Polycystic Ovary Syndrome Cases Research Articles

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. Prospective observational study using data from the Japan Environment and Children's Study (JECS). Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Association between Dietary Inflammatory Index (DII) and the Risk of Polycystic Ovary Syndrome: A Case-Control Study

Background: Polycystic ovary syndrome (PCOS) is an inflammation-related condition and a common metabolic disorder in women at fertility ages. The Dietary Inflammatory Index (DII) is a validated nutritional tool for estimating the inflammatory potential of the diet. It is assumed that a high DII score (indicating a predominantly inflammatory diet) has an association with higher odds of PCOS. The current study aimed to investigate the association between DII and PCOS risk in women.  Methods: This case-control study was conducted in 2019-2020 on 120 newly-diagnosed PCOS cases and 120 healthy controls aged 18-45 years in Khorramabad, Iran. DII was estimated based on a validated 168-item Food Frequency Questionnaire (FFQ). Results: The mean±SD of DII in PCOS patients was 0.40±2.09, while it was 0.45±1.92 in the control group (P&lt;0.001). There was a positive association between increasing DII score and the risk of PCOS (odds ratio= 2.41; 95%CI: 1.15-5.02, P for trend =0.006) in the crude model as the fourth quartile was compared with the lowest one. This association was still significant in several models after adjusting for age and energy intake (P for trend &lt;0.001), in the model adjusted for the physical activity level, education status, and family history of PCOS (P for trend=0.003), and also after additional adjustment for BMI (P for trend= 0.003). Conclusions: The present study revealed that consuming more pro-inflammatory diets with higher DII scores is related to an increased risk of PCOS.

Spirulina versus metformin for controlling some insulin signaling pathway genes in induced polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50–70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and Insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using RT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Comparative analysis of clinical symptoms and biochemical alterations in women with polycystic ovary syndrome: assessing the impact of type 1 diabetes versus non-diabetic controls

BackgroundWomen with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA.ResultsThe mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P < 0.001 and P = 0.010, respectively). PCOS was present in 11 (22.0%) of diabetic women compared to 3 (6.0%) in non-diabetics (P = 0.044). Diabetic women with PCOS received higher doses of insulin than non-PCOS women (72.7 ± 23.9 vs. 55.0 ± 19.8 UI.cc/ml/day, P = 0.023). PCOS women showed more frequent oligomenorrhea (100% vs. 15.4%, P < 0.001) and higher levels of total testosterone and insulin (0.64 ± 0.09 and 23.1 ± 13.0 vs. 0.53 ± 0.11 and 14.1 ± 11.8, P = 0.023 and P = 0.041, respectively). PCOS cases were significantly more frequent in diabetic women receiving intensive insulin therapy than their counterparts with non-intensive insulin therapy (40.9% vs. 7.1%, P = 0.012).ConclusionIntensive insulin treatment in type 1 diabetes potentiates the development of PCOS and its related clinical and biochemical features particularly oligomenorrhea, hyperinsulinemia, and hyperandrogenemia.

Pattern of body fat distribution in patients of PCOS using DEXA-based indices

BackgroundConsidering the close link between polycystic ovary syndrome (PCOS) and metabolic syndrome considerable research has been devoted to studying the pattern of fat distribution in PCOS.ObjectivesThe study aims to assess the usefulness of dual-energy X-ray absorptiometry (DEXA) based regional fat distribution indices as a predictor of the development of PCOS.MethodsThis case–control study recruited diagnosed cases of PCOS using Rotterdam Criteria (cases n = 86) and healthy age-matched controls (n = 90). DEXA was performed in both groups for assessment of total and regional body fat distribution after undergoing ultrasonography (USG) and baseline/biochemical evaluation.ResultsThe study revealed a significant difference between cases and controls in trunk fat percentage (40.2% ± 9.1% vs 26.5% ± 9.1%; p < 0.001), android fat percentage (42.4% ± 41%vs 27.8% ± 1.51%; p < 0.001), total fat percentage (43.8% ± 8% vs28.5% ± 1.6%; p < 0.001), fat mass/ht2 (fat mass index) (8.82 ± 3% vs 4.8 ± 1.7%; p < 0.001), android/gynoid ratio (1.05 ± 0.1 vs 0.7 ± 0.2; p < 0.001), and trunk/limb fat mass ratio (1.06 ± 0.3 vs 0.69 ± 0.3; p 0.001). Multivariate analysis revealed a significant relation of trunk fat mass with android % fat, gynoid fat mass, and android-gynoid ratio.ConclusionsThe study demonstrates that there is a central pattern of fat distribution in patients with PCOS while the overall fat might not be increased which is well analyzed by DEXA. Hence, we suggest its use in the initial diagnostic workup and follow-up of PCOS patients for their body fat distribution and content.

The effect of adipose tissue StAR gene expression on ICSI among Polycystic Ovarian Syndrome cases and matched controls: a case-control study

The effect of adipose tissue StAR gene expression on ICSI among Polycystic Ovarian Syndrome cases and matched controls: a case-control study

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

MALAT1 expression in granulosa cells in PCOS patients with different phenotypes

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Anti-Mullarian Hormone As A Diagnostic Marker of Polycystic Ovary Syndrome

Objective: To determine the utility of Anti-mullerian hormone (AMH) as a diagnostic marker of Polycystic ovarian syndrome (PCOS). Study Design: Comparative cross-sectional study Place and Duration of the Study: Department of Chemical Pathology and Endocrinology, Army Medical College Rawalpindi, Pakistan in collaboration with the Department of Gynaecology and Obstetrics, Pak-Emirates Military Hospital, Rawalpindi Pakistan from Jan 2019 to Jan 2020. Methodology: The study recruited 30 cases of PCOS and 30 age-matched Controls using Rotterdam criteria. Anti-mullerian hormone (AMH) and testosterone were measured for both the study groups. Results: Receiver operator curve (ROC) analysis confirmed the utility of anti-mullerian hormone in diagnosing patients with PCOS. The AUC was 0.754 with 95% CI (0.629-0.880). The optimal cut-off point was 3.22ng/mL (Sensitivity 80%, Specificity 66.7%). Conclusion: The AMH is appraised as an independent screening marker for PCOS patients. Using this single parameter can decrease the patient's inconvenience and financial burden on the health care system and the patient.

Deconvolution at the single-cell level reveals ovarian cell-type-specific transcriptomic changes in PCOS

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood. Transcriptomic characterization of cells isolated from PCOS cases have been assessed using bulk RNA-seq but cells isolated contain a mixture of many ovarian cell types.MethodsHere we utilized the reference scRNA-seq data from human adult ovaries to deconvolute and estimate cell proportions and dysfunction of ovarian cells in PCOS, by integrating various granulosa cells(GCs) transcriptomic data.ResultsWe successfully defined 22 distinct cell clusters of human ovarian cells. Then after transcriptome integration, we obtained a gene expression matrix with 13,904 genes within 30 samples (15 control vs. 15 PCOS). Subsequent deconvolution analysis revealed decreased proportion of small antral GCs and increased proportion of KRT8high mural GCs, HTRA1high cumulus cells in PCOS, especially increased differentiation from small antral GCs to KRT8high mural GCs. For theca cells, the abundance of internal theca cells (TCs) and external TCs was both increased. Less TCF21high stroma cells (SCs) and more STARhigh SCs were observed. The proportions of NK cells and monocytes were decreased, and T cells occupied more in PCOS and communicated stronger with inTCs and exTCs. In the end, we predicted the candidate drugs which could be used to correct the proportion of ovarian cells in patients with PCOS.ConclusionsTaken together, this study provides insights into the molecular alterations and cellular compositions in PCOS ovarian tissue. The findings might contribute to our understanding of PCOS pathophysiology and offer resource for PCOS basic research.

Dynamic changes in AI-based analysis of endometrial cellular composition: Analysis of PCOS and RIF endometrium

BackgroundThe human endometrium undergoes a monthly cycle of tissue growth and degeneration. During the mid-secretory phase, the endometrium establishes an optimal niche for embryo implantation by regulating cellular composition (e.g., epithelial and stromal cells) and differentiation. Impaired endometrial development observed in conditions such as polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) contributes to infertility. Surprisingly, despite the importance of the endometrial lining properly developing prior to pregnancy, precise measures of endometrial cellular composition in these two infertility-associated conditions are entirely lacking. Additionally, current methods for measuring the epithelial and stromal area have limitations, including intra- and inter-observer variability and efficiency. MethodsWe utilized a deep-learning artificial intelligence (AI) model, created on a cloud-based platform and developed in our previous study. The AI model underwent training to segment both areas populated by epithelial and stromal endometrial cells. During the training step, a total of 28.36 mm2 areas were annotated, comprising 2.56 mm2 of epithelium and 24.87 mm2 of stroma. Two experienced pathologists validated the performance of the AI model. 73 endometrial samples from healthy control women were included in the sample set to establish cycle phase-dependent dynamics of the endometrial epithelial-to-stroma ratio from the proliferative (PE) to secretory (SE) phases. In addition, 91 samples from PCOS cases, accounting for the presence or absence of ovulation and representing all menstrual cycle phases, and 29 samples from RIF patients on day 5 after progesterone administration in the hormone replacement treatment cycle were also included and analyzed in terms of cellular composition. ResultsOur AI model exhibited reliable and reproducible performance in delineating epithelial and stromal compartments, achieving an accuracy of 92.40% and 99.23%, respectively. Moreover, the performance of the AI model was comparable to the pathologists’ assessment, with F1 scores exceeding 82% for the epithelium and >96% for the stroma. Next, we compared the endometrial epithelial-to-stromal ratio during the menstrual cycle in women with PCOS and in relation to endometrial receptivity status in RIF patients. The ovulatory PCOS endometrium exhibited epithelial cell proportions similar to those of control and healthy women’s samples in every cycle phase, from the PE to the late SE, correlating with progesterone levels (control SE, r2 = 0.64, FDR < 0.001; PCOS SE, r2 = 0.52, FDR < 0.001). The mid-SE endometrium showed the highest epithelial percentage compared to both the early and late SE endometrium in both healthy women and PCOS patients. Anovulatory PCOS cases showed epithelial cellular fractions comparable to those of PCOS cases in the PE (Anovulatory, 14.54%; PCOS PE, 15.56%, p = 1.00). We did not observe significant differences in the epithelial-to-stroma ratio in the hormone-induced endometrium in RIF patients with different receptivity statuses. ConclusionThe AI model rapidly and accurately identifies endometrial histology features by calculating areas occupied by epithelial and stromal cells. The AI model demonstrates changes in epithelial cellular proportions according to the menstrual cycle phase and reveals no changes in epithelial cellular proportions based on PCOS and RIF conditions. In conclusion, the AI model can potentially improve endometrial histology assessment by accelerating the analysis of the cellular composition of the tissue and by ensuring maximal objectivity for research and clinical purposes.

Polycystic Ovarian Syndrome Treated by Homoeopathy: An Evidence-Based Case Report

Abstract Background Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive women. Cardinal manifestations of PCOS include hyperandrogenism, oligo/anovulation and/or polycystic ovarian morphology. Affected women often display notable metabolic co-morbidities. Plenty of evidence on PCOS favouring homoeopathy is available in the literature. In this case, also individualised medicine portrayed a favourable response within a short span of time. Case Summary A case of PCOS with the complaint of irregular, delayed menses, acne on the face and dark pigmentation on the neck for the last 3 years is presented here. The outcome was assessed by using two validated measurement scales. After 4 months of follow-up, the case was markedly improved on the Outcome Related to Impact on Daily Living (ORIDL) scale (+4) as per the patient's perspective. Clinical improvement was correlated with objective evidence from the ultrasonography report. Modified Naranjo criteria for Homeopathy (MONARCH) score recorded at the final visit (+8 on the ‘−6 to 13’ scale) is suggestive of a high likelihood of improvement by homoeopathic intervention. Conclusion The case report presented here has produced significant evidence of the effect of individualised homoeopathic medicine in the treatment of PCOS within a short time.

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.

Prevalence and Dietary Management of Polycystic Ovary Syndrome among Libyan Women Attending in Infertility Center Tripoli, Libya

Polycystic ovarian syndrome (PCOS) is the most common heterogenic endocrine illness in women of reproductive age, caused mostly by an excess of androgen and ovarian dysfunction. The present study was carried out to estimate the prevalence of PCOS among Libyan women who attended infertility center Tripoli, Libya, from 2020-2022, evaluate hormonal profile, Body Mass Index, weight and west circumferential before and after treatment and diet management. A longitudinal cross-sectional study conducted in the Tripoli Fertility Center in Tripoli, Libya, the study population targeting output Libyan female patients who presented to the gynecology and obstetrics (OPD) department and therapeutic nutrition department. Data Retrospectively collected from 2020 until 2022 and diagnosed using Rotterdam’s criteria. A total of 603 patients visited the gynecology and obstetrics department and the therapeutic nutrition department between January 2020 and December 2022. Out of which 174 women in the PCOS group and 429 in the non-PCOS group. The prevalence of PCOS was 29.56% in 2020, 37.5% in 2021, and 20.27% in 2022. The mean age of PCOS was 34.90 ± 5.5 SD, and all of the PCOS group were married. Worth to mention that all of PCOS cases was insulin resistance type. In terms of weight in the PCOS group, 19.54% were obese BMI &gt;29, 68.96% were morbid obese with BMI &gt;35, and approximately 68.39% of waist circumference measurements were more than 88cm. Hirsutism and oligomenorrhea were the major clinical features, morbid obese seems to be more prevalent in Libyan PCOS patients, low carbohydrate diet and physical activities may play an important role in PCOS management.

Hypermethylation and down-regulation of vitamin D receptor (VDR) as contributing factors for polycystic ovary syndrome (PCOS): a case-control study from Kashmir, North India.

Polycystic ovarian syndrome (PCOS) is a prevailing endocrinopathy affecting a significant population of women of reproductive age across the globe. A myriad set of complex intertwined factors ranging from etiological, genetic, and epigenetic reasons cause this disorder. Out of the different factors, vitamin D shows an imperative aspect in health and fertility of women with polycystic ovary syndrome (PCOS). The importance of vitamin D is facilitated by vitamin D receptor (VDR), a ligand-dependent transcription factor in the steroid/ thyroid hormone receptor superfamily that controls the pleiotropic biological properties of vitamin D. The purpose of this study was to evaluate the role of promoter methylation of the VDR gene, a transcription factor with numerous biological utilities, with its relative expression and clinico-pathological findings and outcomes. A total of 200 blood samples were collected, 100 from PCOS case subjects, and 100 from the normal healthy controls respectively, which were assessed by qRT-PCR for determining the expression summary. MS-PCR technique was used for analyzing the promoter methylation status of the VDR gene. Blood samples were withdrawn, respectively, for each case and the control study separately experimented for different stages for the given study, of which estimation of vitamin D was also a part. In this test-versus-control study, first, the promoter methylation status of VDR gene was identified which was found more prominent i.e., hyper-methylation of the VDR gene was identified in 84 cases (84%), and in the normal healthy controls, it was found (62%). The promoter methylation status of the VDR gene has remarkably shown the results with a significant difference (p value < 0.0001*). Second, the expression analysis of VDR gene was found to be strongly downregulated in majority (64%) of PCOS case samples analyzed by means fold change of 0.8743 (± 0.06466) (p value 0.0054**). This result is, therefore, indicative of VDR gene role in PCOS pathogenesis as the said gene is downregulated. Moreover, compared to the vitamin D parameter, hyper-methylation and expression analysis of the VDR promoter gene were found to correspond to some associations with PCOS. Certain case-and-control study analyses showed that patients with normal vitamin D levels showed less indicative effects of PCOS and vice versa. Our study, being exclusive from Kashmir, one of the foremost specified that VDR confirms anomalous methylation configuration in PCOS with subsequent downregulation in the gene expression i.e., there is an inverse correlation among VDR gene expression (downregulated) and methylation status (hyper-methylated) from the conclusion of our PCOS case-versus-control study.

Serum Irisin in Polycystic Ovary Syndrome and its Alteration with Metformin Intervention.

Studies investigating the alterations of serum irisin and its change with metformin therapy in patients with polycystic ovary syndrome (PCOS) are conflicting. Our aim is to study serum irisin in PCOS patients and the change of irisin levels with metformin therapy over 6 months. This is a randomized control study conducted in 187 PCOS cases and 94 age-matched controls aged 18-40 years. Detailed evaluation of anthropometric, biochemical, and hormonal parameters was performed. A subset of 99 overweight/obese patients with body mass index (BMI) ≥23 kg/m2 were stratified into a metformin group (n = 67) receiving 500 mg thrice daily and a lifestyle intervention-only group (n = 32). The effect of metformin therapy on serum irisin levels was measured at the end of 6 months. Statistical analyses were performed with SPSS version 26.0 Software. Serum irisin was higher in PCOS patients than in controls [12.47 (8.1-17.7) vs 8.3 (7.0-9.6) ng/ml, P < 0.001], independent of BMI. Serum irisin showed a significant positive association with BMI (β =0.168), waist-to-hip ratio (β =0.166), leutinizing hormone (β =0.225), TG (β =0.305), FAI (β =0.151), and testosterone (β =0.135). Serum irisin showed a significant positive association with homeostatic model assessment of insulin resistance (HOMA-IR) (β =0.14, P = 0.04) in overweight/obese PCOS patients only (n = 146) but not in the whole PCOS cohort (n = 187). Metformin reduced the median serum irisin levels significantly (13.9 to 12.1 ng/ml, P < 0.001), and the delta change in irisin levels was associated with HOMA-IR in the metformin group. Serum irisin is increased in PCOS patients independent of BMI. Metformin therapy reduced serum irisin levels in overweight/obese PCOS patients by improving insulin resistance.

Significance of LHCGR polymorphisms in polycystic ovary syndrome: an association study

This study was conducted to analyze the association of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) gene rs4953616 and rs7371084 polymorphisms with the risk of polycystic ovary syndrome (PCOS) in Punjab, India. A total of 823 women (443 PCOS cases and 380 healthy controls) were enrolled in the present study. The polymerase chain reaction-restriction fragment length polymorphism technique (PCR–RFLP) was used for genotyping. Anthropometric parameters, lipid and hormonal profiles, were compared between the two groups. Demographic features were compared using Mann Whitney U test while the Chi-square test and odds ratios (ORs) were used to assess the genetic association and risk towards PCOS, respectively. A one-way analysis of variance (ANOVA) test was employed to analyze the correlation of genotypes with baseline parameters in PCOS cases. A statistically significant difference was revealed in the genotypic and allelic frequencies of rs4953616 polymorphism between PCOS cases and controls (p = 0.01 and p = 0.004, respectively). The mutant genotype (TT), mutant allele (T), and recessive model of rs4953616 polymorphism conferred 1.77, 1.3, and 1.5 times risk towards PCOS, respectively. No significant distribution for genotypes and alleles was found for rs7371084 in both groups (p = 0.25 and p = 0.26, respectively). In addition to dyslipidemia, PCOS women also had significantly higher body mass index (BMI) and waist-to-hip ratio (WHR), testosterone (T), and luteinizing hormone (LH). Upon haplotype analysis, the TT haplotype was found to be significantly associated with the increased risk of PCOS. Our results demonstrated a significant role of LHCGR rs4953616 polymorphism in the development of PCOS.

Investigation of androgen receptor CAG repeats length in polycystic ovary syndrome diagnosed using the new international evidence-based guideline

BackgroundTo study whether CAG repeat polymorphism of androgen receptor (AR) contributes to the risk of polycystic ovarian morphology (PCOM) with antral follicle count (AFC) ≥ 20 in the context of new international guideline of polycystic ovary syndrome (PCOS).MethodsBlood of 109 PCOS cases and 61 controls were collected for the measurement of AR CAG repeats length by sequencing. The mean number and frequency distribution of CAG repeats length were observed. Detailed analysis was conducted by dividing PCOS cases into low AFC group (L-AFC, AFC < 20) and high AFC group (H-AFC, AFC ≥ 20) according to the new international evidence-based guideline.ResultsThe portion of individuals with lower CAG repeats length in H-AFC group was significantly larger than those with higher CAG repeats length. Logistic model revealed individuals with lower CAG length tended to develop H-AFC.ConclusionLower CAG repeats length in the AR gene of PCOS cases increases risk of PCOM.