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Introduction: The present meta-analysis aimed to investigate FTO rs9939609 and KISS1 rs4889, rs372790354 gene polymorphisms and its association with PCOS in Asian population., Methods: The studies included in this article were obtained by using online databases. We searched databases such as Scopus, PubMed, Embase, and Web of Science for case-control articles related to FTO and KISS1 gene polymorphism with PCOS. Metagenyo software was used to determine the 95% confidence interval (CI) and odds ratio (OR)., Results: A total of 13 articles was included in this meta-analysis for FTO (rs9939609) and KISS1 (rs4889; rs372790354) gene polymorphisms related with PCOS in the Asian population. According to the findings of this study, people with FTO rs9939609 show an association with PCOS risk in dominant model. On contradictory, KISS1 gene polymorphism specifically, rs4889 show an association with PCOS risk in allelic, recessive, and dominant models whereas rs372790354 show an association with PCOS risk in allelic and dominant models. Power analysis was performed and PPI is > 0.04. The sting analysis network for FTO and KISS1 gene estimated 12 nodes and 23 edges., Discussion: The FTO rs9939609 variant exhibits an association with an increased risk of PCOS in the dominant model. KISS1 gene polymorphism, particularly rs4889, shows a significant association with PCOS risk in allelic, recessive, and dominant models. Similarly, KISS1 rs372790354 gene is associated with PCOS risk in both allelic and dominant models. Researches were focused only on the Asian population so; it is imperative to conduct further research across diverse populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Women who are of reproductive age can suffer from polycystic ovary syndrome (PCOS), an endocrine disorder. Anovulatory infertility is mostly caused by aberrant follicular development, which is seen in PCOS patients. Due to the dysfunction of reproductive and endocrine function in PCOS patients, assisted reproduction treatment is one of the main means to obtain clinical pregnancy for PCOS patients. Long non-coding RNA (lncRNA) as a group of functional RNA molecules have been found to participate in the regulation of oocyte function, hormone metabolism, and proliferation and apoptosis of granulosa cells. In this study, we investigated the role of lncRNAs in follicular fluid-derived exosomes and the underlying mechanism of lncRNA LIPE-AS1., Methods: We used RNA sequencing to analyze the lncRNA profiles of follicular fluid-derived exosomes in PCOS patients and controls. RT-qPCR was performed to detect the expression levels of these lncRNAs in control (n = 30) and PCOS (n = 30) FF exosome samples. Furthermore, we validated the performance of lncRNA LIPE-AS1 in oocyte maturation by in vitro maturation (IVM) experiments in mouse and steroid metabolism in granulosa cells., Results: We found 501 lncRNAs were exclusively expressed in the control group and another 273 lncRNAs were found to be specifically expressed in the PCOS group. LncRNA LIPE-AS1, highly expressed in PCOS exosomes, was related to a poor oocyte maturation and embryo development in PCOS patients. Reduced number of MII oocytes were observed in the LIPE-AS1 group by in vitro maturation (IVM) experiments in mouse. LIPE-AS1 was also shown to modulate steroid metabolism and granulosa cell proliferation and apoptosis by LIPE-AS1/miR-4306/LHCGR axis., Conclusion: These findings suggested that the increased expression of LIPE-AS1, facilitated by follicular fluid exosomes, had a significant impact on both oocyte maturation and embryo development. We demonstrated the ceRNA mechanism involving LIPE-AS1, miR-4306, and LHCGR as a regulator of hormone production and metabolism. These findings indicate that LIPE-AS1 is essential in PCOS oocyte maturation and revealed a ceRNA network of LIPE-AS1 and provided new information on abnormal steroid metabolism and oocyte development in PCOS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Granulosa cell (GC) proliferation and apoptosis are critical events of the ovum energy supply, which lead to follicular growth retardation or atresia, and various ovulatory obstacles, eventually resulting in the development of ovarian disorders such as polycystic ovarian syndrome (PCOS). Apoptosis and dysregulated miRNA expression in GCs are manifestations of PCOS. miR-4433a-3p has been reported to be involved in apoptosis. However, there is no study reporting the roles of miR-4433a-3p in GC apoptosis and PCOS progression., Methods: miR-4433a-3p and peroxisome proliferator-activated receptor alpha (PPAR-α) levels in GCs of PCOS patients or in tissues of a PCOS rat model were examined by quantitative polymerase chain reaction and immunohistochemistry. Bioinformatics analyses and luciferase assays were used to examine the association between miR-4433a-3p and PPAR-α, as well as PPAR-α and immune cell infiltration, in PCOS patients., Results: miR-4433a-3p expression in GCs of PCOS patients was increased. miR-4433a-3p overexpression inhibited the growth of the human granulosa-like tumor cell line (KGN) and promoted apoptosis, while co-treatment with PPAR-α and miR-4433a-3p mimic rescued miR-4433a-3p-induced apoptosis. PPAR-α was a direct target of miR-4433a-3p and its expression was decreased in PCOS patients. PPAR-α expression was also positively correlated with the infiltration of activated CD4 + T cells, eosinophils, B cells, gamma delta T cells, macrophages, and mast cells, but negatively correlated with the infiltration of activated CD8 + T cells, CD56 + bright natural killer cells, immature dendritic cells, monocytes, plasmacytoid dendritic cells, neutrophils, and type 1 T helper cells in PCOS patients., Conclusion: The miR-4433a-3p/PPAR-α/immune cell infiltration axis may function as a novel cascade to alter GC apoptosis in PCOS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Pentraxin 3 (PTX3) plays a crucial role in cumulus expansion and fertilization. The ovarian PTX3 level in polycystic ovary syndrome (PCOS) remains uncertain. In the present study, we investigated the follicular PTX3 levels and found the influence of reproductive hormones on ovarian PTX3 concentration., Methods: This study was based on 204 healthy-weight women (102 PCOS and 102 normal ovulating subjects) undergoing in vitro fertilization (IVF). Follicular fluid (FF) was collected during oocyte retrieval. The PTX3 levels and other hormone levels in FF samples were analyzed by enzyme-linked immunosorbent assay (ELISA)., Results: The PTX3 level in the follicle was significantly higher in the healthy-weight PCOS women than controls. Positive correlations were found between ovarian PTX3 level and the existence of PCOS, cycle length, basal LH to FSH ratio and TT in serum, antral follicle count, and ovarian insulin and androgen level, and inverse correlations with the basal serum PRL and ovarian SHBG. In multivariant linear regression analysis, the presence of PCOS diagnosis, participants' basal LH to FSH ratio, and ovarian androstenedione level were the main predictors of ovarian PTX3 level among the enrolled subjects., Conclusion: Elevated ovarian PTX3 level supports the low-grade chronic inflammatory state in the follicles of PCOS. The existence of PCOS, disturbed pituitary gland, and ovarian hyperandrogenism might also be related to this state of low-grade chronic inflammation and could be a subject of further study.

Purpose: This review aims to summarize the key findings of several miRNAs and their roles in polycystic ovary syndrome with insulin resistance, characterize the disease pathogenesis, and establish a new theoretical basis for diagnosing, treating, and preventing polycystic ovary syndrome., Methods: Relevant scientific literature was covered from 1992 to 2020 by searching the PubMed database with search terms: insulin/insulin resistance, polycystic ovary syndrome, microRNAs, and metabolic diseases. References of relevant studies were cross-checked., Results: The related miRNAs (including differentially expressed miRNAs) and their roles in pathogenesis, and possible therapeutic targets and pathways, are discussed, highlighting controversies and offering thoughts for future directions., Conclusion: We found abundant evidence on the role of differentially expressed miRNAs with its related phenotypes in PCOS. Considering the essential role of insulin resistance in the pathogenesis of PCOS, the alterations of associated miRNAs need more research attention. We speculate that race/ethnicity or PCOS phenotype and differences in methodological differences might lead to inconsistencies in research findings; thus, several miRNA profiles need to be investigated further to qualify for the potential therapeutic targets for PCOS-IR.

Purpose: Elevated oxidative stress has been proposed as an important factor in the pathogenesis of polycystic ovary syndrome (PCOS)-related infertility. Our study was aimed at simultaneously exploring local and systemic oxidative stress in PCOS individuals and its relationship with embryo quality., Methods: We recruited 86 PCOS cases and 60 controls. Five representative oxidative stress markers, namely, total oxidant capacity (TOC), total antioxidant capacity (TAC), malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), were measured in both follicular fluid (FF) and serum., Results: Women with PCOS compared to normal controls had higher levels of TOC in both FF (10.13 ± 2.68 vs.7.03 ± 2.45, P < 0.001) and serum (11.76 ± 2.92 vs. 8.82 ± 2.57, P < 0.001). The oxidative stress index (OSI, the ratio of TOC to TAC) was also higher in PCOS cases. They were still significant after BMI adjustment (Padj<0.01). In addition, the serum OSI level was much higher than the FF OSI level in both groups. Correlation analysis showed that the FF and serum TOC were negatively correlated with the high-quality embryo rate on day 3 and the later blastocyst formation rate in the PCOS group (P < 0.05). The correlation coefficient was higher in FF. Moreover, as the regression analysis data showed, the FF MDA level was significantly associated with embryo quality indicators (P < 0.05)., Conclusions: PCOS was accompanied by elevated oxidative stress in both serum and FF. Even though serum oxidative stress was severe, the study suggested that FF oxidative stress contributed more to embryo quality, to which we should give more attention in the future.

Objective: To study the association between single-nucleotide polymorphism (SNP) of long-chain non-coding RNA steroid receptor RNA activator (lncRNA SRA1) gene and polycystic ovary syndrome (PCOS) susceptibility., Methods: Sanger sequencing was used to analyze the genotypes of the lncRNA SRA1 gene rs801460, rs10463297, and rs250426 in 315 PCOS patients and 315 control groups., Results: There was no correlation between lncRNA SRA1 gene rs801460, rs250426 SNP, and PCOS susceptibility (p > 0.05). The T allele at the rs10463297 locus of the SRA1 gene has a lower risk of PCOS than the C allele (OR = 0.63, 95%CI: 0.50-0.79, p < 0.01). Among people with a BMI ≥ 26.5 kg/m 2 , when carrying the TC genotype and CC genotype at rs801460, the risk of PCOS susceptibility was lower than the TT genotype (OR = 0.54, 95%CI: 0.33-0.89, p = 0.02). At different ages and BMI stratifications, there was a significant association between rs10463297 SNP and PCOS susceptibility (p < 0.05). Multi-factor dimensionality reduction (MDR) analysis results showed that age, BMI, rs801460, rs10463297, and rs250426 interactions constitute a "high-risk combination." PCOS susceptibility risk was 5.96 times that of a "low-risk combination" (95%CI: 4.14-8.56, p < 0.01). SRA1 gene rs801460, rs10463297, rs250426 constructed TCT haplotype was associated with increased risk of PCOS susceptibility (OR = 1.66, 95%CI: 1.20-2.30, p < 0.01); the CTT haplotype was associated with a decreased risk of PCOS susceptibility (OR = 0.56, 95%CI: 0.36-0.87, p = 0.01). LncRNA SRA1 gene rs10463297 SNP was correlated with the level of lncRNA SRA1 in the peripheral blood leukocytes (p < 0.01)., Conclusion: From this study, we found that the lncRNA SRA1 gene rs10463297 SNP is associated with PCOS susceptibility.

Purpose: Housekeeping genes (HKGs), reference or endogenous control genes, are vital to normalize mRNA levels between different samples. Since using inappropriate HKGs can lead to unreliable results, selecting the proper ones is critical for gene expression studies. To this end, normal human ovaries, as well as those from patients diagnosed with ovarian endometrioid adenocarcinoma (OEA), ovarian mucinous adenocarcinoma (OMA), ovarian serous papillary carcinoma (OSPC), and polycystic ovary syndrome (PCOS), were used to identify the most suitable housekeeping genes., Methods: RNA was isolated from 5 normal human ovaries (52-79 years of age), 9 cancerous ovaries (3 OEA, 3 OMA, 3 OSPC; 49-75 years of age), and 4 PCOS ovaries (18-35 years of age) in women undergoing hysterectomy. cDNA was synthesized using a whole transcriptome kit, and quantitative real-time PCR was performed using TaqMan array 96-well plates containing 32 human endogenous controls in triplicate., Results: Among 32 HKGs studied, RPS17, RPL37A, PPIA, 18srRNA, B2M, RPLP0, RPLP30, HPRT1, POP4, CDKN1B, and ELF1 were selected as the best reference genes., Conclusions: This study confirms recent investigations demonstrating that conventional HKGs, such as GAPDH and beta-actin, are not suitable reference genes for specific pathological conditions, emphasizing the importance of determining the best HKGs on a case-by-case basis and according to tissue type. Our results have identified reliable HKGs for studies of normal human ovaries and those affected by OEA, OMA, OSPC, or PCOS, as well as combined studies of control subjects vs. each cancer or PCOS group.

Objective: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q 10 (CoQ 10 ), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ 10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART., Methods: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I 2 index was employed for heterogeneity., Results: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ 10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ 10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I 2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I 2 34%) and MR (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I 2 0%)., Conclusions: Oral supplementation of CoQ 10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.

Purpose: Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls., Methods: Fourteen women with PCOS aged 18-42 years old with a BMI of 18.5-24.9 kg/m 2 (normal) or 25.0-40.0 kg/m 2 (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225 IU rFSH and underwent serial blood draws over 72 h., Results: Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72 h when compared with overweight/obese PCOS subjects (183.3 vs 139.8 IU*h/L, p = 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8 IU*h/L, p < 0.0001). Within overweight/obese subjects, those with PCOS had a significantly higher AUC FSH compared with normo-ovulatory controls (p = 0.0002). Lean PCOS subjects similarly had the highest AUC of baseline-corrected estradiol (6095 pg h/mL), compared with lean normo-ovulatory subjects (1931 pg h/mL, p < 0.0001) and overweight/obese PCOS subjects (2337 pg h/mL, p < 0.0001)., Conclusion: Lean PCOS subjects exhibited significantly higher baseline-corrected FSH and estradiol levels following rFSH injection compared with overweight/obese PCOS subjects with similar ovarian reserve markers. Amongst overweight/obese subjects, those with PCOS had significantly higher FSH and E2 levels when compared with normo-ovulatory controls.

Purpose: To investigate the effectiveness of a biphasic IVM culture strategy at improving IVM outcomes in oocytes from small follicles (< 6 mm) compared with routine Standard IVM in patients with polycystic ovaries., Methods: This prospective pilot study was performed in 40 women with polycystic ovaries whose oocytes were randomized to two IVM culture methods. Patients received a total stimulation dose of 450 IU rFSH. Cumulus-oocyte complexes (COCs) from follicles < 6 mm and ≥ 6 mm were retrieved and cultured separately in either a prematuration medium with c-type natriuretic peptide followed by IVM (CAPA-IVM), or STD-IVM. Primary outcomes were maturation rate, embryo quality, and the number of vitrified day 3 embryos per patient., Results: Use of the CAPA-IVM system led to a significant improvement in oocyte maturation (p < 0.05), to a doubling in percentage of good and top-quality day 3 embryos per COC, and to an increased number of vitrified day 3 embryos (p < 0.001), compared to STD IVM. Oocytes from follicles < 6 mm benefited most from CAPA-IVM, showing a significant increase in the amount of good and top-quality embryos compared to STD IVM. CAPA-IVM yielded significantly (p < 0.0001) less GV-arrested oocytes and larger oocyte diameters (p < 0.05) than STD IVM., Conclusions: CAPA-IVM brings significant improvements in maturation and embryological outcomes, most notably to oocytes from small antral follicles (< 6 mm), which can be easily retrieved from patients with a minimal ovarian stimulation. The study demonstrates the robustness and transferability of the CAPA-IVM method across laboratories and populations.

Objectives: Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters., Methods: In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR., Results: As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05)., Conclusions: Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.

Purpose: The neurokinin B (NKB)/NK 3 receptor (NK3R) and kisspeptin (KISS1)/kisspeptin receptor (KISS1R), two systems essential for reproduction, are present in human granulosa cells (GCs) of healthy women and contribute to the control of fertility, at least partially, by acting on the gonads. However, little is known about the expression of these systems in GCs of women with polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the expression of NKB/NK3R and KISS1/KISS1R in mural granulosa (MGCs) and cumulus cells (CCs) of PCOS women., Methods: A cross-sectional study was performed in 46 healthy women and 43 PCOS women undergoing controlled ovarian stimulation. MGCs and CCs were collected from pre-ovulatory follicles after transvaginal ultrasound-guided oocyte retrieval and the expression of the genes encoding NKB (TAC3), NK3R (TACR3), KISS1, and its receptor (KISS1R) was analyzed using real-time quantitative RT-PCR., Results: TAC3, TACR3, and KISS1 mRNA levels were decreased in MGCs and CCs of PCOS women. TAC3 positively correlated with KISS1 in MGCs of healthy women and TACR3 was positively associated with KISS1R in CCs from healthy women. These associations were not observed in PCOS women., Conclusion: The NKB/NK3R and KISS1/KISS1R systems are dysregulated in MGCs and CCs of PCOS women. The lower expression of these systems in GCs could contribute to the abnormal follicle development and defective ovulation that characterize the pathogenesis of PCOS.

Purpose: To study the presence and distribution of genes encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles., Methods: A class comparison study on existing granulosa cell transcriptome from primordial (n = 539 follicles) and primary (n = 261) follicles donated by three women having ovarian tissue cryopreserved before chemotherapy was performed and interrogated., Results: In granulosa cells from primordial follicles, 30 genes were annotated 'mitochondrial dysfunction' including transcripts (PRDX5, TXN2) encoding enzymatic free radical scavengers peroxiredoxin 5 and thioredoxin 2. Several apoptosis regulation genes were noted (BCL2, CAS8, CAS9, AIFM1). In granulosa cells from primary follicles, mitochondrial dysfunction signalling pathway was annotated. High expression of transcripts encoding the free radical scavenger peroxiredoxin 3, as well as anti-apoptotic enzyme BCL2, was found. Interestingly, PARK7 encoding the deglycase (DJ-1) protein was expressed in granulosa cells from primary follicles. DJ-1 is implicated in oxidative defence and functions as a positive regulator of the androgen receptor and as a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/serine-threonine protein kinase (AKT) signalling pathway suppressor PTEN., Conclusions: The results indicate extensive energy production and free radical scavenging in the granulosa cells of primordial follicles with potential implications for ovarian ageing, cigarette smoking, premature ovarian failure and polycystic ovarian syndrome. Furthermore, DJ-1 may be involved in androgen responsiveness and the regulation of follicle growth via PI3K/PTEN/AKT signalling pathway regulation in the granulosa cells of primary follicles. The involvement of mitochondrial free radical production in the age-related decline of competent oocytes is becoming apparent.

Purpose: To provide a commentary on our understanding of the role that the Hippo signaling pathway may play in patients with polycystic ovarian syndrome (PCOS) and how this understanding may impact the diagnosis of PCOS., Methods: We assessed publications discussing the role of the Hippo signaling pathway in the ovary. In particular, we discuss how Hippo signaling disruption after ovarian fragmentation, combined with treating ovarian fragments with phosphatase and tensin homolog (PTEN) inhibitors and phosphoinositide-3-kinase stimulators to augment AKT signaling, has been used in treatment of patients with primary ovarian insufficiency. Furthermore, we discuss our own data on variations in Hippo signaling pathway gene expression in cumulus cells isolated from women undergoing IVF with a previous diagnosis of PCOS., Results and Conclusions: Aberrant Hippo signaling in PCOS patients is likely a contributing mechanism to the multifactorial etiology of the disease. Given the challenge of discerning the underlying etiology of oligo-ovulation in some patients, especially those with normal body mass indices, and the need for customized stimulation protocols for PCOS patients who have an increased risk of over-response and higher percentage of immature oocyte yield, it is important to identify these patients prior to treatment. Hippo gene expression fingerprints could potentially be used to more accurately define patients with PCOS. Additionally, targeting this pathway with pharmacologic agents could lead to non-surgical therapeutic options for PCOS.

Purpose: Polycystic ovary syndrome (PCOS) is a complex multifactorial endocrine disorder affecting approximately 5-10% of women of reproductive age. Affected women have menstrual disturbances due to anovulation, infertility, and hyperandrogenism. Ovarian androgen overproduction is the key physiopathologic feature of PCOS. A number of genes encoding major enzymes of the androgen metabolic pathways, such as HSD17B6, CYP19A1, CYP11A1, CYP17A1, and INSR, have been examined. Very few studies have been done in North India. There is an increasing prevalence of PCOS in women in Punjab and it is the leading cause of female infertility. In view of the strong evidence implicating the importance of CYP19A1 and CYP17A1 in androgen metabolic pathways, we investigated the association of rs700519, rs2414096, and rs743572 (- 34T>C) polymorphisms on susceptibility of developing PCOS, in North India., Methods: A total of 500 subjects (women of reproductive age) including 250 PCOS cases and 250 healthy age-matched controls were included in the present study. DNA was extracted from venous blood for all samples, and association analysis for rs2414096, rs700519, and rs743572 was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Lipid profile was done using a biochemical analyzer and body mass index (BMI) was measured for all cases. Statistical analysis was performed., Results: Significant association of - 34T>C polymorphism of CYP17A1 was found with PCOS (p = 0.0005). BMI was statistically different between PCOS cases and controls (p = 0.000). Triglycerides were high in PCOS women. Variations of CYP19A1 were not statistically significant with PCOS., Conclusions: These data suggest that - 34T>C polymorphism in CYP17A1 is associated with PCOS in North India. No polymorphism of CYP19A1 was found to be associated.

Members of the transforming growth factor-beta (TGF-beta) superfamily are key regulators of various physiological processes. Anti-Müllerian hormone (AMH) which is also commonly known as Müllerian-inhibiting substance (MIS) is a member of the TGF-beta superfamily and an important regulator of reproductive organ differentiation and ovarian follicular development. While AMH has been used for diagnostic purposes as a biomarker for over 15 years, new potential therapeutic applications of recombinant human AMH analogues are now emerging as pharmacologic agents in reproductive medicine. Therapeutic uses of AMH in gonadal tissue may provide a unique opportunity to address a broad range of reproductive themes, like contraception, ovulation induction, onset of menopause, and fertility preservation, as well as specific disease conditions, such as polycystic ovarian syndrome (PCOS) and cancers of the reproductive tract. This review explores the most promising therapeutic applications for a novel class of drugs known as AMH analogues with agonist and antagonist functions.

Purpose: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. However, its etiology remains poorly understood. Recent studies indicated that telomere length was related to PCOS. However, the association between telomere length and PCOS has only been shown in leucocytes and remained controversial across different studies. To clarify the association between telomere length and PCOS, the current study interrogated telomere length not only in leucocytes, but also in follicular granulosa cells, which is essential for folliculogenesis and steroidogenesis., Methods: Seventy-five patients with PCOS and 81 controls with mechanical infertility undergoing their first in vitro fertilization cycle were enrolled. Their peripheral blood and granulosa cells were collected on the oocyte retrieval day. Telomere length of both leucocytes in the blood and granulosa cells was assayed by quantitative polymerase chain reaction., Results: No significant difference was found in the leucocyte telomere length between controls and PCOS patients (0.99 ± 0.44 vs. 1.00 ± 0.38, p = 0.93). Interestingly, when comparing telomere length in granulosa cells between controls and PCOS subjects, significantly lengthened telomere length was found in PCOS subjects (1.00 ± 0.37 vs. 1.57±0.67, p < 0.0001). After adjustments for age and body mass index, the p value remained significant (p < 0.0001)., Conclusions: This finding reinforced the association between telomere abnormalities and PCOS. Given the importance of telomere length in cellular proliferation, our findings provided novel insights into the pathophysiology of PCOS that abnormalities in telomere length possibly disturb folliculogenesis and subsequently result in PCOS.

Purpose: Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory dysfunction and female infertility. The etiopathogenetic mechanisms of PCOS have been studied for many years, although exact causes remain unclear. It has been demonstrated that proteoglycan degradation by a disintegrin-like metalloproteinase with thrombospondin type motifs-1 (ADAMTS-1) is essential for ovulation and fertilization. The objective of our study is to analyze the levels of ADAMTS-1 and aggrecan in the follicular fluid (FF) of PCOS patients compared with normal ovulatory women and to determine whether these markers could be a predictor of in vitro fertilization (IVF) success in PCOS patients., Methods: Women with PCOS (n = 21) and normal ovulatory controls (n = 22) undergoing IVF treatment were recruited. ADAMTS-1 and aggrecan levels were analyzed with enzyme-linked immunosorbent assay (ELISA) and compared between PCOS and normal ovulatory controls. The predictor effect of ADAMTS-1 and aggrecan on fertilization rate and implantation was evaluated., Results: FF ADAMTS-1 and aggrecan levels increased in women with PCOS compared to controls. Elevated ADAMTS-1 levels but not aggrecan were related to increased implantation in PCOS., Conclusion: Our study demonstrated that altered levels of ADAMTS-1 and aggrecan may have a partial role in the etiopathogenesis of PCOS, and ADAMTS-1 could be a predictive marker for implantation success in PCOS patients.

Purpose: This study aims to ascertain whether an association exists between hepatocyte nuclear factor 1 alpha (HNF1A) and polycystic ovary syndrome (PCOS)., Methods: One thousand one hundred thirty-eight PCOS and 1125 healthy control Han Chinese women were recruited from Reproductive Hospital Affiliated to Shandong University. Serum hormone, blood lipid level, and genomic DNA were obtained from the peripheral blood for this research. Two single-nucleotide polymorphisms (SNPs)-rs2393791 and rs7305618-located in HNF1A were genotyped using the Sequenom MassARRAY system., Results: The allele frequencies of SNP rs7305618 had significant differences between PCOS patients and controls after adjusting for age and BMI (p = 0.023). Besides, PCOS patients carrying the rs7305618 CC genotype shown a higher testosterone level than the patients with CT + TT genotypes after being adjusted by age and BMI (p = 0.019)., Conclusions: A SNP located in the HNF1A gene is associated with PCOS among Han Chinese women. This suggested that variations in HNF1A might confer risk for PCOS.

Purpose: The purpose of the study is to evaluate existing literature for possible associations between female infertility, infertility-associated diagnoses, and the following areas of disease: psychiatric disorders, breast cancer, ovarian cancer, endometrial cancer, cardiovascular disease, and metabolic dysfunction., Methods: The design of the study is a literature review. The patients were women included in 26 selected studies due to a diagnosis of infertility or a reproductive disorder associated with infertility. This study has no interventions, and the main outcome measure is the association between female infertility or a related diagnosis and psychiatric disorders, breast cancer, ovarian cancer, endometrial cancer, cardiovascular disease, and metabolic dysfunction., Results: Female infertility and related reproductive disorders may have ramifications for women beyond reproductive health. An analysis of publications shows that women with infertility had higher rates of psychiatric disorders and endometrial cancer than the general population [1-10]. Data is conflicting about whether infertile women are at increased risk for breast cancer and ovarian cancer [7, 8, 10-20]. A generalized diagnosis of infertility was not clearly associated with an increased risk of cardiovascular disease or metabolic dysfunction, but women with infertility related to polycystic ovarian syndrome (PCOS) do appear more likely to develop cardiovascular disease and metabolic disorders such as diabetes than the general population [16, 21-26]., Conclusions: Female infertility and associated diagnoses have overall health implications. Beyond treatment of patients' immediate reproductive needs, healthcare professionals must be aware of the broader health impact of specific causes of infertility in order to provide accurate counseling regarding long-term risk.

Purpose: Although many hypotheses regarding the pathogenesis of polycystic ovary syndrome (PCOS) have been generated, genetic studies have not identified specific genes that play a role in PCOS etiopathogenesis. This study aimed to investigate the relationship between TGF-β1 gene polymorphism and PCOS in Koreans., Method: A total of 51 Korean women with PCOS and 69 healthy women were enrolled. We analyzed 4 single nucleotide polymorphisms (SNPs) of the TGF-β1 gene (rs11466313, rs1800469, rs2317130, and rs4803457). We also analyzed laboratory measurements, such as free testosterone, glucose, and cholesterol., Results: The frequencies of rs1800469T allele negativity, rs4803457T allele negativity, the rs1800469CC genotype, and the rs4803457CC genotype showed positive associations with PCOS (P = 0.003, P = 0.027, P = 0.009, and P=0.031, respectively), whereas the haplotypes rs1800469C-rs4803457T and rs1800469T-rs4803457T showed negative associations with PCOS. A strong protective effect of the "rs1800469CT-rs4803457TT" combination (OR = 0.09) and a strong risk effect of "rs1800469CC-rs4803457CC" (OR = 6.23) for PCOS were observed. The rs1800469C/T and rs2317130C/T SNPs exhibited associations with several laboratory measurements with various levels of significance., Conclusion: The results demonstrated an association of TGF-β1 gene polymorphisms with the development and/or characteristics of PCOS in the Korean population.

Purpose: To explore the relationships between the soluble receptor for advanced glycation endproducts (sRAGE) and the outcome parameters following in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) and investigate the protective effect of sRAGE in PCOS development regarding inflammation., Methods: We conducted a prospective analysis of a subsample of 74 participants from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. We quantified sRAGE, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), interleukelin-6 (IL-6), and C-reactive protein (CPR) protein levels in the follicular fluid from 39 PCOS and 35 non-PCOS reproductive-age women. sRAGE and VEGF, TNF-α, IL-6, and CRP in follicular fluid aspirated without blood were measured by ELISA., Results: sRAGE concentrations in the follicular fluid were significantly lower in the PCOS group compared to those in the control group, while VEGF, TNF-α, IL-6, and CRP concentrations were significantly higher in the PCOS group than in the control group (P < 0.05). sRAGE was significantly, inversely correlated with the total dose of gonadotropin (Gn) in the PCOS group undergoing IVF treatment (r = -0.451, P = 0.004). After adjusting for age and Gn dose (in international units used per cycle), sRAGE protein levels in the follicular fluid were significantly, inversely related to VEGF (r = -0.378, P = 0.018), TNF-α (r = -0.450, P = 0.004), IL-6 (r = -0.455, P = 0.004), and CRP (r = -0.375, P = 0.019)., Conclusion: sRAGE in the follicular fluid might exert a protective effect against the inflammatory action of PCOS development.

Purpose: The objective of the study was to investigate whether genetic polymorphisms of the anti-Müllerian hormone (AMH) and its specific receptor anti-Müllerian hormone type II receptor (AMHRII) were associated with the hormone disorder and phenotype of polycystic ovary syndrome (PCOS)., Methods: This case-control study included 141 PCOS patients and 123 normal women. Two polymorphisms of AMH and AMHRII and the clinical characteristics of participants such as body mass index (BMI), serum luteinizing hormone (LH), estradiol levels (E2), total testosterone levels (T), and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed with the case-control sample. Gene-gene interactions of AMH and AMHRII genes were analyzed based multifactor-dimensionality reduction method., Results: A significant difference of AMH gene polymorphisms were observed in IR-PCOS women and controls. The AMH and AMHRII gene polymorphisms were not found a significant difference in non-IR-PCOS and normal groups. To IR-PCOS women, genotypes of AMH were closely related to the serum levels of LH (P = 0.000), testosterone (P = 0.000) and HOMA-IR (P = 0.038), while in the non-IR-PCOS and normal groups, no relationship was found. No impact of AMH and AMHRII gene-gene interactions was demonstrated., Conclusions: Our research suggests that the diversity of AMH genotypes in the AMH signal pathway may be connected with the susceptibility and phenotype of PCOS with insulin resistance.

Purpose: The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function., Methods: Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient., Results: PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02)., Conclusions: Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.

Purpose: To describe the long noncoding RNA (lncRNA) profiles in cumulus cells isolated from polycystic ovary syndrome (PCOS) patients by employing a microarray and in-depth bioinformatics analysis. This information will help us understand the occurrence and development of PCOS., Methods: In this study, we used a microarray to describe lncRNA profiles in cumulus cells isolated from ten patients (five PCOS and five normal women). Several differentially expressed lncRNAs were chosen to validate the microarray results by quantitative RT-PCR (qRT-PCR). Then, the differentially expressed lncRNAs were classified into three subgroups (HOX loci lncRNA, enhancer-like lncRNA, and lincRNA) to deduce their potential features. Furthermore, a lncRNA/mRNA co-expression network was constructed by using the Cytoscape software (V2.8.3, http://www.cytoscape.org/ )., Results: We observed that 623 lncRNAs and 260 messenger RNAs (mRNAs) were significantly up- or down-regulated (≥2-fold change), and these differences could be used to discriminate cumulus cells of PCOS from those of normal patients. Five differentially expressed lncRNAs (XLOC&#95;011402, ENST00000454271, ENST00000433673, ENST00000450294, and ENST00000432431) were selected to validate the microarray results using quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Further analysis indicated that many differentially expressed lncRNAs were transcribed from chromosome 2 and may act as enhancers to regulate their neighboring protein-coding genes. Forty-three lncRNAs and 29 mRNAs were used to construct the coding-non-coding gene co-expression network. Most pairs positively correlated, and one mRNA correlated with one or more lncRNAs., Conclusions: Our study is the first to determine genome-wide lncRNA expression patterns in cumulus cells isolated from PCOS patients by microarray. The results show that clusters of lncRNAs were aberrantly expressed in cumulus cells of PCOS patients compared with those of normal women, which revealed that lncRNAs differentially expressed in PCOS and normal women may contribute to the occurrence of PCOS and affect oocyte development.

Purpose: The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS)., Methods: The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS., Results: Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883., Conclusion: In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS.

Purpose: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation., Methods: Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment., Results: The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR)., Conclusions: These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Purpose: To evaluate basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) cycles and examine the association between basal T levels and ovarian response or IVF pregnancy outcome., Methods: We retrospectively analyzed 1413 infertile Chinese women undergoing their first IVF treatment at our institution's reproductive center from March 2011 to May 2013. The basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) and the relationship between basal T levels and ovarian response or IVF pregnancy outcome were determined. These patients did not have polycystic ovary syndrome (PCOS) or endometriosis, and were treated with a long luteal down-regulation protocol. Subjects were divided into 2 groups according to basal testosterone (T) levels: Group 1, basal T values <20 ng/dl (n = 473), and Group 2, basal T values >20 ng/dl (n = 940). We evaluated the association of basal T levels with ovarian response and IVF outcome in the two groups., Results: In this study, BMI, basal follicle-stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, antral follicle count (AFC), days of stimulation, total gonadotrophin dose, basal FSH/LH ratio, and the number of follicles >14 mm were significantly different (P < 0.05) between the two groups. Basal T level positively correlated with ovarian reserve function, number of follicles >14 mm on human chorionic gonadotrophin (HCG) day, and total gonadotropin dose. However, basal T levels play no role in predicting IVF pregnancy outcome., Conclusion: Basal T level can be used as a good predictor for ovarian response and the number of large follicles on HCG day. Additionally, we may use basal T level as a marker to predict FSH dosage. In general women, lower level of T might relate with potential poor ovarian response. However, based on our data, basal T levels do not predict pregnancy outcome.

Purpose: An association between the INS VNTR polymorphisms and polycystic ovary syndrome (PCOS) susceptibility has been reported in previous studies, but the results were inconsistent. This study was conducted to explore this association using meta-analysis., Methods: PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched according to predefined criteria for all relevant studies published up to August 2013. Four genetic models, together with odds ratios (ORs) and 95 % confidence intervals (CI), were calculated. Subgroup analyses were performed by ethnicity, anovulatory PCOS, and Hardy-Weinberg equilibrium (HWE) in the controls., Results: In total, 13 case-control studies, including 1,767 cases and 4,108 controls, were included. No significant association was detected in overall population in all models (III/III vs. I/I: OR = 1.200, 95%CI = 0.866-1.664, P=0.277; I/III vs. I/I: OR = 1.041, 95%CI = 0.880-1.232, P=0.637; III/III + I/III vs. I/I: OR = 1.191, 95%CI = 0.912-1.554, P=0.199; III/III vs. I/III + I/I: OR = 1.100, 95%CI = 0.816-1.484, P=0.531), the same as in Caucasian and Asian populations. When the studies were limited to conform to HWE, the results remained persistent and robust. The anovulation subgroup showed significantly elevated risk in the I/III vs. I/I (OR = 1.460, 95%CI = 1.017-2.095, P=0.040)., Conclusions: This meta-analysis revealed no significant association between INS VNTR polymorphisms and the risk of PCOS in the overall population, while it supported that variance may be associated with susceptibility to PCOS with anovulation. Further confirmation is needed from more well-designed and larger studies.

Purpose: To determine if microRNAs are differentially expressed in the follicular fluid of women with PCOS compared to fertile oocyte donors and identify associated altered gene expression., Methods: Women undergoing IVF who met Rotterdam criteria for PCOS or who were fertile oocyte donors were recruited from a private IVF center. Individual follicle fluid was collected at the time of oocyte retrieval. MicroRNA analysis was performed using microarray and validated using real-time PCR on additional samples. Potential gene targets were identified and their expression analyzed by real time PCR., Results: Microarray profiling of human follicular fluid revealed expression of 235 miRNAs, 29 were differentially expressed between the groups. Using PCR validation, 5 miRNAs (32, 34c, 135a, 18b, and 9) showed significantly increased expression in the PCOS group. Pathway analysis revealed genes involved in insulin regulation and inflammation. Three potential target genes were found to have significantly decreased expression in the PCOS group (interleukin 8, synaptogamin 1, and insulin receptor substrate 2)., Conclusions: MicroRNAs are differentially expressed in the follicular fluid of women with PCOS when compared to fertile oocyte donors. There is also altered expression of potential target genes associated with the PCOS phenotype.

Purpose: Several studies have reported that excessive amounts of plasminogen activator inhibitor-1(PAI-1) might increase the incidence of polycystic ovary syndrome(PCOS), but so far the published results were inconsistent. The aim of this study was to further investigate the association between PAI-1 gene polymorphism and the susceptibility to PCOS by performing a meta-analysis., Methods: A comprehensive literature search for relevant studies was conducted on google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated., Results: Ten case-control studies were included in this meta-analysis with a total of 2,079 cases and 1,556 controls. The results showed that PAI-1 -675 4G/5G polymorphism may increase the risk of PCOS, especially among Asian populations. However, there was no statistically significant association between the polymorphism and PCOS risk in Caucasians., Conclusion: Our meta-analysis suggests that PAI-1 -675 4G/5G polymorphism may contribute to increasing susceptibility to PCOS in Asians. Detection of the PAI-1 gene polymorphism might be a promising biomarker for the susceptibility of PCOS.

Purpose: Polycystic ovary syndrome (PCOS) is a most common endocrine disorder of reproductive age women. Interleukin-6 is involved in the pathophysiological characteristics associated with polycystic ovary syndrome (PCOS). The-174 G/C IL-6 gene promoter region single nucleotide polymorphism (SNP) may influence or modulate gene function and/or transcriptional efficiency. The current study was aimed to evaluate the association between IL-6 gene -174 G/C promoter polymorphism and Polycystic Ovary Syndrome in South Indian women., Methods: In the present study, we examined the genotypic and allele distribution among the PCOS patients (n = 104) and controls (n = 156). The genotypes of IL-6 -174 G/C SNP were analyzed by polymerase chain reaction (PCR) and sequencing analysis. The allele frequency and genotype distributions of cases and controls were analyzed using Fisher's exact test., Results: The genotype frequencies observed among the 104 cases and 156 controls were G/G 66.3 % and 49.4 %, G/C 29.8 % and 46.8 %, and C/C 3.8 % and 3.8 % (OR: 1.6226, CI: 1.0574-2.4899). The G and C allele frequencies were 81.25 % and 72.8 %, and 18.75 % and 27.2 %, respectively. The genotype and allele distribution revealed significant differences between PCOS patients and controls (all P values < 0.05)., Conclusion: Our findings showed a significant statistical association between IL-6 -174 G/C SNP and PCOS risk in South Indian women. The 'G' allele frequency influences significantly higher in PCOS patients than controls. However, the exact mechanism by which 'G' allele frequency influence PCOS patients is yet to be determined.

Purpose: To identify the leading treatment strategies for infertile women with PCOS on an international scale., Methods: A retrospective evaluation using the results of a web-based survey, (IVF-Worldwide ( www.IVF-worldwide.com ), posted from 1 to 30 September 2010 was performed. Binomial confidence intervals for proportions were calculated by the modified Wald method with significance defined as P < 0.05 using a DataStar software package (DataStar, Waltham, MA, USA). Incomplete surveys were excluded from the analysis., Results: The results from 262 centers in 68 nations were obtained. Clomiphene citrate was the clear first choice, 68 %, for PCOS treatment in the respondent group. Eighty-eight percent of respondents utilized ultrasound follicular monitoring when conducting ovulation induction with oral medications. A significant (p < 0.05) proportion of respondents (66 %) did use some BMI cutoff beyond which IVF treatment was not offered. The preferred IVF protocols for PCOS patients were gonadotropin releasing hormone (GnRH) antagonist, 46 %, and GnRH agonist, 51 %. There was heterogeneity of responses observed regarding the management of a patient at very high risk of OHSS., Conclusions: While some advances, such as the use of GnRH antagonist regimen in IVF cycles, were relatively underutilized, the survey gives an unfiltered snapshot at the practice patterns of a large number of clinics. Results from this survey may be used by researchers and professional organizations to improve the clinical care of PCOS women suffering with infertility.

Purpose: To assesse circulating levels of Anti-Müllerian hormone (AMH) as a predictor of oocyte number and their potential to mature in vitro in both normo-ovulatory (NO) women and in women with Polycystic Ovary Syndrome (PCOS) undergoing in vitro maturation (IVM) treatments., Methods: We prospectively studied NO women and women diagnosed with PCOS, (age range 21-39 years) underwent IVM treatments at our center. Serum AMH levels were quantified before each cycle and correlated to oocytes number, maturation and fertilization during in vitro maturation., Results: 104 NO and 30 PCOS IVM cycles were followed with retrieval of a total of 672 and 491 oocytes, respectively. In NO women, the serum AMH level positively correlated with the number of oocytes retrieved, (R = 0.6; P <0.0001) the number of M2 oocytes at 24 and 48 h (R = 0.4; P <0.01; R = 0.26 p < 0.007, respectively) and with the total number of M2 oocytes (R = 0.47; P < 0.0001). In the PCOS group, the serum AMH level positively correlated only with the number of oocytes retrieved (R = 0.43; P <0.03). Receiver operating characteristic (ROC) analyses showed that a cutoff AMH level of 1.56 (ng/ml) could identify patients with 5 or more oocytes at OPU with a sensitivity of 83 % and a specificity of 75 %. An AMH level of 1.63 (ng/ml) was the threshold for 5 or more matured oocytes (sensitivity = 81 %, specificity = 53 %)., Conclusions: Serum AMH may be used as a marker to identify candidates for IVM treatment in both NO and PCOS women.

Purpose: Human chorionic gonadotrophin (hCG) has been used to induce ovulation and oocyte maturation. Although the most common dose of hCG used in IVF is 10,000 IU, there are reports that suggest 5,000 IU is sufficient to yield similar results. The objective of this study is to evaluate the dose dependent differences in gene expression of granulosa cells following various doses of hCG treatment., Methods: Patients with polycystic ovarian syndrome (PCOS) were stimulated for IVF treatment. The hCG injection was either withheld or given at 5,000 or 10,000 IU. Granulosa cells from the follicular fluids have been collected for RNA isolation and analyzed using Affymetrix genechip arrays., Results: Unsupervised hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered together whereas hCG-treated patients separated to a different group regardless of the dose. A large number of the transcripts were similarly up- or down-regulated across both hCG doses (2229 and 1945 transcripts, respectively). However, we observed dose-dependent statistically significant differences in gene expression in only 15 transcripts., Conclusions: Although hCG injection caused a major change in the gene expression profile of granulosa cells, 10,000 IU hCG resulted in minimal changes in the gene expression profiles of granulosa cells as compared with 5,000 IU. Thus, based on our results, we suggest the use of 10,000 IU hCG should be reconsidered in PCOS patients.

Objective: To determine the relationship between Polycystic Ovary (PCO) morphology and In Vitro Fertilization (IVF) outcome in oocyte donation cycles., Design: Cross sectional study, Setting: Private IVF clinic, Patients: 164 consecutive ovum donors and their recipients were reviewed, 149 were included in the study where 113 patients had normal ovarian morphology and 36 patients had PCO morphology., Interventions: All donors underwent ovarian stimulation in conjunction with GnRH agonist or antagonist in standard fashion., Main Outcome Measures: Baseline donor characteristics were recorded, as well as details of IVF stimulation and embryo data. Recipient data on pregnancy and miscarriage were also collected., Results: Patients with PCO ovaries had significantly higher peak estradiol levels and required less gonadotropins during IVF stimulation. In addition, the baseline characteristics between donor groups did not differ except for ovarian morphology. The number of oocytes retrieved and indicators of embryo quality did not differ between the two groups, and there was no significant difference between pregnancy and miscarriage rates in the recipients., Conclusions: Oocyte donors with PCO morphology have equivalent pregnancy rates and do not need to be excluded as potential donors.

Purpose: To detect expression of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in oocytes, and their receptor type 2 receptor for BMPs (BMPR2) in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if BMPR2, BMP15, and GDF9 expression correlate with hyperandrogenism in FF of PCOS patients., Methods: Prospective case-control study. Eighteen MII-oocytes and their respective cumulus cells were obtained from 18 patients with PCOS, and 48 MII-oocytes and cumulus cells (CCs) from 35 controls, both subjected to controlled ovarian hyperstimulation (COH), and follicular fluid (FF) was collected from small (10-14 mm) and large (>18 mm) follicles. RNeasy Micro Kit (Qiagen) was used for RNA extraction and gene expression was quantified in each oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were used for hormone assays., Results: BMP15 and GDF9 expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between BMPR2 transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group., Conclusion: We inferred that BMP15 and GDF9 transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.

Objective: The aim of our study was to investigate the frequency and compare the prevalence of IRS-1Gly972Arg and IRS-2 Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women. MATERIAL(S) AND METHOD(S): Forty eight Iranian women diagnosed with PCOS were enrolled in this study. Fifty two non-diabetics, non-PCOS women were enrolled as the control group. HemoglobinA1c (HbA1c), fasting blood glucose (FBS), fasting insulin levels (FIL) and 2 h post-prandial blood glucose(2hpp BS) were evaluated from blood samples. Insulin resistance sample was estimated with Homeostasis Model Assessment index for insulin resistance (HOMA-IR). Genotyping of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 was conducted using PCR., Results: No statistically significant differences in the prevalence of IRS-1 Gly972Arg or IRS-2 Gly1057Asp polymorphisms or any combination of both were observed between controls and PCOS patients (P > 0.02). Control subjects with the IRS-1 polymorphism had higher levels of 2hpp BS compared with those with the Gly/Gly genotype (P = 0.037)., Conclusions: Considering that no association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and PCOS were found, the results confirm that these polymorphisms should not be considered as major contributors to the pathogenesis of this disorder.

Purpose: To explore four areas of controversy: the benefits of gonadotropin priming, benefits and timing of hCG trigger as well as the ideal protocols for endometrial preparation and luteal support., Methods: A literature review was performed to explore the current evidence, Results: Current evidence suggests that Gonadotropin priming in combination with hCG prior to collection benefits patients with normal ovaries. In PCOS patients 10,000 IU hCG 38 h before retrieval increases the total number and rate of oocyte maturation. Gonadotropin priming may also benefit PCOS patients. The ideal timing of hCG trigger appears to be when the leading follicle is 10-12 mm. Sparse data exists regarding luteal support protocols., Conclusions: There is still a need for well-designed studies to establish ideal methods for oocyte priming, timing of retrieval, endometrial preparation and luteal support. Further studies must incorporate both clinical and basic science principles of ovarian, follicular and endometrial physiology.

Purpose: To examine the fertilization and developmental potential of sibling mature oocytes collected from different follicle sizes on day of retrieval in in vitro maturation (IVM) cycles., Methods: Two hundred thirty eight hCG-primed IVM cycles were performed in 213 patients with polycystic ovaries. If sibling mature oocytes were retrieved on day of collection, they were divided into two groups, Group 1 (n = 78): M-II oocytes obtained from follicles size 10-14 mm; Group 2 (n = 192): M-II oocytes obtained from follicles size <10 mm., Results: Of the 238 cycles, 63 cycles had more than one M-II oocytes retrieved (total M-II oocytes = 270) both from Groups 1 and 2. There were no significant differences between the two groups for oocyte diameter (117.2 mm vs. 116.9 mm), fertilization (79.5% vs. 72.4%) and good quality embryo on day 3 (66.1% vs. 56.8%)., Conclusions: The M-II oocytes retrieved from the cohort of follicles (<10 mm diameter) can produce the same quality of embryos as that from large follicles, likely contributing to improve the clinical outcome.

Purpose: To estimate frozen zygotes, which developed from in vitro matured oocytes retrieved from polycystic ovarian syndrome-like disease., Methods: Oocyte retrieval was performed on Day 15 following withdrawal bleeding. The oocytes were incubated for 24 h in TCM-199 maturation medium supplemented with follicle fluid, E2, FSH, and hCG., Results: A total of 12 immature oocytes were collected. Seven of the 12 oocytes (58.3%) developed to the metaphase-II stage, and subsequently, all seven fertilized oocytes were frozen at the pronuclear stage. The remaining five oocytes failed to develop to the metaphase-II stage after an additional 24 h of incubation. Three of seven cryopreserved oocytes were thawed and developed to 2-8-cell cleaved stage embryos. The first pregnancy failed. However, the second frozen-thawed embryo transfer resulted in the delivery of healthy twins., Conclusions: Successful delivery using frozen zygotes from an anovulatory woman with polycystic ovarian syndrome-like disease.