BACKGROUND: Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS.
METHODS: Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model.
RESULTS: 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968-1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses.
CONCLUSIONS: A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

Extracellular vesicles (EVs), particles enriched in bioactive molecules like proteins, nucleic acids, and lipids, are crucial mediators of intercellular communication and play key roles in various physiological and pathological processes. EVs have been shown to be involved in ovarian follicular function and to be altered in two prevalent gynecological disorders; polycystic ovarian syndrome (PCOS) and endometriosis.Ovarian follicles are complex microenvironments where folliculogenesis takes place with well-orchestrated interactions between granulosa cells, oocytes, and their surrounding stromal cells. Recent research unveiled the presence of EVs, including exosomes and microvesicles, in the follicular fluid (FFEVs), which constitutes part of the developing oocyte\'s microenvironment. In the context of PCOS, a multifaceted endocrine, reproductive, and metabolic disorder, studies have explored the dysregulation of these FFEVs and their cargo. Nine PCOS studies were included in this review and two miRNAs were commonly reported in two different studies, miR-379 and miR-200, both known to play a role in female reproduction. Studies have also demonstrated the potential use of EVs as diagnostic tools and treatment options.Endometriosis, another prevalent gynecological disorder characterized by ectopic growth of endometrial-like tissue, has also been linked to aberrant EV signaling. EVs in the peritoneal fluid of women with endometriosis carry molecules that modulate the immune response and promote the establishment and maintenance of endometriosis lesions. EVs derived from endometriosis lesions, serum and peritoneal fluid obtained from patients with endometriosis showed no commonly reported biomolecules between the eleven reviewed studies. Importantly, circulating EVs have been shown to be potential biomarkers, also reflecting the severity of the pathology.Understanding the interplay of EVs within human ovarian follicles may provide valuable insights into the pathophysiology of both PCOS and endometriosis. Targeting EV-mediated communication may open avenues for novel diagnostic and therapeutic approaches for these common gynecological disorders. More research is essential to unravel the mechanisms underlying EV involvement in folliculogenesis and its dysregulation in PCOS and endometriosis, ultimately leading to more effective and personalized interventions.

UNASSIGNED: Polycystic ovarian syndrome (PCOS) is a gynaecological problem affecting women within reproductive age, accompanied by several metabolic anomalies, thus leading to alteration in kidney function and hyperuricaemia. Due to the high prevalence of cardiometabolic factors in PCOS, there is a need to anticipate an increased number of kidney impairments amongst these women.
UNASSIGNED: This review aims to investigate the potential link between PCOS, impaired kidney function, and elevated uric acid levels. By elucidating this association, we hope to provide clinicians with a tool to stratify the risk of kidney disease in women diagnosed with PCOS, based on readily available kidney function parameters.
UNASSIGNED: The recommendations used for the analysis were outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Subsequently, eligible studies were identified using several databases (MEDLINE, ProQuest and EBSCOhost) between 1996 and 2022, with a total of 13 studies included. Serum uric acid, serum creatinine, as well as estimated glomerular filtration rate (eGFR) were evaluated as the outcome of interest. Quality assessment for cohort, case-control and cross-sectional studies was conducted utilising the Newcastle-Ottawa Scale, while Review Manager 5.4 was utilised for meta-analysis.
UNASSIGNED: Uric acid was significantly higher in women with PCOS (mean difference [MD] = 0.70, 95% confidence interval [CI] [0.45-0.95], P < 0.00001). Meanwhile, serum creatinine and eGFR were statistically similar in each group (MD = 0.08, 95% CI [-0.05-0.21], P = 0.22 and MD = 3.54, 95% CI [-4.53-11.61], P = 0.39, respectively).
UNASSIGNED: This review showed that PCOS was significantly associated with elevated uric acid. However, no significant difference was found between eGFR and creatinine levels compared to healthy controls. Routine uric acid assessment in PCOS patients is recommended as a simple tool for risk stratification.
UNASSIGNED: No body mass index (BMI) subgroup analysis was done due to limited BMI reporting in our included studies. Quantitative analysis of all kidney function parameters was also limited by sparse data on urea and albumin.
UNASSIGNED: CRD42023410092 (02 April 2023).

Polycystic ovary syndrome (PCOS) is an endocrinological disorder affecting women of reproductive age, characterized by hormonal imbalance leading to metabolic and reproductive dysregulations. This case report revolves around a 30-year-old husband and his 27-year-old partner. The male partner had normozoospermia, and the female spouse had PCOS, according to the couple\'s diagnostic evaluations. The female patient received ovarian stimulation specifically to assist with PCOS, and the retrieved oocytes were then matured in vitro. After intracytoplasmic sperm injection (ICSI), fertilization and embryonic development were successful. Treatment of PCOS-related infertility presents many challenges, and in vitro maturation (IVM) and its potential as an effective assisted fertility method are discussed. To optimize treatment outcomes, the conclusion shows the importance of IVM and other assisted reproductive techniques for infertility. It also focuses on the necessary continuous research and clinical experience. Clinical pregnancy was confirmed by measuring serum beta-human chorionic gonadotropin (β-hCG) levels followed by ultrasound sonography (USG), which showed a normal growth rate of the fetus.

UNASSIGNED: Pathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk.
UNASSIGNED: In this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites.
UNASSIGNED: This study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27-2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30-4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003-1.048, P=0.026).
UNASSIGNED: Genetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.

BACKGROUND: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles.
METHODS: This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups.
RESULTS: Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038).
CONCLUSIONS: A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. At present, the pathogenesis has not been clarified, and the clinical application of drugs and lifestyle intervention may not prevent disease progression. This study aimed to investigate how circ_0043314 regulates ovarian granulosa cell biological functions to provide a theoretical basis for the treatment of patients with PCOS. MicroRNA (miR)-146b-3p/Apelin 13 axis was used to investigate the mechanism by which circ_0043314 regulated ovarian granulosa cell proliferation and apoptosis in PCOS via miR-146b-3p/Apelin 13 axis. Participants/Materials, Methods: Ovarian tissues (cortical tissues) from 35 PCOS patients and 35 normal controls, as well as HEK293T and human ovarian granulosa cell line (KGN, COV434), were included in this study. We examined the expression levels of circ_0043314, miR-146b-3p, and Apelin 13 in PCOS tissues. Ovarian granulosa cells were transfected with corresponding plasmids to clarify the influence of circ_0043314, miR-146b-3p, or Apelin 13 on proliferation and apoptosis of ovarian granulosa cells through MTT and flow cytometry assays. Moreover, the relationships among circ_0043314, miR-146b-3p, and Apelin 13 were analyzed through dual-luciferase and RNA immunoprecipitation assays.
RESULTS: Circ_0043314 and Apelin 13 were highly expressed and miR-146b-3p was lowly expressed in ovarian tissues of PCOS compared with non-PCOS controls. Downregulation of circ_0043314 or upregulation of miR-146b-3p hindered ovarian granulosa cell proliferation and advanced its apoptosis. Downregulation of miR-146b-3p reversed the impacts of downregulation of circ_0043314, and overexpression of Apelin 13 counteracted the influences of upregulation of miR-146b-3p in ovarian granulosa cells. Mechanically, circ_0043314 could bind to miR-146b-3p, and miR-146b-3p directly targeted and modulated Apelin 13 expression.
CONCLUSIONS: This study was limited by the lack of animal experiments.
CONCLUSIONS: Our data demonstrated that circ_0043314 enhances ovarian granulosa cell proliferation and suppresses its apoptosis via miR-146b-3p/Apelin 13 axis.

UNASSIGNED: PCOS is a common gynecologic disorder and recent studies have found that they are more prone in developing depression and anxiety compared to the general population. The Hospital Anxiety and Depression Scale (HADS) is a popular and simple self-administered instrument reliable for detecting states of anxiety and depression. Using this simple screening tool, it may lead to the identification of such mental disorders that may warrant timely psychiatric referral.
UNASSIGNED: The study aims to determine the prevalence of anxiety and depression among PCOS patients using the HADS-P questionnaire and to determine the association between depression and anxiety and disease characteristics.
UNASSIGNED: Convenience sampling was done to recruit PCOS patients >18 years old in Philippine General Hospital. Cross-sectional design was used for the prevalence of depression and anxiety, while nested case control design for the evaluation of the predictors of depression and anxiety. The HADS-P, a self-administered rating scale with independent subscales for anxiety and depression, was administered to the participants after securing consent. A cut-off score of >8 points on either of the depression and anxiety subscale was used to determine their respective prevalence. Logistic regression analysis was used to determine the association of clinical variables with anxiety or depression.
UNASSIGNED: A total of 253 patients with PCOS were recruited. On the basis of a HADS-P score of >8.0 per category, the prevalence of PCOS patients who were suggestive to have anxiety was 46.25% (n: 117, 95% CI: 39.98-52.60%), while 9.09% (n: 23, 95% CI: 5.85-13.33%) of them were suggestive to have depression. Crude logistic regression identified presence of depression, infertility, impaired glucose tolerance, and prominent acne as predictors of anxiety; whereas low parity, hirsutism, and presence of anxiety were predictors of depression. Adjusted logistic regression identified only presence of depression and infertility were significant predictors of anxiety (n: 116, LR χ2 (5): 15.46, p<0.01); while presence of anxiety increased the odds of depression by 2- to 13-fold, it was not statistically significant (n: 116, LR χ2 (5): 9.79, p: 0.08).
UNASSIGNED: There is a high prevalence of anxiety and depression among PCOS patients. The factors that were seen to be significantly associated with the development of anxiety were the presence of depression, impaired glucose tolerance, infertility and prominent acne, while for the development of depression were the presence of anxiety, hirsutism, and low parity. Screening for anxiety and depression is of paramount importance and physicians should be vigilant for the need of possible psychiatric intervention.

UNASSIGNED: Polycystic ovarian syndrome (PCOS) is a common but complex endocrine disorder widely linked to infertility and miscarriage. This study assessed the correlation between PCOS and infertility.
UNASSIGNED: Using the latest data from the Global Burden of Disease 2019 database, we conducted an in-depth assessment of the disease burden attributed to PCOS in China. This analysis was performed using the joinpoint regression, age-period-cohort, and autoregressive integrated moving average (ARIMA) models.
UNASSIGNED: Between 1990-2019, an upward trend was observed in the age-standardized prevalence of PCOS-related female infertility in China. Joinpoint regression analysis revealed an increasing trend in the age-standardized prevalence of PCOS-related female infertility burden indicators as well as the average annual percentage change and annual percentage change across all age groups in China. In terms of the cohort effect, the period rate ratios associated with the age-standardized prevalence of PCOS-related infertility increased steadily over time. The ARIMA model predicted a relatively swift upward trend in the age-standardized prevalence of PCOS-related infertility in China from 2020-2030.
UNASSIGNED: The age-standardized prevalence of PCOS-related female infertility in China has increased between 1990-2019. The ARIMA model predicted that the age-standardized prevalence of this disease may continue to increase over the next decade. This study can increase the public\'s attention, improve women\'s health awareness, and have a certain significance for reducing female infertility related to PCOS.

We aimed to conduct a systematic review of the data in the literature on ovarian reserve and ovarian hormone following laparoscopic ovarian drilling (LOD). The PubMed, ScienceDirect, and ProQuest databases were comprehensively searched using a combination of keywords such as \"ovarian reserve\", \"laparoscopic ovarian drilling\", \"luteinizing hormone\", \"follicle-stimulating hormone\", \"inhibin\", \"LH/FSH ratio\", \"ovulation\", and \"testosterone\". All studies involving females of reproductive age who were officially diagnosed with polycystic ovarian syndrome (PCOS) and had undergone LOD with reported data concerning at least one of the following parameters were considered for inclusion: ovarian reserve, anti-Mullerian hormone (AMH), inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, and testosterone. All the included studies were evaluated by the GRADE scale for bias and their findings were synthesized by four independent coauthors. A total of 38 studies involving 3118 female patients were included. Based on our findings, a significant number of participants experienced spontaneous ovulation along with a significant decrease in ovarian reserve, and a significant decrease in AMH, LH, and testosterone, with no significant changes in FSH and inhibin B. With the end goal of LOD being to improve fertility and pregnancy rates among females with PCOS, it is important to look at the first few steps that enable this. As expected, there was a significant improvement in ovulation while the ovarian reserve decreased. Along with the decrease in ovarian reserve, there was a significant normalization in AMH, LH, and testosterone levels. LOD may exert its main effects through the manipulation of the ovarian reserves.