Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

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).

OBJECTIVE: The study aimed to explore the causal effect of body mass index (BMI) on polycystic ovarian syndrome (PCOS).
METHODS: Genome-wide association data for BMI and PCOS were sourced from the Mendelian randomization (MR) base platform. Significantly associated single nucleotide polymorphisms (SNPs) for BMI served as instrumental variables in bidirectional two-sample MR analyses to investigate the causal relationship between BMI and PCOS. Analytical techniques utilized encompassed the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression.
RESULTS: We identified 427 SNPs significantly associated with BMI (P < 5 × 10-8; linkage disequilibrium r2 < 0.001). Various methods consistently revealed a positive association between BMI and PCOS (IVW: odds ratio (OR) 2.027, 95% confidence interval (CI) 1.599-2.596; weighted median estimator: OR 2.368, 95% CI 1.653-3.392; MR-Egger Method: OR 3.610, 95% CI 1.795-7.263), indicating that higher BMI correlates with an increased risk of PCOS. Additionally, we observed a causal effect of genetic predisposition to PCOS on BMI (IVW: OR 1.020, 95% CI (1.019-1.022); weighted median estimator: OR 1.017, 95% CI (1.015-1.019); MR-Egger Method: OR 1.000, 95% CI (0.995-1.005)).
CONCLUSIONS: The MR analysis furnished compelling evidence suggesting a causal relationship between elevated BMI and the risk of PCOS, as well as indicating that the severity of PCOS may contribute to elevated BMI levels.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a widely seen reproductive and endocrinological disorder. PCOS can exert substantial effects on many aspects of an individual\'s life, including reproductive health and psychological well-being. The objective of this study was to assess the nutritional status, premenstrual syndrome, and mental health of women affected by PCOS in comparison to women without PCOS.
METHODS: A case-control observational study in Palestine included 100 PCOS patients and 200 healthy women. The collected data included socio-demographic information, medical history, premenstrual syndrome, mental health, nutritional status, and lifestyle. Anthropometric measurement and the Mediterranean Diet Adherence Screener (MEDAS) were used to evaluate the nutritional status. The General Health Questionnaire (12-GHQ) was used to evaluate the state of mental health. Premenstrual syndrome (PMS) severity was evaluated using a validated Arabic premenstrual syndrome questionnaire.
RESULTS: The study\'s findings indicated that there was a statistically significant increase in the three dimensions of PMS among participants with PCOS, p < 0.05. Similarly, PCOS patients demonstrated elevated ratings across all aspects of mental health, p < 0.05. In terms of the other variables, it has been observed that PCOS patients have a notably greater prevalence of perceived sleep disturbances and decreased adherence to the Mediterranean diet. Regression analysis revealed that PCOS is associated with mental health problems indicated by a higher GHQ score (OR: 1.09; 95% CI: 1.03; 1.16, p < 0.05), lower adherence to the MD diet (OR: 0.86; 95% CI: 0.76; 0.98, p < 0.05), and pre-menstrual syndrome, especially the physical symptoms (OR: 1.06; 95% CI: 1.003; 1.12, p < 0.05) after adjusting for age, smoking, waist-hip ratio, and body mass index (BMI).
CONCLUSIONS: The study has linked polycystic ovary syndrome to negative mental health outcomes and an increased severity of premenstrual syndrome (PMS). Additional investigation is required in order to establish a causal association between polycystic ovary syndrome (PCOS) and lifestyle behaviors within the Palestinian population. Intervention and instructional studies are necessary to investigate the efficacy of management strategies in alleviating the effects of polycystic ovary syndrome (PCOS) on both physical and mental well-being.

UNASSIGNED: Ovarian stimulation (OS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS.
UNASSIGNED: The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria.
UNASSIGNED: A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON.
UNASSIGNED: For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer.
UNASSIGNED: In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.

Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time. In this comparative cross-sectional analysis, demographic, metabolic, and proteomic data from Caucasian women aged 18-40 years from a PCOS Biobank (137 with PCOS, 97 controls) was analyzed. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for inflammatory proteins, serum markers of chronic kidney disease (CKD), tubular renal injury markers, and complement system proteins. A total of 44.5% of the PCOS cohort had GH (eGFR ≥ 126 mL/min/1.73 m2 (n = 55)), and 12% (n = 17) eGFR ≥ 142 mL/min/1.73 m2 (super-GH(SGH)). PCOS-GH women were younger and had lower creatinine and urea versus PCOS-nonGH. C-reactive protein (CRP), white cell count (WCC), and systolic blood pressure (SBP) were higher in PCOS versus controls, but CRP correlated only with PCOS-SGH alone. Complement protein changes were seen between controls and PCOS-nonGH, and decay-accelerator factor (DAF) was decreased between PCOS-nonGH and PCOS-GSGH (p < 0.05). CRP correlated with eGFR in the PCOS-SGH group, but not with other inflammatory or complement parameters. Cystatin-c (a marker of CKD) was reduced between PCOS-nonGH and PCOS-GSGH (p < 0.05). No differences in tubular renal injury markers were found. A secondary cohort notes review of the biobank subjects 8.2-9.6 years later showed a reduction in eGFR: controls -6.4 ± 12.6 mL/min/1.73 m2 (-5.3 ± 11.5%; decrease 0.65%/year); PCOS-nonGH -11.3 ± 13.7 mL/min/1.73 m2 (-9.7 ± 12.2%; p < 0.05, decrease 1%/year); PCOS-GH (eGFR 126-140 mL/min/17.3 m2) -27.1 ± 12.8 mL/min/1.73 m2 (-19.1 ± 8.7%; p < 0.0001, decrease 2%/year); PCOS-SGH (eGFR ≥ 142 mL/min/17.3 m2) -33.7 ± 8.9 mL/min/17.3 m2 (-22.8 ± 6.0%; p < 0.0001, decrease 3.5%/year); PCOS-nonGH eGFR versus PCOS-GH and PCOS-SGH, p < 0.001; no difference PCOS-GH versus PCOS-SGH. GH was associated with PCOS and did not appear mediated through tubular renal injury; however, cystatin-c and DAF were decreased, and CRP correlated positively with PCOS-SGH, suggesting inflammation may be involved at higher GH. There were progressive eGFR decrements for PCOS-nonGH, PCOS-GH, and PCOS-SGH in the follow-up period which, in the presence of additional factors affecting renal function, may be clinically important in the development of CKD in PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent cause of ovulatory infertility and endocrine abnormalities in reproductive-age women. Although the MIND diet has been introduced to improve brain function, evidence shows that the MIND diet is rich in beneficial food groups that can have a preventive effect on other metabolic disorders. The present study was conducted to investigate the association between adherence to the MIND diet and PCOS.
METHODS: This age and BMI frequency-matched case-control study was conducted on 216 women between January 2018 and March 2019 in Yazd, Iran. PCOS was diagnosed based on Rotterdam criteria. Participants were selected by convenience sampling method. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between the MIND diet and PCOS.
RESULTS: The findings of the present study showed a significant inverse association between adherence to the MIND diet and PCOS in the crude model (OR for T3 vs. T1: 0.12 (95% CI: 0.05-0.25), P-value < 0.001) and multivariable-adjusted model including energy intake, age, BMI, waist circumference, marital status, pregnancy history, drug use history, education and physical activity (OR for T3 vs. T1 = 0.08 (95% CI: 0.03-0.19), P-value < 0.001). Adherence to the MIND diet had a protective effect of 92%.
CONCLUSIONS: Although the results of the present study showed that higher adherence to the MIND diet is associated with a lower risk of PCOS, more studies are needed to confirm these findings in the future.

UNASSIGNED: Zinc is an essential micronutrient, a vital stabiliser and a cofactor in many enzymes such as superoxide dismutase and phospholipase C and also acts as an antioxidant by protecting the sulfhydryl groups of different proteins and enzymes against free radicals. It is unclear if serum zinc levels are correlated with polycystic ovary syndrome (PCOS) and its pathophysiology, although relation between diabetes and insulin resistance has been established.
UNASSIGNED: This study aimed to investigate circulating serum zinc levels in PCOS subjects compared with non-PCOS subjects.
UNASSIGNED: In this cohort study, PCOS subjects were compared with normal subjects aged between 18 and 35.
UNASSIGNED: All the included subjects underwent measurement of anthropometric parameters, fasting insulin, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, progesterone, oestrogen and serum zinc levels. These values were taken on days 2-5 of the menstrual cycle.
UNASSIGNED: Univariate analysis and linear regression were performed for serum zinc levels and fasting insulin levels in PCOS subjects and non-PCOS subjects using SPSS (version 21) and Microsoft Excel (2019).
UNASSIGNED: Serum zinc levels in the PCOS group were lower than in the control group (P = 0.012). Fasting insulin levels in the PCOS group were higher than in non-PCOS subjects (P = 0.001). We found a negative correlation between zinc and fasting insulin (r = -0.580, P < 0.0001) in the normal group and (r = -0.332, P = 0.019) in the PCOS group. A positive correlation was found between body mass index (BMI) and fasting insulin levels in both the PCOS group (r = 0.227, P = 0.112) and normals (r = 0.612, P < 0.0001). A negative statistically significant correlation between BMI and zinc in both the PCOS group (r = -0.378, P = 0.007) and the non-PCOS group (r = -0.7452, P < 0.0001) was seen.
UNASSIGNED: The data suggest that serum zinc levels were found to be lower in PCOS subjects as compared to normal controls and evaluation of these levels may indicate that zinc has a vital role in PCOS pathophysiology.

Background Polycystic ovarian syndrome (PCOS) is a multifaceted complex endocrine disorder showing an alarming rise in women worldwide. Insulin resistance is the chief driving force in the pathogenesis of PCOS. Myo-inositol is an upcoming insulin-sensitizing agent, which is a second messenger responsible for insulin-mediated intracellular glucose transport. This study aims to evaluate the efficacy of myo-inositol and its clinical, hormonal, and metabolic profile in treating women with PCOS. Methodology A prospective clinical study was conducted over 18 months in the Department of Obstetrics and Gynecology at Sree Balaji Medical College and Hospital, Chennai, after obtaining permission from the Institutional Ethical Committee. A total of 90 women diagnosed with PCOS, according to Rotterdam\'s criteria, were included in the study. They received tablet myo-inositol 1 g BD for six months. Before the start of the therapy, detailed history and baseline investigations were recorded and subsequently re-assessed at the end of six months. Results Around 68% of patients restored menstrual cycle regularity. There was a statistically significant decrease in luteinizing hormone (LH) (10.31 ± 7.92 to 7.42 ± 6.25; p = 0.002), LH/follicle-stimulating hormone ratio (2.34 ± 0.34 to 1.91 ± 0.32; p = 0.000), fasting serum insulin levels (16.71 ± 13.92 to 13.18 ± 9.41; p = 0.041), and homeostatic model assessment for insulin resistance (4.52 ± 1.34 to 2.74 ± 1.28; p = 0.041). Conclusions According to our study, it was observed that myo-inositol led to a statistically significant improvement in the hormonal and metabolic profile of PCOS patients. Moreover, it is safe and has good compliance. Hence, we can justify the addition of myo-inositol to the armamentarium for PCOS management.