Polycystic Ovarian Morphology Research Articles

The prevalence and phenotypic manifestations of polycystic ovary syndrome (PCOS) among infertile Sudanese women: a cross-sectional study

BackgroundPolycystic ovary syndrome (PCOS) is a global health problem associated with significant morbidity during reproductive age. Only a few published studies that address the clinical manifestations and phenotypic presentation of the disease have been conducted in Africa, including Sudan. Thus, this study aimed to evaluate the clinical and biochemical presentation of the different PCOS phenotypes among infertile Sudanese women.MethodsA cross-sectional, descriptive study was conducted from January to December 2019. A total of 368 infertile women with PCOS (based on the Rotterdam criteria) were recruited from a fertility center in Khartoum, Sudan. Clinical, hormonal, and ultrasonographic characteristics were described and compared between the four phenotypes of PCOS.ResultsMajority (321 [87.2%]) of the women had oligo/anovulation (OA). Polycystic ovary morphology on ultrasound appeared in 236 (64.1%) women, acne in 171 (46.5%) women, acanthosis nigricans in 81 (22.0%) women, and hirsutism in 101 (27.4%) women. Phenotype D was the most prevalent among infertile Sudanese women (51.6%), followed by phenotype B (22.6%), phenotype C (18.2%), and phenotype A (7.6%). No statistical differences in the body mass index and hormonal profile between the four phenotypes were noted. Women with phenotype A were older and had high mean blood pressure, and a higher waist/hip ratio was observed among women with phenotype D.ConclusionUnlike the global distribution of PCOS phenotypes, Sudanese women uniquely expressed phenotype D as the most prevalent. More epidemiological studies are needed in the region due to geographical, ethnic, and genetic variations.

MicroRNA‐21 Genetic Ablation Exacerbates Insulin Signaling Dysregulation in Hyperandrogenemic Female Mice

IntroductionPolycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive‐age women and is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is associated with obesity and insulin resistance, both being risk factors associated with cardiovascular disease. Micro‐RNAs are small, non‐coding RNAs capable of altering gene expression by binding to specific mRNA targets. MicroRNA‐21(miR21) is cell‐specifically expressed and dynamically regulated in tissues that are implicated in cardiometabolic dysfunction in PCOS including the liver, skeletal muscle, and the heart. We hypothesize that miR‐21 genetic ablation exacerbates androgen‐induced dysregulation of insulin signaling to modify insulin resistance and cardiac damage in a mouse model of PCOS.MethodsThree‐week‐old peripubertal miR‐21 knockout (miR21KO) or wild‐type (WT) C57BL/6N female mice were treated s.c. with dihydrotestosterone (DHT, 8 mg) or vehicle for 90 days. Fasting glucose was determined by an enzymatic method and both fasting insulin and advanced glycation end products (AGES) were measured by ELISA. microRNA, mRNA, and protein levels were quantified by RT‐qPCR and Western‐blot. Data were analyzed by t‐test or two‐way ANOVA. All differences are considered significant p<0.05.ResultsIn WT animals DHT treatment increased miR21 expression in the soleus muscle (2.15±0.47‐fold, p<0.05), with a trend to increase in the tibialis anterior muscle (1.25‐fold), and the liver (1.41‐fold) compared with their vehicle counterparts. DHT‐treated miR21KO females showed exacerbated insulin resistance, having increased HOMA‐IR compared with both vehicle miR21KO and WT groups (6.50 ± 3.64 vs. 3.32±1.83 and 3.16±1.31, p<0.05) calculated using fasting insulin and glucose. In the soleus, miR21KO DHT‐treated mice showed an increase in Irs2 (1.45‐fold, p<0.05) compared with vehicle WT, whereas no increase was found in DHT‐treated WT animals. DHT‐treated miR21KO animals showed significantly increased Akt2 (1.40‐fold) and the glucose transporter Slc2a2 (1.24‐fold) mRNA expression in the liver. Additionally, liver protein expression of total mTOR was increased only in miR21KO DHT‐treated animals (2.40, p<0.05) compared to vehicle WT animals. Lastly, miR21KO increased left ventricular advanced glycation end products (AGEs), having significantly higher AGEs compared to all three treatment groups (3.10±0.52μg /mg protein, p<0.05).ConclusionsOur results suggest that miR21 upregulation in insulin sensitive tissues is a compensatory mechanism to counteract androgen‐inducted dysregulation of insulin signaling pathways and downstream cardiac damage. The differences observed in androgen‐treated mice highlight the potential importance of miR21 in the crosstalk between several insulin signaling networks. Notably, given the worsened DHT‐induced insulin resistance and increased left ventricular AGEs in miR21KO animals, a miR‐21 mimic may be a potential novel therapeutic option for women with PCOS.

Abstract #1167463: Abnormal Visceral Adiposity Index among Females with Polycystic Ovarian Syndrome and its association with Phenotypes and Cardiometabolic risk

Polycystic ovarian syndrome (PCOS) is a frequently encountered endocrine disorder in females of reproductive age. Visceral adiposity index (VAI) is indicative of visceral adiposity and dysfunction. The study aimed to evaluate the visceral adiposity index (VAI) and its association with cardiometabolic risk in females with PCOS. This case-control study was done on 100 females diagnosed with PCOS as per Rotterdam's criteria and 50 age and body mass index (BMI) matched controls. Patients were studied for clinical characteristics, anthropometric, biochemical and hormonal investigations and ultrasound scans. Participants were classified into different phenotypes of PCOS. VAI was calculated using waist circumference (WC), BMI, serum triglyceride (TG), and High-density lipoprotein (HDL) cholesterol levels. The mean age of the subjects with PCOS was 28.8±10.6 years, whereas that of controls was 27.6±9.2 years. The phenotype D of PCOS was predominant form 47%, followed by phenotype C, A and B in 31%, 15% and 7%, respectively. Mean VAI was significantly higher in females with PCOS than controls (2.90 vs. 1.84) (P < 0.001). Mean VAI in phenotype A, B, C, and D was 3.46, 2.48, 2.37, and 1.98, respectively. Metabolic syndrome was prevalent in 28%. A total of 44% of women with PCOS were at risk and 32% at high risk for cardiometabolic disease. VAI was significantly associated with obesity, WC, hirsutism, phenotype A, plasma glucose, testosterone, TG and polycystic ovarian morphology. Logistic regression analysis showed that VAI positively correlated with obesity, WC, phenotype A and testosterone. VAI can be used as a simple and effective tool for assessing the cardiometabolic risk in females with PCOS. VAI had a positive correlation with serum testosterone.

Association between an AMH promoter polymorphism and serum AMH levels in PCOS patients.

STUDY QUESTIONDo polymorphisms in the anti-Müllerian hormone (AMH) promoter have an effect on AMH levels in patients with polycystic ovary syndrome (PCOS)?SUMMARY ANSWERWe have identified a novel AMH promoter polymorphism rs10406324 that is associated with lower serum AMH levels and is suggested to play a role in the mechanism of regulation of AMH gene expression in women.WHAT IS KNOWN ALREADYFollicle number is positively correlated with serum AMH levels, reflected by elevated AMH levels in women with PCOS. In addition, it is suggested that AMH production per follicle is higher in women with PCOS than in normo-ovulatory women, implying an altered regulation of AMH in PCOS.STUDY DESIGN, SIZE, DURATIONA discovery cohort of 655 PCOS women of Northern European ancestry and both an internal and external validation PCOS cohort (n = 458 and n = 321, respectively) were included in this study. Summary-level data of an AMH genome-wide association study meta-analysis including 7049 normo-ovulatory women was included as a control cohort. A genetic approach was taken through association analysis and in silico analysis of the associated variants in the AMH promoter. In vitro analysis was performed to investigate the functional mechanisms.PARTICIPANTS/MATERIALS, SETTING, METHODSAll common two-allelic single-nucleotide polymorphisms (SNPs) in the region Chr19:2 245 353–2 250 827 bp (Build 37) were selected for the analysis. Linear regression analyses were performed to determine the association between SNPs in the AMH promoter region and serum AMH levels. For the in silico analysis, the webtools ‘HaploReg’ v4.1 for ENCODE prediction weight matrices and ‘atSNP’ were used. In vitro analysis was performed using KK1 cells, a mouse granulosa cell line and COV434 cells, a human granulosa tumor cell line. Cells were transfected with the reference or the variant human AMH promoter reporter construct together with several transcription factors (TFs). Dual-Glo® Luciferase Assay was performed to measure the luciferase activity.MAIN RESULTS AND THE ROLE OF CHANCEPolymorphism rs10406324 was significantly associated with serum AMH levels in all three PCOS cohorts. Carriers of the minor allele G had significantly lower log-transformed serum AMH levels compared to non-carriers (P = 8.58 × 10−8, P = 1.35 × 10−3 and P = 1.24 × 10−3, respectively). This result was validated in a subsequent meta-analysis (P = 3.24 × 10−12). Interestingly, rs10406324 was not associated with follicle count, nor with other clinical traits. Also, in normo-ovulatory women, the minor allele of this variant was associated with lower serum AMH levels (P = 1.04 × 10−5). These findings suggest that polymorphism rs10406324 plays a role in the regulation of AMH expression, irrespective of clinical background. In silico analysis suggested a decreased binding affinity of the TFs steroidogenenic factor 1, estrogen-related receptor alpha and glucocorticoid receptor to the minor allele G variant, however in vitro analysis did not show a difference in promoter activity between the A and G allele.LIMITATIONS, REASONS FOR CAUTIONFunctional analyses were performed in a mouse and a human granulosa cell line using an AMH promoter reporter construct. This may have limited assessment of the impact of the polymorphism on higher order chromatin structures. Human granulosa cells generated from induced pluripotent stem cells, combined with gene editing, may provide a method to elucidate the exact mechanism behind the decrease in serum AMH levels in carriers of the −210 G allele. We acknowledge that the lack of follicle number in the external validation and the control cohort is a limitation of the paper. Although we observed that the association between rs10406324 and AMH levels was independent of follicle number in our discovery and internal validation PCOS cohorts, we cannot fully rule out that the observed effects on serum AMH levels are, in part, caused by differences in follicle number.WIDER IMPLICATIONS OF THE FINDINGSThese results suggest that variations in serum AMH levels are not only caused by differences in follicle number but also by genetic factors. Therefore, the genetic context should be taken into consideration when assessing serum AMH levels in women. This may have clinical consequences when serum AMH levels are used as a marker for the polycystic ovarian morphology phenotype.STUDY FUNDING/COMPETING INTEREST(S)No external funding was used. J.S.E.L. has received consultancy fees from the following companies: Ferring, Roche Diagnostics and Ansh Labs and has received travel reimbursement from Ferring. J.A.V. has received royalties from AMH assays, paid to the institute/lab with no personal financial gain. The other authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A.

Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management.

Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging since normal pubertal development overlap typical features of this syndrome. The authors aim to summarize the existing evidence concerning PCOS in adolescence, particularly its diagnostic criteria and therapeutic options. A search throughout medical databases such as PubMed and MedScape was performed. Diagnostic criteria include irregular menstrual cycles according to time postmenarche and evidence of clinical hyperandrogenism and/or biochemical hyperandrogenism, provided other causes have been excluded. Polycystic ovarian morphology ought not to be used as a diagnostic criterion. Treatment should target manifestations and/or comorbidities, even in the absence of a definite diagnosis. Lifestyle interventions are the first-line treatment. Combined oral contraceptives, metformin or antiandrogens may also be considered as adjuvants. Screening for PCOS in adolescence is crucial as it allows an early intervention on the symptoms and comorbidities presented leading to better long-term reproductive and metabolic outcomes.

Effect of the presence of polycystic ovary syndrome-related features on anti-Mullerian hormone and androstenedione levels in adolescents with or without menstrual irregularity.

To determine the variation in anti-Mullerian hormone (AMH) and androstenedione (A4) concentrations in adolescent girls, with or without menstrual cycle disorder in relation to phenotypic features of. PCOS. Adolescent girls (n = 129), age range 14-19years, were recruited in the cohort study. All participants were in the 4th or 5th year after menarche. Sixty-eight had menstrual irregularities, usually oligomenorrhea (OM), and 61 had regular menstruation (RM). AMH and A4 concentrations were measured. Hirsutism was recorded. Polycystic ovarian morphology (PCOM) was evaluated by transabdominal pelvic ultrasonography. Polycystic ovary syndrome (PCOS) features were defined according to Rotterdam consensus criteria. AMH and A4 were significantly higher in adolescent girls with OM than in girls with RM (p < 0.05). A4 and body mass index (BMI) of adolescents with OM was significantly higher in those with hirsutism than those without hirsutism (p = 0.01 and 0.008, respectively). There was a positive correlation between A4 and BMI (r: 0.327, p < 0.01). Logistic regression showed that the frequency of OM in the presence of PCOM was 10.8 times (95% CI 2.04-12.09) compared to those without PCOM. The highest AMH concentrations were found in girls with OM, hirsutism, and PCOM (p < 0.05). AMH and A4 are elevated in adolescents with oligomenorrhoea. High A4 is more prominent in the presence of hirsutism and is associated with increased BMI. PCOM, increases the likelihood of oligomenorrhea by about 10 times. AMH increase as the combination of clinical features of PCOS increases in adolescents with menstrual irregularity.

Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy and cause of infertility in women of reproductive age worldwide. Despite diagnostic features of anovulation, polycystic ovarian morphology, and high androgen secretion indicating the syndrome are the result of ovarian dysfunction, alterations to central neuroendocrine circuits that control reproductive capacity may drive PCOS symptoms. Resistance of gonadotrophin-releasing hormone (GnRH) neurons in the hypothalamus to inhibition by sex steroid hormone-negative feedback leads to a rapid frequency of pulsatile gonadotrophin secretion, which, in turn, drives the ovarian features of the disease. As GnRH neurons do not express steroid hormone receptors, impaired negative feedback is hypothesized to occur within an upstream network that controls GnRH pulse generation. This review will discuss the latest work from preclinical animal models of PCOS used to dissect the specific central mechanisms involved in impaired steroid hormone feedback. In particular, this review will focus on research that indicates neurons in the arcuate nucleus of the hypothalamus that express Kisspeptin, Neurokinin B and Dynorphin (KNDy cells) or γ-aminobutyric acid are targets of androgen-mediated impairment of steroid hormone feedback. Finally, this review will explore the development of therapeutic agents targeting neurons that control LH pulse frequency to resolve PCOS symptoms in the clinic.

Polycystic Ovarian Morphology: Diagnostic Criteria and Prevalence

The purpose of this brief review was to systematize the current information on the diagnosis, prevalence, and ethnic aspects of polycystic ovarian morphology (PCOM). The information search was conducted using Internet resources (Medline, Pubmed, Cochrane Library, and Google Scholar) and literature sources for the period from January 1999 to August 2021. The review includes only full-text articles. Based on the analysis of the literature, we demonstrated that the diagnostic value of PCOM has changed since the moment of the first description of polycystic ovarian syndrome (PCOS). Currently, ovarian size, ovarian volume and antral follicle count are key criteria for most PCOS phenotypes and complications. The diagnostic value of PCOM depends on age and racial characteristics, which requires large-scale epidemiological studies to determine PCOM characteristics in different populations. Standardizing PCOM diagnostic criteria is the key to PCOS effective diagnosis and, consequently, to preventing complications and comorbidities associated with PCOS.

Partially purified non-polar phytocomponents from Aloe barbadensis Mill. gel restores metabolic and reproductive comorbidities in letrozole-induced polycystic ovary syndrome rodent model- an “in-vivo” study

Ethnopharmacological relevanceIn India, Kumaryasava, a popular Aloe barbadensis Mill. gel preparation has therapeutic value in treatment of female reproductive disorders like menstrual disturbances and menopausal problems. Despite their widespread use, only a limited number of studies have probed into the scientific evidence for their varied bioactivities. In this regard, studies have demonstrated that Aloe vera gel has the potential to modulate steroidogenic activity in letrozole induced polycystic ovary syndrome (PCOS) rat. However, isolation and identification of the bioactive molecule/s from Aloe vera gel and studying their molecular targets will underpin the treatment regime for PCOS. Material and methodsThe Partially Purified Non-Polar Phytocomponents (PPNPP)- LP1 and LP3 were isolated from the petroleum ether extract of Aloe vera gel by column chromatography. Based upon the GC-MS analysis, LP1 and LP3 comprised of n-Hexadecanoic acid and Campesterol acetate with an abundance of 97.07%, and 96.07% respectively. For evaluation of their bioactivities, eighty 3–4 months female Balb/c mice were classified as 10 groups with 8 animals in each group. Groups were control (C), PCOS (0.5 mg/kg/day Letrozole orally for 21days), PCOS treated orally for 60 days with Aloe vera gel (AVG) (10 mg/kg/day) (PCOS + AVG), PCOS treated orally for 60 days with petroleum ether extract (PE) of Aloe vera gel (25 μg/kg/day) (PCOS + PE), PCOS treated orally for 60 days with LP1 (0.5 μg/kg/day) (PCOS + LP1), PCOS treated orally for 60 days with commercially available pure compound-n-Hexadecanoic acid (HA) (0.5 μg/kg/day) (PCOS + HA), PCOS treated orally for 60 days with LP3 (0.01 μg/kg/day) (PCOS + LP3), PCOS treated orally for 60 days with commercially available pure compound- Campesterol acetate (CA) (0.01 μg/kg/day) (PCOS + CA), PCOS treated orally for 60 days with Metformin (100 mg/kg/day) (PCOS + Metformin) and PCOS treated orally for 60 days with DMSO (Vehicle) (PCOS + DMSO). Body weight, Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, gene expression of gonadotropin receptors (Fshr and Lhr), steroid receptors (Ar, Esr1, Esr2 and Pgr) and steroidogenic markers (Star, Hsd3b1, Cyp19a1 and Amh) were analysed in the ovaries. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Toxicity markers- SGOT, SGPT and creatinine were also measured at the end of the study. ResultsMice treated with letrozole demonstrated significant increase in body weight, glucose intolerance, fasting insulin levels, HOMA-IR, triglycerides levels as well as testosterone levels, and a significant decline in the progesterone levels as compared to the control animals. PCOS animals also exhibited arrested estrus cyclicity, disrupted ovarian histopathology with the presence of multiple peripheral cysts and abnormal gene expression of gonadotropin receptor, steroid receptor and steroid markers. Oral administration of AVG, PE extract of AVG, LP3 and metformin greatly alleviated these complications in PCOS animals. ConclusionThe above findings indicate the effectiveness of LP3, isolated from Aloe vera gel against letrozole induced PCOS in mice and may be used in the treatment of PCOS as an alternative to metformin.

Prevalence of PCOS and related hyperandrogenic traits in premenopausal women with type 1 diabetes: a systematic review and meta-analysis.

An increased prevalence of functional hyperandrogenism-including polycystic ovary syndrome (PCOS)-has been described in women with type 1 diabetes (T1D). However, heterogeneity between studies is frequent, and prevalence rates vary according to different criteria used for the diagnosis of PCOS and the population studied. We aimed to perform a systematic review and meta-analysis of the prevalence of PCOS and related hyperandrogenic traits in premenopausal women with T1D. This way, we intend to increase the precision of the estimates of prevalence of PCOS and related traits in women with T1D, and to explore sources of heterogeneity while providing prevalence estimates for clinically relevant subgroups such as the different phenotypes. We conducted a systematic review of the literature using Medline-OVID and Embase databases (Open Science Framework registry for systematic review protocols, https://osf.io/6cv9p/). Studies published up to 29 March 2021 were considered. We selected cross-sectional or prospective studies that reported, in patients with T1D, prevalence data on PCOS according to current definitions and different phenotypes, and/or prevalence rates of other related traits (hirsutism, hyperandrogenaemia, oligo-amenorrhoea and/or polycystic ovarian morphology: PCOM). Exclusion criteria for the review were studies addressing types of diabetes other than T1D; and studies using diagnostic definitions of PCOS different than those mentioned above. Two independent researchers performed data extraction. To assess the risk of bias, we used a tool developed specifically to appraise population-based prevalence studies. We selected 19 studies (1042 women) reporting the prevalence of PCOS and/or other hyperandrogenic traits. Regarding bias, 12 studies were considered of low-risk, and the remaining seven studies were considered intermediate risk. The pooled prevalence of PCOS when considering all possible phenotypes (ESHRE- American Society for Reproductive Medicine criteria) in T1D was 26% (95% CI: 19-34%; 13 studies, 684 women). Pooled prevalence of classic PCOS (US National Institutes of Health criteria) was 16% (95% CI: 10-22%; 9 studies, 614 women). Pooled prevalence of hyperandrogenic PCOS (Androgen Excess and PCOS Society criteria) was 26% (95% CI: 16-41%; 5 studies, 329 women). Hirsutism (24%), hyperandrogenaemia (29%), oligomenorrhoea (24%) and PCOM (34%) were also prevalent. Heterogeneity was high in almost all these meta-analyses. This systematic review and meta-analysis showed that PCOS and related hyperandrogenic traits are present in approximately one in every four women with T1D. Larger studies are needed to confirm this association, to address the effect of different variables on the occurrence of PCOS.

Association of antim\xfcllerian hormone with polycystic ovarian syndrome phenotypes and pregnancy outcomes of in vitro fertilization cycles with fresh embryo transfer

ObjectiveThe current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment.MethodsWe performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P < 0.05) among the three groups, Bonferroni test was performed as post-hoc tests to determine where the statistical differences existed. To assess the relationships between AMH and pregnancy outcomes in total patients and PCOS patients, logistic regression analysis, adjusted for potential confounding covariates, were performed.ResultsWomen with high AMH had greater prevalence of hyperandrogenism (HA), polycystic ovarian morphology (PCOM) and amenorrhea than women with low or average AMH. The clinical pregnancy rate were significantly higher in the high-AMH group compared with low- and average-AMH groups (69.9% vs. 58.8% and 64.7% respectively; P < 0.001). The live birth rate was significantly lower in women with AMH ≤ 2.25 ng/mL compared with average- and high-AMH groups (47.6% vs. 55.2 and 59.5% respectively; P < 0.001). However, after controlling for maternal age, oocyte yield, as well as other confounders, AMH was no longer associated with a higher live birth rate (aOR 1.037, 95% CI 0.853–1.261, P = 0.717; aOR 1.099, 95% CI 0.858–1.408, P = 0.455, respectively) and clinical pregnancy rate (aOR 1.064, 95% CI 0.834–1.359, P = 0.617; aOR 1.181, 95% CI 0.875–1.595, P = 0.276, respectively). Moreover, pregnancy outcomes did not differ in PCOS women according to AMH quartiles.ConclusionIncreased AMH levels associated with PCOS severity and greater ovarian stimulation. However, AMH was not associated with clinical pregnancy rate and live birth rate after controlling for other confounders in women undergoing IVF. Thus, AMH should not be used to alter clinical decisions and exclude patients based on a low or even undetectable AMH value.

Single nucleotide polymorphisms in binding site of miRNA-135a and targeted gene IRS2 are correlated with multiple clinical features of PCOS: A study in Chinese women.

BACKGROUND: The etiology of polycystic ovary syndrome (PCOS) remains unclear with highly heterogeneous clinical manifestations, recently growing evidence revealing genetic variants play a crucial part in its pathogenesis.OBJECTIVE: This study aimed to examine the correlation between SNPs in miRNA-135a’s binding site of targeted gene IRS2 and clinical manifestations of PCOS in Chinese females.METHOD: A total of 126 Chinese women with PCOS and 109 healthy women were enrolled, divided into 4 groups based on different clinical features of hyperandrogenemia (HA), insulin resistance (IR), polycystic ovary morphology (PCOM) and obesity. We analyzed 2 single nucleotide polymorphisms (SNPs) of the IRS2 gene (rs2289046 and rs1865434) and clinical features’ laboratory measurements such as sex hormone, fasting plasma glucose (FPG), fasting plasma insulin (FINS).RESULTS: Located in miRNA-135a binding site of IRS2 gene, the rs2289046’s triple genotypes distribution showed a significant difference between PCOS/control group and PCOM/non-PCOM group ( 0.05) while the rs1865434’s triple genotype distribution showed a significant difference between obesity/non-obesity group ( 0.05).CONCLUSION: The results revealed the two SNPs as rs2289046 and rs1865434 in the IRS-2 binding region of miRNA-135a have correlations with the clinical features of PCOS in Chinese population.

The Prevalence of Polycystic Ovary Syndrome, Its Phenotypes and Cardio-Metabolic Features in a Community Sample of Iranian Population: Tehran Lipid and Glucose Study.

ObjectivesThe aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women.MethodsIn this cross-sectional population-based study, a total of 1,960 eligible women, aged (18–45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index.ResultsThe prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts.ConclusionPCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

Analysis of 2-Arachidonoylglycerol Levels in Polycystic Ovary Syndrome in the Context of Hormonal and Metabolic Alterations and Across the Classical Phenotypes.

Introduction: Ovarian folliculogenesis requires a fine balance between extra- and intra-ovarian factors. Endocannabinoids are found in the female reproductive system and are essential for a normal follicular growing process and ovulation. First, our study aimed to analyze levels of the endocannabinoid-2-arachidonoylglycerol (2-AG)-in patients with polycystic ovary syndrome (PCOS) and to compare with healthy controls. In addition, the study aimed to explore the association of 2-AG with hormonal and metabolic alterations, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) across the classical PCOS phenotypes. Methods: Fifty-four women with PCOS were compared with 26 healthy controls. PCOS patients were diagnosed and phenotyped according to the Rotterdam criteria. Further analyses were performed with the classical PCOS phenotypes A and B comprising hyperandrogenism with oligo-anovulation with or without PCOM, respectively. Full medical history, clinical investigations, anthropometric measurements, laboratory tests, and ultrasound investigations were carried out in the follicular phase. Serum levels of 2-AG were measured by enzyme-linked immunosorbent assay. Results: PCOS patients (n=54) and healthy controls (n=26) showed similar metabolic parameters and anthropometric characteristics. PCOS patients were more hirsute than healthy women (p=0.001). Luteinizing hormone/follicle-stimulating hormone ratio and serum levels of androgens were significantly higher in the patient than in the control group (p=0.035, p<0.001, respectively). Free androgen index was also higher in the patient group (p=0.002). Serum levels of 2-AG did not significantly differ when comparing all PCOS patients versus healthy controls; however, further analysis of individual phenotype groups revealed that 2-AG levels in PCOS patients with phenotyope A (n=30) were significantly lower when compared with PCOS patients with phenotype B (n=20) and healthy controls (n=26). Conclusion: Serum levels of 2-AG were similar between PCOS patients and healthy controls. Nevertheless, phenotype A PCOS patients had significantly lower levels of the endocannabinoid compared with phenotype B patients and healthy controls. Collectively, these results suggest that overall serum levels of 2-AG are not a diagnostic marker for PCOS; however, their altered secretion or activity may influence normal follicular processes.

Review on bisphenol A and the risk of polycystic ovarian syndrome: an insight from endocrine and gene expression.

Bisphenol A (BPA) is one of the most widely studied endocrine disrupting chemicals because of its structural similarity to 17-β estradiol; its ability to bind as an agonist/antagonist to estrogen receptors elicits adverse effects on the functioning of the metabolic and endocrinal system. Therefore, BPA has been thoroughly scrutinized concerning its disruption of pathways like lipid metabolism, steroidogenesis, insulin signaling, and inflammation. This has resulted in reports of its correlation with various aspects of cardiovascular diseases, obesity, diabetes, male and female reproductive disorders, and dysfunctions. Among these, the occurrence of the polycystic ovarian syndrome (PCOS) in premenopausal women is of great concern. PCOS is a highly prevalent disorder affecting women in their reproductive age and is clinically characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, along with metabolism-related dysfunctions like hyperinsulinemia, obesity, and insulin resistance. In this review, we analyzed certain researched effects of BPA, while focusing on its ability to alter the expression of various significant genes like GnRH, AdipoQ, ESR1, StAR, CYP11A1, CYP19A1, and many more involved in the pathways and endocrine regulation, whose disruption is commonly associated with the clinical manifestations of PCOS.

Changes in individual polycystic ovary syndrome phenotypical characteristics over time: a long-term follow-up study

To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Cohort study. Tertiary care center. Women with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited our outpatient clinic repeatedly. Comparisons were made between the first visit and consecutive visits. Change in PCOS phenotype groups in terms of clinical and endocrine characteristics. A total of 596 women visited the outpatient clinic repeatedly. An estimated change per 5-year age showed a decrease in the prevalence of phenotype A and an increase in the prevalence of not having PCOS. The serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate as well as the free androgen index decreased significantly. Clinical characteristics showed an increase in terms of body mass index and waist circumference, whereas plasma glucose levels, insulin levels, and insulin resistance did not change significantly. The prevalence of PCOS phenotype groups changes over time. There is an important age effect that indicates a more regular menstrual cycle, decrease in the serum androgen levels, and improvement in polycystic ovarian morphology when aging occurs in women with PCOS.

Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression.

Fine particulate matter and polycystic ovarian morphology

BackgroundPolycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM.MethodsWe conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004–2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI).ResultsCumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 μg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57).ConclusionsIn this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.

Predicting factors of clomiphene citrate responsiveness in infertile women with normogonadotropic anovulation (WHO group II anovulation)

Background: Clomiphene responsiveness has been varied in WHO group II anovulatory patients. Our study evaluates factors associated with clomiphene citrate responsiveness in this population. Various parameters were studied, including anthropometric, hormonal and transvaginal ultrasonographic measurements. Methods: A retrospective case-control study was done over a period of three years. A total of 260 women with WHO group II anovulatory related infertility treated with clomiphene citrate 100 mg/d for five consecutive days were enrolled. 173 women were categorized in clomiphene citrate resonsive group (CCR), defined as patients with at least one dominant follicle ≥17 mm or at least 2 dominant follicles ≥15 mm. 87 women were categorized in the non-ovulatory group (NCCR), defined as patients who not meet the responsive group criteria. Various clinical, metabolic, hormonal and ultrasound features were compared between two groups. Logistic regression analysis was used to analyze the significant factors. Results: Among all participants, the mean age was 32.6 ± 4.0 years. The mean body mass index in CCR and NCCR group was 23.9 ± 10.7 kg/m2 and 24.0 ± 4.0 kg/m2, respectively. The mean waist-hip ratio (WHR) of the NCCR group was higher than that of the CCR group, i.e., 0.83 ± 0.06 vs 0.81 ± 0.05 (p = 0.004). The waist-hip ratio was the most sensitive anthropometric predictor of non-responsiveness to clomiphene: cut-off value of 0.775 (90.8% sensitivity and 20.2% specificity) and cut-off value of 0.805 (73.6% sensitivity and 42.2% specificity). Age, clinical hyperandrogenism, polycystic ovarian morphology, low antral follicle count (≤5 follicles), baseline follicle-stimulating hormones and estradiol levels were not significantly different. Conclusions: The waist-hip ratio is a clinically useful parameter in predicting clomiphene responsiveness in normogonadotropic anovulatory women (WHO group II anovulation).

Different pregnancy outcomes according to the polycystic ovary syndrome diagnostic criteria: a systematic review and meta-analysis of 79 studies

To correlate the distinct diagnostic criteria of polycystic ovary syndrome (PCOS) with the development of maternal and neonatal complications. Systematic review and meta-analysis. Not applicable. Pregnant women with PCOS. Maternal and neonatal complications were compared among women with PCOS diagnosed with different criteria. The primary outcomes of gestational diabetes mellitus and preeclampsia (PE) were assessed for every diagnostic criterion. Seventy-nine studies were included. Regarding gestational diabetes, the overall pooled prevalence was 14% (95% confidence interval [CI], 11%-18%; I2, 97%), reaching the highest level when polycystic ovarian morphology on ultrasound and 1 of the remaining 2 Rotterdam criteria (1/2 Rotterdam criteria) were used (18%; 95% CI, 13%-24%; I2, 20%) and the lowest when polycystic morphology on ultrasound and hyperandrogenism were used (3%; 95% CI, 0%-19%; I2, not applicable). Regarding PE, the overall pooled prevalence was 5% (95% CI, 4%-7%; I2, 82%). The highest PE prevalence was reported when the National Institutes of Health criteria were used (14%; 95% CI, 5%-33%; I2, 90%) and the lowest when menstrual irregularities and 1 of the 2 Rotterdam criteria were used (2%; 95% CI, 1%-3%; I2, not applicable). The prevalence of gestational diabetes mellitus in pregnant women with PCOS does not differ according to the criteria used; however, women diagnosed with PCOS per the National Institutes of Health criteria are at higher risk of PE.