In vitro evaluation of exocytosis-associated SNARE molecules in human granulosa cells in polycystic ovary syndrome.

PURPOSE: Patients with polycystic ovarian morphology (PCOM) make up 20% cases for assisted reproductive technology (ART). Folliculogenesis is impaired in PCOS. Signaling molecules are involved in follicle development. Dysregulations of intrafollicular environment and signaling molecules are observed in PCOS. Granulosa cells (GCs) and oocytes secrete molecules into follicular fluid by exocytosis of SNAREs. The aim of this study is to evaluate vesicle transport and vesicle fusion proteins (SNAREs) in GCs from PCOS patients who have undergone IVF treatment. METHODS: Follicular fluids were collected from patients who undergo IVF/ICSI with the diagnosis of male factor (n = 10) and PCOS (n = 10) patients. GCs were separated and cultured. Each group of GCs was stimulated with FSH-hCG. The cells were examined under electron microscope. Immunofluorescent labeling was performed on cells for Stx6, SNAP25, StxBP1, FSHr, and KITL. Integrated density was analyzed from images of Stx6, SNAP25, StxBP1, FSHr, and KITL. RESULTS: Intercellular communication occurs by signal molecules; Stx6, SNAP25, and StxBP1 fusion proteins involved in exocytosis were decreased in the GCs of PCOS. There was no increase in in vitro stimulation with FSH-hCG either. In the electron microscope, it was observed that exocytosis of the vesicles was disrupted. CONCLUSIONS: Exocytosis and vesicular dynamics are among the basic physiological functions of human steroidogenic granulosa cells. Follicle development is necessary for production of competent oocytes and ovulation. Understanding the pathophysiology of PCOS at follicular level is important for disease management. According to our findings, deficits in vesicular dynamics of human granulosa cells in may be central to the treatment strategy for PCOS patients.

Direct embryonic biopsy with transcervical embryoscopy is an effective method for karyotyping and morphology assessment in miscarriages.

PURPOSE: The main purpose of this study is to compare the validity of transcervical embryoscopy method with standard uterine evacuation method in detecting more accurate karyotypes in miscarriages below tenth week of pregnancy. Additionally, the frequency and distribution of fetal morphological abnormality were evaluated. METHODS: A prospective study was carried out at the Gazi University Faculty of Medicine, Department of Obstetrics and Gynecology. Patients with missed abortions between sixth and tenth gestational weeks were included in the study group, and fetal morphological examination and direct embryonic biopsy were performed by transcervical embryoscopy. The control group consisted of patients who experienced miscarriage and genetic material obtained from routine uterine evacuation between February and October 2023. RESULT: A total of 60 patients in the study group and 189 patients in the control group were evaluated. The median ages, previous miscarriage numbers, median gravida numbers, and median gestational weeks were comparable between groups. Chromosomal abnormality was detected in 24 (42.8%) and 52 embryos (29.9%) in the study and control groups, respectively (p = 0.004). Culture failure rates were 6.6% (n = 4) and 7.9% (n = 15) in the study and control groups, respectively. In the study group, 12 embryos had a morphological abnormality in which 6 of them had normal karyotype. CONCLUSION: Direct embryonic biopsy with transcervical embryoscopy is an effective method to exclude maternal decidual cell contamination and placental mosaicism in miscarriages for karyotype analysis. In addition, detecting anomalies in morphology might contribute our understanding in the process of miscarriages which arises independent from structural/numerical chromosomal abnormalities.

Subcutaneous luteal phase progesterone rescue rectifies ongoing pregnancy rates in hormone replacement therapy vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Will luteal phase rescue with additional progesterone increase serum progesterone concentrations and improve reproductive outcomes in patients with low serum progesterone concentrations undergoing hormone replacement therapy (HRT) cycles? DESIGN: Case-control study including 40 consecutive patients with serum progesterone concentrations <8.75 ng/ml on the 5th day of progesterone supplementation who underwent rescue with a daily bolus of 25 mg s.c. progesterone, starting on the afternoon of the 5th day of progesterone administration. For every patient who underwent progesterone rescue, three patients matched by age, body mass index, number of previous attempts and number of blastocysts transferred, with serum progesterone concentration >8.75 ng/ml on the 5th day of progesterone administration served as controls (n = 120). The main outcome measure was ongoing pregnancy rate (OPR). RESULTS: Baseline demographic features and embryological data of the rescue and control groups were comparable. As expected, the mean serum progesterone concentration was lower in the rescue group on the 5th day of progesterone administration (7.84 ± 0.92 versus 15.32 ± 5.02 ng/ml; P < 0.001). Following rescue, the mean serum progesterone concentration on the day of vitrified-warmed embryo transfer (6th day of progesterone administration) was 33.43 ± 10.83 ng/ml (range 14.61-82.64 ng/ml), and the OPR of the rescue and control groups were comparable. CONCLUSIONS: In patients undergoing HRT vitrified-warmed blastocyst transfer with serum progesterone concentrations lower than 8.75 ng/ml 1 day prior to the scheduled embryo transfer (6th day of progesterone administration), additional supplementation with a 25 mg s.c. daily progesterone dose seems to rescue the cycle, resulting in OPR comparable to those of patients with serum progesterone >8.75 ng/ml.

Comparison of single euploid blastocyst transfer cycle outcome derived from embryos with normal or abnormal cleavage patterns.

RESEARCH QUESTION: To assess incidence of abnormal cleavage among biopsied blastocysts; to compare euploidy rates of the blastocysts with abnormal and normal cleavage; and to compare single euploid blastocyst transfer (SEBT) outcome derived from embryos with normal or abnormal cleavage. DESIGN: Retrospective analysis of prospectively collected data in a private IVF clinic. Consecutive 554 patients (749 cycles) undergoing preimplantation genetic testing for aneuploidy (n = 497; 671 cycles) or monogenic diseases (n = 57; 78 cycles) were included. All assessments for abnormal cleavage were carried out retrospectively; presence of abnormal cleavage was not a factor in deciding which euploid embryo to transfer. A total of 1015 blastocysts were biopsied and 295 SEBT procedures were carried out. Main outcome measure was live birth rate (LBR). RESULTS: Incidence of reverse cleavage, direct cleavage, and reverse plus direct cleavage, were 7.7%, 6.4% and 2.3%, respectively. Of the 1015 biopsied blastocysts, 35.0% were euploid. Blastocysts with abnormal cleavage, in total, had a significantly higher euploidy rate compared with blastocysts with normal cleavage (44.6% [74/166] versus 33.1% [281/849]; P = 0.017). The LBR after SEBT with normal, reverse and direct cleavage, and direct cleavage plus reverse cleavage, was 133/238 (55.9%), 6/26 (23.1%), 8/24 (33.3%) and 0/3 (0.0%) (P < 0.001). Generalized estimating equation analysis showed that the presence of abnormal cleavage pattern was the only independent predictor of LBR (OR 0.316; 95% CI 0.115 to 0.867; P = 0.013). CONCLUSIONS: Blastocysts with direct or reverse cleavage should be biopsied in preimplantation genetic testing cycles if they are morphologically eligible. Euploid blastocysts with abnormal cleavage, however, have approximately half the LBR of those euploid blastocyst with normal cleavage, hence, blastocysts with abnormal cleavage should have lower priority for transfer.

A new isolation and culture method for granulosa cells.

Granulosa cells are the cell population who have an increasing importance in the female genital system and reproduction. Thus, nowadays in vitro studies to address these cells are also gaining importance and attracts researcher's attention. The aim of our study is to develop a more feasible, low-cost granulosa cell isolation and culture method compared to methods defined so far. Granulosa cells were isolated from follicular fluids obtained from both healthy women donors (n = 19) and polycystic ovary syndrome (n = 15) applied to in vitro fertilization treatment process. Granulosa cells were isolated by using Lymphosep® separation fluid that was not used for this purpose before. The isolated cells were cultured in suitable culture dishes with a mixture of BIO-AMFTM-1 and DMEM/F12 in the first seeding and only complete DMEM/F12 in the following feeds. Complete medium contains only 5% fetal calf serum, 4% L-glutamine and 1% penicillin-streptomycin-amphotericin. The new methods we have developed in granulosa cell isolation and in vitro culture have been successful. Reduction in supplement types and amount; improved the proliferation rate of the granulosa cells in culture. Our new methods of isolation and cell culture for granulosa cells from healthy women, have been also successful in samples of polycystic ovarian patients. With these developed methods, granulosa cells, which belong to humans and have an important role in the ovary, could be isolated and subsequently be maintained to reproduce (proliferate) more easily and cheaper.

Addition of intramuscular progesterone to vaginal progesterone in hormone replacement therapy in vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Does intramuscular progesterone supplementation ensure ongoing pregnancy rates (OPR) comparable with vaginal progesterone only in hormone replacement therapy cycles for vitrified-warmed embryo transfer; and is there a window of serum progesterone concentration out of which reproductive outcomes may be negatively affected? DESIGN: Retrospective longitudinal cohort study carried out at a single IVF clinic. In total, 475 consecutive, day-5 to day-6 vitrified-warmed embryo transfer cycles using hormone replacement therapy regimen were included. Vaginal progesterone only was given to 143 patients; supplementation of vaginal progesterone only with intramuscular progesterone supplementation every third day was given to 332 patients. On the sixth day of progesterone administration, immediately before frozen-thawed embryo transfer, circulating progesterone levels were measured. Main outcome measure was OPR. RESULTS: The baseline demographic features and embryological data of the vaginal progesterone only and intramuscular progesterone supplementation groups were comparable. The OPR were 48.3% and 51.8%, respectively (P = 0.477). Neither the circulating progesterone level nor the type of progesterone administration were independent predictors of OPR. The effect of serum progesterone levels on OPR was evaluated by percentiles (<10%, 10-49%, 50-90% and >90%), taking 50-90% as the reference sub-group. All percentiles in the intramuscular progesterone supplementation group and in the vaginal progesterone only group had similar OPR. CONCLUSIONS: Intramuscular progesterone supplementation every third day, overall, does not enhance OPR compared with vaginal progesterone only.

Anti-Müllerian hormone as a diagnostic tool for PCOS under different diagnostic criteria in an unselected population.

RESEARCH QUESTION: Is anti-Müllerian hormone (AMH) a valid tool to diagnose polycystic ovary syndrome (PCOS) according to different subsets of criteria among an unselected group of women? DESIGN: In this cross-sectional study, AMH concentrations were measured in an unselected group of women. The ability of AMH to diagnose PCOS according to National Institutes of Health (NIH), Rotterdam-2003 and Androgen Excess and PCOS Society (AE-PCOS) criteria was tested by using frozen serum aliquots (n = 392) that had been collected from a previous prevalence study of PCOS. RESULTS: The respective age and body mass index adjusted area under the curve (aAUC, 95% confidence interval) values were 0.80 (0.71-0.89), 0.74 (0.67-0.81) and 0.71 (0.64-0.79). When the definition of polycystic ovary morphology (PCOM) was set to an antral follicle count (AFC) of 20 instead of 12, the prevalence of syndrome dropped from 19.9% to 10.2% and from 15.3% to 8.9% according to Rotterdam-2003 and AE-PCOS criteria, respectively. In patients with Phenotype A, who had hyperandrogenism, ovulatory dysfunction and PCOM, AMH had an aAUC of 0.85 (0.77-0.92) to diagnose the syndrome. In Phenotypes B (hyperandrogenism + ovulatory dysfunction), C (hyperandrogenism + PCOM) or D (ovulatory dysfunction + PCOM), AMH had poor to fair ability to diagnose the syndrome. CONCLUSION: AMH has poor to fair validity to diagnose PCOS among an unselected group of women, except for patients bearing all features of the syndrome (Phenotype A). This finding is valid using the NIH, Rotterdam-2003 and AE-PCOS criteria and even after revising the definition of PCOM as AFC ≥20.

PGT for aneuploidy does not affect three-cycle cumulative IVF discontinuation rate in women of advanced maternal age.

RESEARCH QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) influence the discontinuation rate in women with advanced maternal age (AMA) undergoing IVF? DESIGN: Retrospective longitudinal cohort study carried out at a single IVF clinic in Turkey. In total, 401 consecutive AMA cases were included. Discontinuation rates of pre-intervention (conventional IVF; June 2013 to October 2014; 203 couples; 270 cycles) and post-intervention (PGT-A; April 2015 to June 2016; 198 couples; 285 cycles) periods were compared. To delineate the reason for discontinuation, a telephone survey was conducted. Primary outcome measure was cumulative discontinuation rate before completing three cycles of IVF treatment without achieving an ongoing pregnancy. RESULTS: The discontinuation rates after the first and second failed cycles were comparable between the two arms as were the cumulative discontinuation rates before completing three cycles. The cumulative ongoing pregnancy rate per embryo transfer was significantly higher in the PGT-A arm (43.2% versus 16.8%; P < 0.001). The cumulative ongoing pregnancy rate per patient was comparable between the two arms (20.7% versus 16.3%, respectively). Female age was the only significant contributor to treatment discontinuation (hazard ratio [HR] 1.07; 95% CI 1.09 to 1.13). Of the 296 couples discontinuing treatment in both arms, 179 (179/296 [60.5%]) participated in the survey; overall, psychological burden was the main reason for treatment discontinuation (37/179 [20.7%]). CONCLUSIONS: About 90% of AMA cases not achieving an ongoing pregnancy discontinue IVF treatment before completing three cycles. Discontinuation rate is not reduced by carrying out PGT-A. Female ageing is the only significant contributor, with a hazard of discontinuing further IVF treatment of 7% with female ageing of 1-year.

The effect of performing hysteroscopy prior to the first in vitro fertilization (IVF) cycle on live birth rate.

In this retrospective cohort study, a total of 707 couples underwent in vitro fertilization (IVF) at Hacettepe University Hospital between 01 January 2010 and 01 November 2014 with their chronologically first cycle were evaluated. Patients who have diagnostic hysteroscopy prior to first IVF cycle served as a study group (n = 42) and patients without diagnostic hysteroscopy served as control group (n = 282). In study group in all patients, diagnostic hysteroscopy was performed at the follicular phase of previous menstrual cycle, namely immediately before ovarian stimulation (OS) cycle. Demographic features, clinical characteristics and treatment outcomes were compared between the groups. The logistic regression analysis was performed in order to assess independent predictors of live birth rates (LBRs). There was no statistically significant difference between the groups for demographic features and OS cycle characteristics. Implantation rate (22.2% vs. 21.5%, p=.840), clinical pregnancy rate (33.3% vs. 28.7%, p=.541), and LBRs (23.8% vs. 18.5%, p=.420) were comparable. In logistic regression analysis, performing hysteroscopy prior to first IVF cycles per se without correcting anatomic abnormalities was not an independent predictor of LBRs (OR: 0.72, 95% CI: 0.310-1.68, p=.45). In conclusion, performing diagnostic hysteroscopy prior to first IVF treatment cycle without correcting any anatomic abnormalities did not improve LBRs.

Bisphenol A and phthalate levels in adolescents with polycystic ovary syndrome.

Endocrine disruptors have been proposed in the etiology of polycystic ovary syndrome (PCOS) as they have the potency to interfere with hormone-sensitivity systems. The aim of this study was to evaluate the levels of bisphenol A (BPA) and phtalates in adolescents with PCOS. Sixty-two girls with PCOS and 33 controls, age 12-18 years were enrolled in the study. The diagnosis of PCOS was made using modified Rotterdam criteria. Urinary BPA levels were measured using high-performance liquid chromatography. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used phthalate and mono-(2-ethylhexyl)-phthalate (MEHP), its main metabolite were measured by using high-performance liquid chromatography. Adolescents with PCOS had markedly increased BPA levels (15.89 µg/g creatine ± 1.16) when compared with the control group (7.30 µg/g creatine ± 1.38) (p = .016). In adolescents with PCOS, BPA was significantly correlated with polycystic morphology on ultrasound but not with obesity androgen levels, or other metabolic parameters. Patients with PCOS (DEHP: 0.40 ppm ± 0.24, MEHP: 0.13 ppm ± 0.23) and controls (DEHP: 0.49 ppm ± 0.27, MEHP: 0.14 ppm ± 0.3) had similar serum phtalate concentrations (p = .7 and p = .3, respectively). Exposure to specific endocrine disruptors such as BPA could modify neuroendocrine, reproductive, and metabolic regulation favoring PCOS development in adolescents.

Examination of cervical swabs of patients with endometriosis using Fourier transform infrared spectroscopy.

PURPOSE: There is no established non-invasive method to diagnose patients with endometriosis. As a nondestructive type of radiation, infrared light might be used for discrimination by causing vibration of the covalent bonds of the molecules when absorbed by the tissues. The aim of the study was to test whether cervical swab can be used to diagnose women with endometriosis using Fourier transform infrared spectroscopy (FTIR). METHODS: In this prospective case-control study, women between 18-45 years old and undergoing laparoscopy due to various reasons were recruited (n = 20). According to the findings during laparoscopy, patients were stratified as stage I-II or stage III-IV endometriosis groups. Women lacking any visible lesions of endometriosis were recruited as controls. A cervical swab was taken from all patients just before the surgical procedure and pulled into a tube containing saline solution. FTIR spectra were obtained and the fingerprint region (1750-850 cm-1) was used for analyses. RESULTS: Finally, three samples in stage I-II, five samples in stage III-IV and five samples in the control group were analyzed. Hierarchical cluster analysis and principal component analysis were performed as the chemometric method. A total of ten observable peaks were detected in the absorbance spectra of samples. The peaks at 1450 and 1405 cm-1 originating from lipids and proteins significantly increased in the stage III-IV endometriosis group when compared with controls. In addition, nucleic acid/carbohydrate ratio was significantly lower in the stage I-II group indicating that the alteration of the carbohydrate level might be important. CONCLUSIONS: Examination of cervical swab with FTIR spectroscopy might be a proper candidate for a non-invasive diagnostic approach of endometriosis.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas.

STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION NUMBER: None.

Live birth rates in various subgroups of poor ovarian responders fulfilling the Bologna criteria.

The European Society of Human Reproduction and Embryology published Bologna criteria to generate a definition of poor ovarian responders (PORs). However, there are few data on whether PORs are homogenous for ovarian response or live birth rates (LBRs). In this retrospective study, 821 patients fulfilling Bologna criteria and undergoing intracytoplasmic sperm injection were stratified into four groups: Group A: female age ≥40 with a previous poor response (cycle cancelled or ≤3 oocytes) (105 patients, 123 cycles); Group B: female age ≥40 with an antral follicle count (AFC) < 7 (159 patients, 253 cycles); Group C: AFC <7 with a previous poor response (350 patients, 575 cycles); and Group D: female age ≥40 with an AFC <7 and previous poor response (207 patients, 306 cycles). Cluster data analysis was performed. Although median number of oocytes was higher in Group B (P < 0.001), higher implantation (P = 0.024) and LBR per embryo transfer (P < 0.001) or cycle (P = 0.001) were noted in Group C. We conclude that, once a patient fulfils Bologna criteria, prognosis is poor, with fewer than 10% recorded LBRs per cycle. However, the LBRs are not homogenous and 'young proven' PORs have the most favourable pregnancy outcome.

Duration of blastulation may be associated with ongoing pregnancy rate in single euploid blastocyst transfer cycles.

Not all euploid embryos implant, necessitating additional tools to select viable blastocysts in preimplantation genetic screening cycles. In this retrospective cohort study, 129 consecutive patients who underwent 129 single euploid blastocyst transfers in cryopreserved embryo transfer cycles were included. All embryos were individually cultured in a time-lapse incubator from intracytoplasmic sperm injection up to trophoectoderm biopsy. Twenty-three time-lapse morphokinetic variables were tested among patients with (n = 68) or without (n = 61) ongoing pregnancy. All 23 time-lapse morphokinetic variables, apart from duration of blastulation (tB-tSB), were comparable between patients with or without ongoing pregnancy. Duration of blastulation was significantly shorter in patients with ongoing pregnancy (8.1 ± 3.2 versus 9.5 ± 3.4 h; P = 0.014); shorter duration of blastulation remained an independent predictor for ongoing pregnancy, when tested by logistic regression analysis (OR 0.81; 95% CI 0.70 to 0.93). One important limitation of this study, and a reason for caution, is the use of multiple comparisons, which can lead to differences at the 0.05 level simply by chance or random variation. Nonetheless, the study suggests that when more than one euploid blastocyst is available, priority might be given to those with a shorter duration of blastulation.

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PURPOSE: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. METHODS: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. RESULTS: Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. CONCLUSION: This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study.

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis.

STUDY QUESTION: What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? SUMMARY ANSWER: The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. WHAT IS ALREADY KNOWN: PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22-35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively. LIMITATIONS, REASONS FOR CAUTION: The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. WIDER IMPLICATIONS OF THE FINDINGS: Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. STUDY FUNDING/COMPETING INTERESTS: No funding to declare. The authors have no conflicts of interest to declare. REGISTRATION NUMBER: None.

Spontaneous clinical pregnancy following GNRH agonist trigger for final oocyte maturation and freeze-all approach: a case report.

We herein describe a 34-year old infertile woman with polycystic ovary syndrome who was underwent follicle stimulation with a gonadotrophin-releasing hormone (GnRH) agonist, and a freeze-all approach, but still conceived spontaneously without any luteal phase support and without development of ovarian hyperstimulation syndrome. The bilateral antral follicle count of the patient was 22. A fixed GnRH antagonist protocol was used. As the number of follicles wider than 11 mm in diameter on the day of stimulation was 28, the final oocyte maturation was triggered by a GnRH agonist and a freeze-all approach was taken. Although no luteal phase support was used after trigger, the patient conceived spontaneously. In conclusion, the endogenous LH level during the luteal phase may be sufficiently high in selected cases to rescue some of the corpora lutea even when a GnRH agonist has been administered for final oocyte maturation. When a freeze-all approach is taken to avoid ovarian hyperstimulation syndrome, couples should be strictly advised to refrain from sexual intercourse after oocyte retrieval.

The impact of unilateral salpingectomy on antral follicle count and ovarian response in ICSI cycles: comparison of contralateral side.

OBJECTIVE: To determine the impact of salpingectomy on the ovarian reserve. Comparisons are made with the contralateral side in patients with unilateral salpingectomy undergoing intracytoplasmic sperm injection (ICSI) cycles. STUDY DESIGN: Patients under 40 with unilateral salpingectomy and without history of ovarian surgery were selected for the multicentre retrospective study. Women with bilateral salpingectomy and history of endometriosis were excluded from the study. Antral follicle count, controlled ovarian hyperstimulation (COH) parameters and number of collected oocytes were the main outcome measures of the study. RESULTS: A total of 56 patients were eligible for this study. The mean age of the patients was 31.6 ± 4.7 years. The reasons for the salpingectomy were hydrosalpinx (39.3%, n = 22) and ruptured ectopic pregnancy (60.7%, n = 34). The ongoing pregnancy rate per embryo transfer was 30.6%. There was no statistically significant difference between the operated and non-operated sides in antral follicle count (AFC), follicles ≥ 17 mm and 10-17 mm on day of human chorionic gonadotrophin (hCG), or number of aspirated oocytes. In the subgroup analysis, AFC, number of growing follicles on day of hCG and number of collected oocytes were comparable between the ectopic pregnancy group and hydrosalpinx group. CONCLUSION: The study suggests that salpingectomy is not associated with detrimental effects on AFC and ovarian response.

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles. METHODS: This study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared. RESULTS: No statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared. CONCLUSIONS: There is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising.