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.

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.

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%.

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.

Causal relationship between fertility nutrients supplementation and PCOS risk: a Mendelian randomization study.

Background: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age, is mainly ameliorated through drugs or lifestyle changes, with limited treatment options. To date, numerous researchers have found that fertility nutrient supplements may benefit female reproductive health, but their direct impact on polycystic ovary syndrome risk remains unclear. Methods: Our research employs Mendelian Randomization to assess how fertility nutrients affect PCOS risk. Initially, we reviewed 49 nutrients and focused on 10: omega-3 fatty acids, calcium, dehydroepiandrosterone, vitamin D, betaine, D-Inositol, berberine, curcumin, epigallocatechin gallate, and metformin. Using methodologies of Inverse Variance Weighting and Mendelian Randomization-Egger regression, we examined their potential causal relationships with PCOS risk. Results: Our findings indicate omega-3 fatty acids reduced PCOS risk (OR=0.73, 95% CI: 0.57-0.94, P=0.016), whereas betaine increased it (OR=2.60, 95% CI: 1.09-6.17, P=0.031). No definitive causal relations were observed for calcium, dehydroepiandrosterone, vitamin D, D-Inositol, and metformin (P>0.05). Drug target Mendelian Randomization analysis suggested that increased expression of the berberine target gene BIRC5 in various tissues may raise PCOS risk (OR: 3.00-4.88; P: 0.014-0.018), while elevated expressions of curcumin target gene CBR1 in Stomach and epigallocatechin gallate target gene AHR in Adrenal Gland were associated with reduced PCOS risk (OR=0.48, P=0.048; OR=0.02, P=0.018, respectively). Conclusions: Our research reveals that specific fertility nutrients supplementation, such as omega-3 fatty acids, berberine, and curcumin, may reduce the risk of PCOS by improving metabolic and reproductive abnormalities associated with it.

The gut microbiota: emerging biomarkers and potential treatments for infertility-related diseases.

Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.

Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

BACKGROUND: Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. OBJECTIVE AND RATIONALE: The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. SEARCH METHODS: Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. OUTCOMES: The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. WIDER IMPLICATIONS: Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. REGISTRATION NUMBER: Not applicable.

Association of uric acid and fructose levels in polycystic ovary syndrome.

STUDY QUESTION: Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. WHAT IS KNOWN ALREADY: Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. STUDY DESIGN, SIZE, DURATION: In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. LIMITATIONS, REASONS FOR CAUTION: Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

Oocyte-derived growth differentiation factor 9 suppresses the expression of CYP17A1 and androgen production in human theca cells.

OBJECTIVE: To investigate the direct effect of growth differentiation factor 9 (GDF9) on androgen production in human theca cells. DESIGN: Experimental study. SETTING: Tertiary hospital-based research laboratory. PATIENT(S): Women who underwent in vitro fertilization and intracytoplasmic sperm injections at our clinic were included in this study. INTERVENTION(S): Primary cultured human theca cells from women undergoing in vitro fertilization and intracytoplasmic sperm injection treatment were treated with GDF9, an activin receptor-like kinase 5 (ALK5) inhibitor, and a SMAD4 agonist. MAIN OUTCOME MEASURE(S): The expression of androgen synthesis-related genes StAR, CYP17A1, and LHCGR, levels of androstenedione and testosterone, phosphorylation of SMAD2/3, and the interaction between bone morphogenic protein-activated type II receptor and ALK5 were evaluated using reverse transcription-quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assays, and coimmunoprecipitation assays, respectively. RESULT(S): Growth differentiation factor 9 decreased StAR, CYP17A1, and LHCGR expression levels in human theca cells, which was prevented by treatment with the ALK5 inhibitor, and suppressed production of androgen in human theca cells. Growth differentiation factor 9 increased SMAD2/3 phosphorylation, and the ALK5 inhibitor also suppressed this effect. Bone morphogenic protein-activated type II receptor and ALK5 bound to each other after GDF9 stimulation. The SMAD4 agonist kartogenin also decreased messenger RNA levels of StAR and CYP17A1 and protein levels of StAR in human theca cells. CONCLUSION(S): Growth differentiation factor 9 can activate the bone morphogenic protein-activated type II receptor-ALK5-SMAD2/3 signaling pathway, suppress CYP17A1 expression, and decrease androgen production in human theca cells.

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.

Effect of vitamin D supplementation on lipid profile, and hormonal functions in polycystic ovary syndrome: an umbrella systematic review and meta-analysis.

Vitamin D has the potential to therapeutically affect the lipid profile and endocrine parameters of polycystic ovary syndrome (PCOS) patients. However, results from prior studies have been inconsistent. Therefore, we conducted an umbrella meta-analysis of randomized controlled trials (RCTs) to better understand the effectiveness of vitamin D in treating PCOS. We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and Scopus, from their inception to January 2, 2024. Random-effects models were used to perform the umbrella meta-analysis. The analysis included 15 meta-analyses of RCTs. Vitamin D demonstrated a significant reduction in TG levels (SMD = -0.23; 95% CI: -0.42, -0.04, p = 0.02, and WMD = -8.76, 95% CI: -11.81, -5.72; p <0.001), TC (SMD = -0.47, 95% CI: -0.80, -0.13; p = 0.007, and WMD = -8.89, 95% CI: -13.18, -4.59; p < 0.001), LDL-c (SMD = -0.24, 95% CI: -0.38, -0.10; p = 0.001, and WMD = -3.83, 95% CI: -6.49, -1.16; p = 0.005), TT (SMD = -0.15, 95% CI: -0.29 to -0.01; p = 0.02), and DHEA (WMD: -28.03; 95% CI: -56.9 to -0.36; p = 0.04). However, no significant effect on HDL-c, insulin, and BMI. The present meta-analysis revealed that vitamin D supplementation might significantly affect TG, TC, LDL-c, DHEA, and TT while it is not effective in improving BMI, HDL-c, and insulin. Vitamin D showed noteworthy effects in preventing lipid profile and enhancing hormonal function in patients with PCOS.

The association between Lifelines Diet Score (LLDS) and Polycystic Ovary Syndrome (PCOS) in Iranian women: a case-control study.

BACKGROUND: Although adherence to a healthy dietary pattern is one of the primary recommendations for the prevention of polycystic ovary syndrome (PCOS), there is still no conclusive evidence of which specific dietary pattern is best. The Lifelines diet score (LLDS) is a new, evidence-based scoring system to determine diet quality, and its association with PCOS has not been investigated. The present study aimed to assess the association between LLDS and PCOS in Iranian women. MATERIALS AND METHODS: This frequency-matched case-control study was carried out on 108 women with PCOS and 108 women without PCOS as a control group in Yazd, Iran. Healthy controls were matched to PCOS women based on age and BMI. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between LLDS and PCOS. RESULTS: The findings of the present study showed women in the highest tertile of LLDS compared with the participants in the lowest tertile had 90% lower odds of PCOS (Odds Ratio (OR): 0.10; 95% Confidence Interval (CI): 0.04 to 0.21, p for trend: <0.001). This association remained significant after adjustment for energy intake, marital status, pregnancy history, WC, chronic disease history, physical activity, and BMI (Odds Ratio (OR): 0.11; 95% (CI):0.05 to 0.27, p for trend: <0.001). CONCLUSION: Although the present study found a significant protective association between adherence to LLDS and PCOS, more mechanism-based studies are needed to confirm these findings in the future.

GnRH agonist pretreatment for frozen embryo transfer among women with polycystic ovary syndrome: a narrow systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial. PURPOSE: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET. METHODS: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM). RESULTS: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups. CONCLUSIONS: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring.

Cardiometabolic risk in children and adolescents with obesity: a position paper of the Italian Society for Pediatric Endocrinology and Diabetology.

Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.

Ketogenic diet improves fertility in patients with polycystic ovary syndrome: a brief report.

Introduction: Polycystic ovary syndrome (PCOS) affects up to 20 % of reproductive-age individuals and is strongly linked to obesity. The impacts of ketogenic diet on fertility in people with PCOS are unknown. This study aims to determine the effect of a ketogenic diet on restoration of regular menstrual cycles and fertility. Methods: After approval from the Institutional Review Boards of Cleveland Clinic, a retrospective analysis was conducted using the electronic health record system. We analyzed data from thirty patients (n = 30) with polycystic ovary syndrome who followed a ketogenic diet for at least 3 months at the Cleveland Clinic, Cleveland, Ohio, USA. Main outcomes were percentage of women with restoration of regular menstrual cycles and pregnancy rate. Results: All women (n = 30) had restoration of regular menstrual cycles. The overall pregnancy rate of women desiring pregnancy (n = 18) was 55.6% (n = 10). Pregnancy rate was 38.5% for women on metformin and 100% for those who were not (P = 0.036). Pregnancy rate was 62.5% for women using ovulation induction agents and 50.0% for those who did not (P = 0.66). Percent weight change between the pregnant and non-pregnant groups did not significantly differ [-8.1 ± 6.2, vs -6.4 ± 8.4, P = 0.64, respectively]. Conclusion: This study reports a higher rate of pregnancy with the ketogenic diet in women with PCOS compared to existing literature.

Effects of preconceptional vitamin D levels on in vitro fertilization outcomes in infertile patients with polycystic ovary syndrome: A retrospective cohort study.

BACKGROUND: Vitamin D plays various roles in different stages of reproduction, and abnormalities in its levels are associated with diseases such as polycystic ovary syndrome (PCOS). This study aimed to determine the relationship between initial vitamin D levels and in vitro fertilization (IVF) outcomes in PCOS patients. METHODS: This retrospective cohort study included 1174 PCOS patients who consulted the Acibadem Maslak Hospital IVF Clinic between January 2015 and March 2021. We investigated the effect of preconceptional vitamin D levels on IVF outcomes using data analysis with SigmaPlot 14.5. RESULTS: We found a significant positive correlation between preconceptional vitamin D levels and positive clinical pregnancy rates (p < 0.001) as well as increased endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day (p < 0.001, r = 0.262). The optimal vitamin D cut-off value for predicting positive hCG test results was identified as 13.24 ng/mL, as determined by receiver operating characteristic curve analysis (sensitivity = 0.839, specificity = 0.677). No association was observed with other IVF outcome parameters, miscarriage rates, or clinical pregnancy rates based on EMT. CONCLUSIONS: The study suggests that PCOS patients with vitamin D levels above 13.24 ng/mL are more likely to achieve positive hCG results after IVF. These findings highlight the potential importance of vitamin D supplementation in improving pregnancy outcomes for PCOS patients. Additionally, increased EMT on hCG day may explain the higher clinical pregnancy rates associated with elevated vitamin D levels.