Exploration of the Relationship between Polycystic Ovary Syndrome and Recurrent Pregnancy Loss Based on Bioinformatics.

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Polycystic Ovary Syndrome (PCOS) are both common diseases involving women of childbearing age, and their pathogenesis is still not sufficiently known. OBJECTIVE: This study aimed to explore the relationship between RPL and PCOS in bioinformatics. METHODS: Two expression chips, GSE86241 (obtained from 8 PCOS patients and 9 healthy controls) and GSE73025 (obtained from 5 RPL patients and 5 healthy controls), were downloaded from the Gene Expression Omnibus (GEO) database. We used the GEO database to analyze the gene expression profiles of PCOS and RPL to identify the intersection of abnormal miRNA expression, predicted the target genes of the intersecting miRNAs from miRDB, miRTarBase, and TargetScan databases, and then incorporated the miRNA-mRNA modulation network. By using the string database, the PPI network was built, which could screen the Hub genes and enrich them for analysis. Ultimately, the critical miRNA-mRNA regulatory network was set on the basis of the relationship between hub genes and miRNA. RESULTS: A total of 39 significantly altered miRNAs of PCOS and 137 significantly altered miRNAs of RPL were obtained, three miRNAs (miR-767-5p, miR-3196, and miR-187-3p), five signaling pathways (PI3K-Akt, p53, Toll-like receptor, C-type lectin receptor, and TNF signaling pathways), and six Hub genes (CASP8, PIK3R1, ADAMTS2, ADAMTS3, COL3A1, and MDM2) were found to be related to the development and progression of two diseases. More importantly, all Hub genes were regulated by miR-767-5p. CONCLUSION: This research clarifies the possible relationship between miRNA and mRNA with PCOS and RPL for the first time. It provides a basis for illustrating the pathogenic mechanism and a target of therapies for these two diseases.

The prevalence of abnormal semen parameters in male partners of women with anovulatory polycystic ovarian syndrome: a retrospective case-control study.

PURPOSE: Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility, often requiring ovarian stimulation in affected women attempting to conceive. Male partner semen quality and shared lifestyle factors can significantly impact reproductive outcomes. However, current international guidelines lack evidence-based recommendations on the necessity and timing of semen analysis for the fertility management of anovulatory PCOS women. METHODS: In a retrospective case-control study, semen analysis results of male partners of 187 anovulatory PCOS women scheduled for ovarian stimulation were analyzed and compared to a control group of 76 male partners of women with bilateral tubal occlusion. RESULTS: The prevalence of semen analysis results with at least one parameter classified as "borderline" and "pathological" among male partners of women with PCOS eligible to undergo ovarian stimulation was 51.3% and 22.5%, compared to 44.7% and 13.2% in the control group, respectively (p = 0.027). In the PCOS group, male body mass index (odds ratio, OR 1.478, p < 0.001), and smoking status (OR 6.228, p < 0.001) were significant predictors of pathological sperm test results, while no association was observed with any female characteristics (p > 0.05). CONCLUSION: The high frequency of pathological sperm analysis results provides lacking epidemiological data on semen quality in this population, emphasizing the critical need for early male fertility evaluation prior to ovarian stimulation in PCOS women. Moreover, our findings indicate that the risk prediction for abnormal semen quality cannot be based on the female's data.

Unraveling the pathogenic interplay between SARS-CoV-2 and polycystic ovary syndrome using bioinformatics and experimental validation.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among polycystic ovary syndrome (PCOS) is significantly higher than in the general population. However, the mechanisms underlying this remain obscure. This study aimed to explore the mechanisms by identifying the genetic signature of SARS-CoV-2 infection in PCOS. In the present study, a total of 27 common differentially expressed genes (DEGs) were selected for subsequent analyses. Functional analyses showed that immunity and hormone-related pathways collectively participated in the development and progression of PCOS and SARS-CoV-2 infection. Under these, 7 significant hub genes were identified, including S100A9, MMP9, TLR2, THBD, ITGB2, ICAM1, and CD86 by using the algorithm in Cytoscape. Furthermore, hub gene expression was confirmed in the validation set, PCOS clinical samples, and mouse model. Immune microenvironment analysis with the CIBERSORTx database demonstrated that the hub genes were significantly correlated with T cells, dendritic cells, mast cells, B cells, NK cells, and eosinophils and positively correlated with immune scores. Among the hub genes, S100A9, MMP9, THBD, ITGB2, CD86, and ICAM1 demonstrated potential as possible diagnostic markers for COVID-19 and PCOS. In addition, we established the interaction networks of ovary-specific genes, transcription factors, miRNAs, drugs, and chemical compounds with hub genes with NetworkAnalyst. This work uncovered the common pathogenesis and genetic signature of PCOS and SARS-CoV-2 infection, which might provide a theoretical basis and innovative ideas for further mechanistic research and drug discovery of the comorbidity of the two diseases.

Prevalence and accurate diagnosis of polycystic ovary syndrome (PCOS) in adolescents across world regions: a systematic review and meta-analysis.

OBJECTIVES: To examine the global prevalence of PCOS among adolescents across world regions, comparing the 2003 Rotterdam consensus criteria with the current International Evidence-based PCOS Guideline criteria which omits polycystic ovarian morphology (PCOM). DESIGN: Systematic review and meta-analysis, Prospero CRD42022372029. METHODS: OVID MEDLINE, All EBM, PsycInfo, EMBASE and CINAHL were searched from 1990 to November 2023 for studies assessing the prevalence of PCOS in unselected adolescent populations. RESULTS: Overall, 15708 articles were identified. After removal of duplicates, 11868 titles and abstracts and 445 full texts were assessed. Of these, 24 articles reporting on 23 studies from five world regions were included. In meta-analysis of 20 studies (n=14010 adolescents), global prevalence was 9.8% (95% CI 7.2, 12.3) according to original Rotterdam criteria, and 6.3% (95% CI 3.9, 8.8) according to International Evidence-based Guideline criteria. Global PCOS prevalence based on self-report was 9.8% (95% CI 5.5, 14.1).Grouped by WHO region, prevalence ranged from 2.9% (95% CI 2.0, 3.9) in the Western Pacific region to 11.4% (95% CI 7.1, 15.7) in the South-East Asia region according to guideline criteria. CONCLUSION: This paramount global meta-analysis on adolescent PCOS diagnosis directly informed the 2023 International PCOS Guideline. Guideline criteria generated a global PCOS prevalence of 6.3%, compared with 9.8% on Rotterdam criteria (including PCOM). Excluding PCOM, which overlaps with normal pubertal transition, is expected to deter over-diagnosis. To avoid under-diagnosis, the Guideline recommends identifying those with either irregular cycles or hyperandrogenism as being "at risk"; this group should undergo longitudinal serial evaluations until adulthood.

Evaluation of Etiological Factors Associated With Abnormal Uterine Bleeding Among Teenage Girls in a Tertiary Care Center: A Cross-Sectional Study.

BACKGROUND: Abnormal uterine bleeding (AUB) refers to irregularities in the frequency, regularity, duration, and volume of menstrual cycles, impacting about one-third of women at some point in their lives, during menarche and perimenopausal periods. This study aims to evaluate the various causes of menstrual disorders in teenage girls. MATERIALS AND METHODS: This cross-sectional study was conducted in the Department of Obstetrics and Gynecology at AVMCH, Pondicherry, with ethical clearance. It included 150 girls aged 13-18 years who presented with menstrual disorders. Data were collected through structured interviews and clinical evaluations, focusing on menstrual history, socioeconomic status, associated symptoms, and investigations. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States). RESULTS: Among the etiological factors, 61.3% of patients had anovulatory dysfunction, 16.6% had early onset of PCOS, 6% of patients had hypothyroidism, 16% had ovulatory dysfunction, and 0.6% had coagulation disorder. Overall, ovulatory dysfunction (AUB-O) was predominant in teenage girls. CONCLUSION: This study helps in the early identification of the etiology of adolescent AUB and the appropriate management of menstrual disorders to improve well-being and enhance reproductive function in the future.

The impact of dietary interventions on polycystic ovary syndrome patients with a BMI ≥25 kg/m2: A systematic review and meta-analysis of randomized controlled trials.

Background: Dietary interventions, recommended as a primary approach globally, benefit women with polycystic ovary syndrome (PCOS) by inducing weight loss and improving clinical symptoms, metabolism, and pregnancy results. However, the impact of diet on PCOS in individuals with BMI ≥ 25 kg/m2 is unclear. The aim of this review was to offer dietary guidance for these patients. Methods: Six databases, CNKI, Wanfang, VIP, PubMed, Cochrane Library, and Web of Science, were searched systematically from inception to December 2023 for clinical randomized controlled trials (RCT) on dietary interventions for PCOS. Two researchers independently screened and extracted data following pre-defined inclusion criteria, with bias assessment using the Cochrane Handbook and Review Manager (version 5.4) software. Results: Nine RCTs with 559 participants were included. Among women with PCOS and obesity, compared to the control group, individuals who underwent dietary interventions experienced improvements in weight-related Indicators, glycolipid metabolism, hormone-related indicators, and fertility-related outcomes. Subgroup analysis indicated that calorie-restricted diets (CRDs) and low-energy-low-carb combined diets had advantages over other dietary interventions. Moreover, the overweight period was the optimal intervention period. Conclusions: Dietary interventions can improve the clinical manifestations of PCOS and pregnancy rates in patients with a BMI ≥ 25 kg/m2. Particularly, CRDs, low-calorie-low-carb combined diets, and low-calorie-extract combined diets are recommended.

Glucagon-like peptide-1 receptor agonists: Exploring the mechanisms from glycemic control to treatment of multisystemic diseases.

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani, which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for metabolic dysfunction-associated fatty liver disease. We provide supplementary insights to their research, highlighting the broader systemic implications of GLP-1RAs, synthesizing the current understanding of their mechanisms and the trajectory of research in this field. GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond. Beyond glycemic control, GLP-1RAs demonstrate cardiovascular and renal protective effects, offering potential in managing diabetic kidney disease al-ongside renin-angiotensin-aldosterone system inhibitors. Their role in bone metabolism hints at benefits for diabetic osteoporosis, while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling. Additionally, they improve hormonal and metabolic profiles in polycystic ovary syndrome. This editorial highlights the multifaceted mechanisms of GLP-1RAs, emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.

Efficacy of WeChat-Based Digital Intervention Versus Metformin in Women With Polycystic Ovary Syndrome: Randomized Controlled Trial.

BACKGROUND: The first-line treatment for polycystic ovary syndrome (PCOS) is lifestyle modification. However, it is currently unknown whether digital medicine can assist patients with PCOS in maintaining a healthy lifestyle while alleviating PCOS symptoms. OBJECTIVE: This study aims to evaluate the efficacy of WeChat-based digital intervention versus metformin treatment in women with PCOS and insulin resistance. METHODS: A total of 80 women with PCOS and insulin resistance were recruited from an endocrinology clinic and randomly assigned to receive either a WeChat-based digital intervention (n=40, 50%) or metformin (n=40, 50%) for 12 weeks. The WeChat-based digital intervention consisted of 3 modules; a coach assisted the patients in using the intervention. The primary outcome was the change in a homeostatic model assessment for insulin resistance. At baseline and after the 12-week intervention, anthropometric parameters, menstruation frequency, sex hormone levels, metabolic factors, and body fat distribution were measured in the clinic. Furthermore, self-assessed web-based questionnaires on diet, exercise, sleep, anxiety, and depression were obtained. RESULTS: A total of 72 participants completed the follow-up (for a 90% follow-up rate), including 35 of 40 (88%) participants from the digital intervention group and 37 of 40 (93%) participants from the metformin group. The homeostatic model assessment for insulin resistance in the digital intervention group was significantly improved after 12 weeks of treatment with a mean change of -0.93 (95% CI -1.64 to -0.23), but no statistical difference was observed between the groups (least squares mean difference -0.20; 95% CI -0.98 to 0.58; P=.62). Both digital intervention and metformin treatment significantly improved menstruation frequency (digital intervention: P<.001; metformin: P<.001) and reduced body weight (digital intervention: P<.001; metformin: P<.001) and total fat mass (digital intervention: P<.001; metformin: P<.001). Furthermore, the digital intervention had a significant advantage over metformin in improving waist circumference (least squares mean difference -1.84; 95% CI -3.44 to -0.24; P=.03), waist-to-hip ratio (least squares mean difference -0.02; 95% CI -0.03 to 0.00; P=.03), total fat mass (least squares mean difference -1.59; 95% CI -2.88 to -0.30; P=.02), and dehydroepiandrosterone sulfate (least squares mean difference -69.73; 95% CI -129.70 to -9.75; P=.02). In terms of safety, the main adverse events were sensations of hunger in the digital intervention group (2/40, 5%) and gastrointestinal adverse events in the metformin group (12/40, 30%). CONCLUSIONS: Our data suggest that digital intervention is an effective treatment option for patients with PCOS, with an efficacy comparable to that of metformin, and that it can also alleviate the negative effects of medications and make it easier and more efficient to adhere to lifestyle treatments. WeChat-based digital interventions have the potential to provide a new path for the improvement and health of women with PCOS in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386706; https://clinicaltrials.gov/study/NCT05386706.

Optimized polycystic ovarian disease prognosis and classification using AI based computational approaches on multi-modality data.

Polycystic Ovarian Disease or Polycystic Ovary Syndrome (PCOS) is becoming increasingly communal among women, owing to poor lifestyle choices. According to the research conducted by National Institutes of Health, it has been observe that PCOS, an endocrine condition common in women of childbearing age, has become a significant contributing factor to infertility. Ovarian abnormalities brought on by PCOS carry a high risk of miscarriage, infertility, cardiac problems, diabetes, uterine cancer, etc. Ovarian cysts, obesity, menstrual irregularities, elevated amounts of male hormones, acne vulgaris, hair loss, and hirsutism are some of the symptoms of PCOS. It is not easy to determine PCOS because of its different combinations of symptoms in different women and various criteria needed for diagnosis. Taking biochemical tests and ovary scanning is a time-consuming process and the financial expenses have become a hardship to the patients. Thus, early prognosis of PCOS is crucial to avoid infertility. The goal of the proposed work is to analyse PCOS symptoms based on clinical data for early diagnosis and to classify into PCOS affected or not. To achieve this objective, clinical features dataset and ultrasound imaging dataset from Kaggle is utilized. Initially 541 instances of 45 clinical features such as testosterone, hirsutism, family history, BMI, fast food, menstrual disorder, risk etc. are considered and correlation-based feature extraction method is applied to this dataset which results in 17 features. The extracted features are applied to various machine learning algorithms such as Logistic Regression, Naïve Bayes and Support Vector Machine. The performance of each method is evaluated based on accuracy, precision, recall, F1-score and the result shows that among three models, Support Vector Machine model achieved high accuracy of 94.44%. In addition to this, 3856 ultrasound images are analysed by CNN based deep learning algorithm and VGG16 transfer learning algorithm. The performance of these models is evaluated using training accuracy, loss and validation accuracy, loss and the result depicts that VGG16 outperforms than CNN model with validation accuracy of 98.29%.

Polycystic Ovary Syndrome: A Comprehensive Exploration of Diagnosis Experience in Saudi Women.

Background/Objectives: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age, characterized by symptoms such as menstrual irregularities, hyperandrogenism, and polycystic ovaries. This study aimed to explore the diagnostic experiences of women with PCOS in Saudi Arabia, evaluating the timeline to diagnosis, the adequacy of information provided, and overall patient satisfaction with the healthcare process. Methods: A cross-sectional online survey was conducted with 1182 women diagnosed with PCOS across Saudi Arabia. The survey collected data on sociodemographic characteristics, the timeline from symptom onset to diagnosis, the number of healthcare visits required for diagnosis, and satisfaction with the information and support provided during the diagnostic process. Statistical analyses, including linear regression, were performed to identify factors influencing patient satisfaction. Results: The study found that 43.2% of participants sought medical attention within a year of symptom onset, yet significant delays in diagnosis were common, with 28.6% of women waiting six months or more after seeking medical care. Only 42.7% of women reported receiving adequate information at diagnosis, and satisfaction levels varied across different aspects of care. Key predictors of lower satisfaction included marital status and longer time since diagnosis, while quicker diagnosis and more healthcare visits before diagnosis positively influenced satisfaction. Conclusions: The findings highlight critical gaps in the diagnostic process and patient education for PCOS in Saudi Arabia. The widespread dissatisfaction with the information provided underscores the need for improved patient-centered care, comprehensive education, and standardized diagnostic protocols. Addressing these issues could enhance patient satisfaction and lead to better management of PCOS, both in Saudi Arabia and globally.

The Concentration of Follistatin and Activin A in Serum and Selected Biochemical Parameters in Women with Polycystic Ovary Syndrome: Stratification by Tobacco Smoke Exposure, Insulin Resistance, and Overweight/Obesity.

Background/Objectives: The aim of the study was to investigate the concentrations of follistatin and activin A in the serum of women with polycystic ovary syndrome (PCOS) and to assess their relationship with selected biochemical parameters, specifically stratifying the analysis based on tobacco smoke, insulin resistance, and abnormal weight. Methods: The research was carried out within a cohort of 88 women (60 women with and 28 without PCOS). Results: We observed significant differences (p < 0.05) in follistatin concentrations between women with PCOS stratified by homeostatic model assessment for insulin resistance (HOMA-IR) values. These differences were consistent across both smoking and non-smoking subgroups with PCOS. Similar results were observed when comparing normal-weight women with PCOS to those with overweight or obesity. Additionally, activin A concentrations were significantly increased by higher body mass index (BMI) and HOMA-IR values in non-smoking women with PCOS. Moreover, we identified a negative correlation (r = -0.30; p < 0.023) between cotinine levels and Anti-Müllerian hormone. Among smoking women with PCOS, we noted decreased concentrations of sex hormone-binding globulin and high-density lipoproteins, alongside increased fasting glucose, insulin, HOMA-IR, and free androgen index values. Conclusions: Our findings suggest that activin A and follistatin concentrations are more strongly influenced by disruptions in glucose metabolism and BMI than by tobacco smoke exposure. The observed changes were more pronounced in follistatin than in activin A level.

Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women of reproductive age. In addition to reproductive and psychological complications, women with PCOS are also at a higher risk of developing metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease. While weight reduction can help manage these complications in overweight or obese women, many weight loss interventions have been ineffective due to weight stigma and its psychological impact on women with PCOS. Therefore, exploring alternative dietary strategies which do not focus on weight loss per se is of importance. In this regard, omega-3 polyunsaturated fatty acids of marine origin (n-3 PUFAs), which are known for their hypotriglyceridemic, cardioprotective and anti-inflammatory effects, have emerged as a potential therapy for prevention and reversal of metabolic complications in PCOS. Several clinical trials showed that n-3 PUFAs can improve components of metabolic syndrome in women with PCOS. In this review, we first summarize the available clinical evidence for different dietary patterns in improving PCOS complications. Next, we summarize the clinical evidence for n-3 PUFAs for alleviating metabolic complications in PCOS. Finally, we explore the mechanisms by which n-3 PUFAs improve the metabolic disorders in PCOS in depth.

Pharmacological management of polycystic ovary syndrome.

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m2). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions.

Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of berberine as adjuvant therapy for the treatment of reduced fertility potential in women with polycystic ovary syndrome (PCOS) through a meta-analysis. METHODS: We comprehensively searched CNKI, SinoMed, Wanfang, Cochrane Library, PubMed, Embase databases to identify randomized controlled trials (RCTs) evaluating the effect of berberine as adjuvant therapy for treating reduced fertility potential in women with PCOS. RESULTS: A total of 10 RCTs involving 713 patients were included. Berberine in combination with Western medicine significantly improved endometrial thickness (weight mean difference [WMD] 1.62 mm; 95 % confidence interval [CI] 1.39-1.85), ovulation rate (risk ratio [RR] 1.41; 95 % CI 1.26-1.60), and clinical pregnancy rate (RR 1.96; 95 % CI 1.59-2.41) compared to Western medicine alone. Moreover, berberine as adjuvant therapy also significantly reduced the blood levels of luteinizing hormone (WMD -2.07 U/L; 95 % CI -2.62 to -1.51) and total testosterone (standard mean difference -0.70; 95 % CI -1.02 to -0.39) but not the level of follicle-stimulating hormone level (WMD -0.23 IU/L; 95 % CI -0.52 to 0.06). CONCLUSIONS: Berberine may serve as an adjuvant therapy to enhance ovulation and increase clinical pregnancy rates in women with PCOS. The potential advantages of berberine may be linked to improvements in endometrial thickness, total testosterone, and luteinizing hormone level. However, further clinical trials are needed to confirm these findings and establish definitive conclusions.

Beneficial effects of apigenin on ovarian histological changes and angiogenesis gene expression in rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous reproductive disorder and can affect approximately 10% of women of reproductive age. Abnormal vasculogenesis is a common event in polycystic ovary syndrome. This study planned to evaluate the antiangiogenic role of apigenin in ovarian histology, gene expression, and vascular density and stability in an experimental model of PCOS. Twenty-eight rats weighing 180-250 g were divided into 4 groups. Seven rats in the control group remain intact and without treatment. In 21 rats, an ovary polycystic model with a single injection of estradiol valerate was established. The PCOS rats were treated with vehicle, apigenin 10, or apigenin 20 mg/kg in three different PCOS groups for 14 days. At the end, a histological assessment of the ovaries was performed to determine collagen density and follicle counting. The endothelial or periendothelial cells were determined by immunohistochemical assay, and angiogenesis gene expression was determined using molecular assessments. Apigenin treatment partially restored follicular development, decreased the number of cysts, and increased corpora lutea in PCOS rats. Also, apigenin decreased the collagen density in the polycystic ovaries. However, apigenin administration mitigated ovarian angiogenesis by a reduction in endothelial and periendothelial cell numbers. A decrease in VEGF and VEGF R2 (kinase insert domain receptor, KDR) expressions was found after the treatment of rats with apigenin. Conclusively, our data revealed that apigenin improves ovarian histological alterations and follicular dynamics in polycystic ovary rats. The effect is partially mediated by suppression of the VEGF signaling system and reduction in endothelial and periendothelial cell proliferation.

The beneficial influences of vitamin D intake on inflammation and oxidative stress in infertile women with polycystic ovary syndrome.

Objective: Oxidative stress and inflammation play a vital function in the pathophysiology of polycystic ovary syndrome (PCOS) and infertility. The aim of this work was to control the impacts of vitamin D intake on metabolic profiles in infertile subjects with PCOS. Trial design and methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 40 infertile women with PCOS. Subjects were randomly divided into two intervention groups to take either 50 000 IU vitamin D (n=20) or placebo (n=20) weekly for 8 weeks. Metabolic profiles and few inflammatory cytokines expression evaluated on peripheral blood mononuclear cells (PBMCs) of participants, using real-time polymerase chain reaction (RT-PCR) method. Results: Vitamin D intake decreased high-sensitivity C-reactive protein (hs-CRP) (-0.9±1.1 vs. 0.3±0.9 mg/l, P=0.002) and elevated total antioxidant capacity (TAC) levels (49.2±60.2 vs. -50.6±161.8 mmol/l, P=0.02) compared with placebo; but no significant effects on other metabolic parameters were observed. Moreover, a significant downregulation of tumor necrosis factor alpha (TNF-α) expression (P=0.03) was observed after taking vitamin D compared with the placebo. Conclusions: Overall, vitamin D intake for eight weeks had beneficial impacts on hs-CRP, TAC, and TNF-α among infertile women with PCOS.

Transcription repression of estrogen receptor alpha by ghrelin/Gq/11/YAP signaling in granulosa cells promotes polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrinological disorder affected by ghrelin. This study aimed to investigate the molecular mechanisms underlying the effects of ghrelin on PCOS manifestations in mice and to assess the therapeutic potential of ghrelin. Female C57BL/6 mice were subcutaneously injected with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 days to induce PCOS. Alterations in reproductive cycles, ovarian morphology, serum sex hormone levels, and related signaling markers were examined. Furthermore, ghrelin-induced effects on granulosa cells and the role of ghrelin/Gq/11/ Yes-associated protein (YAP) signaling were studied by silencing Gαq/11 or YAP using si-RNAs. Finally, we evaluated the therapeutic potential of anti-ghrelin antibodies in DHEA-induced PCOS mice. DHEA administration led to significant PCOS-associated changes including weight gain, disrupted estrous cycles, ovarian morphological alterations, and hormonal imbalances in mice, with elevated Gαq/11 and acylated ghrelin expression, which was also noted in PCOS patients. However, treatment with anti-ghrelin antibodies effectively managed DHEA-induced damage in PCOS mice. In vitro, ghrelin exposure resulted in granulosa cell injury and modulated estrogen receptors alpha (ERα) and YAP protein levels, whereas silencing YAP and Gαq/11 reversed ghrelin-induced detrimental effects and up-regulated ERα expression. This study revealed that DHEA-induced PCOS traits in mice could be improved by anti-ghrelin antibodies, with the ghrelin/Gq/11/YAP signaling pathway identified as a crucial mediator in granulosa cells, affecting ERα transcription to regulate PCOS. These findings suggest a potential therapeutic strategy for the treatment of PCOS.

How Frequently Is Ultrasound Required to Diagnose Polycystic Ovary Syndrome in a Clinical Population?

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting up to 20% of reproductive aged women worldwide. Polycystic ovarian morphology (PCOM) may be present, but is not required for diagnosis. Our study seeks to evaluate the utility of ultrasound in diagnosing or excluding PCOS by 2023 International Guidelines Criteria. Materials and Methods: Subjects were patients seen in a tertiary care referral clinic in whom other causes of hyperandrogenism (HA) were ruled out. All underwent complete history, physical, modified Ferriman Gallwey scoring, and serum androgen testing; followed by transvaginal ultrasound (TVUS) to assess ovarian morphology if indicated. PCOM was identified as antral follicle count ≥20 and/or ovarian volume >10 mL in at least one ovary. After clinical classification, PCOS was diagnosed by at least two of three: biochemical/clinical HA, ovulatory dysfunction (OD), and PCOM. Statistics were calculated using Fisher's exact test and chi-square. Results: In total, 454 subjects were included. 299 were classified as group A/B and did not require TVUS for diagnosis. Of 82 subjects with HA alone, 50 (61.0%) were classified as group C after demonstrating PCOM. Fifty-five subjects had OD alone, 37 (67.3%) of which were classified as group D based on PCOM. In total, 137/454, or 30.2% of subjects required TVUS for diagnosis or exclusion of PCOS. Conclusions: TVUS was necessary in less than one-third of subjects, primarily identifying PCOS groups C or D. Selective use of ovarian ultrasonography may reduce the costs and complexity of epidemiological and clinical studies for PCOS.

Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study.

INTRODUCTION: Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS. MATERIAL AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta-analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome-Wide Association Study Project database. Inverse variance weighted (IVW), MR-Egger, constrained maximum likelihood-based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR-Egger intercept tests were employed to measure the heterogeneity. RESULTS: A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30-0.99, p = 0.04), Bacilli (1.76, 1.07-2.91, p = 0.03), Bilophila (0.42, 0.23-0.77, p < 0.01), Blautia (0.16, 0.03-0.79, p = 0.02), Burkholderiales (2.37, 1.22-4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43-0.98, p = 0.04), Cyanobacteria (0.51, 0.31-0.83, p = 0.01), Holdemania (0.53, 0.35-0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04-3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR-Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91-0.98, p < 0.01; 0.97, 0.94-0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS. CONCLUSIONS: Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.

Clinical patterns and treatment outcomes of polycystic ovarian syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common chronic endocrine disorder in women with complex and poorly understood etiologies. The present study aimed to describe the clinical features of PCOS in a sample of Syrian women as well as the risk factors, associated comorbid diseases, and patterns and efficacy of treatment. METHODS: The present study is cross-sectional observational study conducted on a sample of Syrian women diagnosed with PCOS, using self-administered questionnaire during the period between December 25, 2023 and January 18, 2024. Overall, 1666 women with PCOS were recruited through online platforms. RESULTS: Higher frequency of PCOS was observed in young women aged 15-25 years (63.1%) and in single ladies (76.5%). The main chief complaints experienced by patients with PCOS were hirsutism (71.25%), irregular menstrual cycle (70.95%), depressed mood (53.9%), acne (49.52%), abdominal obesity (43.88%), alopecia (38.12%), and weight gain (34.57%). The most common risk factors observed in patients with PCOS were lack of physical exercise (76.4%), unhealthy food habits (51.6%), family history (38.5%), and history of taking anabolic steroids (17.2%). Comorbid diseases were found in 11.5% of PCOS patients. These diseases were hypothyroidism (5.7%), hypertension (3.06%), dyslipidemia (1.68%), heart diseases (1.56%), and diabetes mellitus (0.78%). Most patients were treated with oral contraceptive pills (82.11%) or metformin (64.83%). The efficacy of treatment was observed as complete cure in 430 patients (25.8%) and partial response alleviating symptoms in 819 patients (49.2%), while and no benefit was found in 417 patients (25%). CONCLUSIONS: PCOS is associated with widespread dermatological and metabolic aberrations that pose psychological burden on women and increase their risk for having comorbid diseases. Most patients with PCOS do not receive adequate therapy. Understanding the risk factors and clinical features for each patient is essential to choose the proper treatment.