in accordance with the ethical standards described in an appropriate version of the 1975 Declaration of Helsinki, as revised in 2013.

for this type of retrospective study. This study has been approved by the Local Ethics Committee of the Akdeniz University (date and approval number: 2012/1205). The study was performed in accordance with the ethical standards described in an appropriate version of the 1975 Declaration of Helsinki, as revised in 2013. As a routine policy of our institution, patients with newly diagnosed EC were offered treatment with total hysterectomy and bilateral salpingo-oophorectomy with systematic pelvic lymphadenectomy. Paraaortic LN dissection was added to pelvic LN dissection in patients with at least one of the following risk factors: a) non-endometrioid histology, b) grade 2 or 3 endometrioid adenocarcinoma, c) deep (≥50%) myometrial invasion on intraoperative frozen-section examination. The primary endpoint of the study was determination of independent factors influencing LN metastasis. The Stata software package was used for statistical analyses (Special Edition v11.2 for Macintosh OSX, StataCorp, Texas, USA). Mann-Whitney U, chi-square, and Fisher’s exact tests were used for univariate analyses when appropriate. Variables with a p value <0.05 in the univariate analysis were included into a multivariate logistic regression analysis. The effects of variables on LN involvement are reported using adjusted odds ratios (ORs) and 95% confidential intervals (95% CI).

er’s exact tests were used for univariate analyses when appropriate. Variables with a p value <0.05 in the univariate analysis were included into a multivariate logistic regression analysis. The effects of variables on LN involvement are reported using adjusted odds ratios (ORs) and 95% confidential intervals (95% CI). RESULTS The mean age at surgery was 59.3±11.2 years and the majority of patients (86.7%) had open surgery. Sixty-six patients (51.6%) had pelvic lymphadenectomy alone, and 62 (48.4%) had combined pelvic and paraaortic lymphadenectomy. The median number of pelvic LNs removed, paraaortic LNs removed, and total LNs removed (both pelvic and paraaortic) were 24, 15, and 32, respectively. Most patients had endometrioid histology (75%). LN involvement was detected in 17.9% of the patients, deep myometrial invasion in 45.3%, LVSI in 25%, cervical involvement in 16.4%, adnexal involvement in 11.7%, omental involvement in 4.7%, and positive peritoneal cytology in 8.6% (Table 1).

4, 15, and 32, respectively. Most patients had endometrioid histology (75%). LN involvement was detected in 17.9% of the patients, deep myometrial invasion in 45.3%, LVSI in 25%, cervical involvement in 16.4%, adnexal involvement in 11.7%, omental involvement in 4.7%, and positive peritoneal cytology in 8.6% (Table 1). In the univariate analysis, grade 2-3, tumor size, deep (≥50%) myometrial invasion, presence of cervical, adnexal or omental involvement, positive peritoneal cytology, surgical approach (laparotomy vs. laparoscopy), combined pelvic and paraaortic lymphadenectomy, and the total number of LNs removed were found associated with LN involvement (Table 2). A receiver operating characteristic analysis was performed to determine the tumor size that would be the most significant in predicting LN involvement (Figure 1). The cut-off value was found as 3 cm with an area under the curve of 0.626 [CI: (0.51-0.74); p=0.06]. However, in the multivariate analysis, the total number of LNs removed (>30) remained as the only independent variable that predicted LN involvement after adjustment for other confounders [OR: 15.08; 95% CI: (1.28-177.59); p=0.03] (Table 2). DISCUSSION The current study examined factors influencing LN involvement in patients with EC. Our results identified the total number of LNs removed as the only independent predictor of LN metastasis; this finding emphasizes that as many LNs as possible should be removed irrespective of preoperative tumor characteristics in order to determine LN metastasis.

actors influencing LN involvement in patients with EC. Our results identified the total number of LNs removed as the only independent predictor of LN metastasis; this finding emphasizes that as many LNs as possible should be removed irrespective of preoperative tumor characteristics in order to determine LN metastasis. Defining the role and extent of lymphadenectomy is one of the main controversies in the management of patients with EC. Lymphadenectomy provides pathologic and prognostic data, determines the exact extent of disease, and need for adjuvant therapy. It may also have a potential therapeutic effect in patients, particularly with extrauterine disease(5,6,7).

phadenectomy is one of the main controversies in the management of patients with EC. Lymphadenectomy provides pathologic and prognostic data, determines the exact extent of disease, and need for adjuvant therapy. It may also have a potential therapeutic effect in patients, particularly with extrauterine disease(5,6,7). Overall LN metastasis in patients with EC has been reported to range from <1% to 34%, according to tumor grade, histotype, and depth of myometrial invasion(3). It is widely accepted that in a subset of patients (low-risk group) with low-grade endometrioid histotype, small tumor size (<2 cm) and no deep myoinvasion, lymphadenectomy may be omitted without a negative impact on prognosis(8). This group of patients has a relatively small risk (1-3%) for lymphatic dissemination(3). However, it is difficult to identify these low-risk patients preoperatively because of variability in tumor grade and depth of myoinvasion on final histopathology(9,10). Therefore, the true risk may be greater than that estimated. Although two randomized controlled trials (RCTs) reported that lymphadenectomy did not improve the outcomes of patients, there are some critical issues with regard to these RCTs including adjuvant therapies, number of LNs removed, and extent of lymphadenectomies(11,12). Radiotherapy was given to an equal number of patients in each treatment arm, which led to overtreatment of non-lymphadenectomy groups.

t improve the outcomes of patients, there are some critical issues with regard to these RCTs including adjuvant therapies, number of LNs removed, and extent of lymphadenectomies(11,12). Radiotherapy was given to an equal number of patients in each treatment arm, which led to overtreatment of non-lymphadenectomy groups. Sentinel LN biopsy can represent a compromise between no lymphadenectomy (leaving a small risk for LN metastasis) and full lymphadenectomy (adding a potentially morbid procedure for a significant part of the patients). It improves detection of LN metastases by allowing detection of micrometastases using ultrastaging (serial sectioning) of target LNs. In a multicenter study of 304 women with presumed low- or intermediate-risk disease, sentinel LN biopsy and ultrastaging detected metastatic LNs in three-fold greater than standard lymphadenectomy (16% vs. 5%)(13). However, the implications and management of micrometastases or isolated tumor cells detected through ultrastaging are not yet clear. No prospective RCTs have compared outcomes of disease between patients who underwent sentinel LN biopsy and those who received systematic LND. In addition, risk of non-sentinel LN positivity (false negativity), which has been reported as approximately 5%, is a potential handicap for sentinel LN biopsy(14).

t yet clear. No prospective RCTs have compared outcomes of disease between patients who underwent sentinel LN biopsy and those who received systematic LND. In addition, risk of non-sentinel LN positivity (false negativity), which has been reported as approximately 5%, is a potential handicap for sentinel LN biopsy(14). Today, systematic pelvic lymphadenectomy is still the safest way to detect LN metastasis in patients with EC who have low-risk features. It allows elimination of LN metastasis in approximately 99% of patients. Potentially missed cases are patients with isolated paraaortic LN metastasis(15). Combined pelvic and paraaortic lymphadenectomy may be reserved for selected patients with high-risk features(16). Study Limitations As with all studies, the results of this study are not without limitations. Retrospective single center studies, such as the current one, are inherently susceptible to selection and referral bias. On the other hand, the main strengths of our study include the detailed analyses of various clinicopathologic factors that may have an impact on LN metastasis, and performance of uniform staging surgeries using a consistent surgical policy by subspecialized gynecologic oncologists. CONCLUSION In conclusion, the current study demonstrates that the more LNs removed during staging of EC, the greater the probability of finding LN metastasis. Following clarification of the most appropriate adjuvant therapy regimens for sentinel LN biopsy procedures in pending trials, the role and therapeutic effect of lymphadenectomy may be assessed more effectively. Ethics

CONCLUSION In conclusion, the current study demonstrates that the more LNs removed during staging of EC, the greater the probability of finding LN metastasis. Following clarification of the most appropriate adjuvant therapy regimens for sentinel LN biopsy procedures in pending trials, the role and therapeutic effect of lymphadenectomy may be assessed more effectively. Ethics Ethics Committee Approval: This study has been approved by the Local Ethics Committee of the Akdeniz University (Date and approval number: 2012/1205), Informed Consent: A written informed consent is not required for this type of retrospective study. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: T.T., T.Ş., Ş.K., Concept: T.T., T.Ş., Design: T.T., T.Ş., Data Collection or Processing: T.T., Ş.K., Analysis or Interpretation: T.T., Literature Search: T.T., Writing: T.T., T.Ş. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Clinical and pathologic characteristics of patients Table 2 Univariate and multivariate logistic regression analysis of factors predicting lymph node metastasis Figure 1 Receiver operating characteristic analysis for calculating cut-off value of tumor size in predicting lymph node metastasis ROC: Receiver operating characteristic, CI: Confidential interval

INTRODUCTION Women prefer to postpone their pregnancy plans to older ages due to career concerns(1,2,3). Consequently, these women face a high risk of failure at conceiving in spontaneous cycles and seek assisted reproduction, especially in industrialized countries. This demand from health care providers leads to growing numbers of difficult infertile patients to be treated through assisted reproductive techniques. Moreover, these patients fail to respond to standard stimulation protocols due to poor ovarian reserve. The European Society of Human Reproduction and Embryology introduced the Bologna criteria in 2011 in order to standardize the definition of poor ovarian response(4). Some stimulation protocols modified with adjuvant therapies and increased gonadotropin doses were tried to obtain favorable outcomes in poor responders(5). In a study on the association between the number of eggs and live birth, the number of eggs in in vitro fertilization (IVF) was accepted to be an indirect indicator for clinical success. Analyses of data revealed a non-linear relationship between the number of eggs and live birth rate following IVF treatment. The maximum live birth rates were obtained when approximately 15 eggs were retrieved(6). Harvesting of 4-6 oocytes has been defined to be poor response(7).

indirect indicator for clinical success. Analyses of data revealed a non-linear relationship between the number of eggs and live birth rate following IVF treatment. The maximum live birth rates were obtained when approximately 15 eggs were retrieved(6). Harvesting of 4-6 oocytes has been defined to be poor response(7). Several studies compared the cycle outcomes of gonadotropin-releasing hormone antagonist administration with flexible (according to follicular size) and fixed starting days. Meta-analyses on this issue revealed no statistically significant difference in pregnancy rate between flexible and fixed protocols. There was a statistically significant reduction in the amount of recombinant follicle-stimulating hormone (rFSH) with the flexible protocol(8). An inter-cycle variability of responses to gonadotropin stimulation was shown in a recently published study. In the study, the authors categorized patients according to the number of follicles on the day of human chorionic gonadotropin (hCG) administration as low (0-<6), normal (6-<18), and high (≥18), and showed that only 73.9% of patients remained in the same category after a new cycle(9). In this study, we tried to determine some major characteristic differences between two consecutive successful and unsuccessful cycles in patients with poor ovarian response.

An inter-cycle variability of responses to gonadotropin stimulation was shown in a recently published study. In the study, the authors categorized patients according to the number of follicles on the day of human chorionic gonadotropin (hCG) administration as low (0-<6), normal (6-<18), and high (≥18), and showed that only 73.9% of patients remained in the same category after a new cycle(9). In this study, we tried to determine some major characteristic differences between two consecutive successful and unsuccessful cycles in patients with poor ovarian response. MATERIALS AND METHODS After approval of the hospital ethics committee, this retrospective study was conducted from January 2014 to December 2014 in the IVF/intracytoplasmic sperm injection (ICSI) unit of Zeynep Kamil Women and Children’s Health Training and Research Hospital (approval number: 2014-183). A total of 60 women with a failed and subsequent successful ICSI cycle were retrospectively screened from the hospital database and cycles with and without successful outcomes were compared in terms of cycle characteristics. In order to determine the minimum number of subjects needed to be enrolled in this study in order to have sufficient statistical power, sample size calculation was performed before the study. The probability of a type-1 error (α), a difference being found although a difference does not exist, was calculated. We used an alpha cut-off of 5% (0.05). All participants had regular menstrual cycles, normal serum prolactin levels, and had not received hormone treatment in the last 3 months. The patients’ ages ranged from 30 to 42 years.

ype-1 error (α), a difference being found although a difference does not exist, was calculated. We used an alpha cut-off of 5% (0.05). All participants had regular menstrual cycles, normal serum prolactin levels, and had not received hormone treatment in the last 3 months. The patients’ ages ranged from 30 to 42 years. All patients underwent assisted reproductive technology treatment because of their previous poor response and/or poor ovarian reserves. At least two of the following three criteria had to be fulfilled to establish the definition of poor ovarian reserve: (1) advanced maternal age (>40 years) or any other risk factor for poor ovarian response; (2) a previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol); (3) an abnormal ovarian reserve test [i.e. antral follicle count (AFC) less than 5-7 follicles or anti-Müllerian hormone below 0.5-1.1 ng/mL]. Women whose cycles did not reach the embryo transfer stage, and those with endometriosis, male factor infertility, and previous ovarian surgery were excluded from the study. An antagonist protocol was used in all patients for both cycles. On the second day of the menstrual cycle, depending on the patient’s response, rFSH 300-450 IU were administered and follicular growth was monitored using transvaginal sonography. The dosage of rFSH was adjusted starting from day 5 of stimulation according to the ovarian response. Follicle monitorization was performed using two dimensional measurements of growing follicles and a calculation of the mean value at each visit.

stered and follicular growth was monitored using transvaginal sonography. The dosage of rFSH was adjusted starting from day 5 of stimulation according to the ovarian response. Follicle monitorization was performed using two dimensional measurements of growing follicles and a calculation of the mean value at each visit. Antagonist (Cetrorelix, Merck-Serono, Geneva, Switzerland) 0.25 mg/day was administered when the follicular size was 12-14 mm. After the follicular size reached 18 mm, recombinant hCG 250 µg was administered, and follicular puncture was performed after 34-36 hours. Next, the application of 8% vaginal progesterone gel twice/daily was started. The serum hCG level was measured 2 weeks later; if the serum hCG level was more than or equal to the normal level, ultrasonography was performed in the days following serum hCG level measurement to detect a fetal pulse to confirm clinical pregnancy. Age, body mass index (BMI), serum FSH, estradiol, AFC, stimulation protocol, gonadotropin type and dosage, duration of stimulation, duration of antagonist administration, menstrual day at embryo transfer, embryo cell number, endometrial thickness at trigger day, total number of oocytes and fertilized oocytes and fertilization rates were compared between failed and successful consecutive trials with a maximum interval of 2 months. Data were analyzed using SPSS 15.0 for Windows. The paired samples t-test was used to compare continuous variables between two separate cycles within the group. A p value <0.05 was accepted as statistically significant.

Age, body mass index (BMI), serum FSH, estradiol, AFC, stimulation protocol, gonadotropin type and dosage, duration of stimulation, duration of antagonist administration, menstrual day at embryo transfer, embryo cell number, endometrial thickness at trigger day, total number of oocytes and fertilized oocytes and fertilization rates were compared between failed and successful consecutive trials with a maximum interval of 2 months. Data were analyzed using SPSS 15.0 for Windows. The paired samples t-test was used to compare continuous variables between two separate cycles within the group. A p value <0.05 was accepted as statistically significant. RESULTS The mean age, BMI, FSH, estradiol concentrations, AFC were 35.9 years (range, 30-42 years), 25.9 (range, 18.4-33.5 kg/m2), 10.9 IU/mL (range, 7-13 IU/mL), 52.9 (range, 11.6-75 pg/mL), 4.7 (range, 2-10) respectively (Table 1). A comparison of cycle characteristics showed a significantly higher total oocyte number and fertilized oocytes in successful cycles. The fertilization rate was also significantly higher in cycles with clinical pregnancy. Early initiation of antagonist was shown to result in favorable outcomes. A comparison of embryo characteristics showed that transfer of higher-stage embryos and embryos a higher number of cells had a significant impact on cycle outcomes. All comparisons of variables between the two cycles are summarized in Table 2.

y. Early initiation of antagonist was shown to result in favorable outcomes. A comparison of embryo characteristics showed that transfer of higher-stage embryos and embryos a higher number of cells had a significant impact on cycle outcomes. All comparisons of variables between the two cycles are summarized in Table 2. DISCUSSION In this study, we assessed cycle characteristics in poor responders with and without successful clinical pregnancy such as age, BMI, serum FSH, estradiol, AFC, stimulation protocol, gonadotropin dosage, duration of stimulation, duration of antagonist administration, antagonist starting day, menstrual day at embryo transfer, embryo cell number, endometrial thickness at trigger day, number of total and fertilized oocyte and fertilization rates. Our data revealed that early initiation of antagonist, higher number of total, mature and fertilized oocyte number with higher fertilization rates and transferring significantly higher stage of embryo development and embryo cell numbers led to favorable outcomes in ICSI cycles.

ertilized oocyte and fertilization rates. Our data revealed that early initiation of antagonist, higher number of total, mature and fertilized oocyte number with higher fertilization rates and transferring significantly higher stage of embryo development and embryo cell numbers led to favorable outcomes in ICSI cycles. Despite introduction of many protocols with different initial doses and types of gonadotropins, optimal management of patients who are poor responders is still a concern. In this study, we tried to identify characteristics of a successful cycle compared with a preceding failed cycle in the same patients with poor ovarian response. Most of the time, when responses to the standard dose of gonadotropins (225-300 IU) for a proper multifollicular growth fails, dose increments are attempted to obtain a better outcome. Therefore, high doses of gonadotropins were proposed for a couple of decades in poor responders. However, there are some conflicting data regarding the success of increased gonadotropin doses in the management of poor responders. Previous studies showed no enhanced ovarian response and/or better pregnancy rates when 450 U of increased doses of gonadotropins were used(10,11,12). Furthermore, a recently published study indicated that an increased starting dose of FSH did not result in higher pregnancy rates, and outcomes were similar between groups with different gonadotropin starting doses (300 UI, 450 UI, and 600 UI) of gonadotropins with regard to retrieved oocytes, number of embryos obtained, and pregnancy rates(13). In our study, the mean starting and total gonadotropin doses were similar between the two cycles. However, we found significantly earlier antagonist initiation in successful cycles. The modified early antagonist start protocol was introduced to improve cycle outcomes. It was claimed that improved mature oocyte yield could be enhanced through follicular synchronization. Additionally, significantly higher clinical pregnancy rates compared with the conventional antagonist protocol were reported(14). Furthermore, delayed-start of antagonist protocol was proposed to result in favorable outcomes in terms of number of dominant follicles and mature oocytes retrieved, mature oocyte yield, and fertilization rates in poor responders. The authors concluded that this was the result of the promoting and synchronizing effect on follicle development without impairing oocyte developmental competence(15).

vorable outcomes in terms of number of dominant follicles and mature oocytes retrieved, mature oocyte yield, and fertilization rates in poor responders. The authors concluded that this was the result of the promoting and synchronizing effect on follicle development without impairing oocyte developmental competence(15). Besides a higher rate of fertilization, we also found significantly higher numbers of total, mature oocyte and earlier antagonist initiation in successful cycles. Especially in patients with poor ovarian reserve, the number of oocytes has a critical role for cycle outcome. Studies on this issue showed a significant relationship between the number of eggs and live birth in all age groups. A study proposed that the number of eggs in IVF was an indirect indicator for clinical success. The best outcome was obtained when approximately 15 eggs were retrieved(6). However, a yield lower than 4-6 oocytes after stimulation has been considered to be poor response(7). In our study, the mean total number of oocytes harvested during failed and successful cycles were 4.8 and 5.6, respectively. Although both results are within the range of the poor response definition, it seems that a minimal increase in total oocyte numbers with increased fertilization rates resulted in favorable outcomes.

ur study, the mean total number of oocytes harvested during failed and successful cycles were 4.8 and 5.6, respectively. Although both results are within the range of the poor response definition, it seems that a minimal increase in total oocyte numbers with increased fertilization rates resulted in favorable outcomes. Another factor is the fertilization rate, which was thought to be an indirect finding for oocyte quality and was shown to be a significant predictor for embryo implantation(16). Some morphologic characteristics of oocytes, such as zona pellucida thickness, cytoplasm appearance, and polar bodies were investigated to select the best embryos to transfer and therefore further minimize the number of embryos transferred(17,18,19,20). However, according to the accumulated data, most of these parameters had a minimal impact for this purpose(21,22). Embryo grading systems were developed and found correlated with pregnancy outcomes. Despite their limitations, grading systems are the most commonly applied procedures in the selection of the most qualified embryo for transfer. Further embryo assessments focused on the zygote stage, evaluation of embryo behavior at early cleavage, and extended culture performed to day 5 showed improved pregnancy outcomes(23,24). There are also some data at the molecular level for implantation prediction(25). However, after adjustment of the aforementioned covariates, the fertilization rate was shown as a significant predictor for embryo implantation in a previous study(16). As mentioned above, our data also showed significantly increased fertilization rates in cycles with clinical pregnancy.

or implantation prediction(25). However, after adjustment of the aforementioned covariates, the fertilization rate was shown as a significant predictor for embryo implantation in a previous study(16). As mentioned above, our data also showed significantly increased fertilization rates in cycles with clinical pregnancy. The relationship between embryo quality and pregnancy rates has been shown in several studies(26,27,28). Early cleaving 2-cell embryos have been shown to have higher pregnancy rates than patients without early-cleaving 2-cell embryos(29), and furthermore, transfer of 4-cell embryos resulted in significantly higher implantation and pregnancy rates compared with transfers of 2 and 3-cell embryos. Additionally, cell number was found as the strongest predictor of pregnancy in day 3 embryos in a scoring system based on cell number, fragmentation, and other morphologic criteria deemed specific to day 3 embryos(30,31,32). According to a Cochrane review, cumulative clinical pregnancy rates from cleavage stage resulted in higher clinical pregnancy rates than from blastocyst cycles(33). Data showed a decreased overall embryo quality score in embryos that were kept in culture till day 3(34). In our assisted reproductive technology clinic, we try to avoid keeping embryos in culture media for more than 3 days, except when the top quality embryo has not been determined. In majority of cases, we prefer 2 to 3-day embryo transfers, especially in the event of a low number of embryos. Our data showed that number of cells in 2 to 3-day embryo transfers had a critical role in ICSI cycles; the number of cells was significantly higher in cycles with clinical pregnancy (4.1 vs. 5.9, p<0.05).

. In majority of cases, we prefer 2 to 3-day embryo transfers, especially in the event of a low number of embryos. Our data showed that number of cells in 2 to 3-day embryo transfers had a critical role in ICSI cycles; the number of cells was significantly higher in cycles with clinical pregnancy (4.1 vs. 5.9, p<0.05). CONCLUSION Early initiation of antagonist, higher number of total, mature oocyte yield, higher fertilization rates and transfer of embryos with higher number of cells were significant factors of successful outcomes in poor responders. Further research on this topic should be conducted with larger study populations to elaborate on the implications of our study, and to obtain more data to modify cycles for better results in poor responders. Ethics Ethics Committee Approval: The study was approved by the Zeynep Kamil Women and Children’s Health Training and Research Hospital Local Ethics Committee (Approval number: 2014-183), Informed Consent: Consent form was filled out by all participants. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: E.Ö., T.K., P.K., H.A., B.D., İ.S., Y.Ş., B.S., A.K., Concept: T.K., Design: T.K., Data Collection or Processing: E.Ö., T.K., P.K., H.A., B.D., İ.S., Y.Ş., B.S., A.K., Analysis or Interpretation: E.Ö., Literature Search: E.Ö., Writing: E.Ö., T.K. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: E.Ö., T.K., P.K., H.A., B.D., İ.S., Y.Ş., B.S., A.K., Concept: T.K., Design: T.K., Data Collection or Processing: E.Ö., T.K., P.K., H.A., B.D., İ.S., Y.Ş., B.S., A.K., Analysis or Interpretation: E.Ö., Literature Search: E.Ö., Writing: E.Ö., T.K. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Table 1 Summary of some demographic characteristics of study population Table 2 Comparison of some parameters of successful and preceding failed cycle in women with poor ovarian response

PRECIS: Frameless design intrauterine device implantation appears to represent a major advance, suitable for general use due to its lack of timing restraints and its simplicity of attachment. INTRODUCTION The ideal time for postpartum contraception either as a precautionary measure or as a family planning tool is immediately post-delivery. Immediate contraception is convenient and timely because a woman is actively evaluating her current and future family planning options. A woman’s return to fertility post-delivery is not always predictable because it can occur as soon as 3 weeks in non-lactating women and may not necessarily be accompanied by menses. The pregnancy environment represents the near-ideal timing for discussions with patients in need of contraception, the nature of the products available, and their individual benefit and risks. The patient’s receptiveness and willingness to select a given form of contraception is a critical component in allowing a woman to adequately manage her contraception needs.

ideal timing for discussions with patients in need of contraception, the nature of the products available, and their individual benefit and risks. The patient’s receptiveness and willingness to select a given form of contraception is a critical component in allowing a woman to adequately manage her contraception needs. Various contraceptive methods are available to postpartum women including hormonal and nonhormonal barriers, as well as injectable forms. Unfortunately, as reviewed by Trussell(1), many of these methods although effective, have a high degree of failure when used imperfectly. For parous women, most physicians and the World Health Organization recommend an interdelivery interval of 18 to 24 months, because a second pregnancy too soon after the first could have detrimental effects on the woman herself, her ability to carry the baby to term, the viability of the infant, and its overall growth/development(2). Women undergoing cesarean sections with an interdelivery interval shorter than 18 months have the added risk of possible uterine rupture(3). Use of contraception as early as possible post-delivery would assure prevention of uterine rupture post-cesarean section, thus allowing for the wound to heal as well as for the woman to fully recover from her pregnancy. Effective contraception in these women will be valuable in reducing the risk of unintended pregnancies, and may allow for many women to have follow-on vaginal over cesarean deliveries.

terine rupture post-cesarean section, thus allowing for the wound to heal as well as for the woman to fully recover from her pregnancy. Effective contraception in these women will be valuable in reducing the risk of unintended pregnancies, and may allow for many women to have follow-on vaginal over cesarean deliveries. Of all the available birth control methods, intrauterine devices (IUD) are felt by many to be the near-ideal form of contraception, and are recommended by advocacy groups, physicians, and gynecological organizations worldwide. IUDs have the advantage of high effectiveness as well as having an extremely low failure rate, in part because of the lack of involvement by the women. Immediate postpartum IUD insertion deserves greater attention because it can provide immediate contraception, prevents repeat unintended pregnancies, and may serve to reduce the incidence or need for secondary cesarean delivery(4). Unfortunately, insertion of conventional T-shape IUDs immediately post placenta delivery is limited by their high expulsion and displacement rates(5,6). A study conducted by Çelen et al.(7) in Turkey in 2011 noted an expulsion rate of 17.6% at 12 months with the TCu380A IUD inserted immediately following cesarean section delivery. The inability of these devices to be retained clearly affects their effectiveness, but as importantly, overall patient acceptance. Women, especially those undergoing cesarean delivery, could benefit from immediate post-placenta IUD insertion because it would allow a sufficient period for the uterus, as well as the woman, to recover from surgery via a highly effective and long-lasting contraceptive. In these women, a low expulsion risk is therefore paramount with women having the added benefit of the IUD being easily reversible with a rapid return to fertility.

use it would allow a sufficient period for the uterus, as well as the woman, to recover from surgery via a highly effective and long-lasting contraceptive. In these women, a low expulsion risk is therefore paramount with women having the added benefit of the IUD being easily reversible with a rapid return to fertility. Over the past decades, attempts have been made to solve the expulsion problem encountered with conventional T-shape IUDs by modifying existing devices, such as adding absorbable sutures (delta-T) or additional appendages. These attempts were minimally successful. Expulsion rates varying from 5% at 12 months to up to 50%, and even higher if partial expulsions are included, have been reported(8,9,10). Timing of insertion post-placenta delivery is of critical importance with T-shape devices. Studies have shown that if inserted at times beyond 10 minutes post-delivery, expulsion rates were higher than those observed in normal women.

Over the past decades, attempts have been made to solve the expulsion problem encountered with conventional T-shape IUDs by modifying existing devices, such as adding absorbable sutures (delta-T) or additional appendages. These attempts were minimally successful. Expulsion rates varying from 5% at 12 months to up to 50%, and even higher if partial expulsions are included, have been reported(8,9,10). Timing of insertion post-placenta delivery is of critical importance with T-shape devices. Studies have shown that if inserted at times beyond 10 minutes post-delivery, expulsion rates were higher than those observed in normal women. Anchoring of frameless design IUDs that lack conventional cross-arms to the uterine fundal surfaces has been medically and commercially available throughout Europe for many years in the form of GyneFix (Contrel Research, Belgium). The placement technique is simple, has minimal patient discomfort, and high long-term patient acceptance due to its high degree of uterine compatibility as a consequence of its small size and segmented design. Since its inception, the technology has passed through several phases of improvement, design modifications, and clinical testing intended to maximize patient comfort and tolerability producing 5-year continuation rates in excess of 90%. Clinical studies were also conducted to evaluate the impacts of immediate insertion of a frameless IUD during cesarean section, as well as after vaginal delivery, on the bleeding pattern, duration of lochia, and healing of uterus. Accordingly, no significant difference in postpartum hemorrhage, continuance of lochia, and healing of uterus, was observed(11). A novel minimally invasive surgical approach was devised for suspending the frameless copper IUD for intra-cesarean insertion, which takes advantage of the full visualization and access to the uterus that is achieved during cesarean delivery. The technique consists of the precise placement of the anchoring knot immediately below the serosa of the uterine fundus, followed by fixing the knot in place with a conventional absorbable suture (Figure 1a, 1b). In several weeks, the uterus regains its normal tonicity, the suture is absorbed, and the anchor retained as seen in women undergoing conventional interval insertion. The procedure is simple and can be performed at any convenient post-delivery period, and takes less than 4 minutes with no discomfort to the patient and minimal surgical risk. The IUD tail is looped in the cervical canal or is cut at the level of the cervix. The anchoring technique has been shown to be easy, quick and safe in a pilot trial with no expulsions at 12 months. Ongoing studies conducted in Turkey confirm the efficacy of the technique and high acceptability of the frameless IUD by women.

D tail is looped in the cervical canal or is cut at the level of the cervix. The anchoring technique has been shown to be easy, quick and safe in a pilot trial with no expulsions at 12 months. Ongoing studies conducted in Turkey confirm the efficacy of the technique and high acceptability of the frameless IUD by women. To check IUD placement, a follow-up sonography can be performed to localize the stainless steel marker attached to the anchoring knot (Figure 1c). Removal of the IUD is similar to the removal after interval insertion of the device accomplished by simply pulling on the IUD string. In the event that the tail is in the cavity, it is accessible by using thin alligator forceps (3 mm) if/when removal is requested. The copper releasing frameless IUD and inserter, which were specifically designed to facilitate use immediately post-placental delivery after cesarean deliveries, is now available in Turkey. Conventional insertion of frameless IUDs in normal women is already available in Turkey. The developers are also finalizing the development of a levonorgestrel-releasing frameless system, which may have additional advantages in some women.

y post-placental delivery after cesarean deliveries, is now available in Turkey. Conventional insertion of frameless IUDs in normal women is already available in Turkey. The developers are also finalizing the development of a levonorgestrel-releasing frameless system, which may have additional advantages in some women. Frameless-design IUD implantation appears to represent a major advance, suitable for general use due to its lack of timing restraints and its simplicity of attachment, which only requires limited training. It affords the patient and her physician additional options for contraceptive control that may likely serve to reduce the number and frequency of unintended pregnancies. Frameless IUDs appear to have advantages over framed T-shaped IUDs because the latter may cause discrepancy with the uterine cavity and embedment during involution of the uterus, particularly during prolonged lactation as hyperinvolution in these women is not uncommon(12). Disclosure Dr. Dirk Wildemeersch has been involved in the development of novel contraceptive systems for use in the uterus. He is currently an advisor in devising new concepts in controlled release for contraception and gynecological treatment. Ethics Peer-review: Internally peer-reviewed. Authorship Contributions Surgical and Medical Practices: A.K., A.T., Ö.Ö., D.W., Concept: A.K., D.W., Design: A.K., A.T., Data Collection or Processing: A.T., Ö.Ö., D.W., Analysis or Interpretation: A.K., A.T., D.W., Literature Search: Ö.Ö., D.W., Writing: A.K., A.T., Ö.Ö., D.W. Conflict of Interest: No conflict of interest was declared by the authors.

Surgical and Medical Practices: A.K., A.T., Ö.Ö., D.W., Concept: A.K., D.W., Design: A.K., A.T., Data Collection or Processing: A.T., Ö.Ö., D.W., Analysis or Interpretation: A.K., A.T., D.W., Literature Search: Ö.Ö., D.W., Writing: A.K., A.T., Ö.Ö., D.W. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 a) Insertion apparatus for the insertion of the frameless intrauterine devices following cesarean section delivery b) Illustration of the anchoring technique; a biodegradable suture holds the anchor in place in the uterine fundus until involution c) Coronal ultrasound of the position of the frameless intrauterine devices after involution of the uterus with an anchor marker in the fundus (arrow)

INTRODUCTION Chondrosarcoma is considered as a common primary bone sarcoma, which is ranked as the third primary bone malignancy. One in five cases of bone sarcomas are due to chondrosarcoma, and half of all cases affect the pelvis(1). Moreover, this tumor arises predominantly after the second decade with a peak in the middle-aged period. Many heterogeneous groups of neoplasms are related to chondrosarcoma and cartilage matrix production is a typical feature of this tumor(2). These sarcomas form large masses without any specific symptoms because there are no barriers in the pelvic anatomy to prevent the enlargement of tumors(3). In this case report, we present a patient who had a tumor of undefined origin according to preoperative imaging methods, and a pelvic chondrosarcoma mimicking an adnexal mass. To the best of our knowledge, this is only the third case of pelvic chondrosarcoma in the English literature of obstetrics and gynecology.

s(3). In this case report, we present a patient who had a tumor of undefined origin according to preoperative imaging methods, and a pelvic chondrosarcoma mimicking an adnexal mass. To the best of our knowledge, this is only the third case of pelvic chondrosarcoma in the English literature of obstetrics and gynecology. CASE REPORT A 37-year-old single woman presented to our clinic with symptoms of pelvic pain, abdominal distension, and vaginal bleeding. During the pelvic examination, a mass that filled the pelvis was detected. The carcinoma antigen 125 (CA125) level was 40 U/mL. Ultrasonographic and magnetic resonance imaging (MRI) examinations revealed a solid mass 20x10 cm in diameter including calcified areas, and a mass consistent with myoma of 3.5 cm in diameter was observed in the cervico-isthmic region of the uterus. The endometrial thickness was 8 mm (Figure 1). During surgery, a mass of 18x8 cm was observed that was displacing the uterus and extending from the symphysis pubis to the pelvis with a myoma of 3.5 cm in diameter, posterior to the uterus corpus. The ovaries were normal on inspection. Specialists from the urology and orthopedics departments were consulted intraoperatively and it was decided that the tumor originated from the pelvic bone. Partial resections with myomectomy were performed because the tumor could not be completely removed (Figure 2). The postoperative pathologic examination was reported as grade 1, well-differentiated chondrosarcoma (Figure 3). The orthopedics department requested computerized tomography (CT) imaging, which revealed masses consistent with metastasis in the liver, and a 9x8 cm diameter mass in the pubic area. The patient was referred to another healthcare unit because a skilled orthopedics team with experience of pelvic chondrosarcoma was unavailable.

opedics department requested computerized tomography (CT) imaging, which revealed masses consistent with metastasis in the liver, and a 9x8 cm diameter mass in the pubic area. The patient was referred to another healthcare unit because a skilled orthopedics team with experience of pelvic chondrosarcoma was unavailable. DISCUSSION That a pelvic chondrosarcoma could masquerade as an ovarian mass was considered the peculiar part of our case. This camouflage exposes the limited role of imaging techniques and tumor markers in diagnosing pelvic tumors. Generally, chondrosarcoma has a silent course due to the special pelvic structure, which allows masses to grow feasibly without any boundaries and only become symptomatic after enlarging enough, as in our case. Thus, this tumor has a larger size in comparison with other pelvic masses when the diagnosis was established; the mean size is commonly 11 cm(4). After reviewing all operated cases of pelvic mass in our department within the last 15 years, chondrosarcoma was the only case that was misdiagnosed as an ovarian mass, which reflects the sporadic incidence of this condition. Although all available imaging techniques, even CT and MRI, were used to assist us in mapping this tumor, we could not identify the exact margins, neither the exact organ from which this tumor derived. Moreover, the elevated CA125 was another misleading factor that increased our suspicion of ovarian mass. The surgical management of chondrosarcoma is a destructive operation for orthopedic surgeons due to the following principles: increased risk of vital organ injuries, high susceptibility to damage pelvic structural stability, challenging anatomic interactions of the pelvis, and devastating extension of the tumor. The mass could not be completely removed and the patient was considered as non-resectable and referred to another orthopedics clinic because we did not have an orthopedic surgical team skilled in pelvic chondrosarcoma. Vast majority of chondrosarcoma become symptomatic after reaching a large size and this can be explained by the slow growth rate of this these tumors(5). Grade 1 chondrosarcomas consist of profuse hyaline cartilage matrix surrounding a little cellular mass and metastasize infrequently(1). In our case, the pathologic result was grade 1 chondrosarcoma, and there were metastatic lesions observed in the liver in abdominal tomography.

low growth rate of this these tumors(5). Grade 1 chondrosarcomas consist of profuse hyaline cartilage matrix surrounding a little cellular mass and metastasize infrequently(1). In our case, the pathologic result was grade 1 chondrosarcoma, and there were metastatic lesions observed in the liver in abdominal tomography. Pelvic chondrosarcomas can appear in various pathologic neoplasms, other than pure chondrosarcoma arising from the pelvic bone, such as chondrogenic tumors of the ovaries or heterologous carcinosarcomas of the uterus. However, all mentioned types have very low incidence rates(6). Moreover, mixed mesodermal tumors, commonly called carcinosarcoma, another manifestation of chondrosarcoma, are the most common heterologous sarcomas, originating from the uterus in most cases. The histologic appearance is a mixture of ectoderm and mesoderm-derived tissues. Either homologous or heterologous mesodermal tissue can be commonly found to be high grade. Heterologous tumors consist of a differentiated mesenchymal component accompanied by endometrial, stromal or undifferentiated sarcomas. Occasionally, these uterine tumors may enlarge and convert to giant pelvic masses that can destroy the uterine structure to the point where it can become unrecognizable(7). The cornerstone of treatment in managing this tumor is wide surgical excision, that still first line treatment(8). After performing extensive intralesional curettage, local adjuvant treatment has encouraging long-term outcomes and adequate control of local recurrence in low-grade chondrosarcomas. Local adjuvant treatment is only effective in cases with well-defined boundaries with no extension beyond the bone(9). However, giant tumor or pelvic localization of chondrosarcoma can alter the treatment method, even in low-grade conditions, as in our case, which require wide resection as a first-line management, rather than intralesional curettage(1).

fective in cases with well-defined boundaries with no extension beyond the bone(9). However, giant tumor or pelvic localization of chondrosarcoma can alter the treatment method, even in low-grade conditions, as in our case, which require wide resection as a first-line management, rather than intralesional curettage(1). CONCLUSION Pelvic chondrosarcoma should be considered in patients who have pelvic masses with solid components because preoperative evaluations (imaging studies, pelvic examination) in daily practice may be inadequate for the diagnosis of pelvic masses. As a consequence, it should be kept in mind that interventions should be performed at centers where there are orthopedic surgeons with experience of this subject. Ethics Informed Consent: Consent form was filled out by all participants. Peer-review: External and internal peer-reviewed. Authorship Contributions Surgical and Medical Practices: H.Ç.Ö., Ö.B., Concept: Z.B., Design: H.Ç.Ö., Data Collection or Processing: Z.B., S.S., Analysis or Interpretation: S.S., Literature Search: A.M., Writing: A.M. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: H.Ç.Ö., Ö.B., Concept: Z.B., Design: H.Ç.Ö., Data Collection or Processing: Z.B., S.S., Analysis or Interpretation: S.S., Literature Search: A.M., Writing: A.M. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 Magnetic resonance imaging showing a solid mass with 20x10 cm in diameter including calcified areas, and a mass consistent with myoma of 3.5 cm in diameter was observed in the cervico-isthmic region of the uterus Figure 2 The macroscopic appearance of the lesion, which is seen in pieces, and has the solid-brilliant cartilaginous appearance of cross-sectional surface Figure 3 Microscopic appearance of the lesion, which was separated by fibrous septa, and was formed by nodular infiltrating, atypical chondrocytes, hematoxylin and eosin x40

INTRODUCTION Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare anomaly in females that affects 1 in 5000 live births(1,2), in which there is dysgenesis of the Mllerian ducts leading to failure of development of the uterus and vagina. Ovarian function is preserved and the external genitalia are normal. The karyotype is 46, XX. There is normal development of secondary sexual characteristics at puberty. Primary amenorrhea at adolescence is the most common presenting symptom in patients with MRKH syndrome. However, when associated with anorectal malformation, this condition presents early at birth or in infancy and requires proper management(3). MRKH syndrome has been divided into two types (Schmid-Tannwald and Hauser, 1977); type A, or the typical form, is an isolated anomaly also known as the Rokitansky sequence(4,5). The patient has symmetrical uterine remnants and normal fallopian tubes(5). Type B, the atypical form, is characterized by asymmetric uterine buds or abnormally developed fallopian tubes (CAMP). This atypical form is associated with anomalies that involve other systems, especially the renal, cardiac, otologic, and skeletal systems(1,4). Anorectal malformations are uncommonly reported to be associated with MRKH syndrome, and among them, rectovestibular fistula and cloacal malformations have been commonly described(1,2,6). We present a girl aged one year with atypical MRKH syndrome associated with rectovestibular fistula.

MRKH syndrome has been divided into two types (Schmid-Tannwald and Hauser, 1977); type A, or the typical form, is an isolated anomaly also known as the Rokitansky sequence(4,5). The patient has symmetrical uterine remnants and normal fallopian tubes(5). Type B, the atypical form, is characterized by asymmetric uterine buds or abnormally developed fallopian tubes (CAMP). This atypical form is associated with anomalies that involve other systems, especially the renal, cardiac, otologic, and skeletal systems(1,4). Anorectal malformations are uncommonly reported to be associated with MRKH syndrome, and among them, rectovestibular fistula and cloacal malformations have been commonly described(1,2,6). We present a girl aged one year with atypical MRKH syndrome associated with rectovestibular fistula. CASE REPORT A girl aged one year presented with an absent anal orifice since birth. She had been passing stools from an orifice within the introitus since birth. There was no constipation or abdominal distension. Per abdominal and systemic examinations were unremarkable. On perineal examination, there were two openings in the introitus. There was no anal opening at the normal site (Figure 1). The anterior opening was small and the child was passing urine through this opening, which suggested a urethral opening. The posterior opening in the vestibule discharged fecal matter, thereby suggesting a fistula. No vaginal opening could be appreciated.

roitus. There was no anal opening at the normal site (Figure 1). The anterior opening was small and the child was passing urine through this opening, which suggested a urethral opening. The posterior opening in the vestibule discharged fecal matter, thereby suggesting a fistula. No vaginal opening could be appreciated. Abdominal ultrasound revealed absent uterus and vagina. Both ovaries were normal and the right kidney was small. Barium enema showed a dilated rectum. Voiding cystourethrography was normal. A radio nucleotide renal study suggested a non-functioning right kidney and adequately functioning left kidney. Cystogenitoscopy showed normal urethra and bladder, absent vagina, and the presence of rectovestibular fistula confirming the diagnosis of uterovaginal agenesis (MRKH syndrome type B). A right transverse stoma was performed. Magnetic resonance imaging (MRI) confirmed uterovaginal agenesis (Figure 2). Posterior sagittal anorectoplasty (PSARP) with a neovagina creation using the distal end of rectum with vestibular opening was planned. Approximately 3-4 cm of the distal ano-rectum (i.e. the rectovestibular fistula itself) was retained as a neo-vagina and the proximal rectum was brought down posteriorly within the sphincter complex (Figure 3). At follow-up after 6 weeks, a neovagina of about 6-cm length along with minimal mucus discharge was present. The colostomy was closed after 8 weeks.

Posterior sagittal anorectoplasty (PSARP) with a neovagina creation using the distal end of rectum with vestibular opening was planned. Approximately 3-4 cm of the distal ano-rectum (i.e. the rectovestibular fistula itself) was retained as a neo-vagina and the proximal rectum was brought down posteriorly within the sphincter complex (Figure 3). At follow-up after 6 weeks, a neovagina of about 6-cm length along with minimal mucus discharge was present. The colostomy was closed after 8 weeks. DISCUSSION The clinical appearance of two orifices in the introitus with an absent anal opening leads to the differential diagnosis of anorectal agenesis without fistula, a rectovaginal fistula (high or low) or a rectovestibular fistula with either a urogenital sinus or MRKH syndrome. The association of rectovestibular fistula with MRKH syndrome is rare with few reports in the literature(1,2). Levitt et al.(6), Gross(7), Ein and Stephens(8) reported 8, 2, and 2 such cases respectively(1). Mahajan et al.(9) described MRKH syndrome associated with H-type anovestibular fistula in 2009(9). Ein and Stephens(8) in 1971 first reported preservation of the rectum as a neovagina(1). Gupta et al.(1) recently reported this method of neovaginal reconstruction in a girl aged one year.

nd 2 such cases respectively(1). Mahajan et al.(9) described MRKH syndrome associated with H-type anovestibular fistula in 2009(9). Ein and Stephens(8) in 1971 first reported preservation of the rectum as a neovagina(1). Gupta et al.(1) recently reported this method of neovaginal reconstruction in a girl aged one year. The etiology of MRKH syndrome is unknown; however, it is believed that there is interruption in the embryologic development during the sixth or seventh gestational week(10,11). The spectrum of malformations associated with atypical MRKH syndrome suggests a developmental field defect involving organ systems that are closely related during embryogenesis(4,12,13). MRKH syndrome has been attributed to an initial affection of the intermediate mesoderm, consequently leading to an alteration of the blastema of the cervicothoracic somites and pronephric ducts(4,12). Mutations of the WNT4 and TCF2 genes have recently been found associated with MRKH syndrome(4,14).

ryogenesis(4,12,13). MRKH syndrome has been attributed to an initial affection of the intermediate mesoderm, consequently leading to an alteration of the blastema of the cervicothoracic somites and pronephric ducts(4,12). Mutations of the WNT4 and TCF2 genes have recently been found associated with MRKH syndrome(4,14). The importance of the clinical examination of the perineum in a female neonate cannot be over-emphasized. This diagnosis of utero-vaginal agenesis should be made at birth itself. The clinical presentation with two openings in the introitus with fecal matter deflating through the posterior opening requires investigations to confirm diagnosis before proceeding to the definitive management. Ultrasonography, a contrast study through the opening in the vestibule, MRI, and cystogenitoscopy through both openings in the introitus help in the definitive diagnosis of absent vagina and cervix(4). This is essential for planning the definitive management. A possible scenario that should not be forgotten is that failure of the neonate to pass meconium through the second opening within 24 hours of birth leads to a colostomy because of the assumption of anorectal agenesis without fistula(1,6). Due to this presumed misdiagnosis, at the time of definitive repair, the rectum would not be found because of the incorrect assumption that the rectum was the vagina(1,6). However, a distal colostogram performed before the definitive repair would surely help in suspecting this malformation(1,6).

s without fistula(1,6). Due to this presumed misdiagnosis, at the time of definitive repair, the rectum would not be found because of the incorrect assumption that the rectum was the vagina(1,6). However, a distal colostogram performed before the definitive repair would surely help in suspecting this malformation(1,6). There are two surgical options for the definitive repair in patients with MRKH syndrome with rectovestibular fistula(1,6). In the first method, the fistula is mobilized, traditionally by either PSARP or anterior sagittal anorectoplasty approach, and fixed within the sphincter muscle complex at the proposed anal site and a neoanus is created(1,6). A vaginoplasty is performed at later date in these patients(1,15). This type of repair is well suited for patients in whom MRKH syndrome was not diagnosed at infancy and presented at adolescence with symptoms of primary amenorrhea(16). Wang et al.(17) reported three patients who presented with MRKH syndrome and rectovestibular fistula with imperforate anus and symptoms of primary amenorrhea and loose stools. A single-stage anorectovaginoplasty was performed in these patients with laparoscopic assistance in one patient(17). The second option is to preserve the fistula at the vaginal site and leave an approximately 10-cm distal stump as a neovagina and to pull the proximal colon through the sphincter muscle complex as the neo-anorectum(1,3,6). However, this procedure can only be performed when the correct diagnosis of MRKH syndrome with rectovestibular fistula is made pre-operatively(1).

he vaginal site and leave an approximately 10-cm distal stump as a neovagina and to pull the proximal colon through the sphincter muscle complex as the neo-anorectum(1,3,6). However, this procedure can only be performed when the correct diagnosis of MRKH syndrome with rectovestibular fistula is made pre-operatively(1). This second option is the preferred technique because it is relatively simple to perform; there is no chance of damaging any neural innervations, and both the neovagina and neoanus are created in the same operation(1). Neovaginas have not been reported to show tendency for stricture formation; sphincter tone is good and patients are continent(6). Levitt et al.(6) used the PSARP approach for this procedure. The abdominoperineal approach is required when the uterus is present to allow for the anastomosis of the rectal pouch (now the neovagina) to the uterus, thereby creating continuity of the reproductive system(1). The association of MRKH syndrome with rectovestibular fistula is rare and should be suspected as the differential diagnosis in a female neonate with two openings in the introitus. A correct pre-operative diagnosis helps to correct both malformations in the same operative procedure. Early diagnosis and simultaneous vaginal reconstruction and anorectoplasty in infancy offers added advantages; it prevents psychological trauma and avoids the need of delayed vaginoplasty through scarred perineum in these patients. Ethics Informed Consent: The informed consent was taken and form filled by the father of the patient. Peer-review: Externally peer-reviewed.

The association of MRKH syndrome with rectovestibular fistula is rare and should be suspected as the differential diagnosis in a female neonate with two openings in the introitus. A correct pre-operative diagnosis helps to correct both malformations in the same operative procedure. Early diagnosis and simultaneous vaginal reconstruction and anorectoplasty in infancy offers added advantages; it prevents psychological trauma and avoids the need of delayed vaginoplasty through scarred perineum in these patients. Ethics Informed Consent: The informed consent was taken and form filled by the father of the patient. Peer-review: Externally peer-reviewed. Authorship Contributions Surgical and Medical Practices: C.T., H.S., K.K., M.W., Concept: C.T., H.S., K.K., M.W., Design: C.T., H.S., K.K., M.W., Data Collection or Processing: C.T., Analysis or Interpretation: C.T., H.S., Literature Search: C.T., Writing: C.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 The perineum of the patient showing two orifices in the introitus Figure 2 Magnetic resonance imaging pelvis showing uterovaginal agenesis and the dilated rectum Figure 3 Intra-operative image of the patient showing the neovagina (retained distal end of rectum opening in the vestibule) (white arrow) and the pulled down bowel (black arrow)

Dear Editor, Penoscrotal transposition (PST) is an infrequent congenital external genital malformation in which the scrotum is located superior and anterior to the penis(1). PST can be defined as either complete or incomplete according to the positional exchanges between the penis and scrotum and both forms of PST are generally linked with hypospadias. Incomplete transposition is the common form of this entity and the penis lies in the middle of the scrotum, but in complete transposition, the scrotum almost entirely covers the penis, which emerges from the perineum(2). Both of these conditions are commonly reported to be linked with a wide variety of abnormalities and pathologies that affect distinct organ systems. In this case report, we present a complete PST in a patient with urinary tract abnormalities including hypospadias, polycystic renal disease, and malpositioned right kidney.

th of these conditions are commonly reported to be linked with a wide variety of abnormalities and pathologies that affect distinct organ systems. In this case report, we present a complete PST in a patient with urinary tract abnormalities including hypospadias, polycystic renal disease, and malpositioned right kidney. A gravida 2, para 1 woman aged 35 years was admitted to the emergency department of our institute with premature membrane rupture when she was 36 weeks’ pregnant. The patient had undergone one prior cesarean delivery. The ultrasound examination revealed severe oligohydramnios. No previous histories of genetic abnormalities, illicit drug use, cigarette or alcohol consumption were reported. During her pregnancy, perinatal evaluations with ultrasound were performed at 26+6 weeks of gestation, which demonstrated a single umbilical artery, bilateral pelvic kidney, megacystitis, and penile curvature extending to the anal sphincter. Unfortunately, we were not able to obtain prenatal ultrasound pictures or a genetic analysis report because of the nature of the emergency hospital admission of the patient. A final prenatal diagnosis of PST and severe hypospadias was made based on these perinatal evaluations.

curvature extending to the anal sphincter. Unfortunately, we were not able to obtain prenatal ultrasound pictures or a genetic analysis report because of the nature of the emergency hospital admission of the patient. A final prenatal diagnosis of PST and severe hypospadias was made based on these perinatal evaluations. The patient underwent a cesarean section and gave birth to a male baby of 3070 grams with 8/9 Apgar score. Physical examination revealed a PST and severe hypospadias (Figure 1). Laboratory examinations were all reported to be normal. Ultrasonographic examination revealed a malpositioned right kidney (low lying) with multiple anechoic cysts of varying sizes. The newborn was transferred to the neonatal intensive care unit for further treatment. PST is a very rare clinical situation in which the scrotum is located anterior and superior to the penis and a severe degree of PST, as in our case, with hypospadias and normal scrotum have been infrequently reported in medical literature(1,3,4). During normal human maturation, scrotal swellings move inferomedially during the 9th-11th week, and fuse in the midline caudal to the penis by the 12th week of gestation(4). The primary cause of this rare clinical disorder is a fusion defect or delay of urethral folds. Embryologically, PST is considered to result from abnormal genital tubercle development around the 6th-7th week of gestation(1).

he 9th-11th week, and fuse in the midline caudal to the penis by the 12th week of gestation(4). The primary cause of this rare clinical disorder is a fusion defect or delay of urethral folds. Embryologically, PST is considered to result from abnormal genital tubercle development around the 6th-7th week of gestation(1). The differential diagnosis for PST should include pseudohermaphroditism, micropenis, penile amputation in the intrauterine period, penoscrotal hypospadias, and agenesis of the penis accompanying a midline skin tag anterior to the anal region(5). Moreover, a complete physical examination must be performed to detect abnormalities of the cardiovascular, central and peripheral nervous system, digestive system, urinary tract, and genital system because PST may present itself with a broad range of clinical manifestations that cause significant morbidity and mortality(6). Surgery is the gold standard of PST management, which is usually preferred to be performed between 12-18 months. Although complete PST is rarely reported in the literature, considerable surgical skill is needed to reconstruct the penile anatomy. Ethics Peer-review: External and internal peer-reviewed. Authorship Contributions Surgical and Medical Practices: F.B., Concept: F.B., H.A., Design: F.B., Data Collection or Processing: E.P., Analysis or Interpretation: F.B., E.P., Literature Search: F.B., E.P., Writing: F.B., H.A. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support.

Surgical and Medical Practices: F.B., Concept: F.B., H.A., Design: F.B., Data Collection or Processing: E.P., Analysis or Interpretation: F.B., E.P., Literature Search: F.B., E.P., Writing: F.B., H.A. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Figure 1 Complete penoscrotal transposition of a newborn a) Shows the scrotum without the penis b) Showing the penis under the scrotum

INTRODUCTION Diagnosing many complications related to gestation, such as intrauterine growth retardation, preeclampsia, placental abruption in early gestational weeks by several safe tests is of vital importance in terms of reducing morbidity and mortality rates. Biochemical indicators started to be used for researching fetal genetic disorders in 1980s and 90s. In the beginning, these tests that were started to be used only for researching the pregnant under risk in terms of neural tube defects, but subsequently they were started to be used also for researching other anatomical malformations, aneuploidy and third trimester complications later(1,2). Upon understanding that median values of alpha feto protein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG) concentrations of the serums of the pregnants who have normal fetus in the sixteenth gestational week are different from the median value of trisomy 21 fetus carrying pregnants, triple test run was suggested considering that these hormones can be used in screening the high risk group. Besides though test results were not in risk area for trisomy, it was detected that structural fetal anomalies such as open neural tube defect (NTD), abdominal wall defect and placental anomalies were accompanied by high AFP and\or high hCG levels. AFP and\or hCG levels can be found high in approximately 1% of the pregnant women without gestational age estimating mistake, structural or a chromosomal anomaly, or multiple pregnancy(3).

Upon understanding that median values of alpha feto protein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG) concentrations of the serums of the pregnants who have normal fetus in the sixteenth gestational week are different from the median value of trisomy 21 fetus carrying pregnants, triple test run was suggested considering that these hormones can be used in screening the high risk group. Besides though test results were not in risk area for trisomy, it was detected that structural fetal anomalies such as open neural tube defect (NTD), abdominal wall defect and placental anomalies were accompanied by high AFP and\or high hCG levels. AFP and\or hCG levels can be found high in approximately 1% of the pregnant women without gestational age estimating mistake, structural or a chromosomal anomaly, or multiple pregnancy(3). The relation between unexplained high AFP and\or hCG and adverse antenatal outcomes has been recognized in the last 20 years(4,5). It was shown that unexplained high AFP may be related with preterm labor, IUGR, preeclampsia and fetal death(6,7). On the other hand it was stated that elevated maternal hCG in the 2. trimester was related with preeclampsia(8,9) and increased fetal death rates(7,10,11). The purpose of this study is to evaluate the relationship between gestational complications like preterm labor, preterm birth, PPROM, stillbirth, IUGR, preeclampsia and high MSAFP and/or beta hCG levels. Also we aimed to detect whether these markers are effective predictors of adverse pregnancy outcomes or not.

The relation between unexplained high AFP and\or hCG and adverse antenatal outcomes has been recognized in the last 20 years(4,5). It was shown that unexplained high AFP may be related with preterm labor, IUGR, preeclampsia and fetal death(6,7). On the other hand it was stated that elevated maternal hCG in the 2. trimester was related with preeclampsia(8,9) and increased fetal death rates(7,10,11). The purpose of this study is to evaluate the relationship between gestational complications like preterm labor, preterm birth, PPROM, stillbirth, IUGR, preeclampsia and high MSAFP and/or beta hCG levels. Also we aimed to detect whether these markers are effective predictors of adverse pregnancy outcomes or not. MATERIALS AND METHODS Between June 2009 - November 2010, total 500 pregnant women who had applied to Prenatal Clinic of Etlik Zübeyde Hanım Education and Research Hospital for triple test between 15 to 20 gestational weeks were enrolled in this study. The patients were divided into 4 groups considering AFP and HCG MoM values. While group 1, consisting of 200 patients with normal ranges (0.5-2.0 MoM) of both AFP and HCG MoM values, is determined as control group, group 2, consisting of 100 patients with high HCG values (above 2.0 MoM) and AFP values within normal ranges, group 3 consisting 100 patients with HCG values within normal ranges and high AFP values (above 2.0 MoM) and group 4 consisting 100 patients with both AFP and HCG MoM values above are identified as study groups.

roup 2, consisting of 100 patients with high HCG values (above 2.0 MoM) and AFP values within normal ranges, group 3 consisting 100 patients with HCG values within normal ranges and high AFP values (above 2.0 MoM) and group 4 consisting 100 patients with both AFP and HCG MoM values above are identified as study groups. All cases were informed about the screening test and detailed consent forms were obtained. The study protocol was approved by the local ethical committee. Inclusion criteria were stated as follows: 1) Single live pregnancy 2) Gestational age between 15-20 week 3) Regularly antenatal follow-up Exclusion criteria were: 1) Discordant gestational age according to first trimester ultrasounds 2) Multiple pregnancy 3) Lack of antenatal follow-up 4) Fetoplacental and chromosomal anomaly 5) Insulin-dependent diabetes mellitus 6) Over 35 years old Research was started with 679 pregnants and 12 patients due to diabetes with insulin, 6 patients due to fetoplacental and chromosomal anomaly, and 161 patients due to not being screened were taken out of the research. After it was confirmed that current pregnancy was matching with the last menstrual period (LMP) with the help of ultrasonography (USG) measurement, AFP (ng\ml) and hCG (mIU\ml) laboratory assessment were measured with Irma CT irrigation method via E170 brand device by using Roche brand AFP and hCG kits. Estriol (ng\ml) was measured with the RiA method by using Roche brand E3 kit.

h the last menstrual period (LMP) with the help of ultrasonography (USG) measurement, AFP (ng\ml) and hCG (mIU\ml) laboratory assessment were measured with Irma CT irrigation method via E170 brand device by using Roche brand AFP and hCG kits. Estriol (ng\ml) was measured with the RiA method by using Roche brand E3 kit. MoM rates were calculated by using stated pregnancy week, maternal age, sample obtaining date and AFP, hCG, uE3 rates for each patient. MoM rates were measured by dividing into median values of the gestational week on the date of sample obtaining. Cases with at least 2.0 MoM AFP rates were considered as positive test for neural tube defect. Patients with at least 1\250 down syndrome risk were considered positive for the screening test and were presented the option of invasive procedures. When the literature was analysed; some studies showed that pregnancy complications are increased when AFP and hCG values are more than 2 MoM and pregnancies with the higher values of AFP and hCG are terminated for fetal anomalies, so 2.0 MoM was taken as limit value. With the laboratory results taken on basis, obstetric care were not changed by increasing specific fetal methods such as non-stress test or USG. Antepartum tests or additional USG were not performed out of the obstetric indications. Patients’ data was evaluated after delivery.

MoM rates were calculated by using stated pregnancy week, maternal age, sample obtaining date and AFP, hCG, uE3 rates for each patient. MoM rates were measured by dividing into median values of the gestational week on the date of sample obtaining. Cases with at least 2.0 MoM AFP rates were considered as positive test for neural tube defect. Patients with at least 1\250 down syndrome risk were considered positive for the screening test and were presented the option of invasive procedures. When the literature was analysed; some studies showed that pregnancy complications are increased when AFP and hCG values are more than 2 MoM and pregnancies with the higher values of AFP and hCG are terminated for fetal anomalies, so 2.0 MoM was taken as limit value. With the laboratory results taken on basis, obstetric care were not changed by increasing specific fetal methods such as non-stress test or USG. Antepartum tests or additional USG were not performed out of the obstetric indications. Patients’ data was evaluated after delivery. The relation between obstetric and neonatal pathologies (preeclampsia, intrauterine growth retardation (IUGR), preterm labor, PPROM, intrauterine fetal death, neonatal and perinatal morbidity) and high MSAFP and / or beta HCG levels were investigated.

With the laboratory results taken on basis, obstetric care were not changed by increasing specific fetal methods such as non-stress test or USG. Antepartum tests or additional USG were not performed out of the obstetric indications. Patients’ data was evaluated after delivery. The relation between obstetric and neonatal pathologies (preeclampsia, intrauterine growth retardation (IUGR), preterm labor, PPROM, intrauterine fetal death, neonatal and perinatal morbidity) and high MSAFP and / or beta HCG levels were investigated. Statistical Analysis Data analysis was carried out using SPSS (Statistical Program of Social Sciences) ver. 17.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean, median, minimum and maximum, whereas percentages and frequencies were used for categorical variables. Groups were controlled in terms of conformity to normal distribution by graphical check and Shapiro Wilk test. Kruskall-Wallis variance analysis was performed for not normally distributing continuous variables and ANOVA was used for normally distributed continuous variables. Intergroup differences for categorical values were assessed with chi square test. Crosstabs and Roc curve were used for calculating sensitivity, specificity, positive predictive value and negative predictive value. The Pearson correlation analysis was used for determining the relations between perinatal outcomes and AFP, hCG and uE3. A p-value <0.05 was considered statistically significant.

re test. Crosstabs and Roc curve were used for calculating sensitivity, specificity, positive predictive value and negative predictive value. The Pearson correlation analysis was used for determining the relations between perinatal outcomes and AFP, hCG and uE3. A p-value <0.05 was considered statistically significant. RESULTS Demographic and obstetric characteristics of the patients were presented in Table 1. There was no significant differences for demographic and obstetric characteristics between the groups (p>0.05). According to the last menstruation period and ultrasonographic assessment, pregnancy weeks were similar. In Table 2, the mean and standard deviation values of AFP, hCG and uE3 for all groups were presented. When we analyze occurrence rates of maternal complications in group 1, 2, 3 and 4, the rates were determined as 8.5% (n=17), 25% (n=25), 21% (n=21) and 35% (n=35) respectively. Pregnancy complications were statistically significant higher in group 2, 3 and 4 when compared with control group (group 1) (p=0.001, p=0.002, p=0.001). Pregnancy-related complications and type of delivery of the groups were shown in Table 3.

termined as 8.5% (n=17), 25% (n=25), 21% (n=21) and 35% (n=35) respectively. Pregnancy complications were statistically significant higher in group 2, 3 and 4 when compared with control group (group 1) (p=0.001, p=0.002, p=0.001). Pregnancy-related complications and type of delivery of the groups were shown in Table 3. Sensitivity of isolated elevation of hCG (group 2) in predicting pregnancy complications was calculated as 25% whereas specificity as 91.5%, positive predictive value as 59.52% and negative predictive value as 70.93%. Sensitivity of isolated elevation of AFP (group 3) in predicting pregnancy complications was calculated as 21% whereas specificity as 91.5%, positive predictive value as 55.26% and negative predictive value as 69.85%. And for the last sensitivity of both high levels of hCG and AFP (group 4) in predicting pregnancy complications was calculated as 35% whereas specificity as 91.5%, positive predictive value as 67.31% and negative predictive value as 73.79%. Odd’s ratios were determined for group 2, 3 and 4 as 3.56 (95% CI= 1.83-7.02), 2.86 (95% GA = 1.43-7.02) and 5.80 (95% CI= 3.04-11.04), respectively Table 4. When cesarean indications were analysed, it was determined that the lowest cephalopelvic disproportion rate and the highest fetal distress and abnormal umbilical artery doppler rates were in group 4 while the rate of fetal macrosomia is the highest in group 2.

Sensitivity of isolated elevation of hCG (group 2) in predicting pregnancy complications was calculated as 25% whereas specificity as 91.5%, positive predictive value as 59.52% and negative predictive value as 70.93%. Sensitivity of isolated elevation of AFP (group 3) in predicting pregnancy complications was calculated as 21% whereas specificity as 91.5%, positive predictive value as 55.26% and negative predictive value as 69.85%. And for the last sensitivity of both high levels of hCG and AFP (group 4) in predicting pregnancy complications was calculated as 35% whereas specificity as 91.5%, positive predictive value as 67.31% and negative predictive value as 73.79%. Odd’s ratios were determined for group 2, 3 and 4 as 3.56 (95% CI= 1.83-7.02), 2.86 (95% GA = 1.43-7.02) and 5.80 (95% CI= 3.04-11.04), respectively Table 4. When cesarean indications were analysed, it was determined that the lowest cephalopelvic disproportion rate and the highest fetal distress and abnormal umbilical artery doppler rates were in group 4 while the rate of fetal macrosomia is the highest in group 2. For the neonatal outcomes, it was seen that birth weight, pregnancy week of delivery and Apgar score were significantly lower in group 3 and 4 (p>0.001) when compared with group 1 and 2. Also, the neonatal intensive care need and neonatal death were significantly higher in group 4 when compared with the other groups.

When cesarean indications were analysed, it was determined that the lowest cephalopelvic disproportion rate and the highest fetal distress and abnormal umbilical artery doppler rates were in group 4 while the rate of fetal macrosomia is the highest in group 2. For the neonatal outcomes, it was seen that birth weight, pregnancy week of delivery and Apgar score were significantly lower in group 3 and 4 (p>0.001) when compared with group 1 and 2. Also, the neonatal intensive care need and neonatal death were significantly higher in group 4 when compared with the other groups. DISCUSSION With the development of prenatal biochemical screening test programs, studies about relationship between increased AFP and hCG rates and adverse perinatal outcomes started to be published(12). In a prospective study conducted by Konachuk and friends, 35% of the pregnants with unexplained increased AFP level had at least one adverse perinatal outcome(13). Similarly in many retrospective studies, it was found that in second trimester, increased hCG rates were in relation with increased antenatal complications(9,14,15).

pective study conducted by Konachuk and friends, 35% of the pregnants with unexplained increased AFP level had at least one adverse perinatal outcome(13). Similarly in many retrospective studies, it was found that in second trimester, increased hCG rates were in relation with increased antenatal complications(9,14,15). It is thought that adverse perinatal outcomes are associated with placental function disorders in patients with unexplained increase of maternal serum markers. Elevation of AFP was related to increased transition from feto-maternal circulation due to the placental feto-maternal surface damage(16). Abnormally increased hCG levels are thought to have occured as a result of decreased placental perfusion related to low oxidation stemming, cytotrophoblasts’ abnormal placentation induced by hypoxia were shown in the histological studies conducted by Lieppman et al.(15). Brock et al. have stated that low birth weight (<2500 g) incidence is 10.7% when AFP level is above 2.3 MoM with no situation resulting this elevation such as twin pregnancy, NTD or fetal death, while 4.2% in the control group(17). Similarly, Wald et al. reported that an increased incidence of low birth weight, prematurity and perinatal death in pregnants with AFP level above 3 MoM(18).

Brock et al. have stated that low birth weight (<2500 g) incidence is 10.7% when AFP level is above 2.3 MoM with no situation resulting this elevation such as twin pregnancy, NTD or fetal death, while 4.2% in the control group(17). Similarly, Wald et al. reported that an increased incidence of low birth weight, prematurity and perinatal death in pregnants with AFP level above 3 MoM(18). When Heinonen and his friends analyzed the relation between hCG rates above 2.0 MoM and maternal complications and adverse perinatal outcomes, they have concluded that above this value, preeclampsia, low birth weight, IUGR, velamentous umbilical cord insertion risks have increased but there has not been a statistical significant difference in preterm birth, fetal distress, fetal-perinatal death and newborn intensive care units admission rates compared to the control group(19). Sorensen et al. have stated that there could be a high risk factor for preeclampsia when hCG increases. In a retrospective study conducted by David et al., 28743 pregnant records have been analysed and it has been determined that in 2561 patients, hCG MoM rate was above 2 and that in these patients, preeclampsia incidence has increased. In spite of that, a relation between gestational diabetes, PPROM, IUGR and small (SGA) according to gestational age has not been determined(20).

regnant records have been analysed and it has been determined that in 2561 patients, hCG MoM rate was above 2 and that in these patients, preeclampsia incidence has increased. In spite of that, a relation between gestational diabetes, PPROM, IUGR and small (SGA) according to gestational age has not been determined(20). Persson and friends, in a research they have conducted on 10147 pregnants, have taken AFP cut-off rate as 2.3 MoM and have reported that 2.8-fold increase in low birth weight, 2-fold increase in preterm labor risk, 3-fold increase in perinatal death risk. Besides, in this research, 10-fold increase in placental abruption risk was reported(21). In a study, Milunsky and friends were investigated 13486 pregnant women and they reported that 4-fold increase in low birth weight risk, 3-fold increase in placental abruption risk, 8-fold increase in intrauterine fetal death risk and 2.3-fold increase in preeclampsia risk when AFP value was above 2 MoM(22). In another study Williams and friends compared obstetric complications of 201 patients with AFP MoM rate above 2.0 and 211 patients with AFP MoM rate below 2. Increase in preterm birth risk (OR=3.6), IUGR (OR=4), preeclampsia (OR=3.8), and placental abruption (OR=4.8) were determined and it was suggested that in these patients, placenta must be analysed carefully with USG(23).

mplications of 201 patients with AFP MoM rate above 2.0 and 211 patients with AFP MoM rate below 2. Increase in preterm birth risk (OR=3.6), IUGR (OR=4), preeclampsia (OR=3.8), and placental abruption (OR=4.8) were determined and it was suggested that in these patients, placenta must be analysed carefully with USG(23). In the previous studies, it has been observed that, similarly to our research, obstetric complication rate has increased in more than one marker(24,25). Dugoff and friends have reported that in first and second trimester fatal aneuploidy risk (FASTER) study, obstetric complication risks such as preterm birth, preeclampsia, fetal death have increased correspondingly with number of abnormal marker(24). After relation between unexplained increased AFP and\or hCG levels and antepartum complications in the second trimester, the question of “What can be done to increase the antenatal survival in pregnancy?” has been raised. In a study Huerta-Enochian and friends has shown that among the women with unexplained AFP rate early and frequent follow-ups to increase antenatal survival did not improve outcomes(26). However these results contradicts with other studies conducted by performing biophysical profile and umbilical artery doppler as their basis in which they reported increased fetal survival(27,28).

After relation between unexplained increased AFP and\or hCG levels and antepartum complications in the second trimester, the question of “What can be done to increase the antenatal survival in pregnancy?” has been raised. In a study Huerta-Enochian and friends has shown that among the women with unexplained AFP rate early and frequent follow-ups to increase antenatal survival did not improve outcomes(26). However these results contradicts with other studies conducted by performing biophysical profile and umbilical artery doppler as their basis in which they reported increased fetal survival(27,28). Although there is a relationship between the abnormal maternal serum levels and poor obstetric outcomes, these tests remain only as a research tool due to their low sensitivity and positive predictive values. Therefore, they can not be used in clinical practice as screening test. In our research, too, even though relationship with high AFP and\or hCG level and maternal complications have been found statistically significant (p=0.001), our sensitivity and positive predictive rates were low. Even though some researchers have stated that adverse pregnancy outcomes would be decreased by performing serial ultrasound and uterine artery doppler measurements on pregnants with unexplained high maternal serum AFP and hCG rates, in a study conducted by Hamid and friends reported that such kind of an observation cannot make an improve in the outcomes(29).

that adverse pregnancy outcomes would be decreased by performing serial ultrasound and uterine artery doppler measurements on pregnants with unexplained high maternal serum AFP and hCG rates, in a study conducted by Hamid and friends reported that such kind of an observation cannot make an improve in the outcomes(29). How early to start evaluation of the fetal well-being and to whom to apply serial tests with pregnants diagnosed with unexplained increased AFP and\or hCG are other questions. Van Rijn and friends have stated that, if there occurs a fetal death, it occurred approximately the 28th week of gestation in women whose serum markers are normal, and it occurred approximately the 20th week of gestation in women with increased AFP and hCG rates(30).

lained increased AFP and\or hCG are other questions. Van Rijn and friends have stated that, if there occurs a fetal death, it occurred approximately the 28th week of gestation in women whose serum markers are normal, and it occurred approximately the 20th week of gestation in women with increased AFP and hCG rates(30). Although our purpose has been to determine a distinctive limit value between the pregnants to be diagnosed with normal and complications for AFP and hCG, in our study especially the limit value we have accepted for AFP (for the reason that pregnancies having higher rates are ended with the diagnose of fetal anomaly) is low (2.0 MoM) and working with only one serum sample have effected the results. Because about this issue, besides a distinctive limit value for AFP and hCG rates in pregnancies to be ended normally and abnormally are not known, there has been studies suggesting that in a population analysed in a rational approach (complication expected) AFP rates must be triply increased rates. Also, in studies which AFP cut off value was taken over 2 MoM for two different serum samples or 2.5 MoM or above just one sample and hCG is over 4 MoM higher predictive rates can be reached, increasing of the limit value accepted and practice with much wider populations, may increase predictivity(9,31).

creased rates. Also, in studies which AFP cut off value was taken over 2 MoM for two different serum samples or 2.5 MoM or above just one sample and hCG is over 4 MoM higher predictive rates can be reached, increasing of the limit value accepted and practice with much wider populations, may increase predictivity(9,31). As a result of our research, in the second trimester unexplained AFP and hCG rates have been found related to adverse perinatal outcomes. Pregnancies in which both AFP and hCG rates increasing together are being more complicated with adverse perinatal outcomes more and in a more serious manner than pregnancies in which rates increase one by one. In the second trimester screening test, without the chromosomal or structural anomaly in a single pregnancy whose pregnancy week calculation is correct, increased AFP and hCG levels must be stimulant in terms of adverse perinatal outcomes, and by starting the follow-up in early period, effort should be made for increasing the fetal survival. Prospective studies are needed for decreasing adverse perinatal outcomes. Table 1 Demographic characteristics of the groups Table 2 Laboratory data of the groups Table 3 Pregnancy-related complications and type of delivery of the groups Table 4 The sensitivity, specificity and predictive rates of serum AFP and hCG levels for predicting pregnancy complications

INTRODUCTION Intrahepatic cholestasis of pregnancy (ICH) is a disease characterized with severe pruritus and increased levels of serum bile acids (SBA), seen in second and third trimesters of pregnancy. It is reported to complicate 0.1-15% of pregnancies in different series and is the most common pregnancy associated hepatic disorder(1,2,3). Major symptom is pruritus of all body especially located to palms and soles and which increases at nights(4). The prevalence of ICH is significantly increased in twin pregnancies(5). Since there are studies trying to explain etiologic factors (such as hormonal, genetic and inflammatory) causing the increased levels of maternal SBA levels, the etiology is not clear yet. There is increased level of liver enzymes but diagnosis should be based on elevated levels of SBA. Other laboratory findings of cholestasis also accompany this increased level of bile acids. The differential diagnosis of viral hepatitis should be made in patients with severely-increased levels of aminotransferases(6). The diagnosis of ICH should be based on laboratory findings of liver dysfunction in patients with severe pruritus(7). The pruritus and the deteriorated liver enzymes typically returns normal levels 4 weeks after delivery(8). Ursodeoxycholic acid (UDCA) is used in the treatment of IHC(9). It is found to be more effective on maternal symptom, decreasing serum bile acid and liver enzymes levels than cholestyramine and dexamethasone(9,10). UDCA is also found to regulate the plasental bile acid transport(10,11).

There is increased level of liver enzymes but diagnosis should be based on elevated levels of SBA. Other laboratory findings of cholestasis also accompany this increased level of bile acids. The differential diagnosis of viral hepatitis should be made in patients with severely-increased levels of aminotransferases(6). The diagnosis of ICH should be based on laboratory findings of liver dysfunction in patients with severe pruritus(7). The pruritus and the deteriorated liver enzymes typically returns normal levels 4 weeks after delivery(8). Ursodeoxycholic acid (UDCA) is used in the treatment of IHC(9). It is found to be more effective on maternal symptom, decreasing serum bile acid and liver enzymes levels than cholestyramine and dexamethasone(9,10). UDCA is also found to regulate the plasental bile acid transport(10,11). In contrast to benign maternal course in ICH, the fetuses face with complications such as preterm labor, meconium stained amniotic fluid and intrauterine fetal demise(12). There is no ideal fetal follow up protocol for ICH cases. Fetal complications cannot be anticipated by ultrasonography or cardiotocography. In this retrospective study we aimed to evaluate perinatal outcomes of ICH cases in our clinic and to evaluate the relation of ICH with preterm labor.

ntrauterine fetal demise(12). There is no ideal fetal follow up protocol for ICH cases. Fetal complications cannot be anticipated by ultrasonography or cardiotocography. In this retrospective study we aimed to evaluate perinatal outcomes of ICH cases in our clinic and to evaluate the relation of ICH with preterm labor. MATERIAL AND METHODS Study Participants Patients with ICP were selected from medical records of our perinatology clinic enclosing the interval between June 2009 and June 2013. Elevated serum bile acid levels above 10 μmol/L in patients who are in between 24th and 40th gestational weeks of pregnancy, having complaints of pruritus, and/or elevated liver enzymes were diagnosed as ICP. Patients with active viral hepatitis, dermatologic causes of pruritus, gall bladder and liver disorders, and preeclampsia were excluded from the study. Patients who are diagnosed as ICP were followed-up with serial ultrasonographic examinations and fetal biophysical profile weekly for the assessment of fetal well-being. Ursodeoxycholic acid was administered in 10 to 15 mg/kg/day in divided dosages according to the severity of symptoms and serum levels of liver enzymes. During follow-up, labor was induced in presence of non-reassuring non-stress test and/or an increase in serum levels of the liver enzymes above 10 times of the normal values.

oxycholic acid was administered in 10 to 15 mg/kg/day in divided dosages according to the severity of symptoms and serum levels of liver enzymes. During follow-up, labor was induced in presence of non-reassuring non-stress test and/or an increase in serum levels of the liver enzymes above 10 times of the normal values. Age, gravidity, parity, gestational age at diagnosis, body mass index (BMI), highest SBA value, liver aminotransferase level, severity of symptoms, delivery time, mode of delivery of the patients and APGAR score at 5th minute, birth weights of the newborns were recorded. Deliveries before 37th gestational week for the singletons, and deliveries before 36th gestational week for the twin pregnancies were defined as preterm delivery. Additionally, full-term and preterm deliveries were divided into iatrogenic and spontaneous delivery groups. Statistical Analyses Statistical analyses were conducted by Statistical Package for the Social Sciences (SPSS) 22.0 (Chicago, IL.). Student’s t-test and Mann-Whitney U-test were used in the comparisons of continuous variables, which are distributed normally and abnormally, respectively. Spearman’s rank correlation coefficient was calculated for the definition of the strength of possible associations. Pearson’s chi-squared test was used in the comparisons of groups consisting categorical variables. A p-value <0.05 was accepted as the statistical significance.

uted normally and abnormally, respectively. Spearman’s rank correlation coefficient was calculated for the definition of the strength of possible associations. Pearson’s chi-squared test was used in the comparisons of groups consisting categorical variables. A p-value <0.05 was accepted as the statistical significance. Sixty-two patients were diagnosed as ICP at study period. One patient was excluded from the study because she had triplet pregnancy. Eight (13%) of the 61 patients had twin pregnancies, while 53 (87%) patients were singletons. Median age of the study participants was 28 (20-43) years. Median gestational age at the diagnosis was 34 weeks (26-36 weeks) in patients with twin pregnancies, and 37 weeks (25-39 weeks) for singletons. At the time of diagnosis, median SBA level was 36µmol/L, median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 191 IU/L and 109 IU/L, respectively (Table 1). Delivery was achieved by cesarean section in 42.6% of the participants. The ratio of cesarean section was %60 for singletons, and %62.5 for twin pregnancies. The most common indication for cesarean section was fetal distress with a rate of %46. In our follow-up, there were not perinatal or maternal deaths. Only one of the patients needed blood transfusion because of peripartum hemorrhage as a complication of delivery.

was %60 for singletons, and %62.5 for twin pregnancies. The most common indication for cesarean section was fetal distress with a rate of %46. In our follow-up, there were not perinatal or maternal deaths. Only one of the patients needed blood transfusion because of peripartum hemorrhage as a complication of delivery. Twenty-nine patients had spontaneous labor and 32 patients (52%) were induced for labor because of the fetal and maternal reasons. Mean gestation age at delivery was 35 weeks for spontaneous delivery group and 37 wks for induction group. Mean SBA value was 26.9 µmol/L in the induction group and it was 34.5 µmol/L in spontaneous delivery group but the difference was not statistically significant (p=0.094) (Table 2). Number of the patients with iatrogenic preterm delivery was less than iatrogenic term delivery group (4 vs. 28 patients) (p=0.001) (Table 3). Sixty two point five percent (n=5) of twin pregnancies and 24.5% (n=13) of singleton pregnancies had preterm labor. Iatrogenic preterm delivery ratio was 20% in twin pregnancy and 23% in single pregnancy. In preterm delivery group, only one patient (5.5%) had a previous preterm birth history. We found that preterm delivery group had statistically higher levels of SBA versus term delivery group (p=0.001) (SBAs=100.8 µmol/L versus 29.9 µmol/L) (Table 3). When neonatal outcomes were examined; there was no significant relation between SBA levels and 5th minutes Apgar scores or neonatal birth weights (p=0.353 and p=0.156, respectively).

ivery group had statistically higher levels of SBA versus term delivery group (p=0.001) (SBAs=100.8 µmol/L versus 29.9 µmol/L) (Table 3). When neonatal outcomes were examined; there was no significant relation between SBA levels and 5th minutes Apgar scores or neonatal birth weights (p=0.353 and p=0.156, respectively). Nine of 61 patients had the diagnosis of gestational diabetes (14.75%) and another 6 were complicated with preeclampsia (9.8%). The patients with gestational diabetes had the diagnosis of ICP in a mean of 31 weeks. The 6 patients had the diagnosis of preeclampsia after 3 weeks of their diagnosis of ICP (mean 35 weeks). There was not a statistically significant difference in mean values of SBAs between uncomplicated patients and patients complicated with GDM, and preeclampsia (31.6 mmol/L, 43.5 mmol/L, and 51.07 mmol/L, respectively; p=0.669 and p=0.622, respectively). DISCUSSION Although intrahepatic cholestasis of pregnancy is a benign condition and has a mild to moderate derangements to the mother’s health status, it is known to be associated with unfavorable consequences for the pregnancy and the fetus. However, the studies that investigate the correlation between serum bile acids and fetal consequences are inadequate, so far.

pregnancy is a benign condition and has a mild to moderate derangements to the mother’s health status, it is known to be associated with unfavorable consequences for the pregnancy and the fetus. However, the studies that investigate the correlation between serum bile acids and fetal consequences are inadequate, so far. In this study, SBA values in patients with preterm delivery were found to be higher, which was statistically significant, when compared to the patients who delivered at term. This finding was compatible with the previous studies(8,9,13,14,15). In a study, frequency of preterm delivery was reported to be 18.7% in patients with ICP, and SBA measurements in those patients were reported to be increased significantly compared to the term parturient(13). But, the latter study enclosed lesser participants than current study. In a cross-sectional study from Sweden, increased frequency of preterm delivery in the previous pregnancies of patients with ICP was established(15). Also, a positive linear correlation between SBA and preterm delivery with every 1-2 mmol/L increase in SBA was asserted in that study. Additionally, authors reported that frequencies of fetal complications, besides preterm delivery, were to be increased particularly when SBA levels were measured over 40 mmol/L. The reported rate of spontaneous preterm delivery was 11%, whereas this ratio was reported as high as 16.7% in patients with ICP in study of Glantz et al.(15). In another Swedish study, 3.3 times increased risk for spontaneous preterm delivery was established in patients with ICP when preterm deliveries between 32th and 37th gestational weeks were evaluated(8). Moreover, patients who were diagnosed to have ICP were found to have 5 times increased risk for iatrogenic preterm delivery, in the same study(8). In this study, 77% of preterm deliveries were spontaneous deliveries among the singleton pregnancies, iatrogenic preterm delivery risk was found not to be increased. Similar to the previous studies, Geenes et al reported that frequency of preterm delivery in singleton pregnancies with severe ICP increased 5.3 times compared to the healthy singletons(14). Contrary to the results of the previously mentioned studies, Rook et al. reported absence of any association between any biochemical marker related to ICP and increased fetal complications(16).

uency of preterm delivery in singleton pregnancies with severe ICP increased 5.3 times compared to the healthy singletons(14). Contrary to the results of the previously mentioned studies, Rook et al. reported absence of any association between any biochemical marker related to ICP and increased fetal complications(16). In the current study, we found that SBA measurements were not correlated with the weight and APGAR scores of the newborns who were born to mothers with ICP. The exact mechanism of preterm delivery in patients with intrahepatic cholestasis is not known. It is thought that biliary products increase the sensitivity, and therefore, contractility of the myometrium. Particularly, Germain et al. demonstrated an increased response for oxytocin and increased expression of oxytocin receptors in myometrial tissues incubated with cholic acid(17). Similar to that study, Israel et al demonstrated a similar phenomenon(18). In the latter study, an increased response to the oxytocin was achieved in myometrial cells which were obtained directly from pregnant women with ICP(18).

sed expression of oxytocin receptors in myometrial tissues incubated with cholic acid(17). Similar to that study, Israel et al demonstrated a similar phenomenon(18). In the latter study, an increased response to the oxytocin was achieved in myometrial cells which were obtained directly from pregnant women with ICP(18). The other major complication of ICP is intrauterine fetal demise, particularly at term. In the literature, a pregnancy beyond 37th weeks of gestation is addressed as a risk for this unpredicted-, undesired-situation, in a patient with ICP(8,16,19). In the current study, there is no case with antenatal fetal demise. Absence of any fetal loss could be due to close follow-up of the patients and administration of ursodeoxycholic acid (UDCA) treatment where appropriate. The etiology of fetal mortality in patients with ICP is not readily evident. However, there are theories which link this condition to the toxic effects of SBAs(19,20). In a study which was conducted on rats, taurocholic acid-one of the bile acids- was asserted to cause sudden fetal demise by triggering cardiac arrhythmias due to its toxic effects on cardiomyocytes(21). He et al. reported a 29% decrease in volume of placental lobular villous vessels in patients with ICP(22). Placental dysfunction as it is mentioned by He et al. is the other possible cause of intrauterine fetal loss. For this reason, Doppler examination of the fetal umbilical arteries during the follow-up of fetuses in patients with ICP is enounced as a valuable method(23). However, presence of acute anoxia signs rather than chronic anoxia features, presence of correlated fetal weights with the other fetuses at the same gestational age, and presence of normal umbilical artery signs in the examination of fetuses who were lost due to ICP asserted the cause of fetal death due to acute toxic effects of SBA rather than chronic placental insufficiency(24). Therefore, planned preterm deliveries are addressed in the studies to decrease the frequency of intrauterine fetal losses(25,26). Low frequencies of intrauterine fetal demise in this study and other studies in which iatrogenic preterm delivery rates were increased is due to active treatment of the patients.

ciency(24). Therefore, planned preterm deliveries are addressed in the studies to decrease the frequency of intrauterine fetal losses(25,26). Low frequencies of intrauterine fetal demise in this study and other studies in which iatrogenic preterm delivery rates were increased is due to active treatment of the patients. Lausman et al. did not find increased risk for poor perinatal outcomes in patients with multiple pregnancies complicated by ICP(27). In the current study, there was no statistically significant difference between singleton pregnancies and multiple pregnancies with respect to mean SBAs, frequencies of preterm delivery, and other perinatal morbidities. Complication rates like postpartum hemorrhage and preeclampsia in patients with ICP were similar to the healthy pregnant women in a retrospective study which comprise 1210 patients(28). But, there are studies that indicate a possible genetic relationship between ICP and preeclampsia(8,29). In this study, the occurrence of preeclampsia among patients with ICP was 9.8%. There was not a statistically significant difference with regard to SMAs between patients with ICP and patients with ICP who were complicated with preeclampsia.

at indicate a possible genetic relationship between ICP and preeclampsia(8,29). In this study, the occurrence of preeclampsia among patients with ICP was 9.8%. There was not a statistically significant difference with regard to SMAs between patients with ICP and patients with ICP who were complicated with preeclampsia. The efficacy of UDCA in treating itching and liver enzyme elevation was shown in plenty of studies(9,10). Additionally, Palma et al. demonstrated efficacy of UDCA in improving fetal results also(30). Furthermore, there are studies, which show that UDCA reduces SBA measurements in fetal chord blood and amniotic fluid, and improves maternal clinical outcome after parturition(31). More studies investigating the favorable effects of UDCA on perinatal outcomes are required. CONCLUSION Patients with ICP constitute a high-risk pregnancy group with respect to fetal and maternal outcomes. Antenatal follow-up of these patients should be performed cautiously for a possible onset of preterm delivery, and scheduled prior to unfavorable fetal conditions occur. Table 1 Maternal and Fetal Demographic Values Table 2 Comparison of spontaneous and induced births of IHC patients Table 3 Comparison of preterm and term births of IHC patients

INTRODUCTION Sexuality is the emotional, spiritual, and behavioral interaction between two individuals, which is surrounded by cultural values, taboos, and social norms(1). Human sexuality varies with culture. In our society, independent of the educational level, there is a widespread presence of sexual problems and sexual ignorance. However, the people’s refraining from, shame of, and hiding their sexuality prevent them from discussing sexual problems and getting help. The human sexual response cycle is a four-stage model of physiological responses to sexual stimulation, which, in order of their occurrence, are the arousal phase, plateau phase, orgasm phase, and the resolution phase(2,3). Men’s sexual response has one single pattern, differing only in terms of duration. On the other hand, women can have responses that differ both in intensity and duration. In the International Classification of Diseases and Related Health Problems (ICD-10) published by The World Health Organization (WHO), sexual dysfunction is defined as the inability to fully enjoy sexual intercourse(4). According to the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders published in 1999 [DSM-4], sexual dysfunction is classified as sexual desire disorder, sexual arousal disorder, orgasmic disorder, and pain related disorders(5).

ion is defined as the inability to fully enjoy sexual intercourse(4). According to the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders published in 1999 [DSM-4], sexual dysfunction is classified as sexual desire disorder, sexual arousal disorder, orgasmic disorder, and pain related disorders(5). The management and therapy of sexual problems and sexual function impairment in men have yielded significantly good results. On the other hand, success in the diagnosis and therapy of female sexual dysfunction has been limited. One of the most important causes of this situation is that women are inhibited from expressing their sexual problems and seeking therapy due to prejudices, wrong beliefs, and sense of shame. Studies on the female sexual dysfunction in Turkey are limited in number. However, recently, the interest in female sexual dysfunction has increased and problems related to female sexuality and sexual problems have been discussed to a greater extent than formerly. The most frequently used scale for evaluating female sexual dysfunction is the Female Sexual Function Index (FSFI). The FSFI form, which was developed by Rosen et al.(6), includes 19 questions that evaluate the sexual activity. The questions are related to six topics: Sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The form has been validated for the Turkish community, and its Turkish version has been written(7).

he FSFI form, which was developed by Rosen et al.(6), includes 19 questions that evaluate the sexual activity. The questions are related to six topics: Sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The form has been validated for the Turkish community, and its Turkish version has been written(7). The purpose of this study was to assess the prevalence of sexual problems and the association between sexual problems and demographic variables, and some probable factors in married women living in the North Eastern Black Sea region of Turkey. MATERIALS AND METHODS This investigation was a cross-sectional and descriptive study carried out in the outpatient clinic of obstetrics and gynecology of a university hospital. Married women aged 18-50 presenting for routine gynecological examination, were included in the study. Women who did not have sexual intercourse in last month, were pregnant or delivered in last 6 months or whose husband had sexual dysfunction were excluded from the study. Permission for the study was obtained from the Ethics Committee of the Faculty. Since the study was based on voluntary participation of the patients, the purpose of the study was first explained to the patients, and then those volunteering to participate were included in the study. The participating women were first questioned on their socio-demographic features, which included age, pregnancy, number of children, duration of marriage, education, and income level. Consequently, the women were asked to fill in the FSFI form.

MATERIALS AND METHODS This investigation was a cross-sectional and descriptive study carried out in the outpatient clinic of obstetrics and gynecology of a university hospital. Married women aged 18-50 presenting for routine gynecological examination, were included in the study. Women who did not have sexual intercourse in last month, were pregnant or delivered in last 6 months or whose husband had sexual dysfunction were excluded from the study. Permission for the study was obtained from the Ethics Committee of the Faculty. Since the study was based on voluntary participation of the patients, the purpose of the study was first explained to the patients, and then those volunteering to participate were included in the study. The participating women were first questioned on their socio-demographic features, which included age, pregnancy, number of children, duration of marriage, education, and income level. Consequently, the women were asked to fill in the FSFI form. The scaling system of FSFI, which included questions on 6 topics, namely sexual desire, arousal, lubrication, orgasm, satisfaction, and pain, has been presented in (Table 1). The lowest score was calculated as 2 and the highest score as 36. The total FSFI score under 26.55 was accepted as sexual dysfunction(8).

The participating women were first questioned on their socio-demographic features, which included age, pregnancy, number of children, duration of marriage, education, and income level. Consequently, the women were asked to fill in the FSFI form. The scaling system of FSFI, which included questions on 6 topics, namely sexual desire, arousal, lubrication, orgasm, satisfaction, and pain, has been presented in (Table 1). The lowest score was calculated as 2 and the highest score as 36. The total FSFI score under 26.55 was accepted as sexual dysfunction(8). The data were statistically evaluated using the SPSS Statistics 17.0 package program. In the statistical analysis of the relationship between the groups, the Kruskall-Wallis test was used for the multiple independent variables (age, income level, educational level, contraceptive method), and the Mann-Whitney test was used for the two independent variables. A p value of <0.05 was accepted as statistically significant. The Pearson’s test was performed for the correlation between numerical values. RESULTS A total of 175 married women of age 18-50 participated in the study. When the cut-off value for sexual dysfunction in the FSFI scale was taken as 26.55, 70.9% of the participants showed indices under the limit value. The socio-demographic features of the participants have been displayed in Table 2, and the distribution of their sexual function indices according to their socio-demographic features has been presented in (Table 3).

on in the FSFI scale was taken as 26.55, 70.9% of the participants showed indices under the limit value. The socio-demographic features of the participants have been displayed in Table 2, and the distribution of their sexual function indices according to their socio-demographic features has been presented in (Table 3). There was a significant relationship between the participants’ age groups and the subgroups of sexual desire (p=0.011 χ2= 9.021), arousal (p=0.002 χ2=12.207), lubrication (p=0.018 χ2=8.038), satisfaction (p=0.002 χ2=12.443) and total scores (p=0.011 χ2=8.974). According to these results, sexual desire in women of age 31-40 was significantly higher, and arousal, lubrication, satisfaction, and the total score in women of age 41-50 were significantly lower, than those of the other age groups. However, there was no significant difference between the age groups in terms of orgasm and pain (p=0.162 and p=0.381, respectively). As the number of children increased, the total FSFI score decreased (p=0.049). With the increase in the duration of marriage, the total FSFI score decreased (p=0.007). The income level did not have a significant effect on the sexual function (p>0.05). When the sexual function indices of employed and unemployed women were compared, there was a significant difference in terms of lubrication (p=0.041, z=-2.042) and the total score (p=0.044, z=-2.017) (p<0.05). The values of lubrication and total score were significantly higher employed women than in unemployed women.

. When the sexual function indices of employed and unemployed women were compared, there was a significant difference in terms of lubrication (p=0.041, z=-2.042) and the total score (p=0.044, z=-2.017) (p<0.05). The values of lubrication and total score were significantly higher employed women than in unemployed women. There was a significant difference between all the subgroups, except for pain (sexual desire: p=0.000, χ2= 16.981; arousal: p=0.000, χ2=19.455; lubrication: p=0.008, χ2=9.709; orgasm: p=0.000 χ2=18.804; satisfaction: p=0.007 χ2=10.008) and the total score (p=0.000, χ2=16.740) in terms of the educational level. The level of sexual function was higher in women with secondary school education than in women with primary school and lower education, and in women with university and higher education. However, there was no significant difference between all levels of education in terms of pain (p=0.880).

ms of the educational level. The level of sexual function was higher in women with secondary school education than in women with primary school and lower education, and in women with university and higher education. However, there was no significant difference between all levels of education in terms of pain (p=0.880). In terms of the contraception method used, there was a significant difference between arousal (p=0.048, χ2=9.568), orgasm (p=0.004 χ2=15,181), satisfaction (p=0.006 χ2=14.640), and the total score (p=0.020, χ2=11.657); however, women using no contraceptive method displayed lower scores in all subgroups. The arousal level was higher in women using hormonal contraception (p=0.023). The score of orgasm was higher in women having a contraception method than in those not using contraception (p=0.000). Sexual satisfaction scores were found to be higher in women using condom and hormonal contraception. Women using the methods of interrupted coitus and hormonal contraception had high total FSFI scores.

The score of orgasm was higher in women having a contraception method than in those not using contraception (p=0.000). Sexual satisfaction scores were found to be higher in women using condom and hormonal contraception. Women using the methods of interrupted coitus and hormonal contraception had high total FSFI scores. DISCUSSION The FSFI has been tested in many populations and accepted as a useful scale in screening sexual dysfunction with a cut-off value of 26.55(8). The prevalence of sexual dysfunction differs based on community samples. The prevalence of sexual dysfunction determined by FSFI ranges from 43% to 69%(9). A study on women of age 18-59 in the United States reported the prevalence of sexual dysfunction as 43%(10). Cayan et al.(11) reported this prevalence as 46.9% in Turkey. In our study, in contrast to the studies mentioned above, we determined a low sexual function index in 70.9% of the participants. The prevalence of sexual dysfunction in sexually active women was determined as 70% in Ghana by Amidu et al.(12) and over 71% in Nigeria by Ojomu et al.(13). Both studies reported that sexual dysfunction was associated with age, years of marriage, and number of children. Furthermore, the educational level, the working status, and use of contraceptive methods were found to have predictive values. However, no relationship was determined between the income level and sexual function(12,13).

reported that sexual dysfunction was associated with age, years of marriage, and number of children. Furthermore, the educational level, the working status, and use of contraceptive methods were found to have predictive values. However, no relationship was determined between the income level and sexual function(12,13). In this study, the sexual function indices of married women living in the North Eastern Black Sea region were evaluated using the FSFI scale, and their scores for each of sexual desire, arousal, lubrication, orgasm, satisfaction and pain subgroups, in addition to their total scores were calculated. According to these findings, the sexual function level was inversely affected by age and duration of marriage. It was known that menopause negatively affects the sexual functions(14). In our study, we evaluated women in the reproductive ages, and although our participants were not in menopause, we observed that advancing age in women negatively affected the sexual functions. Additionally, we also determined that a long marriage life negatively affected the sexual functions. This situation may be due to the advancing age of the woman or the couple’s loss of interest for each other, or problems arising between the man and wife. Güvel et al.(15) determined that the decrease in sexual function was parallel to the duration of marriage. Oniz et al.(16) reported that sexual problems increased in marriages continuing for more than 11 years.

e of the woman or the couple’s loss of interest for each other, or problems arising between the man and wife. Güvel et al.(15) determined that the decrease in sexual function was parallel to the duration of marriage. Oniz et al.(16) reported that sexual problems increased in marriages continuing for more than 11 years. The level of sexual function was found to be higher in women with secondary school education than in women with primary school and lower education and in women with university and higher education. In the literature, the relevant data are different. Aslan et al.(17) reported that sexual dysfunction was more prevalent in women with low educational level. Güvel et al.(15) reported that the educational level had no effect on sexual functions, but they also stated this result could be due to the low educational level of women participating in their study. Many studies performed abroad have shown the association of low educational level with sexual dysfunction(18,19,20). Studies in Nigeria(21) and Malaysia(22) reported that as the educational level rose, the incidence of sexual dysfunction increased. In contrast to these studies, we found higher sexual function indices in women with medium level of education. This finding can be explained by the interaction of other factors such as age, working status, and duration of marriage, with the educational level.

l level rose, the incidence of sexual dysfunction increased. In contrast to these studies, we found higher sexual function indices in women with medium level of education. This finding can be explained by the interaction of other factors such as age, working status, and duration of marriage, with the educational level. Our results showed that with an increase in the number of children, the sexual functions decreased (p=0.049). Likewise, Özerdoğan(23) and Cayan et al.(11) showed that an increase in parity negatively affected the sexual functions. As factors associated with the number of children, also the woman’s advancing age and type of delivery negatively affected the sexual functions. Our study showed that the income level had no effect on sexual functions. It was seen that working women had higher total scores and lubrication scores. However, former studies performed in Turkey reported that the income level was closely associated with sexual functions. Özerdoğan et al.(23) reported a close relationship between the income level and SFI and higher values of SFI in unemployed women. Özkan et al.(24) reported that as the income increased, the sexual desire, lubrication, and satisfaction decreased, and that there was no association between sexual functions and the working status of women.

23) reported a close relationship between the income level and SFI and higher values of SFI in unemployed women. Özkan et al.(24) reported that as the income increased, the sexual desire, lubrication, and satisfaction decreased, and that there was no association between sexual functions and the working status of women. It was seen that women not practicing contraception had lower scores in all subgroups of FSFI and total scores. A study carried out in Colombia(25) reported that the total FSFI score was low in women practicing natural contraception, whereas it was higher in women using modern contraception methods; however, the difference between these two groups was insignificant. İbrahim et al.(26) reported that women practicing hormonal contraception and using intrauterine device had worse FSFI, whereas FSFI was not affected in women practicing no contraception. In our study, we found low FSFI scores in women practicing no contraception, which may be due to the fear of unwanted pregnancies. An interesting finding in our study was that women practicing hormonal contraception had higher indices in arousal, satisfaction, and total score. Furthermore, sexual satisfaction was found to be high in women using condom. Additionally, orgasm indices were higher in all women using contraceptive methods than in women practicing no contraception. In contrast to the former finding of no association between the contraception method and the sexual function levels in Turkey(11), our study demonstrated that contraceptive methods positively affected the sexual functions of women.

gher in all women using contraceptive methods than in women practicing no contraception. In contrast to the former finding of no association between the contraception method and the sexual function levels in Turkey(11), our study demonstrated that contraceptive methods positively affected the sexual functions of women. In our study, we determined high pain scores in all women independent of age, duration of marriage, educational level, working status, and contraceptive method. Since dyspareunia was frequent in the participants, although none of them had expressed sexual dysfunction on presentation, and since the pain index was high independent of the demographic features, we can conclude that sexuality is still a taboo in our society. The women in our society cannot freely express their sexual problems, due to social and cultural factors and religious beliefs. The prevalence of dyspareunia in Turkey varies between 7.8% and 47.2%(27,28). This high prevalence of dyspareunia, independent of the educational level may be due to absence of sexual education in schools and the low level of sexual knowledge even in women with high educational level.

ral factors and religious beliefs. The prevalence of dyspareunia in Turkey varies between 7.8% and 47.2%(27,28). This high prevalence of dyspareunia, independent of the educational level may be due to absence of sexual education in schools and the low level of sexual knowledge even in women with high educational level. Sexual life and sexual satisfaction are affected by physiological, psychological, and socio-cultural factors(29). The diagnosis and determination of the prevalence of sexual dysfunction are closely associated with the methods used. The FSFI is a widely used scale for screening sexual dysfunction, but is insufficient on its own for the diagnosis of sexual dysfunction. Female sexual dysfunction is a multi-dimensional health problem caused by organic, psychological, and social factors. Anamnesis is very important in the diagnosis of sexual dysfunction. Beside FSFI, various questionnaire forms have been developed. But the greatest obstacle in front of diagnosing SFI is the refrain of the individual to express her problem as a complaint. Every woman, in whatever age or social status, presenting to the gynecologist should be questioned on sexual health and, if needed, should receive consultancy. Women should be fully informed on sexuality, so that they can express their sexuality and increase their awareness of sex. We express our thanks to Associate Professor Dr. Nurhayat Özdemir, who contributed to the statistical analyses of our study.

Sexual life and sexual satisfaction are affected by physiological, psychological, and socio-cultural factors(29). The diagnosis and determination of the prevalence of sexual dysfunction are closely associated with the methods used. The FSFI is a widely used scale for screening sexual dysfunction, but is insufficient on its own for the diagnosis of sexual dysfunction. Female sexual dysfunction is a multi-dimensional health problem caused by organic, psychological, and social factors. Anamnesis is very important in the diagnosis of sexual dysfunction. Beside FSFI, various questionnaire forms have been developed. But the greatest obstacle in front of diagnosing SFI is the refrain of the individual to express her problem as a complaint. Every woman, in whatever age or social status, presenting to the gynecologist should be questioned on sexual health and, if needed, should receive consultancy. Women should be fully informed on sexuality, so that they can express their sexuality and increase their awareness of sex. We express our thanks to Associate Professor Dr. Nurhayat Özdemir, who contributed to the statistical analyses of our study. Table 1 Subgroups of FSFI Table 2 Demographic characteristics of the patients Table 3 Distrubition of FSFI according to demographic characteristics

INTRODUCTION Ovarian hyperstimulation is characterised by cystic enlargement of the ovaries, gastrointestinal symptoms, hypovolemia, hemoconcentration, thromboembolic events, respiratory distress and renal failure(1,2). The incidence of moderate form is approximately 3%-6%, where as the potentially life-threatening severe forms occur in 0.1%-3% of all cycles(2). The main risk factors of the syndrome are young age, polycystic ovary syndrome (PCOS), high absolute or rapidly raising serum estradiol levels and high basal antimullerian hormone (AMH)(3,4). The pathophysiology of Ovarian hyperstimulation syndrome (OHSS) depends on increased capillary permeability with fluid shift from intravascular compartment to the extravascular area(2,5,6). OHSS remains as a clinical problem for hyperresponder patients during controlled ovarian hyperstimulation for in vitro fertilization (COH-IVF). The endogenous or exogenous hCG exposure in patients with a large number of follicles (≥20) on both ovaries and E2 concentration >3000 pg/ml is the initiating factor for OHSS. Several treatment strategies with different clinical outcomes have been recommended for OHSS prevention(7,8).

in vitro fertilization (COH-IVF). The endogenous or exogenous hCG exposure in patients with a large number of follicles (≥20) on both ovaries and E2 concentration >3000 pg/ml is the initiating factor for OHSS. Several treatment strategies with different clinical outcomes have been recommended for OHSS prevention(7,8). Coasting has been widely used successfully in IVF centers since the 1980s as an effective method to avoid OHSS(9,10,11,12). Coasting is withholding gonadotropin stimulation and delaying the hCG trigger until serum estradiol levels drop to a safe level while GnRH agonist administration continues. It may lower the incidence and severity of OHSS in high risk patients but does not totaly eliminates the risk of OHSS(13). Despite many studies done in the literature, there is no consensus for a specific coasting protocol on how to apply it, such as when to start coasting, duration of coasting or a threshold for the pecentage of serum estradiol level decrement that would not compromise the IVF outcome. In this study, we evaluated the COH-IVF outcomes of the hyperresponder patients managed with coasting for OHSS prevention regarding the establishment of clinical pregnancy as an endpoint of the treatment cycle.

Coasting has been widely used successfully in IVF centers since the 1980s as an effective method to avoid OHSS(9,10,11,12). Coasting is withholding gonadotropin stimulation and delaying the hCG trigger until serum estradiol levels drop to a safe level while GnRH agonist administration continues. It may lower the incidence and severity of OHSS in high risk patients but does not totaly eliminates the risk of OHSS(13). Despite many studies done in the literature, there is no consensus for a specific coasting protocol on how to apply it, such as when to start coasting, duration of coasting or a threshold for the pecentage of serum estradiol level decrement that would not compromise the IVF outcome. In this study, we evaluated the COH-IVF outcomes of the hyperresponder patients managed with coasting for OHSS prevention regarding the establishment of clinical pregnancy as an endpoint of the treatment cycle. MATERIALS AND METHODS This retrospective cohort study was undertaken in the assisted reproduction unit of a tertiary education and research hospital. All investigations related to this study have been approved by the local ethical committee and that consent has been obtained from all patients. The database of all patients who underwent ovarian stimulation for assisted reproduction between 2008 and 2013 was retrospectively examined. The medical records of 119 hyperresponder patients who have exhibited a serum estradiol level greater and equal to 3000 pg/mL have been evaluated following COH treatment for an ART procedure. The study was conducted on 119 patients totally, 98 of whom have been treated by coasting. Twenty one patients who have not been managed with coasting treatment have been selected as the control group. COH procedures of the patients were commenced with antagonist protocol for all patients.

eatment for an ART procedure. The study was conducted on 119 patients totally, 98 of whom have been treated by coasting. Twenty one patients who have not been managed with coasting treatment have been selected as the control group. COH procedures of the patients were commenced with antagonist protocol for all patients. During antagonist protocol, patients have received recombinant FSH starting on days 2 or 3 and 0.25 mg cetrorelix (Cetrotide; Asta Medica, Frankfurt, Germany) was administered daily when two or more follicles reached 14 mm in diameter. Human menopausal gonadotropin (hMG) was adminstered to individual patients when clinically indicated based on the ovarian response to COH treatment. The doses of hMG and recombinant FSH have been adjusted according to the ovarian response for both groups until the day of final oocyte maturation by using hCG. One or two days of coasting strategy was commenced for the study group preceding the ovulation trigger regardless of the serum estradiol levels on hCG day. In our practice, when estradiol levels were greater than 3000 pg/mL in the presence of at least 20 follicles, each measuring ≥10 mm in diameter with ≥20% of them of diameter ≥15 mm, recombinant FSH administration was discontinued. For the control group and the study group (following the coasting application), recombinant hCG (250 micrograms sc., Ovitrelle, Serono, İstanbul, Turkey) was administered when at least two leading follicles reached a mean diameter of 17 milimeters. Thirty six hours after hCG injection transvaginal oocyte retrieval was performed. Following oocyte retrieval, metaphase 2 oocytes were reviewed and day 3 embryo transfer (ET) was performed via using pelvic ultrasonography for all patients. Luteal phase support was applicated by vaginal progesterone (Crinone 8% gel, Serono, İstanbul, Turkey) supplementation twice a day until menstruation or for 12 weeks following ET procedure in case of a clinical pregnancy establishment. The presence of a gestational sac with accompanying fetal heartbeat by ultrasound at least 4 weeks after ET was defined as a clinical pregnancy. The COH and IVF-ET outcomes of 119 patients were compared based on the coasting receivement status.

weeks following ET procedure in case of a clinical pregnancy establishment. The presence of a gestational sac with accompanying fetal heartbeat by ultrasound at least 4 weeks after ET was defined as a clinical pregnancy. The COH and IVF-ET outcomes of 119 patients were compared based on the coasting receivement status. Statistical analysis was performed by using IBM SPSS Statistics Software (19.0, SPSS Inc., Chicago, IL, USA). The categorical variables were compared with Fisher’s exact or Pearson chi-square tests when available. Kolmogorov-Smirnov test was used to determine the normality of the distributions of data. The continuous variables were presented as mean± standard deviation values and compared by using the independent samples t test when distributed normal. Mann-Whitney U test was used when the results were not found to be distributed normal or for comparison of non-parametric data. The potential negative influence of coasting was evaluated in a multivariate logistic regression models considering biochemical pregnancy rate as a dependent variable, after testing each factor in a univariate analysis. Odds ratio (OR) and 95% confidence intervals (CI) were estimated, adjusting the multivariate analysis for confounding variables (using chi-squared test of heterogeneity to control for confounders) and excluding variables with high collinearity. P values <.05 were considered statistically significant.

ivariate analysis. Odds ratio (OR) and 95% confidence intervals (CI) were estimated, adjusting the multivariate analysis for confounding variables (using chi-squared test of heterogeneity to control for confounders) and excluding variables with high collinearity. P values <.05 were considered statistically significant. RESULTS The COH-IVF cycle otcomes of the study population have been demonstrated in (Table 1). The mean E2 level on hCG day, gonadotropin stimulation days, p level on hCG day, fertilization rate for the coasting group were significantly lower than control group. All other COH-IVF cycle outcome parameters including retrieved oocye numbers and clinical pegnancy rates were similar between the study and control groups. The comparison for IVF-ICSI outcomes of the coasting group patients regarding the pregnancy occurence as endpoint has been presented in (Table 2). The duration of the coasting treatment was significantly lower in the patients who achieved a clinical pregnancy. Among patients who received coasting treatment, the number of patients demonstrating E2 level decrement and also E2 level decrement rate after coasting was similar between patients with and without clinical pregnancy. Total gonadotropin dose, 2PN number, embryo number and fertilization rate were significantly higher in the patients with a clinical pregnancy. All other COH-IVF cycle outcome parameters were similar between the patients with and without a clinical pregnancy. The rate of coasting with a GnRH antagonist cotreatment was also similar between these groups. Positive pregnancy test, the outcome variable studied in a logistic regression model, was correlated to coasting treatment status, age, basal FSH, number of oocytes retrieved, number of embryos transferred and blastocyst-stage embryo development (coasting treatment status: RR=7.6, 95% CI:1.73-33.49, p=0.007; age: RR=0.93, 95% CI: 0.85-1.02, p=0.14; basal FSH: RR=0.94, 95% CI:0.71-1.23, p=0.66; number of oocytes retrieved: RR=1.03, 95% CI:0.94-1.12, p=0.47; number of embryos transferred: RR=0.73, 95% CI:0.46-1.15, p=0.18; blastocyst-stage embryo development: RR=0.22, 95% CI:0.07-0.67, p=0.007) (Hosmer and Lemeshow Test p value was 0.49 that demonstrated the logistic regression model’s validity).

1.23, p=0.66; number of oocytes retrieved: RR=1.03, 95% CI:0.94-1.12, p=0.47; number of embryos transferred: RR=0.73, 95% CI:0.46-1.15, p=0.18; blastocyst-stage embryo development: RR=0.22, 95% CI:0.07-0.67, p=0.007) (Hosmer and Lemeshow Test p value was 0.49 that demonstrated the logistic regression model’s validity). DISCUSSION In the coasting group, the mean E2 level on hCG day, gonadotropin stimulation days, the number of gonadotropin ampules used and fertilization rate were significantly lower than control group. However metaphase 2 oocytes, total oocytes retrieved, 2PN number, embryo grades, number of embryos transferred, clinic pregnancy and OHSS rates were similar between coasting cycles and the control group. In this study, cotreatment with GnRH antagonist accompanying with coasting has also not been found to be related to clinical pregnancy probability. The coasting duration (days) of patients who achieved clinical pregnancy was significantly lower than the patients who have not achieved a clinical pregnancy. This result supports the usual consideration of the fact that higher coasting duration decreases the pregnancy rates as mentioned in the previous studies.

ility. The coasting duration (days) of patients who achieved clinical pregnancy was significantly lower than the patients who have not achieved a clinical pregnancy. This result supports the usual consideration of the fact that higher coasting duration decreases the pregnancy rates as mentioned in the previous studies. The duration of coasting that is effective in reducing the incidence of OHSS without compromising the cycle outcomes has not been established yet. Most studies showed that withholding gonadotropins up to 3 days did not affect the cycle outcomes(9,13). However other studies demonstrated that prolonged coasting for >3 days compromise the IVF outcomes. Ulug et al. found that coasting for more than 3 days reduced the implantation and pregnancy rates while oocyte and embryo quality did not appear to be affected(14). In a large cohort of patients, Mansour et al. reported that coasting more than 3 days reduced significantly the mean number of oocytes retrieved, the implantation and clinical pregnancy rates, but on the other hand the incidence of OHSS was reduced to 0.13% in all stimulated cycles and to 1.3% in patients at risk for OHSS(15). Owj et al. concluded their study as prolonged coasting (>3 days) had a negative effect on the number and quality of oocytes(16). Waldenstrom et al. showed that coasting more than 3 days decreases the number of oocytes retrieved and the pregnancy rates. They claimed that withholding gonadotropins reduces the LH receptor levels and if the duration of this period lasts longer, the LH receptor levels decreases severely. The follicles with severely decreased LH receptors respond poorly to exogenous hCG so the oocytes with mature sized follicules will not complete the final maturation. The immature oocytes will stick to the follicule wall and this will cause reduction in the number of oocytes retrieved(17). Nardo et al. compared the coasting cycles with 1-3 days with more than 3 days. Coasting more than 3 days reduced the number of oocytes retrieved and decreased the implantation rate. There was no difference in pregnancy and live birth rate. The lower implantation rate was assosiated with negative effect on endometrial receptivity(18). Isaza et al. suggested that if the duration of coasting was more than 5 days or if a severe fall in the level of estradiol (<1000 pg/ml) observed, the oocyte quality might be affected(19).

e in pregnancy and live birth rate. The lower implantation rate was assosiated with negative effect on endometrial receptivity(18). Isaza et al. suggested that if the duration of coasting was more than 5 days or if a severe fall in the level of estradiol (<1000 pg/ml) observed, the oocyte quality might be affected(19). In our study we found that the duration of coasting was significantly lower in the patients who achieved a clinical pregnancy just like the previous studies. Besides, based on the logistic regression analysis results, we demonstrated that coasting strategy increased the clinical pregnancy achievement probability more than the expectant (control group) management strategy. Interestingly, lower clinical pregnancy rates have been found for blastocyst transfer in our study that might be a result of longer coasting duration among patients who received blastocyst transfer. When compared with the control group; the total gonadotropin dose, 2PN number, embryo number and fertilization rates were significantly higher among the patients who received coasting treatment with a clinical pregnancy that demonstrates the clinical effectiveness of coasting strategy. Gonadotropins upregulate the gonadotropin receptors and inhibit the granulosa cell apoptosis of small immature follicules. The FSH concentration decrease due to withholding gonadotropins that induce apoptosis of small immature follicules, which are more sensitive to FSH paucity, results with reduced levels of the vasoactive substances responsible for capillary permeability and fluid extravasation(20).

poptosis of small immature follicules. The FSH concentration decrease due to withholding gonadotropins that induce apoptosis of small immature follicules, which are more sensitive to FSH paucity, results with reduced levels of the vasoactive substances responsible for capillary permeability and fluid extravasation(20). There is no consensus for a specific coasting protocol on how to apply it, despite many studies done in the literature. In most studies the estradiol cutoff value for withholding gonadotropins is between 2500 and 4000 pg/ml(9). We started coasting in our IVF cycles when the serum estradiol levels were >3000 pg/ml. Mansour et al. started coasting according the size of follicules instead of the level of estradiol. When the leading follicules reached 16 mm in size, they withhold gonadotropins and waited estradiol levels to fall under 3000 pg/ml for hCG administration(15). Al-Shawaf et al. suggested that falling in FSH levels by 25% daily during coasting period and a decline in serum FSH to 5 mIU /ml was safe for hCG injection(10).

hen the leading follicules reached 16 mm in size, they withhold gonadotropins and waited estradiol levels to fall under 3000 pg/ml for hCG administration(15). Al-Shawaf et al. suggested that falling in FSH levels by 25% daily during coasting period and a decline in serum FSH to 5 mIU /ml was safe for hCG injection(10). It is still a controversial issue whether the rate of decrease in serum estradiol level compromises IVF outcome. Many authors similarly found that the rate of estradiol level decrement during coasting treatment did not effect the pregnancy and implantation rate(13,14). However in some studies cycle cancellation was recommended when the rate of estradiol level decreased by more than >20% after hCG injection(21). Abdalla et al. demonstrated that neither E2 increase nor E2 decrease following coasting treatment has a negative effect on implantation, miscarriage, or live birth rates, except extremely low (<1.000 pmol/L) or high (>20.000 pmol/L) serum E2 levels at hCG triggering(22). In our study we also have not found a relationship between E2 level decrement or increment following coasting treatment and clinical pregnancy occurance.

egative effect on implantation, miscarriage, or live birth rates, except extremely low (<1.000 pmol/L) or high (>20.000 pmol/L) serum E2 levels at hCG triggering(22). In our study we also have not found a relationship between E2 level decrement or increment following coasting treatment and clinical pregnancy occurance. GnRH antagonist salvage has been used for patients with high serum estradiol levels at risk of developing OHSS. Gustofson et al. observed that with GnRH antagonist cotreatment the estradiol levels sharply decreased to a safe level without affecting negatively on oocyte maturation, embryo quality and fertilization rates(23). In a prospective randomized study Aboulghar et al. compared the effect of GnRH antagonist cotreatment with coasting among the patients with long GnRH agonist protocol. In the antagonist arm the mean number of oocytes retrieved and high quality embryos was significantly higher than in the coasting group. There were more days of coasting as compared with days of antagonist administration. There were no significant differences in the clinical pregnancy and multiple pregnancy rates between the two groups(24). We found that the (+) and (-) pregnancy rates in the patients who received antagonist cotreatment were comparable (26.2% vs. 39.3%). Also fertilization rate, 2PN and embryo number was higher in the patients who are pregnant.

differences in the clinical pregnancy and multiple pregnancy rates between the two groups(24). We found that the (+) and (-) pregnancy rates in the patients who received antagonist cotreatment were comparable (26.2% vs. 39.3%). Also fertilization rate, 2PN and embryo number was higher in the patients who are pregnant. In conclusion, the coasting treatment is a clinically useful preventive strategy for OHSS avoidance. GnRH antagonist cotreatment decreases the duration of coasting although any detrimental or ameliorating impact of this effect on pregnancy rates has not been seen. The E2 level decrement or increment following coasting treatment seems not to be related to cycle outcomes. Declaration of Interest The authors report no declarations of interest. There remain no relevant potential conflicts of interest related to this original article. Also, there remains no affiliation with any organization with a financial interest, direct or indirect, in the subject matter or materials discussed in the manuscript (such as consultancies, employment, paid expert testimony, honoraria, speakers bureaus, retainers, stock options or ownership, patents or patent applications or travel grants. We did not receive any funding and/ or financial support from any commercial or other association for this study. Medical writing of this manuscript has been completed by the authors own. None

Declaration of Interest The authors report no declarations of interest. There remain no relevant potential conflicts of interest related to this original article. Also, there remains no affiliation with any organization with a financial interest, direct or indirect, in the subject matter or materials discussed in the manuscript (such as consultancies, employment, paid expert testimony, honoraria, speakers bureaus, retainers, stock options or ownership, patents or patent applications or travel grants. We did not receive any funding and/ or financial support from any commercial or other association for this study. Medical writing of this manuscript has been completed by the authors own. None Table 1 The comparison for IVF-ICSI outcome of the coasting group and the control group (n=119) Table 2 The comparison for IVF-ICSI outcomes of the coasting group patients regarding the pregnancy occurence as end-point (n=98)

INTRODUCTION Abortion is the termination of pregnancy from the uterus at a woman’s own request or due to a medical requirement by a physician via several methods upon acquiring consent. In this regard, elective abortion is described by the World Health Organization (WHO) as the termination of pregnancy before the fetus has developed sufficiently to live outside the uterus(1). The frequency of abortions varies, parallel with the countries and their social, cultural, and economic levels(1,2). One fifth of women (during the childbearing period) in Turkey had spontaneous abortion and 22% had elective abortion according to the Turkey Demographic and Health Survey 2008 data(3). In the last five years, the rate of elective abortion among the married women between the ages of 15-49 is 10% and the rate of elective abortion among the women between the 15-19 age group, which is 3%, increases with age and reaches 39% in the 45-49 age group. When analyzed according to the regions, the rate of elective abortion is the highest in İstanbul (31%) and the lowest in Southeastern Anatolia (12%). According to the education level, there is very little change to the rate of abortion among the women. However, the rate of elective abortion among women at the level of the lowest household welfare is 15% increases to 29% among women at the level of the highest welfare(3).

nd the lowest in Southeastern Anatolia (12%). According to the education level, there is very little change to the rate of abortion among the women. However, the rate of elective abortion among women at the level of the lowest household welfare is 15% increases to 29% among women at the level of the highest welfare(3). Elective abortion was used as a family planning in the past; however, it is not used for this purpose today since there are effective family planning methods. Nevertheless, today, it is reported that one in every five women experiences one or more abortion attempts during their lifetime and there are 40 million abortion attempts every year(4). Around the world, each country has its own rules and practices for elective abortion. In Turkey, the second law regulating the family planning services was re-arranged in 1983, and Article 5 of the “Population Planning Law,” Number 2827 states that: “Until the tenth week of pregnancy, the uterus can be evacuated upon request until there is no medical objection for the health of the mother”. According to this law, the elective abortions up to the 10th week can be performed by competent physicians under the supervision of specialists upon the consent of the partners(5). By this means, the aim is to minimize undesired pregnancies and maternal mortality rates due to the abortions carried out under improper health conditions or performed by the self-intervention of the women.

an be performed by competent physicians under the supervision of specialists upon the consent of the partners(5). By this means, the aim is to minimize undesired pregnancies and maternal mortality rates due to the abortions carried out under improper health conditions or performed by the self-intervention of the women. Although abortion can be performed within the frame of the legal regulations and practices, it is still among the controversial topics in terms of sociocultural, moral, philosophical, and religious aspects. The first of the two main matters of debate is “the right of fetus to live” and the other is “the right of a woman to make decisions about her own body”(6). Around these arguments, maybe the women are to be emphasized and asked about their opinions. As the debate about abortion law has gained momentum, recently in Turkey in particular, an analysis of the opinions of the women via a medical disciplinary approach may be very useful and may also provide guidance on the legal practices. Due to these facts, the present study aimed to analyze the opinions of women applying to university hospitals about abortion and their attitudes towards abortion. MATERIALS AND METHODS The population of this descriptive study consisted of women over 18 years of age, who applied to a University Research Hospital for any reason between March 2013 and April 2013, and agreed to participate in the study.

Although abortion can be performed within the frame of the legal regulations and practices, it is still among the controversial topics in terms of sociocultural, moral, philosophical, and religious aspects. The first of the two main matters of debate is “the right of fetus to live” and the other is “the right of a woman to make decisions about her own body”(6). Around these arguments, maybe the women are to be emphasized and asked about their opinions. As the debate about abortion law has gained momentum, recently in Turkey in particular, an analysis of the opinions of the women via a medical disciplinary approach may be very useful and may also provide guidance on the legal practices. Due to these facts, the present study aimed to analyze the opinions of women applying to university hospitals about abortion and their attitudes towards abortion. MATERIALS AND METHODS The population of this descriptive study consisted of women over 18 years of age, who applied to a University Research Hospital for any reason between March 2013 and April 2013, and agreed to participate in the study. Based on the records, the monthly mean number of individuals who applied to a university research hospital in 2013 was 19.213; 10.960 of these individuals were women over 18 years of age. The prevalence of elective abortion from the previous studies was accepted as 22%, and the sample size calculated by Epi Info 7.0 program under a confidence interval of 97% and a deviation of d=0.04 was found to be at least 483. The study included 500 women, who were selected through random sampling among the women over 18 years of age, who applied to a hospital for any reason and agreed to participate in the study between the date ranges of the research.

nder a confidence interval of 97% and a deviation of d=0.04 was found to be at least 483. The study included 500 women, who were selected through random sampling among the women over 18 years of age, who applied to a hospital for any reason and agreed to participate in the study between the date ranges of the research. A survey form consisting of 20 questions in total, “6” described the socio-demographic attributes of the participants and “14” evaluated the attitudes and opinions of the participants about elective abortion, which was prepared by the researchers for data collection as guided by the respective literature and applied to all participants through face-to-face interviews. The dependent variables of the study included the knowledge and attitudes of the women who applied to a university hospital; and the independent variables included the socio-demographic attributes of the women such as educational status, occupational status, and marital status. Prior to the study, approval was obtained from the ethics committee of the university. The data collected were analyzed using a statistical program, PAWS version 18.0. Chi-square and Fisher’s exact tests were used in the statistical analysis. A value of p<0.05 was considered as the level of statistical significance. The descriptive data of the participants were expressed in mean ± standard deviation and n (%).

ta collected were analyzed using a statistical program, PAWS version 18.0. Chi-square and Fisher’s exact tests were used in the statistical analysis. A value of p<0.05 was considered as the level of statistical significance. The descriptive data of the participants were expressed in mean ± standard deviation and n (%). RESULTS The mean age of the participants was 31.5±11.9 (18-75) years. Twenty-six (5.2%) women were illiterate; 141 (28.2%) were primary-school graduates; 15 (3%) were high-school students; 48 (9.6%) were high-school graduates; 161 (32.2%) were university students; and 109 (21.8%) were university graduates. The rate of participants with a profession was 25.2%, whereas 74.8% were unemployed. Regarding marital status, 55.4% were married and 44.6% were single. The question, “Which one is more applicable to you?” regarding elective abortion was answered by 18.6% (93) as “a natural right,” 67.8% (339) as “must be performed only in health-endangering situations,” and 13.6% (68) as “absolutely not.” Seventy point eight percent (354) of the women stated that they were against elective abortion. Of the women stating that they were against elective abortion, 53.1% reported the reason for being against elective abortion as “forbidden by religion,” 35.3% as “against human rights,” and 7.1% as “unhealthy for the mother” (Table 1).

nt eight percent (354) of the women stated that they were against elective abortion. Of the women stating that they were against elective abortion, 53.1% reported the reason for being against elective abortion as “forbidden by religion,” 35.3% as “against human rights,” and 7.1% as “unhealthy for the mother” (Table 1). Among the questions analyzing the reasons for elective abortion from social indications, the question, “Do you approve of abortion if the married couple does not want any more children?” was answered by 18.8% as “yes”; 70.4% as “no”; and 10.8% as “undecided”. The question, “Do you approve abortion in extramarital situations?” was answered by 29.2% as “yes”; and the question “May elective abortion be performed due to financial incapacity?” was answered by 14.4% as “yes” and 73.8% as “no”. The question, “Do you approve abortion if the married couple does not want any more children?” and the question, “Do you approve abortion in extramarital situations?” were found to receive a higher rate of “yes” by the participants over 40 years of age than the other participants (p<0.05). Additionally, the question as to whether to forbid abortion completely or not was answered as “yes” at a rate ranging between 6.8% and 13.3%, based on the age group, and the same answer applied to all age groups (p=0.202) (Table 2).

of “yes” by the participants over 40 years of age than the other participants (p<0.05). Additionally, the question as to whether to forbid abortion completely or not was answered as “yes” at a rate ranging between 6.8% and 13.3%, based on the age group, and the same answer applied to all age groups (p=0.202) (Table 2). When the opinions of the participants were analyzed based on their educational levels, the highest rate of positive approach to the elective abortion was found in the group consisting of university students (39.1%; p<0.001). The frequency of “yes” as a response to completely forbid abortion based on the groups was zero (0%) of the illiterate participants, 26 (18.4) of the primary-school graduates, two (13.3%) of the high-school students, eight (16.7%) of the high-school graduates, seven (4.3%) of the university students, and five (4.6%) of the university graduates, respectively (Table 3).

forbid abortion based on the groups was zero (0%) of the illiterate participants, 26 (18.4) of the primary-school graduates, two (13.3%) of the high-school students, eight (16.7%) of the high-school graduates, seven (4.3%) of the university students, and five (4.6%) of the university graduates, respectively (Table 3). Ninety-six (19.2%) of the participants answered “yes” to the question of whether they had an abortion compared to 404 (80.8%) answering “no”. When the reasons for the procedure were asked of the women who had an abortion, 26% responded with “undesired pregnancy,” 37.5% responded with “due to health problems,” 9.4% responded with “the notice from their doctors that the baby would be disabled,” and 27.1% responded with “other”. The question, “May elective abortion be performed if there are no health related issues?” was answered as “yes” by 38.5% and as “no” by 61.5% among the women who had abortion compared to the rates 27% and 73% among the women who did not have abortion, respectively (p=0.025). The question, “Do you approve of abortion if the married couple does not want any more children?” was answered as “yes” by 37.5% of the women who had an abortion compared to 14.4% among the women who did not have an abortion previously (p<0.001). Thirty-nine point six percent of the participants who had a history of abortion approved of extramarital abortion compared to 26.7% of the women who had not had an abortion (p=0.042) (Table 4).

by 37.5% of the women who had an abortion compared to 14.4% among the women who did not have an abortion previously (p<0.001). Thirty-nine point six percent of the participants who had a history of abortion approved of extramarital abortion compared to 26.7% of the women who had not had an abortion (p=0.042) (Table 4). Four hundred fifty (90%) women reported that abortion was not a contraceptive method, 2.6% reported that it might be used as a contraceptive method, and 7.4% reported that they did not have any knowledge about the matter. With regard to completely forbidding abortion by law, 48 (9.6%) of the participants answered as “it should be completely forbidden,” 412 (82.4%) answered as “it may be performed under necessary conditions,” and 40 (8%) answered as “it should never be forbidden”. The arguments of the total 354 participants who provided “no” as an answer to the question of whether to forbid elective abortion were respectively: “it should be completely forbidden” by 13%; “it may be performed under necessary conditions” by 86.4%; and “it should never be forbidden” by 0.6%.

uld never be forbidden”. The arguments of the total 354 participants who provided “no” as an answer to the question of whether to forbid elective abortion were respectively: “it should be completely forbidden” by 13%; “it may be performed under necessary conditions” by 86.4%; and “it should never be forbidden” by 0.6%. DISCUSSION In the present study, 18.6% of the participants defined abortion as “a natural right” and 70.8% reported that they were against elective abortion. In addition, only 9.6% reported that abortion should be completely forbidden by law. It is understood that the majority of the participants report that they are against elective abortion; however, only 9.6% had a positive approach to the complete ban of abortion. In the study by Baykan et al. on this matter, they reported that most of the women thought that elective abortion was not appropriate when the opinions of the women regarding abortion were analyzed in moral, ethical, and social terms. Despite this, women also stated that deciding the fate of the pregnancy was a natural right of the women and the government should not intervene in elective abortion(7). It is seen that abortion, which is still an ethical issue today, may be due to social causes such as rape as well as due to an undesired pregnancy resulted from not using proper and correct family planning method, and therefore service accessibility and availability and raising the awareness of women through health education in this regard are considered as the important steps for the solution of the problem(8).

ch as rape as well as due to an undesired pregnancy resulted from not using proper and correct family planning method, and therefore service accessibility and availability and raising the awareness of women through health education in this regard are considered as the important steps for the solution of the problem(8). The study by Bilgin et al. that evaluated the opinions of university students about elective abortion reported that the students did not consider elective abortion as a family planning method, they knew its damages to the health, and although they tended to be against elective abortion, they wanted it to be a matter of free choice(9). In another study in which the opinions of health college students were collected, 52.1% of the students assessed elective abortion as morally incorrect, whereas 28.7% stated that they did not share this opinion(10). In the present study, 90% of the participants reported that abortion was not a contraceptive method. Additionally, 53.1% of the participants who were against abortion provided the reason for being against it as being “forbidden by religion” and only 7.1% were against as it as being “unhealthy for the mother”. It is quite interesting that the women with the history of abortion have more liberal thoughts about abortion in case of social indications such as excessive children and financial incapacity. On the other hand, in the present study, the group consisting of university students was also found to be more liberal towards abortion than the other groups with lower education levels.

abortion have more liberal thoughts about abortion in case of social indications such as excessive children and financial incapacity. On the other hand, in the present study, the group consisting of university students was also found to be more liberal towards abortion than the other groups with lower education levels. It was also seen that women had an intense feeling of responsibility prior to elective abortion and the majority had feelings of guilt due to religious and moral concerns; however, 70% of these women did not change their decisions about abortion despite the feelings of guilt, fear, anger, regret, suffering, shame, and loss(11,12,13). In the study by Doganer et al., half of the women stated that they would not have an abortion in case of a potential undesired pregnancy because of the thought that it would be a sin(14). In the present study, it is also seen that the participants who are against abortion provided religion as the main reason for their objection (53.1%). Furthermore, 86.4% of the participants who were against abortion answered as “it may be performed only when necessary” rather than completely forbidding it.

e a sin(14). In the present study, it is also seen that the participants who are against abortion provided religion as the main reason for their objection (53.1%). Furthermore, 86.4% of the participants who were against abortion answered as “it may be performed only when necessary” rather than completely forbidding it. In a study analyzing the reasons for admission to legally elective abortion among the women who applied for elective abortion, the first reason was the thought of having enough children (33.3%). This was followed by financial reasons (20.5%), having a young child (15.4%), exposure to teratogen (11.5%), own request (9%), extramarital relations (3.8%), employment (2.6%), experiencing a difficult pregnancy before (1.3%), presence of a chronic disease (1.3%), and request of the partner (1.3%), respectively(15). In the present study, the first among the reasons for having an abortion among the women with a history of abortion was “health problems” (37.5%), followed by “undesired pregnancy” (26%), and “notice from the doctor that the baby would be disabled” (9.4%), respectively. It should also be kept in mind that the psychological trauma after elective abortion may also occur in the women if the health conditions of the procedural environment and pre- and post-abortion care are not sufficiently provided during the elective abortions, as well as addressing religious beliefs, such as the woman having physical health problems due to the impact of the social and cultural structure. In a study evaluating the problems and the levels of anxiety experienced by the women after elective abortion, it was reported that the most frequently reported complaint after abortion was pain (25.5%) and the second most frequently reported complaint was the sorrow due to the loss of the baby (15.4%). Moreover, it was also emphasized that the pre-procedure anxiety scores were higher than the post-procedure scores(16). Psychological trauma was observed much severe among women, especially when the abortion was not legal(17).

second most frequently reported complaint was the sorrow due to the loss of the baby (15.4%). Moreover, it was also emphasized that the pre-procedure anxiety scores were higher than the post-procedure scores(16). Psychological trauma was observed much severe among women, especially when the abortion was not legal(17). Limitations of the Study The results cannot be generalized to the community since the study included only the women who applied to the university hospital. It is believed that studies that employ proper sampling methods representative of the community should be conducted in order to evaluate the opinions of women in the community about elective abortion in a more correct manner. CONCLUSION In conclusion, a majority of the participants has reported that they have a negative opinion about elective abortion, whereas a similar rate of the participants has stated that abortion may be performed in case of necessity. In conclusion, the authors believe that the opinions of the women should be evaluated by community-based studies as preparing legal regulations on situations that can affect the public health such as abortion, and the adverse medical outcomes due to abortion under unhealthy conditions if forbidden should also be considered. Table 1 Reasons of participants for being against elective abortion Table 2 Opinions of participants about elective abortion by age distribution Table 3 Opinions of participants about elective abortion by educational status Table 4 Opinions of participants about elective abortion by the history of abortion

INTRODUCTION Pelvic organ prolapse (POP) is defined as the descent of uterus and vaginal walls through vaginal canal. Pelvic organs move downwards due to anatomical and or functional deformities of the tissues that support pelvic organs. As a component of pelvic floor dysfunction, POP which is a common health problem affecting about 30% of the women between 20-59 years of age and more than half of the women over 50 years of age attending to the clinics is the most common surgical indication following hysterectomy(1,2). The life-time risk of a woman for POP surgery is estimated to be 19% and the reoperation risk even with an appropriate surgery is about 30%(3,4). It is not only an important health problem but also is an important extra burden to the health expenditures.

the most common surgical indication following hysterectomy(1,2). The life-time risk of a woman for POP surgery is estimated to be 19% and the reoperation risk even with an appropriate surgery is about 30%(3,4). It is not only an important health problem but also is an important extra burden to the health expenditures. The natural progress of POP is not yet completely understood. Studies assessing the epidemiology of POP are limited because standardized measures that can objectively evaluate its presence or absence, degree or the impact of the associated symptoms had not been used(5). The staging process of POP with physical examination and the diagnostic methods also differ. In many studies Baden-Walker Halfway and Women Initiative Staging systems had been used(6,7). Even though pelvic organ prolapse quantification (POPQ) system that has been recently developed in order to standardize physical examination generated a common language among the clinicians, it has not gained wide spread all over the world(8,9). Evaluation of the epidemiology and natural history of the disease is limited because POP has a subjective nature of associated symptoms, is a diagnosis determined by physical examination and following large populations with interval standardized pelvic examinations is expensive and has logistical difficulties(10).

,9). Evaluation of the epidemiology and natural history of the disease is limited because POP has a subjective nature of associated symptoms, is a diagnosis determined by physical examination and following large populations with interval standardized pelvic examinations is expensive and has logistical difficulties(10). Some risk factors have been determined for POP. Advanced age, white race, menopause, some systemic diseases, obesity, vaginal delivery, smoking, chronic constipation and giving birth to large babies have been proposed as risk factors in various studies(10). Most of these studies are from foreign countries and studies from Turkish population are scarce. The aim of this study was to assess the prevalence and the related factors of POP in a general women-population attending to our clinic in the city of Mersin to whom health care services are offered.

in various studies(10). Most of these studies are from foreign countries and studies from Turkish population are scarce. The aim of this study was to assess the prevalence and the related factors of POP in a general women-population attending to our clinic in the city of Mersin to whom health care services are offered. MATERIALS AND METHODS A total of 3.000 consecutive women who attended the university hospital between June 2008 and December 2008 were included in this prospective study. The study cohort was recruited from the hospital database. Brief information about the study, procedures and the nature of the questionnaires were explained to each patient. One thousand three hundred fifty-four women agreed to participate. Thirty-four women because they had undergone a kind of pelvic surgery (such as hysterectomy, anterior/posterior colporraphy, sacrospinous fixation, sacral colpopexy) were excluded. Medical histories were obtained with a standardized form designed to assess obstetric and gynecologic histories, chronic diseases (e.g., diabetes mellitus, hypertension, rheumatologic disorders, cardiac, pulmonary, gastrointestinal, and renal diseases) and prescriptions. Height and weight of the patients were measured on the day of interview. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Waist-to-hip ratio (WHR) was calculated by dividing waist to hip. Each participant gave written informed consent, and the protocol was approved by the Local Ethical Committee on Research with Human Subjects.

y of interview. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Waist-to-hip ratio (WHR) was calculated by dividing waist to hip. Each participant gave written informed consent, and the protocol was approved by the Local Ethical Committee on Research with Human Subjects. Pelvic examination was performed to all of the patients by the investigators. The staging of pelvic organ prolapse was done with POP-Q (pelvic organ prolapse quantification) system conformed to the standards and terminology set forth by the International Continence Society(8). POP-Q examination was performed while the patient was in dorsal lithotomy position. Subjects underwent the POP-Q examination in the dorsal lithotomy position. All points for the POP-Q examination, except for total vaginal length, were recorded at maximal protrusion with Valsalva maneuver. If the subject was not able to perform a Valsalva maneuver, she was first coached by the examiner in the performance of a Valsalva maneuver. If they still could not perform a Valsalva maneuver, the measurements were recorded with the subject forcefully coughing. An overall stage was assigned to each patient, according to the most severely prolapsing compartment. Women with stage 2 prolapse were considered as having genital prolapse(11).

a Valsalva maneuver. If they still could not perform a Valsalva maneuver, the measurements were recorded with the subject forcefully coughing. An overall stage was assigned to each patient, according to the most severely prolapsing compartment. Women with stage 2 prolapse were considered as having genital prolapse(11). Statistical analysis was accomplished with SPSS (version 17, demo, SPSS Inc., Chicago, IL, USA). Data of women with POP and without POP were compared with student t test for normally distributed continuous variables and with chi square or Fisher’s exact tests for binary data. Logistic regression analysis was used to determine independent predictors of POP. A p value of <0.05 was considered as significant. RESULTS The prevalence of genital prolapse was 27.1% in the assessed 1320 women. The general characteristics of the patients with and without prolapse are depicted in (Table 1). As shown in the table women with prolapse were significantly older, heavier, had an increased waist to hip ratio and had given more birth (Table 1). When we look at the mode of delivery, the rate of delivery with cesarean section was significantly lower in women with prolapse (10.6% vs 20.8%, p<0.001, respectively) and the mean birth weight of the women with prolapse was significantly higher when compared to the women without prolapse (3584±574 vs 3490±389 g, p=0.004) (Table 1). The level of education was found to be significantly lower in women with prolapse compared to women without prolapse (Table 1).

%, p<0.001, respectively) and the mean birth weight of the women with prolapse was significantly higher when compared to the women without prolapse (3584±574 vs 3490±389 g, p=0.004) (Table 1). The level of education was found to be significantly lower in women with prolapse compared to women without prolapse (Table 1). In order to find the independent predictors of POP a logistic regression analysis including age, BMI, WHR, parity, mode of delivery, menopausal status, presence of chronic diseases, smoking, level of education and yearly income was performed. According to this analysis especially waist-to-hip ratio, then parity, vaginal birth history and menopausal status were found to be the independent predictors that increase the risk of POP (Table 2). DISCUSSION In order to devise optimal and cost-effective preventive and therapeutic strategies to deal with POP problem in a population, one should start by defining the prevalence of the condition and its risk factors in that population(12). From that point a cross sectional population based study aimed to find the prevalence and the associated risk factors of POP was conducted in the population that health service was offered and it was found that increase in WHR and parity, giving vaginal birth and being in the menopause were independent predictors of POP development. Although not found to be independent predictors of POP development, patients with POP were significantly older, heavier, had higher maximum birth weight, had lower rate of cesarean section and had a lower education level when compared to women without POP.

n the menopause were independent predictors of POP development. Although not found to be independent predictors of POP development, patients with POP were significantly older, heavier, had higher maximum birth weight, had lower rate of cesarean section and had a lower education level when compared to women without POP. There are limited studies that assessed the prevalence of POP in our country when the literature was reviewed. Çam et al used POP-Q system and reported stage ≥2 POP rate as 33% and 38% in Turkish women with and without episiotomy respectively in their study that they assessed the effect of mediolateral episiotomy on the pelvic floor(13). In another study that assessed the validation of the prolapse-related quality of life questionnaire in a selected Turkish population, stage ≥2 POP was found in 123 of the 218 assessed women (56.2%)(14). In the present study the prevalence of POP was found to be 27.1%. The differences in the results may be due to the methodological differences and the geographic differences of the assessed populations. Çam et al enrolled only parous women in their study whereas in the present study all the women including nulliparous were enrolled. And in Seven et al’s study there is a difference that may originate from the differences in the study’s inclusion criteria(14). However, all these data support that POP is a common health problem in our country.

parous women in their study whereas in the present study all the women including nulliparous were enrolled. And in Seven et al’s study there is a difference that may originate from the differences in the study’s inclusion criteria(14). However, all these data support that POP is a common health problem in our country. In literature some modifiable and non-modifiable risk factors have been defined for POP development(10). Obesity, vaginal birth, parity, smoking, chronic straining and large infant size are among the modifiable risk factors; whereas, age, race, menopause / estrogen deficiency, chronic lung disease, connective tissue disorders and neuropathy constitute the non-modifiable risk factors(10,15,16). All these risk factors cause POP by resulting in damage to the support of the pelvic floor(17).

e infant size are among the modifiable risk factors; whereas, age, race, menopause / estrogen deficiency, chronic lung disease, connective tissue disorders and neuropathy constitute the non-modifiable risk factors(10,15,16). All these risk factors cause POP by resulting in damage to the support of the pelvic floor(17). Vaginal delivery and parity were found to be independent modifiable risk factors for POP development which is parallel to the literature. In addition increase in waist-to-hip ratio was also found to be another modifiable risk factor for POP development in the present study. POP development following vaginal delivery is believed to result from structural disruption due to overstretching, compression and avulsions during childbirth and or secondary to denervation injury to the levator ani muscle(5,18,19,20). Quiroz et al. reported that one vaginal delivery increases the risk of POP development 9.7 times (95% confidence interval: 2.68-35.35)(21). Again a study from Italy reported that vaginal delivery compared with cesarean delivery increased POP risk 1.82 times (95% CI: 1.04-3.19)(22). In the present study vaginal delivery was found to increase risk of POP development 1.5 times in the assessed population. The significant lower rate of POP in patients who delivered abdominally (10.6% vs 20.8%, p<0.001) is in line with these results. When we look at the parity as the second factor, in the epidemiological study of Oxford Family Planning Association parity was suggested to be the most important risk factor(23). Similarly in the present study both vaginal and cesarean deliveries were considered as parity and parity was found to be a risk factor independent of the mode of delivery for development of POP. Levator ani muscle injury which is suggested to be a factor for development of POP and is more common during vaginal delivery, may be seen in both types of deliveries and therefore parity independent from delivery route comes out as an important risk factor for POP.

ndent of the mode of delivery for development of POP. Levator ani muscle injury which is suggested to be a factor for development of POP and is more common during vaginal delivery, may be seen in both types of deliveries and therefore parity independent from delivery route comes out as an important risk factor for POP. WHR is considered as an indicator of visceral obesity. Increased WHR was found to be an important risk factor for the development of POP in the assessed population. The relationship between WHR and POP has been also shown by Kudish et al. These investigators had shown that a change in WHR, evaluated in 0.1 increment decreases, was found to be associated with regression of both cystocele and rectocele(24). The hypothesized mechanism is that this ratio is a reflection of larger mechanical forces directed toward the pelvic floor at rest or during cough or Valsalva maneuver and its reduction decreases the reflection of these forces to the pelvic floor(24). BMI and the maximum birth weight did not come out to be independent predictors of POP development although they were found to be significantly higher in the women with POP compared to women without POP in the assessed population. Smoking was also not a risk factor.

he reflection of these forces to the pelvic floor(24). BMI and the maximum birth weight did not come out to be independent predictors of POP development although they were found to be significantly higher in the women with POP compared to women without POP in the assessed population. Smoking was also not a risk factor. Among the non-modifiable risk factors only menopausal status was found to be a risk factor for POP development and being in menopause was found to increase POP development risk 1.2 times. Atrophy that developed in the setting of estrogen deficiency after menopause is a concern for all the pelvic structures and as a result POP may develop. In addition, kyphotic changes due to osteoporosis that developed secondary to advanced age and estrogen deficiency causes a horizontal shift in the pelvic brim which results in reflection of the abdominal contents to the pelvic floor and urogenital hiatus rather than the pelvic brim(25,26). Age has been reported to be an independent risk factor for the development of POP in many studies; however, in the present study although it was found that women with POP were significantly older, age itself did not come out to be a risk factor for POP development.

urogenital hiatus rather than the pelvic brim(25,26). Age has been reported to be an independent risk factor for the development of POP in many studies; however, in the present study although it was found that women with POP were significantly older, age itself did not come out to be a risk factor for POP development. Giving birth with cesarean section was not found to be a preventive factor for the development of POP in the current study. However, this study has some limitations with regard to this issue. The women who gave birth with cesarean section after a vaginal delivery in their previous pregnancies were not assessed separately and it was impossible to assess because of significant recall bias how many of the women and how long did they experience labor before cesarean section. These factors must be kept in mind while interpreting the data about the preventive effects of cesarean section on the development of POP. In conclusion in Turkey, the number of epidemiological studies on POP is very limited. In the present study it was aimed to assess the prevalence and the associated factors of POP in women admitting to our clinics and POP was found to be a common health problem in Turkish women that we offer service. Parity, WHR, vaginal delivery and menopausal status were found to be the independent predictors of POP development. To clarify the issue and to establish the possible geographical differences in our country, large epidemiological studies including different geographical places that will reflect the overall situation in Turkey are needed.

l delivery and menopausal status were found to be the independent predictors of POP development. To clarify the issue and to establish the possible geographical differences in our country, large epidemiological studies including different geographical places that will reflect the overall situation in Turkey are needed. Table 1 The general characteristics of women with and without genital prolapse Table 2 Multivariate analysis of the factors that affect pelvic organ prolapse*

INTRODUCTION The glucose intolerance occurring for the first time or diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). Of all pregnancies, 7% are complicated with GDM (ranging from 1% to 14% depending on the population studies and diagnostic tests employed) the rate of which differs from one country to another, and this rate corresponds to 200.000 cases per year(1). In addition to increased perinatal mortality and morbidity, intrauterine hyperglycemia results in an increased risk of obesity, metabolic and cardiovascular disorders, and malignancy in future life of fetus after delivery(2). Most of the above-mentioned changes recover after delivery; however, it is also likely that these changes may persist after delivery. With regards to general distribution of obesity and diabetes in the population, it is more likely for women with childbearing potential to have type 2 diabetes mellitus, and the rate of women with unrecognized type 2 diabetes is increasing among pregnancy women. The diagnostic criteria for GDM were first described 40 years age; however, there is no single screening method complying with the international standards. It is obvious that there is a great demand for a uniform strategy in the diagnosis and classification of GDM, the challenges to adopt such strategy is well-known and discussed for years. The tests that have been used until recently have mostly focused on the risk of developing diabetes in future life after pregnancy and not on perinatal outcomes of GDM(3).

mand for a uniform strategy in the diagnosis and classification of GDM, the challenges to adopt such strategy is well-known and discussed for years. The tests that have been used until recently have mostly focused on the risk of developing diabetes in future life after pregnancy and not on perinatal outcomes of GDM(3). DIAGNOSTIC CRITERIA FOR GESTATIONAL DIABETES GDM brings some risks to the mother and newborn baby. The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study published in 2008 has caused questioning of conventional method used in the diagnosis of GDM. In this epidemiological study, a total of 25.505 pregnant women from 15 centers in 9 countries and between 24 and 36 weeks of gestation were examined with 75 gr OGTT, and the probability of maternal, fetal, and neonatal side effects was shown to have increased in relation to glycemic status between at 24-28 weeks of gestation (even with blood glucose levels previously regarded as normal)(4). The study concluded that maternal blood glucose level, even if it was lower than the threshold required for the diagnosis of GDM, was found to be associated with increased birth weight and cord blood C-peptide levels, and these results prompted the researchers to revise diagnostic criteria for gestational diabetes. The study group recommended 75 grams OGTT to be performed in all pregnant women between 24-28 weeks of gestation. This also pointed to the need to change the threshold for plasma glucose level while fasting and at 1 hour and 2 hours to diagnose GDM.

he researchers to revise diagnostic criteria for gestational diabetes. The study group recommended 75 grams OGTT to be performed in all pregnant women between 24-28 weeks of gestation. This also pointed to the need to change the threshold for plasma glucose level while fasting and at 1 hour and 2 hours to diagnose GDM. After having extensive discussions between years 2008 and 2009, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) declared a consensus report with the participation of 220 delegates from 40 countries. Accordingly, a two-step screening has been recommended(5). In the first step, blood glucose (fasting or random) level and HbA1C measurements are performed during the first prenatal visit, and women who are found to have high risk for diabetes are diagnosed with “overt diabetes” instead of gestational diabetes using standard criteria. The second-step screening strategy of IADPSG is as follows: - Perform 75 grams OGTT * (as to include fasting, 1-hour, and 2-hour plasma glucose levels between 24-28 weeks of gestation for pregnant women who were not previously diagnosed with overt diabetes) *OGTT must be performed in the morning after at least 8 hours of fasting. - The diagnosis of GDM is established is any plasma glucose measurement is above the following limits: Fasting ≥ 92 mg/dl (5.1 mmol/lt) 1-hour ≥ 180 mg/dl (10.0 mmol/lt) 2-hour ≥ 153 mg/dl (8.5 mmol/lt)

- Perform 75 grams OGTT * (as to include fasting, 1-hour, and 2-hour plasma glucose levels between 24-28 weeks of gestation for pregnant women who were not previously diagnosed with overt diabetes) *OGTT must be performed in the morning after at least 8 hours of fasting. - The diagnosis of GDM is established is any plasma glucose measurement is above the following limits: Fasting ≥ 92 mg/dl (5.1 mmol/lt) 1-hour ≥ 180 mg/dl (10.0 mmol/lt) 2-hour ≥ 153 mg/dl (8.5 mmol/lt) These new criteria may cause a significant increase in the prevalence of GDM due to the fact that one abnormal value (and not two) is sufficient to diagnose GDM. On the other hand, these criteria will allow more pregnant women to receive “medications” and thereby produce good outcomes for the mother and the baby. The results of follow-up studies using these diagnostic criteria are not currently sufficient, and well-designed clinical studies are warranted. In one of the first large randomized studies that evaluated the effects of treating mild hyperglycemia during pregnancy on the health status of mother and the baby showed that severe neonatal complications have been reduced and postpartum well-being was positively affected(6).

These new criteria may cause a significant increase in the prevalence of GDM due to the fact that one abnormal value (and not two) is sufficient to diagnose GDM. On the other hand, these criteria will allow more pregnant women to receive “medications” and thereby produce good outcomes for the mother and the baby. The results of follow-up studies using these diagnostic criteria are not currently sufficient, and well-designed clinical studies are warranted. In one of the first large randomized studies that evaluated the effects of treating mild hyperglycemia during pregnancy on the health status of mother and the baby showed that severe neonatal complications have been reduced and postpartum well-being was positively affected(6). According to another multicenter randomized study, pregnant women with abnormal OGTT but normal fasting blood glucose (FBG<95 mg/dl or 5.3 mmol/lt) were considered to have mild GDM, and the treatment of these cases did not have significant consequences in terms of severe complications of DM such as hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma; however, there was a decrease in the incidences of fetal overgrowth, shoulder dystocia, C/S rates, and hypertensive disorder in the mother(7).

eatment of these cases did not have significant consequences in terms of severe complications of DM such as hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma; however, there was a decrease in the incidences of fetal overgrowth, shoulder dystocia, C/S rates, and hypertensive disorder in the mother(7). The studies have indicated a linear relationship between maternal hyperglycemia and perinatal outcomes but no point value for increased risk. The treatment of even mild maternal hyperglycemia provide good perinatal outcomes(5). Based on the results of these findings, IADPSG considered it necessary to publish new guidelines for gestational diabetes in order to minimize unfavorable perinatal outcomes. Accordingly, it is recommended to obtain 2-hour glucose level with 75 grams OGTT and consider the patient to have GDM if ≥1 abnormal test result is obtained. However, adoption of these new diagnostic criteria will raise the prevalence of GDM up to 18% in the population(8). There is still no consensus as to how pregnant women diagnosed with these criteria will be monitored but it is obvious that more stringent follow-up is necessary. It must also be emphasized that 80%-90% of pregnant women recently being diagnosed with these criteria have mild GDM which may only require life style change. In other words, it seems possible to raise a healthy generation with simple measures such as diet and exercise. In cases where this remains inadequate, short and long-term insulin therapy must be planned or the patient must be assessed for the use of oral anti-diabetic medications.

h may only require life style change. In other words, it seems possible to raise a healthy generation with simple measures such as diet and exercise. In cases where this remains inadequate, short and long-term insulin therapy must be planned or the patient must be assessed for the use of oral anti-diabetic medications. NEW APPROACHES IN THE TREATMENT OF GESTATIONAL DIABETES It still remains unclear which treatment option is more appropriate when the women with a known GDM and diabetes become pregnant. The most appropriate option would be tailored treatment program in which diet, oral anti-diabetics and/or insulin therapy are selected according to the needs of individual patient. As in patients with diabetes, body weight, height, BMI, and waist to hip ratio (WHR) must be obtained prior to treatment in patients with GDM. The main elements of the therapy include education, nutritional therapy, exercise, and medical treatment. The recommended daily calorie intake is 30 kcal/kg for women with a BMI of 22-25, 24 kcal/kg for women with a BMI of 26-29, and 12-15 kcal/kg for women with a BMI of >30. The recommended diet composition contains 33%-40% complex carbohydrates, 35%-40% fat, and 20% protein. This calorie intake may turn 75%-80% of women with GDM into normoglycemic state(9).

is 30 kcal/kg for women with a BMI of 22-25, 24 kcal/kg for women with a BMI of 26-29, and 12-15 kcal/kg for women with a BMI of >30. The recommended diet composition contains 33%-40% complex carbohydrates, 35%-40% fat, and 20% protein. This calorie intake may turn 75%-80% of women with GDM into normoglycemic state(9). The pregnant women in whom blood glucose control cannot be achieved with exercise and diet regulation must be switched to insulin or oral anti-diabetics. There is also no consensus on when to initiate insulin therapy, which has been reported to reduce the risk of macrosomia and other complications during infancy. There are two approaches for the initiation of insulin therapy one of which requires measurement of fasting glucose concentration >90 mg/dl with two weeks intervals and other approach requires postprandial 1-hour glucose measurement >120 mg/dl. The insulin preparations used in GDM include neutral protamine Hagedorn (NPH) and regular insulin. NPH is a moderate-acting insulin and particularly effective in the presence of high fasting glucose levels(9).

mg/dl with two weeks intervals and other approach requires postprandial 1-hour glucose measurement >120 mg/dl. The insulin preparations used in GDM include neutral protamine Hagedorn (NPH) and regular insulin. NPH is a moderate-acting insulin and particularly effective in the presence of high fasting glucose levels(9). The use of oral anti-diabetics (OAD) during pregnancy is a relatively new practice. In a review of the literature regarding this topic, 12 randomized studies were evaluated, and the effects of the use of oral anti-diabetic agents was investigated on pregnant women with a known diabetes and those with impaired glucose tolerance in the current or previous pregnancy(10). According to this review, the disadvantages of OAD agents include lack of clear evidence for the safety of these agents during pregnancy and controversial efficiency of Glyburide (glibenclamide) and Metformin, the most commonly used OAD agents during pregnancy, in preventing postprandial glycemic peaks observed in type 2 diabetes(11). The advantages of OAD agents include easy administration compared to insulin therapy and better patient compliance with relatively less extensive education. OAD agents also offers the advantage of combination with insulin therapy where oral agents remain insufficient, and oral agents also widen the dose range and reduce the amount of insulin.

ents include easy administration compared to insulin therapy and better patient compliance with relatively less extensive education. OAD agents also offers the advantage of combination with insulin therapy where oral agents remain insufficient, and oral agents also widen the dose range and reduce the amount of insulin. In a study conducted in South Africa, no significant difference was found in terms of the rates of fetal abnormality between patients who received OAD agents during pregnancy and patients who were placed on or switched to insulin therapy from diet(12). However, this study found higher rate of perinatal mortality in OAD group compared to insulin therapy group. In a meta-analysis that compared the use of OAD agents and insulin therapy in the management of GDM, a total of 6 randomized controlled studies comprising 1388 cases were evaluated that investigated glycemic control and maternal and perinatal outcomes. This study found no significant difference between OAD group and the insulin group in terms maternal fasting and postprandial glycemic control. There was no significant relationship between the use of OAD agents and neonatal hypoglycemia, increased birth weight, rate of cesarean section, and the incidence of delivering a large baby, and in terms pregnancy outcomes, use of OAD agents or insulin therapy were not found to be significantly different in achieving glycemic control(13).

cant relationship between the use of OAD agents and neonatal hypoglycemia, increased birth weight, rate of cesarean section, and the incidence of delivering a large baby, and in terms pregnancy outcomes, use of OAD agents or insulin therapy were not found to be significantly different in achieving glycemic control(13). MAJOR ORAL ANTI-DIABETIC AGENTS Biguanides: Metformin falls into this group. These agents decrease peripheral insulin resistance, inhibit gluconeogenesis and reduce plasma triglyceride concentrations(14,15,16). Metformin can pass across the placenta. In a study that compared the use of insulin versus metformin during pregnancy, use of metformin did not result in an increase in perinatal complications, and it was even less prone to cause severe neonatal hypoglycemia and it resulted in lesser maternal weight gain and provided better patient compliance. However, metformin was used between 20 and 34 weeks of gestation in this study. There is not sufficient evidence for the safety of metformin in early periods of pregnancy(17,18). In a study that evaluated 126 infants aged 18 months born to 109 mothers, no significant difference was found between mother who received metformin during pregnancy versus those who did not in terms of motor and social development and growth(19). In another study that compared metformin and insulin therapy, no significant difference was found between the two groups in terms of the rate of perinatal complications. Although 46.3% of the women receiving metformin therapy required addition of insulin therapy, the women rather preferred metformin therapy(20). In a recent randomized study, 47 pregnant women with GDM who received metformin or insulin therapy were evaluated, and metformin group had better daily glycemic control, lesser weight gain neonatal hypoglycemia. The logistic regression analysis showed that the need for additional insulin therapy in metformin group was associated with gestational age at diagnosis and mean glucose level before the initiation of therapy(21).

valuated, and metformin group had better daily glycemic control, lesser weight gain neonatal hypoglycemia. The logistic regression analysis showed that the need for additional insulin therapy in metformin group was associated with gestational age at diagnosis and mean glucose level before the initiation of therapy(21). Sulfonylureas: Glyburide (glibenclamide) and Glimepiride fall into this group. These drugs increase insulin secretion and peripheral sensitivity to insulin and decrease hepatic clearance of insulin(22,23,24,16). The primary side effect of these drug is hypoglycemia. The first generation sulfonylureas pass across the placenta. It remains unclear whether or not second generation sulfonylureas such as glyburide can pass across the placenta or cause some effects on the fetus(11,25,26,27). The most frightening side effect of sulfonylureas is the stimulation of fetal hyperinsulinemia(28). In a randomized and controlled study, there was no significant between the two patient groups that received glyburide or insulin therapy due to GDM in terms of delivering babies with macrosomia and LGA(29). It was reported that glyburide was equivalent to insulin therapy in terms of achieving glycemic control and comparable to insulin therapy in terms of maternal and fetal complications(30,31). The data regarding the use of alpha-glycosidase inhibitors, thiazolidines, meglitinides, and peptide analogues are insufficient and mostly experimental.

Sulfonylureas: Glyburide (glibenclamide) and Glimepiride fall into this group. These drugs increase insulin secretion and peripheral sensitivity to insulin and decrease hepatic clearance of insulin(22,23,24,16). The primary side effect of these drug is hypoglycemia. The first generation sulfonylureas pass across the placenta. It remains unclear whether or not second generation sulfonylureas such as glyburide can pass across the placenta or cause some effects on the fetus(11,25,26,27). The most frightening side effect of sulfonylureas is the stimulation of fetal hyperinsulinemia(28). In a randomized and controlled study, there was no significant between the two patient groups that received glyburide or insulin therapy due to GDM in terms of delivering babies with macrosomia and LGA(29). It was reported that glyburide was equivalent to insulin therapy in terms of achieving glycemic control and comparable to insulin therapy in terms of maternal and fetal complications(30,31). The data regarding the use of alpha-glycosidase inhibitors, thiazolidines, meglitinides, and peptide analogues are insufficient and mostly experimental. FOLLOW-UP OF A DIABETIC PREGNANT WOMEN The pregnant women who are known to have diabetes or who are diagnosed to have diabetes in the first visit should be placed on a closer follow-up program. General physical examination in addition to neurological examination and fundoscopic examination must be performed at the first visit. Plasma glucose and HbA1 c levels are obtained, and insulin therapy is initiated if required or the dose is adjusted in existing users, and the efficacy of oral anti-diabetics and insulin therapy is evaluated with the measurement of plasma glucose levels at each antenatal visit. In subsequent weeks (generally after 32 weeks), fetal health status is evaluated with antenatal tests.

erapy is initiated if required or the dose is adjusted in existing users, and the efficacy of oral anti-diabetics and insulin therapy is evaluated with the measurement of plasma glucose levels at each antenatal visit. In subsequent weeks (generally after 32 weeks), fetal health status is evaluated with antenatal tests. CASES WITH HIGHER RISK OF DEVELOPING GESTATIONAL DIABETES - Previous delivery of a stillbirth baby, anomalous baby, large for gestational age (>4000 grams) or multiple miscarriages, - GDM in the previous pregnancy, - BMI > 27 before pregnancy, - Age > 35 years, - Diabetes in one of the first degree relatives, - Recurrent urinary tract infection or fungal infection during pregnancy is a risk factor for developing GDM. Furthermore, particular attention must be paid to women, - having large fetus than gestational week, - having excessive weight gain during pregnancy, - having polyhydramnios with an unknown cause, - IUMF, - With polyuria, polydipsia or glycosuria for possible GDM that remained unnoticed.

- Recurrent urinary tract infection or fungal infection during pregnancy is a risk factor for developing GDM. Furthermore, particular attention must be paid to women, - having large fetus than gestational week, - having excessive weight gain during pregnancy, - having polyhydramnios with an unknown cause, - IUMF, - With polyuria, polydipsia or glycosuria for possible GDM that remained unnoticed. The blood glucose level must be regularly tested in a pregnant women with gestational diabetes, compliance to diet or therapy with OAD agent or insulin must be monitored, and the women must be examined with USG for the development of polyhydramnios during routine controls, and the weight of the fetus must be evaluated. The ideal fasting glucose level is 60-90 mg/dl and postprandial 1-hour glucose level is 120 mg/dl during pregnancy. It is useful to test for blood glucose once in every two weeks until 34 weeks of gestations and then 4-7 times daily (before and after meals and before bed). The follow-up blood glucose must be more stringent in patients who receive insulin therapy and in those with uncontrolled glucose levels. NST and BPP must be performed weekly after 36 weeks of gestation. The mother must be education on how to monitor baby movements, and pregnant women with GDM that require insulin therapy must be monitored in the hospital setting after 38 weeks of gestation. The pregnancies complicated with GDM are not desired to extend beyond 40 weeks, and delivery is induced or cesarean section is performed when applicable, if delivery does not start spontaneously. If natural delivery has been planned, close delivery follow-up is necessary.

e hospital setting after 38 weeks of gestation. The pregnancies complicated with GDM are not desired to extend beyond 40 weeks, and delivery is induced or cesarean section is performed when applicable, if delivery does not start spontaneously. If natural delivery has been planned, close delivery follow-up is necessary. All pregnant women who were found to have GDM should undergo OGTT at 6 weeks postpartum. Even if this test returns normal, the patient should be explained for her higher risk of developing diabetes in subsequent pregnancies or later in her life compared to general population. CONCLUSION Gestational diabetes is a condition that complicates significant portion of the pregnancies and having significant consequences on the health status of the mother and the baby. However, there is no universally accepted screening test. IADPSG recommended the use of two-step screening program and 75 grams OGTT. Recent studies showed positive effects of decreasing the diagnostic threshold for GDM on perinatal outcomes; however, this will also increase the rate of GDM up to 18% that will bring significant financial burden and over-diagnosis.

ening test. IADPSG recommended the use of two-step screening program and 75 grams OGTT. Recent studies showed positive effects of decreasing the diagnostic threshold for GDM on perinatal outcomes; however, this will also increase the rate of GDM up to 18% that will bring significant financial burden and over-diagnosis. Also, it still remains unclear which treatment option would be more appropriate when the women with a known GDM or diabetes become pregnant. The use of oral anti-diabetic agents during pregnancy is a relatively recent matter of debate. The current reports suggest that metformin and glyburide could be used during pregnancy. The most appropriate approach would be to tailor a treatment program in which diet, oral anti-diabetics and/or insulin therapy are selected according to the needs of an individual patient.

INTRODUCTION Cervical malignancy is the second most common malignancy in women worldwide(1). Up to 25% of women with FIGO stage IB-IIA cervical cancer may recur after initial therapy(2). Frequently, these recurrences may be treated with radiotherapy; however, radical surgery may offer an alternative for curative treatment. Long-term survival is directly correlated with complete tumor resection, so establishing resectability is a key aspect of preoperative planning(3). Pelvic exenteration (PE) is an ultraradical surgery that was first described by Brunschwig in 1948(4). This surgery involves en bloc resection of the pelvic organs, including the internal reproductive organs, bladder, and rectosigmoid. Traditionally, PE has been used for centrally recurrent cervical carcinoma(5). The purpose of the present case is to share our experience of total pelvic exenteration (TPE) in a patient with recurrent endocervical carcinoma regarding survival outcome.

Pelvic exenteration (PE) is an ultraradical surgery that was first described by Brunschwig in 1948(4). This surgery involves en bloc resection of the pelvic organs, including the internal reproductive organs, bladder, and rectosigmoid. Traditionally, PE has been used for centrally recurrent cervical carcinoma(5). The purpose of the present case is to share our experience of total pelvic exenteration (TPE) in a patient with recurrent endocervical carcinoma regarding survival outcome. CASE A 51-year-old woman underwent type 1 hysterectomy at outer center, has been reported with histopathology of leiomyoma uteri and endocervical adenocarcinoma. She has been observed without treatment for 15 months until presenting with abnormal vaginal bleeding at outer center. Vaginal cuff biopsy has revealed adenocarcinoma. Due to recurrence of cervical carcinoma, she has undergone pelvic radiotherapy and vaginal brachytherapy with 7 courses of weekly cisplatin (concurrent chemoradiotherapy). After 6 months of following chemoradiotherapy, on account of recurrent complaint of vaginal bleeding and cuff biopsy with histopathology of adenocarcinoma, patient has been referred to our clinic for advanced evaluation and management. Pelvic examination revealed fullness (size 35x20 mm) on vaginal cuff and infiltration of left parametrium. Irregularity and more wall thickening at the right superolateral side of the vaginal cuff, nearly 23x22 mm, were detected on magnetic resonance imaging (MRI). MRI of the upper abdomen and computerized tomography (CT) of thorax confirmed no residual mass.

e 35x20 mm) on vaginal cuff and infiltration of left parametrium. Irregularity and more wall thickening at the right superolateral side of the vaginal cuff, nearly 23x22 mm, were detected on magnetic resonance imaging (MRI). MRI of the upper abdomen and computerized tomography (CT) of thorax confirmed no residual mass. Based on the findings and clinical status of the patient, we decided to perform surgery of exenteration as a therapeutic option. We performed TPE + paraaortic lymphadenectomy + indiana pouch + ileocolic anastomosis + colostomy + omental J-plasty (Figure 1). Histopathology of the paraffin section of specimens was reported as metastasis of adenocarcinoma (grade 1) to the vagina, the left ovary and right tuba uterine. The surgical border on the lower margin of the vagina was free. We did not detect any short or long-term morbidity due to surgery. Adjuvant chemotherapy with paclitaxel and cisplatin was given due to ovarian metastasis. After premedication, initially paclitaxel (175 mg/m2) was infused in 3 hours. Then, cisplatin (75 mg/m2) was infused in 2 hours. Six courses of this combination were given every 3 weeks. The complete clinical response was obtained after treatment.

erapy with paclitaxel and cisplatin was given due to ovarian metastasis. After premedication, initially paclitaxel (175 mg/m2) was infused in 3 hours. Then, cisplatin (75 mg/m2) was infused in 2 hours. Six courses of this combination were given every 3 weeks. The complete clinical response was obtained after treatment. Patient was evaluated every 3 months for the first 2 years, every 6 months for the following 3 years and annually thereafter. Follow-up included physical examination, abdominal sonography (abdominal MRI at first year and then if necessary), chest X-ray (every year or if necessary), complete blood count, serum biochemistry and CA-125 level (because of ovarian metastasis). There was no recurrence of the disease in follow-up. The patient is alive with no evidence of recurrence for more than 80 months after TPE. DISCUSSION The management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence(6,7). In the present case, the patient has recently completed a treatment of chemoradiation after central pelvic recurrence, around vaginal cuff, has been determined 15 months after type 1 hysterectomy.

management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence(6,7). In the present case, the patient has recently completed a treatment of chemoradiation after central pelvic recurrence, around vaginal cuff, has been determined 15 months after type 1 hysterectomy. The original classification of PE into three groups, i.e., anterior (removal of the bladder and internal reproductive organs but spares the gastrointestinal tract), posterior (remove the internal reproductive organs and the rectosigmoid but spares the anterior vagina, urinary bladder, and ureters) and total (anterior + posterior), addresses only the nature of the pelvic viscera removed. The patient underwent total pelvic exenteration in our case.

ively] in LPS-administered groups as compared with LPS-free groups. In the subgroup analyses, LPS was reported to significantly increase BPR, CPR, and LBR only in the gonadotropin-stimulated IUI cycles compared with the LPS-free group. However, none of the studies present data regarding the number of follicles yielded. In addition, Miralpeix et al.(21) categorized the five studies assessed in their meta-analyses as either low risk of bias (if all the questions were answered yes) or high risk of bias (if at least one question was answered no) with respect to the responses to six parameters, which were “sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues.” Consequently, studies conducted by Kyrou et al.(22) and Ebrahimi et al.(23) were defined as having a high risk of bias, whereas the others had a low risk of bias.

pares the gastrointestinal tract), posterior (remove the internal reproductive organs and the rectosigmoid but spares the anterior vagina, urinary bladder, and ureters) and total (anterior + posterior), addresses only the nature of the pelvic viscera removed. The patient underwent total pelvic exenteration in our case. In the literature, there are specific criteria for surgical resection. Patients with resectable central recurrences that involve the bladder and/or rectum, without evidence of intraperitoneal or extra-pelvic spread, and who have a dissectible tumor-free space along the pelvic side wall are potentially suitable for exenteration(7). Similarly, one study defined the candidates for exenteration is those with central local recurrences that have not extended to the pelvic sidewalls(6). In addition, in the same study, it was noticed that all patients who have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. According to Shingleton et al., the best candidates for cure by PE were the patients with recurrent small (<3 cm), mobile central tumors and with a disease free interval of one year or longer(8). In the present case, our indicated parameters for TPE were no documented distant metastasis, central pelvic recurrence with no extension to the pelvic sidewall, tumor size smaller than 3 cm and the history of previous radiation therapy.

), mobile central tumors and with a disease free interval of one year or longer(8). In the present case, our indicated parameters for TPE were no documented distant metastasis, central pelvic recurrence with no extension to the pelvic sidewall, tumor size smaller than 3 cm and the history of previous radiation therapy. PE is a major surgery with significant morbidity(5). The clinical improvements obtained in the last decades may be mainly due to better surgical techniques and more intensive postoperative care. We have no detected any complication or morbidity after operation. One study noticed that the more strict criteria for the patient selection (central disease, no paraaortic involvement, no peritoneal disease), the greater the chance for a favorable clinical outcome(9). A better definition of patient selection criteria made easier by the availability of new diagnostic techniques such as positron emission tomography scanning (PET scan), CT, MRI(10,11). The patient was pre-operatively evaluated by MRI of the upper and lower abdomen, and CT of thorax for metastasis and recurrence.

me(9). A better definition of patient selection criteria made easier by the availability of new diagnostic techniques such as positron emission tomography scanning (PET scan), CT, MRI(10,11). The patient was pre-operatively evaluated by MRI of the upper and lower abdomen, and CT of thorax for metastasis and recurrence. PE remains the only therapeutic option that offers the possibility of long-term survival for most patients(6). In a recent series, the 5-year overall survival after PE ranged from 22% to 48%, respectively(3,8,12,13). In presented case, patient is alive and free of disease for more than 80 months after TPE. Free surgical margins(3,8,12), negative lymph nodes(12,14), small tumor size(8) and long disease-free interval(3,8,12) were associated with a more favorable prognosis. In our case, histopathological findings after PE surgery have been reported as negative lymph nodes, level of lower vagina margins remained free, metastasis to the left ovary and right tuba uterina. Independent from stage of the disease ovarian metastasis is a poor prognostic factor in cervical carcinoma(15). It leads to a regression of overall survival with decrease in quality of life. Despite the presence of ovarian metastasis, the patient lives for more than six years with no evidence of disease recurrence.

na. Independent from stage of the disease ovarian metastasis is a poor prognostic factor in cervical carcinoma(15). It leads to a regression of overall survival with decrease in quality of life. Despite the presence of ovarian metastasis, the patient lives for more than six years with no evidence of disease recurrence. Marnitz et al. reported that survival correlated significantly with the time interval between primary treatment and recurrence(3). In that study, 5-year survival was 16.8% for disease failure in first 2 years, 28% for 2-5 years and 83.2% for after 5 years. In the present case, recurrence after primary surgery was identified 15 months later. According to the study of Mourton et al., 68% of patients subsequently developed recurrence after TPE. The median time from TPE to recurrence was 7 months (range 2-73 months), 92% occurring within 2 years(16). In the presented case, no evidence with recurrence was noticed for 80 months after exenteration. One study showed that affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement(17). In our case, there were no pelvic wall and rectal involvement. At present, pelvic reconstructive procedures are strongly recommended after exenteration. An ileocolonic segment is currently employed for continent urinary diversion(18). Indiana pouch (Indiana continent urinary reservoir), firstly described by Rowland et al. in 1987(19), was performed to our case. Colostomy was performed for fecal diversion. Omental J-plasty was performed for pelvic floor coverage.

ation. An ileocolonic segment is currently employed for continent urinary diversion(18). Indiana pouch (Indiana continent urinary reservoir), firstly described by Rowland et al. in 1987(19), was performed to our case. Colostomy was performed for fecal diversion. Omental J-plasty was performed for pelvic floor coverage. In conclusion, the present case showed that total pelvic exenteration has a potential to provide long-term survival despite the second recurrence which is seen in 2 years after primary surgery and presence of ovarian metastasis. Figure 1 Exenteration; Perineal region

INTRODUCTION The female genital system includes the uterus, the cervix, fallopian tubes and upper third of the vagina, all formed from the mullerian ducts during the 7th week of gestation. Anomalies during the fusion of the mullerian ducts are the basis of rudimentary horn. Because most cases are asymptomatic, the incidence is not well known, and most rudimentary horn cases exist generally in benign form. Only cases with endometrial cavity are noticed if dysmenorrhea and chronic pelvic pain occurs during puberty or if rupture and intraabdominal hemorrhage occur during a rudimentary horn pregnancy. Suspicion plays a key role in the diagnosis of these cases. In order to decrease complications during rudimentary horn pregnancy, preoperative diagnosis services need to be usedappropriately and timely. Even though recent medical developments have made the diagnosis of the rudimentary horn pregnancy easier, lack of experience in the diagnosis criteria and symptomatology are the most predominant issues that affect the rise of complications during rudimentary horn pregnancy. This paper presents the techniques and criteria used during preoperative diagnosis of a rudimentary horn pregnancy. As a result of this diagnosis, it is shown that minimally invasive techniques can be used for treatment. CASE A 37-year-old, gravida 3 and parity 2 patient with abdominal pain was admitted to the hospital. The anamnesis revealed primary infertility, and unikornuate uterus in a previous hysterosalpingography (HSG) (Figure 1). Both of the patient’s pregnancies were spontaneous.

INTRODUCTION The female genital system includes the uterus, the cervix, fallopian tubes and upper third of the vagina, all formed from the mullerian ducts during the 7th week of gestation. Anomalies during the fusion of the mullerian ducts are the basis of rudimentary horn. Because most cases are asymptomatic, the incidence is not well known, and most rudimentary horn cases exist generally in benign form. Only cases with endometrial cavity are noticed if dysmenorrhea and chronic pelvic pain occurs during puberty or if rupture and intraabdominal hemorrhage occur during a rudimentary horn pregnancy. Suspicion plays a key role in the diagnosis of these cases. In order to decrease complications during rudimentary horn pregnancy, preoperative diagnosis services need to be usedappropriately and timely. Even though recent medical developments have made the diagnosis of the rudimentary horn pregnancy easier, lack of experience in the diagnosis criteria and symptomatology are the most predominant issues that affect the rise of complications during rudimentary horn pregnancy. This paper presents the techniques and criteria used during preoperative diagnosis of a rudimentary horn pregnancy. As a result of this diagnosis, it is shown that minimally invasive techniques can be used for treatment. CASE A 37-year-old, gravida 3 and parity 2 patient with abdominal pain was admitted to the hospital. The anamnesis revealed primary infertility, and unikornuate uterus in a previous hysterosalpingography (HSG) (Figure 1). Both of the patient’s pregnancies were spontaneous. When admitted to the hospital, the patient’s vitals were stable. The patient’s arterial blood pressure was measured as 120/70 mmHg and her pulse rate was measured as 78 bpm. Palpation examination of the abdomen showed tenderness with no observed defense or rebound. Gynecological examination showed the perineum, vagina and vulva were normal and collum forme as closed. No vaginal hemorrhage was observed. Uterus was at an 8-week size, left adnex was nonpalpable and a mobile mass with a diameter of 5 to 6 cm was palpated on the right adnex. Transvaginal ultrasonography showed an adnexal mass having an embryo with an observed fetal heart rate, a gestational sac of 30x27 mm, and a crown-rump-length (CRL) of 12.4 mm corresponding to pregnancy of 7 weeks 3 days (Figure 2). The uterine cavity had no visible gestational sac. The pouch of douglas had no free fluid inside. Patient’s bloodwork showed a beta-hCG level of 30742 mlIU/ml, hemoglobin level of 12.5 g/dl and Htc level of 37.5%. From the above results, along with the anamnesis of primary infertility and unicornuate uterus, it was thought that the patient might have rudimentary horn pregnancy, and therefore, a laparoscopic surgery was planned. Laparoscopic pelvic anatomy showed the right ovary and tuba uterina, along with a noncommunicating rudimentary horn with a diameter of 5-6 cm, in the right adnexal region. Left ovary and tuba uterina were both normal, and uterus was unicornuate (Figure 3). A rudimentary horn excision was also performed. The rudimentary horn was pulled out of the abdomen with the help of an endobag extractor (Figure 4). In addition, a right salpingectomy was performed. Surgical operation concluded after a check for bleeding. The pathology report was consistent with rudimental uterus and pregnancy.

tary horn excision was also performed. The rudimentary horn was pulled out of the abdomen with the help of an endobag extractor (Figure 4). In addition, a right salpingectomy was performed. Surgical operation concluded after a check for bleeding. The pathology report was consistent with rudimental uterus and pregnancy. DISCUSSION Rudimentary horn is a mullerian anomaly that is a variant of unicornuate uterus. Rudimentary horn pregnancy is very rare with an incidence level between 1/76000 and 1/140000(1). According to the American Society for Reproductive Medicine (ASRM) mullerian anomalies can be divided into 7 sub-groups, and unicornuate uterus is categorized into 4 groups(2). ASRM indicates that the most common unicornuate uterus case is the horn with a fibrous joint to the unicornuate uterus without endometrial cavity. Most patients are asymptomatic and incidental. Rudimentary horn pregnancy is an ectopic pregnancy that exhibits pregnancy ruptures. It is easy to understand the pathophysiology when there is a communication between the rudimentary horn and the other uterus and servix. In the absence of this continuity, it is still possible to observe a horn pregnancy, and it is thought that the pregnancy is possible with sperm transperitoneal migration(3,4). Due to previous hysterosalpingogram (HSG) results showing no contrast agents, it is thought that the pregnancy is related to the sperm transperitoneal migration in this case. In this case, corpus luteum was observed on the same side as the rudimentary horn.