Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine.

BACKGROUND: Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yielding infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology. METHODS: 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. FINDINGS: A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromosomal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link. INTERPRETATION: We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogenesis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility. FUNDING: Université Paris Saclay, Agence Nationale de Biomédecine.

A blind spot: Manchester Fothergill operation for cervical elongation without uterine descensus.

OBJECTIVE: To evaluate the anatomical results of Manchester Fothergill operation performed due to cervical elongation cases without uterine descensus and its effects on quality of life and sexual function. MATERIALS AND METHODS: Thirty-six women who underwent Manchester Fothergill operation for cervical elongation without uterine descensus were analyzed retrospectively. Pre- and postoperative Pelvic Organ Prolapse-Quantification (POP-Q) measurements, Prolapse Quality of Life (P-QoL) Questionnaire and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) scores were collected. RESULTS: There were significant improvements in POP-Q measurements, P-QoL Questionnaire and PISQ-12 scores postoperatively. There was no relationship between the change in POP-Q measurements and the changes in questionnaires scores. Reoperation was performed in only one patient due to anterior compartment prolapse. No serious complications were detected. CONCLUSION: Manchester Fothergill operation is an effective and safe surgical option in the surgical treatment of cervical elongation cases without uterine descensus. It provides anatomical improvement, increases the quality of life and improves sexual function in women.

Investigation of the role of serum telomerase levels in patients with occult primary ovarian insufficiency: a prospective cross-sectional study.

This study was designed to investigate serum telomerase levels of occult primary ovarian insufficiency (POI) and the relationship between in vitro fertilisation (IVF) results of these patients and serum telomerase levels. A cross-sectional case-control study was conducted between May and October 2017 including 78 patients at University of Health Science, Turkey. Occult POI was defined as women with a history of follicle-stimulating hormone (FSH) elevation between 12 and 25 IU/L and low ovarian reserve before initiation of IVF (n = 39). The control group were patients attending the hospital for contraception, with no history of infertility, having at least one healthy child (n = 39). Telomerase levels in serum samples were determined using enzyme-linked immunosorbent assay method. There was no statistically significant difference in serum telomerase levels in occult POI patients when compared with the control group.Impact statementWhat is already known on this subject? Clinical studies investigating the role of telomerase on reproductive function and in vitro fertilisation (IVF) outcomes in occult primary ovarian insufficiency (POI) patients are limited with no clear consensus and in all these studies polymerase chain reaction technique was used to evaluate telomere length. Regarding our knowledge, this is the first study in the literature investigating the role of serum telomerase levels in occult POI patients.What do the results of this study add? In contrast to the previous studies, in this study no statistically significant difference was found in serum telomerase levels in occult POI patients when compared with the fertile control patients.What are the implications of these findings for clinical practice and/or further research? The occult POI patients examined in this study are overlooked until they apply with infertility. Serum telomerase measurement is not useful to support the diagnosis of occult POI. Nevertheless, in order to confirm these findings, further studies in larger populations are needed.

Impact of Isthmocele on Assisted Reproductive Treatment Outcomes: An Age-matched Retrospective Study.

STUDY OBJECTIVE: To evaluate whether the presence of an ultrasonographic visible isthmocele has an impact on the chance of pregnancy in women undergoing embryo transfer. DESIGN: Age-matched retrospective study. SETTING: Private-assisted reproductive center. PATIENTS: The study included a total of 150 patients with a history of cesarean delivery with 75 isthmocele cases and 75 controls. All patients underwent embryo transfer from January 2017 through June 2018. The diagnosis of isthmocele was based on transvaginal ultrasound assessment. Isthmocele was defined as an anechoic indentation on the previous cesarean scar at the midsagittal plane, with a depth of >1 mm. INTERVENTIONS: Embryo transfer. MEASUREMENTS AND MAIN RESULTS: The groups were similar in patient and treatment characteristics. The live birth rate was 44% in the isthmocele group and 46.7% in the control group (odds ratio [OR] 0.89; 95% confidence interval [CI], 0.47-1.71; p = .743). The clinical pregnancy rates were 49.3% and 50.7%, respectively (OR, 0.94; 95% CI, 0.50-1.79; p = .870). The miscarriage rate was greater in the isthmocele group (8%) than in the control group (4%); however, it did not reach statistical significance (OR, 2.09; 95% CI, 0.50-8.67; p = .302). The multiple pregnancy rate was similar between the groups (8% vs 5.3%, respectively; OR, 1.54; 95% CI, 0.41-5.70; p = .513). The groups were also similar in ectopic pregnancy rates (p = .560). These outcomes remained similar when adjusted for potential confounders on the regression analysis. CONCLUSION: Isthmocele does not seem to have a significant impact on the chance of pregnancy in assisted reproductive treatment settings. However, the embryo transfer procedure may be more difficult in the presence of an isthmocele.

Parameters impacting the live birth rate per transfer after frozen single euploid blastocyst transfer.

BACKGROUND: To assess the predictive value of patient characteristics, controlled ovarian stimulation and embryological parameters on the live birth outcome of single euploid frozen-warmed blastocyst transfer (FBT). METHODS: This was a retrospective cohort study including 707 single FBTs after preimplantation genetic testing for aneuploidy (PGT-A) that were performed from October 1, 2015, to January 1, 2018. The effects of patient-, cycle- and embryology-related parameters on the live birth outcome after FBT were assessed. RESULTS: In the subgroup analysis based on live birth, patients who achieved a live birth had a significantly lower body mass index (BMI) than patients who did not achieve a live birth (22.7 (21.5-24.6) kg/m2 vs 27 (24-29.2) kg/m2, p<0.001). The percentage of blastocysts with inner cell mass (ICM) A or B was significantly higher among patients achieving a live birth, at 91.6% vs. 82.6% (p<0.001). Day-5 biopsies were also more prevalent among patients achieving a live birth, at 82.9% vs 68.1% (p<0.001). On the other hand, the mitochondrial DNA (mtDNA) levels were significantly lower among cases with a successful live birth, at 18.7 (15.45-23.68) vs 20.55 (16.43-25.22) (p = 0.001). The logistic regression analysis showed that BMI (p<0.001, OR: 0.789, 95% CI [0.734-0.848]), day of trophectoderm (TE) biopsy (p<0.001, OR: 0.336, 95% CI [0.189-0.598]) and number of previous miscarriages (p = 0.004, OR: 0.733, 95% CI [0.594-0.906]) were significantly correlated with live birth. Patients with elevated BMIs, cycles in which embryos were biopsied on day-6 and a higher number of miscarriages were at increased risks of reduced live birth rates. CONCLUSION: A high BMI, an embryo biopsy on day-6 and a high number of miscarriages negatively affect the live birth rate after single euploid FBT.

The impact of serum oestradiol concentration prior to progesterone administration on live birth rate in single vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Can serum oestradiol concentrations on the day of progesterone initiation predict live birth rates in single, autologous vitrified-warmed blastocyst transfers following artificial endometrial preparation? DESIGN: This retrospective study included the first transfers of 468 patients with unexplained or tubal factor infertility who underwent freeze-all cycles using single, top-quality blastocysts after artificial endometrial preparation from January 2015 to January 2018. Patients were stratified into four groups based on serum oestradiol concentration percentiles on the day of progesterone initiation: Group 1 (<25th percentile), Group 2 (25-50th percentile), Group 3 (51-75th percentile) and Group 4 (>75th percentile). The primary outcome was live birth rate. The secondary outcomes were implantation, clinical pregnancy and multiple pregnancy rates. Receiver operating characteristic (ROC) curves were generated to evaluate serum oestradiol concentrations in predicting implantation, clinical pregnancy and live birth. RESULTS: Similar live birth rates of 51.6%, 55.1%, 54.9% and 56.4% for Groups 1, 2, 3 and 4, respectively, were found. The groups also showed similar implantation and clinical pregnancy rates. ROC analysis revealed that serum oestradiol concentrations on the day of progesterone initiation were not predictive for implantation (area under the curve [AUC] 0.490, 95% CI 0.445-0.554), clinical pregnancy (AUC 0.507, 95% CI 0.453-0.561) or live birth (AUC 0.514, 95% CI 0.461-0.566). CONCLUSIONS: Serum oestradiol concentration monitoring just prior to progesterone administration does not appear to be predictive for live birth rates in good prognosis patients undergoing single, autologous vitrified-warmed blastocyst transfer after artificial endometrial preparation. Therefore, the current practice of monitoring serum oestradiol concentration is not supported by this study.

Comparison of female sexual function in women who underwent abdominal or vaginal hysterectomy with or without bilateral salpingo-oophorectomy.

OBJECTIVE: To compare the effect of abdominal and vaginal hysterectomy with or without bilateral salpingo-oophorectomy on female sexuality. METHODS: Perimenopausal, sexually active, aged 45-50 years women who underwent abdominal or vaginal hysterectomy with or without bilateral salpingo-oophorectomy due to benign indications were included in this retrospective study. For the assessment of preoperative and postoperative female sexual function, Turkish validated Female Sexual Function Index form was used. RESULTS: Of the study population, 82 women (Group A) underwent hysterectomy + bilateral salpingo-oophorectomy and 78 women (Group B) underwent hysterectomy-only operations. The groups were statistically similar in terms of mean age, number of gravida and parity, body mass index, duration of postoperative evaluation, type of hysterectomy and presence of preoperative female sexual dysfunction. Both in Group A and B, postoperative total Female Sexual Function Index scores increased significantly compared to preoperative total scores. And there were no differences between the groups regarding the total preoperative and postoperative Female Sexual Function Index scores. However, postoperative arousal and orgasm scores were higher while pain score was lower in Group B than in Group A. CONCLUSION: Abdominal and vaginal hysterectomy with or without bilateral salpingo-oophorectomy for benign causes positively affect female sexuality in general. But, premenopausal bilateral oophorectomy may cause more pain during intercourse, decreased libido and orgasm than ovary conservation.

Pregnancy outcomes after transvaginal sacrospinous hysteropexy.

AIM: To evaluate the pregnancy outcomes in women who underwent transvaginal sacrospinous hysteropexy with the review of the literature STUDY DESIGN: 54 women who underwent transvaginal sacrospinous hysteropexy due to ≥grade 2 uterine prolapse during six-year period were identified from a computer based database. 8 of these who had pregnancy resulted in live birth subsequent to transvaginal sacrospinous hysteropexy were enrolled in this study. They were examined in case of pelvic organ prolapse recurrence and were questioned about their current self satisfaction status and PISQ-12 questionnaire. RESULTS: The median age of women was 36 years (range 29-43 years). All of the women were multiparous and there were no women with a previous cesarean section. All of the subsequent conceptions following operation occured spontaneously. The median time between hysteropexy and conception was 16 months (range 10-30 months). The pregnancies continued at least 37 weeks with only one preterm delivery (due to twin pregnancy). All 8 pregnancies were delivered by cesarean section. The median follow-up period after cesarean section was 45 months (range 7-60 months). Majority of women (7/8, 87.5%) were satisfied with current outcomes of sacrospinous hysteropexy and PISQ12 questionnaire scores revealed improvement in 87.5% (7/8) of women. CONCLUSION: Transvaginal sacrospinous hysteropexy is an appropriate surgical treatment method for symptomatic uterovaginal descensus in women who wish to preserve their uterine and future childbearing. And cesarean section is a reliable and satisfactory delivery route for women who underwent transvaginal sacrospinous hysteropexy.

Risk factors for postoperative urinary tract infection following midurethral sling procedures.

OBJECTIVE: To identify the potential risk factors for urinary tract infections following midurethral sling procedures. STUDY DESIGN: 556 women who underwent midurethral sling procedure due to stress urinary incontinence over a four-year period were reviewed in this retrospective study. Of the study population, 280 women underwent TVT procedures and 276 women underwent TOT procedures. Patients were evaluated at 4-8 weeks postoperatively and were investigated for the occurrence of a urinary tract infection. Patients who experienced urinary tract infection were defined as cases, and patients who didn't were defined as controls. All data were collected from medical records. Multivariate logistic regression model was used to identify the risk factors for urinary tract infection. RESULTS: Of 556 women, 58 (10.4%) were defined as cases while 498 (89.6%) were controls. The mean age of women in cases (57.8±12.9years) was significantly greater than in controls (51.8±11.2years) (p<0.001). The presence of menopausal status, previous abdominal surgery, preoperative antibiotic treatment due to urinary tract infection, concomitant vaginal hysterectomy and cystocele repair, TVT procedure and postoperative postvoiding residual bladder volume ≥100ml were more common in cases than in controls. However, in multivariate regression analysis model presence of preoperative urinary tract infection [OR (95% CI)=0.1 (0.1-0.7); p=0.013], TVT procedure [OR (95% CI)=8.4 (3.1-22.3); p=0.000] and postoperative postvoiding residual bladder volume ≥100ml [OR (95% CI)=4.6 (1.1-19.2); p=0.036] were significant independent risk factors for urinary tract infection following midurethral slings CONCLUSION: Urinary tract infection after midurethral sling procedures is a relatively common complication. The presence of preoperative urinary tract infection, TVT procedure and postoperative postvoiding residual bladder volume ≥100ml may increase the risk of this complication. Identification of these factors could help surgeons to minimize this complicationby developing effective strategies.

Correlation of bladder wall thickness and treatment success in types of urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to investigate the correlation between mean bladder wall thickness (BWT) and treatment success in patients diagnosed with urinary incontinence, based on urodynamic test results. METHODS: In this prospective study, patient urinary incontinence type was identified using urodynamic tests. Patients (N = 125) were categorized into three groups: urodynamic stress incontinence (SUI), detrusor over-activity (DO) and mixed urinary incontinence. Measurements from the bladder dome, anterior wall and trigone were averaged to calculate BWT. Student's t test and Mann-Whitney U test were used to compare pre-treatment BWT. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for BWT to predict treatment success. RESULTS: Mean pre-treatment BWT significantly differed between success and non-success groups for each urinary incontinence type (p value for the SUI, DO and MUI groups was 0.043, 0.001 and 0.002 respectively). Using ROC curves to anticipate the treatment success, a threshold was calculated for mean pre-treatment BWT; 5.05 mm for SUI (sensitivity 74 %, specificity 66 %, positive predictive value [PPV] 85 %, negative predictive value [NPV] 50 %), 4.98 mm for DO (sensitivity 73 %, specificity 92 %, PPV 95 %, NPV 63 %) and 5.31 mm for mixed type (sensitivity 88 %, specificity 73 %, PPV 79 %, NPV 85 %). CONCLUSIONS: The study results suggest a significant relationship between the pre-treatment BWT and the success of urinary incontinence treatment. The mean BWT may be used as a benchmark in assessing the responsiveness to treatment of urinary incontinence types.

A comperative study for short-term surgical outcomes of midurethral sling procedures in obese and non-obese women with stress urinary incontinence.

There is little data comparing the surgical outcomes of tension-free vaginal tape (TVT) and transobturator tape (TOT) procedures in obese women. Therefore, we aimed to compare the surgical outcomes of TOT and TVT procedures among obese women with a diagnosis of stress urinary incontinence (SUI). One hundred and eighty-nine women who underwent TVT or TOT procedures due to pure SUI were included. Women in whom the body mass index (BMI) was ≥30 kg/m2 were considered as obese, while <30 kg/m2 were non-obese. And women with BMI ≥35 kg/m2 was defined as morbidly obese. At sixth month postoperative follow-up, neither the comparison of TVT and TOT results in obese women nor the comparison of TVT or TOT results between obese and non-obese women showed any significant differences in terms of objective and subjective cure rates, quality of life improvements, or intra/postoperative complications. TVT and TOT procedures also have similar effectiveness among morbidly obese women. We have concluded that TVT and TOT operations seem to be equally effective and safe surgical treatment procedures for female SUI regardless of BMI.

Should we interpret the results of 'two-step' glucose screening again according to the obstetric outcomes?

We aimed to re-evaluate the 'two-step' antenatal glucose screening programme in relation to maternal and foetal outcomes in pregnant women screened for gestational diabetes mellitus and to compare maternal and foetal outcomes between different groups divided according to glucose tolerance test results. Two-thousand four-hundred and two pregnant women attending for antenatal care were recruited retrospectively for the study. Mean birthweight for pregnancies with single-value abnormality (SVA) in 100-g oral glucose tolerance test (OGTT) was significantly higher than the control group [3420 ± 378 vs. 3294 ± 444]. We found a significantly higher rate of macrosomia in the subgroup of 50-g glucose challenge test (GCT) between 130 and 140 mg/dl [9.7% vs. 4.8%]. Pregnant women whose 50-g GCT results are between 130 and 140 mg/dl or who have SVA in 100-g OGTT not only have gestational diabetes, but are also at increased risk for diabetic complications.

The short-term and long-term adverse ocular effects of fesoterodine fumarate.

AIM: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA). METHOD: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4 mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically. RESULTS: The mean age of 120 women was 52.06 ± 9.39 years (30-70 years). The mean PD, IOP and AA values were 4.12 ± 0.61 mm (3.00-5.70 mm), 15.58 ± 1.74 mmHg (11-20 mmHg) 2.28 ± 1.26 Diopter (D) (0.50-5.50 D) at baseline; 4.68 ± 0.65 mm (3.20-5.80 mm), 16.11 ± 1.72 mmHg (11-20 mmHg), 1.68 ± 1.04 D (0.25-4.50 D) at 30th day; and 4.28 ± 0.58 mm (3.10-5.70 mm), 16.09 ± 1.96 mmHg (11-19 mmHg), 2.18 ± 1.19 D (0.50-5.00 D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p < 0.001 for each), the changes in IOP values were not as such (p = 0.642). Visual complaint was not observed in any patient. DISCUSSION: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.

Dry eye findings worsen with anticholinergic therapy in patients with urge incontinence.

INTRODUCTION AND HYPOTHESIS: To evaluate the effects of oral anticholinergic (OAC) drugs on tear secretion in women with overactive bladder over a 3-month follow-up period. METHODS: In this prospective study, 108 women with a diagnosis of overactive bladder were evaluated. All patients were examined ophthalmologically at baseline (day 0), and after 1 month (day 30) and 3 months (day 90) of OAC treatment. Tear film break-up time (BUT) and Schirmer 1 test results were recorded. The subjective complaints of the patients including dry mouth, and burning, dryness and foreign body sensation in the eyes, were also recorded. The chi-squared test or the paired sample t test as appropriate, was used for statistical analysis. RESULTS: The mean age of the patients was 51.8 ± 9.2 years (30 - 69 years). The most frequent subjective complaints were dry mouth and dry eyes and both complaints were significant on both day 30 and day 90. Both tear film BUT and Schirmer 1 test results were significantly lower on day 30 and day 90. Dry eye measurement values worsened with prolongation of OAC treatment (p = 0.037 and p = 0.012 for BUT, and p = 0.046 and p = 0.035 for Schirmer 1 test, on day 30 and day 90, respectively). CONCLUSIONS: OAC treatment in women with overactive bladder significantly and progressively affects tear secretion.

McCall Culdoplasty vs. Sacrospinous Ligament Fixation after vaginal hysterectomy: comparison of postoperative vaginal length and sexual function in postmenopausal women.

OBJECTIVES: To compare preoperative and postoperative vaginal length in sexually active postmenopausal women who underwent vaginal hysterectomy with McCall Culdoplasty or Sacrospinous Ligament Fixation and investigate whether these findings are correlated with sexual function. STUDY DESIGN: Fifty-eight sexually active postmenopausal women planned to undergo vaginal hysterectomy during the reconstructive surgical treatment of stage 2 or 3 uterine prolapse were included. They were classified into two groups according to their self-selections. Twenty-nine women underwent McCall Culdoplasty adjunct to hysterectomy while 29 women had Sacrospinous Ligament Fixation with hysterectomy. Vaginal length was measured before and after vaginal surgery at 6-week and 6-month follow-up. Sexual function were assessed by Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire-12 form, preoperatively and 6 months postoperatively. RESULTS: It was found that McCall Culdoplasty and Sacrospinous Ligament Fixation adjunct to vaginal hysterectomy shortened vaginal length significantly. And, the decrease in vaginal length was greater in McCall Culdoplasty group compared to Sacrospinous Ligament Fixation group. However, preoperative and postoperative sexual function questionnaire scores were not correlated with vaginal lengths. CONCLUSION: McCall Culdoplasty or Sacrospinous Ligament Fixation adjunct to vaginal hysterectomy shortens vaginal length postoperatively. However these changes do not affect sexual function in postmenopausal women.

Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary.

The ovaries are common site of metastasis in a variety of primary neoplasms. Multiple tumors such as breast, lung, and pancreas have been reported to metastasize to the ovary, however; the colon and stomach are the most common primary cancer sites that of ovarian metastasis. An ovarian mass mostly originates from its self-tissue, but sometimes it can be a metastasis of a gastrointestinal system tumor. Such cases are often misdiagnosed as primary ovarian cancers. A 42-year-old woman was admitted to our hospital with pelvic pain. She had a history of her complaints for two months. Bilateral large ovarian mass was detected in transvaginal ultrasound. Laparotomy was performed, the pathologist suggested inspection of the stomach after the frozen section analysis; therefore, an irregular mass on the stomach was detected. The general surgeon was attended to the operation, and an inoperative stomach tumor was reported by the general surgeon. After that due to the partial obstruction of jejunum, a gastrojejunostomy was performed. It is in fact difficult to distinguish between metastatic mucinous carcinomas and primary mucinous carcinomas of the ovary, due to the similar appearance of as cystic tumors on gross examination. The clinicians should be aware of the likely concomitant gastrointestinal system tumor when a large and bilaterally mass was detected on physical examination. This case also reminds that a systemic examination is necessary even if the large ovarian tumors suspicious of primary malignancy were noticed.

Effect of the non-specific matrix metalloproteinase inhibitor Doxycycline on endometriotic implants in an experimental rat model.

The aim of this study was to investigate the possible therapeutic effects of Doxycycline (Dox) on endometriotic lesions in an experimental rat model. Thirty-seven female Wistar albino rats with surgically induced endometriosis were randomized and divided into four groups. The rats were administered 5 mg/kg/day oral Dox in Group 1 (low-dose Dox group, n=9), 20 mg/kg/day oral Dox in Group 2 (high-dose Dox group, n=10) and 1 mg/kg single dose, subcutaneous leuprolide acetate in Group 3 (leuprolide acetate group, n=9). The rats in Group 4 (control group, n=9) were given no medication. The rats received medication for three weeks and were then sacrificed to evaluate the morphological and histological features of the implants. Matrix metalloproteinase (MMP)-9 immunoreactivity of the implants was also evaluated. The size of the endometriotic implants decreased in Groups 1-3 but statistically significant differences were not observed among the groups. The mean surface area of the endometriotic implants decreased from 69.3±30.8 to 52.1±27.0 mm² in Group 1 (P>0.05), from 60.2±18.9 to 38.6±28.7 mm² in Group 2 (P>0.05) and from 58.1±33.1 to 26±9.0 mm² in Group 3 (P=0.03). The epithelial MMP-9 immunohistochemical score was significantly higher in Group 1 and lower in Group 3 when compared with the control group (Group 4) (P=0.042 and P=0.014, respectively). When the stromal MMP-9 immunohistochemical and histopathological scores of the endometriotic implants were compared, no statistically significant differences were found among the groups. Although there was no statistically significant difference, Dox reduced the endometriotic implant area in the rat endometriosis model. Further studies are required to investigate the potential efficacy of Dox in endometriosis due to its widespread use and tolerability.

Clinical significance of serum follistatin levels in the diagnosis of ovarian endometrioma and benign ovarian cysts.

OBJECTIVE: To determine the clinical significance of serum follistatin levels in women with an ovarian endometrioma. MATERIALS AND METHODS: This is a prospective study of 89 women, 56 with an ovarian endometrioma (endometrioma group) and 33 with a benign ovarian cyst (control group) who underwent laparoscopic excision. Age, parity, body mass index, serum CA-125, serum CA 19-9, and serum follistatin levels were determined for all participants and evaluated as potential prognostic factors prior to laparoscopic cystectomy. RESULTS: There were no significant differences in demographic factors between the endometrioma group and the control group. However, serum follistatin levels were significantly higher in the endometrioma group (9350 ± 895 pg/mL vs. control group 725 ± 72 pg/mL, p < 0.05). The optimal diagnostic cut-off values (sensitivity and specificity) of CA-125, CA 19-9, and follistatin for ovarian endometrioma were 23.2 IU/mL (82.14% and 72.73%), 30.14 IU/mL (45.28% and 87.50%), and 2350 pg/mL (53.7% and 60.61%), respectively. CONCLUSION: Despite the increased serum follistatin levels in patients with ovarian endometrioma, CA-125 was determined to be a more sensitive and specific marker than follistatin for the diagnosis of ovarian endometrioma and endometriosis.

Preliminary Outcomes of a New, Safe, Tension-free Vaginal Tape Trocar.

The aim of this study is to introduce a new, safe, tension-free vaginal tape (TVT) trocar. Twenty-eight women with stress urinary incontinence who underwent a TVT procedure with a new trocar during a 6-month period were prospectively enrolled in this study. All the operations were performed by the same surgeon who developed the trocar. The trocar has two buttons, which make the tip of the device sharp or blunt. Median age of the study population was 52 years (range, 30-76 years), median number of vaginal deliveries was 3 (range, 1-10). And 57.1% of women were at menopause. Median body mass index was 30.0 kg/m² (range, 23.8-35.2 kg/m²). Preoperative median Valsalva leak point pressure was 78 cmH2O (range, 50-94 cmH2O), while the median maximum urethral closure pressure was 50 cmH2O (range, 14-74 cmH2O). Concomitant prolapse surgery was present in 23 women (82.1%). At the 6-month postoperative visit, objective and subjective cure rates were 89.3% for each. No serious intraopeartive or postoperative complication such as bladder, intestine, or major vessel injury occured. Only 3 women (10.7%) needed blood transfusion, and 2 women (7.1%) had postoperative voiding difficulty. Due to the modifiable tip, this new sling trocar seems safer than the conventional trocars. But large studies are necessary to prove this assumption. Due to the modifiable tip, this new sling trocar seems safer than the conventional trocars. But large studies are necessary to prove this assumption.