Polycystic Ovary Syndrome Population Research Articles

The Clinical Use of Myo-Inositol in IVF-ET: A Position Statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies.

Background: Myo-inositol plays a vital role in human health, functioning as a second messenger of FSH and facilitating the transport of glucose into the cell. Consequently, myo-inositol is regularly utilized in the treatment of polycystic ovary syndrome (PCOS), wherein it acts upon metabolic factors, improving insulin sensitivity and reducing total androgen levels. Patients with PCOS frequently suffer from infertility; thus, the use of myo-inositol has been explored in improving assistive reproductive technique (ART) procedures. This is by no means limited to patients with PCOS, as inositol has found applications in non-PCOS patient groups in addition to in male factor infertility. This joint statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies discusses the latest evidence on this topic, with the aim of interrogating whether myo-inositol could be implemented in everyday ART patient care. Methods: The authors conducted a narrative review performed via an independent literature search between July and August 2024, using the search platforms PubMed, Web of Science, and Google Scholar. Results: In both non-PCOS and PCOS populations seeking IVF care, MI supplementation prior to ovarian stimulation may positively affect gonadotropin use and duration, oocyte and embryo quality, fertilization, and clinical pregnancy rates. Conclusions: This position statement recommends that myo-inositol be considered as a potential pretreatment strategy prior to ovarian hyperstimulation with gonadotropins.

Adverse Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome with Pre-Conceptional Hyperandrogenism: A Multi-Institutional Registry-Based Retrospective Cohort Study

Background/Objectives: Women with polycystic ovarian syndrome (PCOS) are at higher risk for pregnancy complications. The PCOS population is heterogeneous, with different phenotypes linked to varying risks of adverse outcomes. However, literature on pre-conceptional hyperandrogenism is limited and based on small sample sizes. Methods: This multi-institutional registry-based retrospective cohort study included pregnant patients diagnosed with PCOS with or without pre-conceptional hyperandrogenism. Utilizing the TriNetX platform, one-to-one propensity score matching was conducted to adjust for confounding factors. Exclusion criteria included multiple pregnancies and patients who received assisted reproductive technology, oral contraceptives, or spironolactone. 571 patients with PCOS and pre-conceptional hyperandrogenism and 13,465 patients with PCOS without hyperandrogenism were identified. Post-propensity matching, each cohort consisted of 564 patients. Results: Pregnant women diagnosed with PCOS and pre-conceptional hyperandrogenism showed a higher risk of large for gestational age (6.6% vs. 3.9%, OR = 1.73, 95% CI [1.007–2.972], p-value = 0.045) and preterm birth (10.3% vs. 5.9%, OR = 1.844, 95% CI [1.183–2.876], p-value = 0.006), but had no significant increase in the risk of gestational hypertension, preeclampsia/eclampsia, gestational diabetes, missed abortion, intrauterine growth restriction, placenta abruption, or cesarean section. Conclusions: Women with PCOS and pre-conceptional hyperandrogenism have an increased risk of pregnancy complications, especially large for gestational age and preterm birth. Further research is needed to clarify the underlying mechanisms, and whether treatment can improve outcomes.

A Review on the Effects of Aerobic Exercise on Immune Dysregulation in Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-aged females. However, much of its pathophysiology is not well investigated or understood. Research has demonstrated an association between PCOS and metabolic dysfunction, including insulin resistance. The aim of this review was to investigate how immunological dysregulation might be mediating these metabolic disturbances, as well as how exercise might modulate the over-inflammatory state that has been observed in the PCOS population. A review of literature was conducted using PubMed, following the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guidelines. Results indicated that women with PCOS had higher levels of immunological mediators at baseline when compared to their counterparts without PCOS, suggestive of dysregulated immunological mechanisms. Despite exercise demonstrating benefits in lowering these inflammatory markers in women with PCOS, participants enrolled in exercise programs were unsuccessful in reaching the levels of inflammation comparable to women without PCOS. Further research is warranted to continue investigation into the mechanisms behind the over-inflammatory state observed in women with PCOS and how to best advise patients in managing such inflammation for an improved quality of life.

Impact of Comorbid Polycystic Ovary Syndrome on Clinical and Laboratory Parameters in Female Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings.

Women with polycystic ovary syndrome are at risk of emotional and uncontrolled eating at midlife: a population-based cohort study

To investigate eating behavior domains-emotional, uncontrolled, and cognitive restraint eating-in women with polycystic ovary syndrome (PCOS) with different PCOS phenotypes and women without PCOS at midlife. A prospective cohort study. Eating behavior domains were assessed at age of 46 years. Predictors of eating behaviors were evaluated using variables collected at ages of 31 and 46 years. Not applicable. Women identified as having PCOS (n = 251) at age of 31 years using the updated Rotterdam criteria were compared with women without any PCOS criteria (n = 935). The PCOS population comprised women with the classic A+B-phenotype (hyperandrogenism and oligomenorrhea, with or without elevated antimüllerian hormone, n = 60), C-phenotype (hyperandrogenism and elevated antimüllerian hormone, n = 84), and D-phenotype (oligomenorrhea and elevated antimüllerian hormone, n = 86). Not applicable. Revised Three-Factor Eating Questionnaire-18 scores for eating behavior domains. Compared with women without PCOS, women with PCOS exhibited higher scores for emotional (33.1 ± 27.8 vs. 39.0 ± 29.9) and uncontrolled eating (26.7 ± 18.2 vs. 30.7 ± 19.4) but no difference in cognitive restraint (46.6 ± 18.6 vs. 45.9 ± 18.5) at age of 46 years. Emotional and uncontrolled eating scores were higher in the A+B-phenotype compared with women without PCOS, whereas uncontrolled eating scores in the C-phenotype were higher than in women without PCOS and the D-phenotype. At age of 46 years, the perception of overweight was an independent predictor of emotional eating among women with PCOS (B = 11.96 [95% confidence interval {CI}: 2.81-20.29]), whereas a history of weight loss attempts was a predictor of uncontrolled eating (B = 6.06 [95% CI: 1.05-10.83]). Among women with PCOS, higher psychological distress at age of 31 years was a significant risk factor for scoring in the highest quartile of emotional (adjusted odds ratio [aOR]: 2.85 [95% CI: 1.19-6.85]) and uncontrolled eating (aOR: 4.37 [95% CI: 1.77-10.80]) at age of 46 years. Women with PCOS at midlife showed a high tendency for unfavorable eating behaviors. Our findings emphasize the need for sensitivity in weight management counseling and addressing psychological distress to prevent unfavorable eating in this population.

Association between IL-6 -174 G/C (rs1800795) and IL-1A -889 C/T (rs1800587) cytokine variants with polycystic ovary syndrome in Iranian women: A case-control study

Background and AimInfertility in women has various causes, one of which is ovulation disorders. Polycystic ovary syndrome (PCOS) affecting ovulation is a complex idiopathic disease in which genetic polymorphisms may be involved. This study aimed to investigate the relationship between IL-6 -174 G/C and IL-1A -889 G/A cytokine polymorphisms with polycystic ovary syndrome in a population of Iranian women. Materials and MethodsIn this case-control pilot study, 120 PCOS patients (60 infertile, LPI, and 60 women with recurrent pregnancy abortion, LPA) and 60 controls, CTRLs) participated. After genomic DNA extraction from peripheral blood, we investigated for the polymorphisms rs1800795 of the IL-6 -174 and rs1800587 of the IL-1A-889 using specific primers and PCR-RFLP followed by NlaIII enzyme digestion and PCR-ARMS techniques. ResultsThere was a significant difference in the studied groups in terms of clinical characteristics (p-value < 0.05) except for the levels of HDL and LDL. Regarding demographic and clinical characteristics of patients, a significant correlation was observed between C/G and G/G genotypes of rs1800795 and FBS level (p value = 0.002). Also, rs1800587 showed a substantial relationship between CC and CT genotypes with the level of LH in LPI and the level of FBS in the LPAs (p value = 0.04). There was no significant difference between the frequencies of rs1800795 and frequencies of rs1800587 genotypes in the three studied groups (p value > 0.05).The studied variants were in Hardy-Weinberg equilibrium. ConclusionThe present work showed that rs1800795 and rs1800587 were not directly associated with PCOS in Iranian patients while the SNPs showed an indirect relationship with some factors affecting the disease.However, using genome-wide association analysis is a proper suggestion to obtain more reliable information about the disease’s genetic view. To our knowledge, this is the first report that implicates the role of the examined SNPs in an Iranian PCOS population.

The impact of hyperandrogenemia on pregnancy complications and outcomes in patients with PCOS: a systematic review and meta-analysis

ABSTRACT Background Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder. Current research findings present conflicting views on the effects of different PCOS phenotypes on outcomes in pregnancy and for newborns. Methods This research study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A thorough search of literature was carried out using the Cochrane Menstrual Disorders and Subfertility Group trials register, Web of Science, and EMBASE databases from their start to December 2023. The search focused on studies examining the links between hyperandrogenic and non-hyperandrogenic PCOS phenotypes and risks in pregnancy and neonatology. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using either a fixed-effects or random-effects model. Results Our analysis incorporated 10 research studies. Expectant mothers with a hyperandrogenic PCOS subtype had increased ORs for gestational diabetes mellitus (GDM) and preeclampsia (PE) compared to those with a non-hyperandrogenic PCOS subtype, with respective values of 2.14 (95% CI, 1.18–3.88, I2 = 0%) and 2.04 (95% CI, 1.02–4.08, I2 = 53%). Nevertheless, no notable differences were detected in ORs for outcomes like preterm birth, live birth, miscarriage, cesarean delivery, pregnancy-induced hypertension, small for gestational age babies, large for gestational age newborns, and neonatal intensive care unit admissions between pregnant women with hyperandrogenic PCOS phenotype and those without. Conclusions This meta-analysis highlights that the presence of hyperandrogenism heightens the risks of GDM and PE within the PCOS population. Healthcare providers ought to be aware of this connection for improved patient management.

Altered expression of kisspeptin, dynorphin, and related neuropeptides in polycystic ovary syndrome: A cross-sectional study.

Since kisspeptin (KISS1) in the hypothalamus is affected by the inhibitory effect of dynorphin, it raises questions about the controlled balance of these 2 neuropeptides in women with and without polycystic ovary syndrome (PCOS). This study compares the expression levels of KISS1, dynorphin, neurokinin-B, leptin, and neuropeptide-Y in women with and without PCOS. In this cross-sectional study, the peripheral blood samples of 20 women with PCOS and 20 women without PCOS who referred to Yamin Kencana Clinic, Cipto Mangunkusumo hospital, Jakarta, Indonesia were enrolled from August-December 2022. mRNA relative expression of genes related to the central factors associated with PCOS, such as leptin, neuropeptide-Y, KISS1, tachykinin-3, and prodynorphin (PDYN), in PCOS and non-PCOS populations were examined. Gene quantification was carried out by the quantitative polymerase chain reaction method. The KISS1/PDYN ratio was significantly higher in the PCOS group than in the control group (p = 0.02), and the PDYN was lower in the PCOS group than the control group (p 0.001). Moreover, the positive correlation between KISS1 and the KISS1/PDYN ratio was significantly stronger in the PCOS group than in the control group (R = 0.93; p 0.001 vs. R = 0.66, p 0.001). Our results suggest that an increased KISS1/PDYN ratio in PCOS women is related to diminished dynorphin expression. Low expression of the gene encoding dynorphin and a high KISS1/PDYN ratio is highly specific to PCOS.

Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.

Vitamin D deficiency, insulin resistance, and antimüllerian hormone level: a tale of trio in the expression of polycystic ovary syndrome

To study the association between altered vitamin D profiles and different indices as well as clinical features of polycystic ovary syndrome (PCOS), including antimüllerian hormone (AMH) levels, phenotypes (A [hyperandrogenism {HA} + ovulatory dysfunction {OD} + polycystic ovarian morphology {PCOM}], B [HA + OD], C [HA + PCOM], and D [OD + PCOM]), insulin resistance, oligomenorrhea, hyperandrogenism, obesity indices, and stress biomarkers in the ethnic population of West Bengal. Case-control observational study. Outpatient department of gynecology and obstetrics and environing. Sample size: case group (PCOS, n = 160), age: 16-38 years, and their gender, age, as well as ethnicity-matched healthy control (n = 160). In this observational study, a structured questionnaire for menstrual status and to determine the scores of cutaneous manifestations, a bioelectrical impedance analyzer for measurement of anthropometric indices, relevant biochemical assessments (vitamin D, AMH, insulin, glucose, and other associated hormonal profiles), statistical software for the social sciences, and Microsoft Office Excel were used to evaluate as well as analyze different indices. Study of the association of vitamin D deficiency with differential manifestations of PCOS such as phenotypes of the syndrome, altered AMH levels, and risk of insulin resistance. An attempt has been made to determine the cutoff value of AMH of the patients with PCOS belonging to the ethnic population of West Bengal using receiver operating characteristic (ROC). Vitamin D deficiency was found to be directly correlated with AMH level in PCOS phenotype A (67%), oligomenorrhea, and PCOM, along with a substantial agonistic relationship with insulin resistance in the PCOS population under study. In the PCOS phenotype B, the AMH level was highest, with a cutoff value of 5.27 ng/mL (asymptotic sig. = 0.000, 95% confidence interval: 8.37-9.95, derived by ROC analysis, with area under the ROC curve- area under the curve value = 0.949, sensitivity=0.882, and specificity = 0.880). Oligomenorrhic women with PCOS possess significantly higher values of AMH levels (8.70 ± 3.66 > 3.09 ± 1.86 ng/mL) level than the regular menstrual rhythm within the same group. Patients with PCOS had significantly less skeletal muscle mass and greater subcutaneous fat content than the control group. 25-hydroxy-vitamin D might be intermeshed with the underlying pathophysiology and severity of PCOS, as well as associated metabolic disorders like insulin resistance. The AMH level is finely tuned by most of the plausible effectors of PCOS and contends to be a promising biomarker for the diagnosis as well as prognosis of PCOS.

Meteorin-like Protein and Zonulin in Polycystic Ovary Syndrome: Exploring Associations with Obesity, Metabolic Parameters, and Inflammation.

Polycystic ovary syndrome (PCOS) is a prevalent hormonal and metabolic disorder, wherein the adipose tissue and gut microbiome have been demonstrated to contribute to its pathogenesis. This study aims to assess the concentrations of the adipokine, meteorin-like protein (Metrnl) and the protein, zonulin, related to intestine permeability, in individuals with PCOS with a particular emphasis on their relationship with obesity, clinical manifestations, hormonal profiles, and metabolic parameters. A cohort comprising 58 women with PCOS, classified according to the Rotterdam criteria, was enrolled. The study also considered age, body mass index (BMI), and ethnicity-matched controls (n = 30). Comprehensive anthropometric and clinical evaluations, hormonal assays, and biochemical analyses were conducted during the follicular phase. Subsequent subgroup analyses were executed within the PCOS cohort based on waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum concentrations of Metrnl and zonulin were quantified via the enzyme-linked immunosorbent assay (ELISA) technique. The Metrnl and zonulin levels exhibited no significant disparity between PCOS patients and controls. Nevertheless, within the entire participant cohort and the PCOS group exclusively, overweight/obese participants demonstrated higher Metrnl concentrations relative to their normal-weight counterparts (p < 0.001, p = 0.001, respectively). Furthermore, higher Metrnl concentrations were identified in subgroups characterized by high WHtR and IR in comparison to those with low WHtR (p = 0.001) and without IR (p = 0.001), respectively. A correlation emerged between Metrnl levels and various anthropometric and metabolic parameters, as well as sex-hormone-binding globulin (SHBG) and interleukin-18 (IL-18) within the PCOS group. Multiple linear regression analysis identified HOMA-IR as the sole independent predictor of Metrnl levels. While Metrnl and zonulin levels do not serve as diagnostic indicators of PCOS, elevated Metrnl concentrations exhibited robust associations with proinflammatory and metabolic irregularities within the PCOS population.

THU626 Impact Of Body Mass Index On Clinical And Endocrinological Characteristics Of Indian PCOS Population

Abstract Disclosure: S. Pandey: None. K. Ojha: None. K. Jayprakasan: None. K. Khanduri: None. The prevalence of polycystic ovarian syndrome (PCOS), defined based on the Rotterdam criteria, in Indian women is about 10% and the clinical characteristics can be different compared to western PCOS population. The objectives of this study are to evaluate the baseline clinical characteristics of PCOS women and to compare the characteristics in different population categorised based on body mass index (BMI). Material &amp; Methods: In this observational study done at a tertiary fertility unit in Northern India, all PCOS women, defined based on the Rotterdam criteria, attended the clinic during 2018-2022 were included (n=554). Women with known endocrine issues were excluded. The baseline characteristics - age, BMI, blood pressure (BP), hirsutism assessed by Ferriman-Galleway (FG) score, acanthosis nigricans, AMH, prolactin, TSH- were assessed. Results: While the mean (±standard deviation) age of patients the study population was found to be 27.2 ±4.1 years, the mean BMI was 25.8±4.4 Kg/m2 and Acanthosis nigricans was observed in 87 (17.51%) women. The mean B.P. was 116/76 (±9/8) mmHg and the mean FG score was 3±1. The mean AMH, TSH and prolactin were 7.26±4.39ng/mL, 3.42±5.21mIU/mL and 17.07±15.92ng/mL respectively. BMI was classified in four categories- ≤22.9 (normal, n=121), 23-24.99 (overweight, n=111), 25-29.99 (pre-obese, n=182) and ≥30.0 (obese, n=76). The mean age across the four BMI groups were 26.1±3.9, 27.5±3.9, 27.2±4.2 and 29.0±4.0 years respectively (P&amp;lt;.001). The BP increases as the BMI increases (114/74 (±8/8), 116/76 (±8/8), 117/76 (±9/8) &amp; 120/77 (±11/8) Kg/m2 respectively; P= &amp;lt;0.05). There was no difference in FG scores across the four BMI groups (3±1, 3±1, 3±2, 3±2, respectively; P=0.8). While the AMH (7.42±4.66, 6.99±4.30, 7.49±4.43, 6.87±3.95ng/mL, respectively; P=0.644) and prolactin (17.38±19.02, 17.84±14.92, 17.55±16.22, 14.27±9.62ng/mL, respectively; P=0.42) were similar across the four BMI groups, the TSH tend to be higher in the higher BMI groups (2.77±1.70, 3.09±1.93, 3.45±4.07, 4.88±11.23mIU/mL respectively; P=0.038). The prevalence of Acanthosis nigricans (12(9.4%), 20(18%), 29 (15.9%), 26 (34.2%), respectively; P=&amp;lt;0.001) was also found higher in the higher BMI groups. After conducting post-hoc analysis, it was found out that obese (≥30) group has highest mean of TSH (4.88±11.23) level, Age (28.97±4.04), B.P. count (120/77 (±11/±8)) and prevalence of acanthosis nigricans (34.2%). Discussion-While the mean (±SD) age of the study population was 27±4.1 years, the mean BMI was 25±4 Kg/m2. When categorized based on BMI (n=182; 32.9%) fell into the pre-obese group. While BMI showed a positive correlation with age, B.P., TSH and Acanthosis nigricans, nevertheless, the mean AMH, prolactin and FG score were similar across the 4 BMI groups. Presentation: Thursday, June 15, 2023

Pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome: a Korean National Health Insurance Service study

ObjectivePolycystic ovarian syndrome is associated with diverse pregnancy related complications and endometrial cancer. However, research on the relationship between pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome...

Circulating bile acid profile characteristics in PCOS patients and the role of bile acids in predicting the pathogenesis of PCOS.

The metabolic profile of bile acids and their potential role as biomarkers in the pathogenesis of polycystic ovary syndrome (PCOS) have not been thoroughly characterized. Assessing their predictive value for PCOS is of significant importance. In this study, we enrolled 408 women with PCOS and 204 non-PCOS controls. The serum bile acid profile was measured using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). We analyzed the differences in serum bile acid profiles between PCOS patients using the OPLS-DA model. Additionally, we examined the relationship between bile acid profiles and parameters related to glucose metabolism and hyperandrogenism. ROC analysis was employed to identify potential biomarkers for PCOS pathogenesis. XGboost was utilized for cross-validation. The bile acid profile was found to be altered in PCOS patients. Specifically, the primary and secondary unconjugated bile acid fractions were significantly higher in the PCOS population. We identified five bile acid metabolite candidates that exhibited the most significant differences between PCOS and non-PCOS controls. DCA was associated with deposition index, fasting and postprandial insulin but was influenced by testosterone. CDCA and LCA combined with testosterone showed potential as biomarkers for the pathogenesis of PCOS. The circulating bile acid profile undergoes changes in PCOS. DCA is associated with deposition index, fasting and postprandial insulin and its level is influenced by testosterone. CDCA and LCA combined with testosterone have the potential to serve as biomarkers for the pathogenesis of PCOS.

Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients.

Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a nonobese, non-insulin-resistant PCOS population in a proteomic analysis to investigate this. Plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin-resistant population (24 with PCOS and 24 controls). Slow off-rate modified aptamer (SOMA) scan plasma protein measurement was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, factor B, factor D, factor H, factor I, Mannose-binding protein C (MBL), complement decay-accelerating factor (DAF) and complement factor H-related protein 5 (CFHR5). The alternative pathway of the complement system was overexpressed in both obese and nonobese PCOS, with increased C3 (p < 0.05) and properdin (p < 0.01); additionally, factor B increased in obese PCOS (p < 0.01). For inhibitors of this pathway, factor I was increased (p < 0.01) in both slim and obese PCOS, with an increase in CFHR5 and factor H in obese PCOS (p < 0.01). Complement factors iC3b, C3d and C5a, associated with an enhanced B cell response and inflammatory cytokine release, were increased in both slim and obese PCOS (p < 0.05). C3a and its product, C3adesArg, were both significantly elevated in nonobese PCOS (<0.01) but not altered in obese PCOS. Hyperandrogenemia correlated positively with properdin and iC3b in obese PCOS (p < 0.05) but not in nonobese PCOS. There was no association with insulin resistance. BMI correlated positively in both groups with factor B, factor H and C5a. Additionally, in obese PCOS, BMI correlated with C3d, factor D, factor I, CFHR5 and C5a (p < 0.05), and in nonobese PCOS, BMI correlated with properdin, iC3b, C3, C3adesArg, C3a, C4, C5, C5a and C1q. In obese controls, BMI correlated with C3, C3desArg, C3a, C3d, C4, factor I, factor B, C5a and C5, whilst in nonobese controls, BMI only correlated negatively with C1q. Comparison of nonobese and obese PCOS showed that properdin, C3b, iC3b, C4A, factor D, factor H and MBL differed. The upregulation of the alternative complement pathway was seen in nonobese PCOS and was further exacerbated in obese PCOS, indicating that this is an inherent feature of the pathophysiology of PCOS that is worsened by obesity and is reflected in the differences between the nonobese and obese PCOS phenotypes. However, the increase in the complement proteins associated with activation was counterbalanced by upregulation of complement inhibitors; this was evident in both PCOS groups, suggesting that insults, such as a cardiovascular event or infection, that cause activation of complement pathways may be amplified in PCOS.

Oxidative Stress Markers and Heat Shock Proteins in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D.

Oxidative stress (OS) is recognized in the pathophysiology of polycystic ovary syndrome (PCOS). OS results in intracellular reactive oxygen species generation, causing oxidative protein damage that is protected by heat shock proteins (HSPs). Vitamin D is thought to reduce and protect against OS; therefore, OS, HSP, and vitamin D levels may be associated with PCOS. However, their expression in PCOS without underlying inflammation is unknown. In this exploratory study, the plasma levels of 7 OS proteins and 10 HSPs that are affected by the OS process were measured using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurements in non-obese, non-insulin resistant women with PCOS (n = 24) without systemic inflammation and control (n = 24) women; the cohorts were matched for weight and age. The OS proteins and HSPs were correlated with 25-hydroxy vitamin D3 (25(OH)D3) and the active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), as measured by isotope-dilution liquid chromatography tandem mass spectrometry. The PCOS women versus the controls had comparable insulin resistance and systemic inflammation (C-reactive protein 2.0 mg/L vs. 2.3 mg/L, p > 0.05), but higher free androgen index and anti-mullerian hormone levels. Among the OS proteins, only esterase D (ESD; p < 0.01) was elevated in PCOS and the HSPs did not differ between the PCOS and control women. There was no correlation of 25(OH)D3 or 1,25(OH)2D3 with any of the proteins. In a PCOS population that was non-obese and without insulin resistance and systemic inflammation, only ESD was elevated in PCOS, whilst the other OS proteins and HSPs were not elevated. Further, none of the OS proteins or HSPs were correlated with either 25(OH)D3 or 1,25(OH)2D3 in either cohort of women or when both cohorts were combined, indicating that the OS and HSP responses were largely absent and not affected by vitamin D in a non-obese PCOS population.

P-647 Underlying mechanisms in clinical manifestations of polycystic ovarian morphology (PCOM) and PCOS women

Abstract Study question Does the D19S884 allele 8 (A8) equally affect the pathogenesis and ovarian gene expression of PCOS and PCOM patients? Summary answer A8-allele produces metabolic, endocrine, and ovarian alterations regardless diagnose. The mechanisms involved in PCOM alterations are different from those of the ovarian phenotype of PCOS. What is known already The specific D19S884 allele 8 of the FBN3 gene may be related to polycystic ovarian syndrome (PCOS) clinical manifestations. The A8 allele participates in alternative splicing of FBN3 and produces Asprosin-3, related to glucose modulation, and Fibrillin-3. Fibrilin-3 is an extracellular matrix protein, and together with a dysregulation of the Hippo pathway, could be responsible for constraining follicular growth in the PCOS ovaries. However, it is still unknown how these pathways act in PCOS, and whether these mechanisms are also involved in pathophysiology of polycystic ovarian morphology (PCOM) in apparently normal women with regular menses. Study design, size, duration Cross-sectional and descriptive study with 139 women (24-39 years-old) undergoing an IVF cycle between 2019-2022 at Hospital La Fe (Valencia, Spain). Thirty-one patients were considered PCOS, twenty-eight were classified as PCOM while the remaining eighty were controls. After recruitment women were screened for A8 allele, metabolic status, hormone profile, follicular fluid protein determination and expression of Hippo pathway and extracellular matrix genes. The IVF cycle parameters were recorded to determine their relationship with study variables. Participants/materials, setting, methods Women with two or more Rotterdam-criteria were considered as PCOS. PCOM patients were defined by polycystic ovarian morphology on ultrasound with regular ovulatory cycles. Genomic DNA was isolated from blood samples to assess the presence of A8 allele by capillary electrophoresis and FBN3 concentration was measured on follicular fluid by ELISA. TaqMan qPCR assay was used to analyze the expression of Hippo pathway (BIRC1 and CCN2) and extracellular matrix (ECM) genes in cumulus cells. Main results and the role of chance PCOS patients showed statistically significant metabolic and endocrine alterations with higher BMI, free androgen index (FAI), and glucose levels compared to controls. Despite having increased AMH levels (PCOS:45.0±21.7; PCOM:33.8±21.5; Control:17.6±7.19pmol/L, p &amp;lt; 0.05), and AMH/AFC ratio (PCOS:1.9±0.9; Control:1.2±0.5, p = 0.008), PCOS showed lower fertilization rates (PCOS:64±26; Control:80±18%, p = 0.008), reduced good quality (PCOS:0.6±1.0; Control:1.3±1, p = 0.003) and transferred embryos (PCOS:1.3±0.9; Control:1.9±1.0, p = 0.018). In PCOM, metabolic and androgen profiles were not different from controls. Although AMH, AFC (PCOM:24.4±13.7; Control:15.5±7.1, p = 0.007) and aspirated follicles (PCOM:17.3±5.7; Control:14.3±7.0, p = 0.026) were increased, fewer embryos were transferred (PCOM:1.2±1.1; Control:1.9±1.0, p = 0.027). PCOM women also showed ovarian downregulation of the Hippo-pathway (CCN2-PCOM:-4.8±10.8; Control:0.1±3.0, p = 0.010) and increased FBN3 concentration (PCOM:19.6±8.8; Control:14.7±5.6ng/ml, p=N.S). The A8 allele was detected in 17% of our patients: 4% PCOS, 50% PCOM and 46% controls. Overall, A8 presence associated a Hippo-pathway downregulation (BIRC1-A8+:-2.7±4.5; A8-:0.3±2.2, p = 0.034) and increased ECM expression (EMILIN1-A8+:2.1±1.0; A8-:1.2±1.5, p = 0.04). Interestingly, in controls, higher glucose (A8+:95.1±6.7; A8-:83.5±10.1mg/dl, p = 0.002), cholesterol (A8+:182.5±11.1; A8-:165.4±27.3mg/dl, p = 0.029), LDL (A8+:117.8±10.4; A8-:83.9±29.4mg/dl, p = 0.002), and DHEAS levels (A8+:2633.0±670.7; A8-:1585.8±670.0ng/ml, p = 0.026) were found, consistent with a reduction in HDL (A8+:51.8±8.8; A8-:67.4±15.43mg/dl, p = 0.026) and a downregulation of the Hippo-pathway (BIRC1-A8+:-4.8±4.6; A8-:0.2±4.6, p = 0.013). In PCOM, A8+ promoted higher FAI (A8+:1.6±1.5; A8-:0.8±0.7, p=N.S), and less embryos obtained (A8+:5.9±3.8; A8-:10.7±3.8, p = 0.04). Limitations, reasons for caution Due to the low prevalence of A8 in our PCOS population, its effects cannot be evaluated in this group. Further validation of gene expression results by RNA-seq will be required to assess the broad spectrum of ovarian transcriptomic changes induced by both, the PCOM phenotype and the A8 allele. Wider implications of the findings Polycystic ovarian morphology is not unique to clinical disorder of PCOS and the triggering mechanisms appear to be distinct from those observed in women with regular cycles. Our findings suggest that the presence of A8 allele impacts on metabolic profile, androgen levels, and ovarian pathway dysregulations, despite the clinical diagnose. Trial registration number Not applicable

Staying up late increases cardiovascular disease risk in women with polycystic ovary syndrome.

What is the association between late bedtime, night sleep duration, and lifetime cardiovascular disease (CVD) risk in women with polycystic ovary syndrome (PCOS)? Both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among women with PCOS. Previous studies indicated that sleep disturbances, including altered sleep duration and staying up late (SUL), occurred more frequently among women with PCOS compared to women without PCOS. Studies have shown that both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term. However, there are limited data regarding the possible association between sleep disturbances and CVD risk among reproductive-aged women with PCOS. From the original 393 women identified at our center, a total of 213 women with PCOS aged 18-40 years were enrolled in a cross-sectional study between March 2020 and July 2022. Bedtime and night sleep duration were obtained from a standardized self-administered questionnaire. The prediction for atherosclerotic CVD risk in the China risk model was applied to estimate the lifetime CVD risk in the PCOS population. Restricted cubic spline regression was applied to explore the non-linear association between sleep duration and lifetime CVD risk in a series of models. Multivariable logistic regression analyses were performed to determine the association between bedtime, night sleep duration, and lifetime CVD risk. In our study, we found that the proportion of SUL was 94.25% and the mean (±SD) of night sleep duration was 7.5 ± 1.1 h in women with PCOS. Restricted cubic spline regression analysis showed a U-shaped relation between sleep duration and lifetime CVD risk. After adjusting for occasional drinking, fasting insulin, triglyceride, low-density lipoprotein cholesterol, and testosterone in multivariable logistic analyses, compared with going to bed at 23-24 o'clock, those who went to bed after 1 o'clock were independently associated with high-lifetime CVD risk [odds ratio (OR) = 3.87, 95% CI: 1.56-9.62]; compared with optimal sleep duration (7-8 h/night), short sleep (<7 h/night) was also independently associated with high-lifetime CVD risk (OR = 2.46, 95% CI: 1.01-5.97). Inferring causality is limited owing to the cross-sectional design. All sleep variables data were obtained from a standardized self-administered questionnaire rather than measurements using objective approaches. Even after adjusting for potential confounders, we still cannot completely rule out the possibility of residual confounding from unmeasured factors such as socioeconomic status. Future studies with larger sample sizes are needed to further explore the relation between long sleep duration and lifetime CVD risk. Although these findings are not generalizable to non-SUL PCOS populations, they could be used for guiding multidimensional treatment. Lastly, there is no non-PCOS group in the current cross-sectional study, which limits the interpretation of the findings from the PCOS group. This is the first study to report that both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among reproductive-aged women with PCOS, in a sample of Chinese adults. Predicting cardiovascular risk and examining the association between sleep disturbances and predicted CVD risk among women with PCOS help to highlight the need for early interventions on sleep to improve their cardiovascular outcomes. This study was funded by the Natural Science Foundation of Fujian Province (No. 2020J011242), the Fujian provincial health technology project (No. 2022CXB016), the Joint Research Projects of Health and Education Commission of Fujian Province (No. 2019-WJ-39), and the Medical and Health project of Xiamen Science & Technology Bureau (No. 3502Z20214ZD1001). The authors declare that they have no conflict of interest. N/A.

Vitamin D and pathophysiology of polycystic ovary syndrome: A case–control study

Abstract Context: Polycystic ovarian syndrome (PCOS) is a polygenic and multifactorial endocrinopathy. Vitamin D deficiency (VDD) is found to be interlinked with insulin resistance (IR), dyslipidemia, and obesity in PCOS. Aims: To find out the correlation of VDD with IR and dyslipidemia in PCOS population of West Bengal (WB). Settings and Design: The study was conducted in and around Kolkata, WB with PCOS patients and their age-matched controls. Materials and Methods: Nutritional status, vitamin D profile, obesity indices, and IR index of both PCOS and control groups were studied. Statistical Analysis Used: The statistical analysis was performed to estimate the difference and correlation of quantitative variables by using Statistical Package for the Social Sciences (SPSS, version 20, IBM). Results: Dietary fat and carbohydrate intake was significantly higher in PCOS individuals relative to recommended dietary allowance (RDA) and the control group. Deficiency of serum 25-OH vitamin D (VDD) is evident in both the control and PCOS groups. However, the prevalence of IR among PCOS patients is significantly higher (64%) than in control (4%), and it is significantly correlated with VDD (P &lt; 0.01). homeostatic model assessment for insulin resistance is found to be a comorbidity of dyslipidemia in PCOS patients. Conclusions: VDD, IR, and obesity potentially aggravate the phenotypic manifestations of PCOS. VDD in the control individuals of young age might be an alarming forecast for the development of PCOS in future life.

Value of the triglyceride-glucose index and non-traditional blood lipid parameters in predicting metabolic syndrome in women with polycystic ovary syndrome.

Insulin resistance (IR) is common in patients with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) includes, inter alia, IR, hypertension, dyslipidemia, and disturbances in glucose metabolism. The triglyceride-glucose (TyG) index and non-traditional lipid parameters are strong predictors of IR and cardiovascular disease and can be considered as screening indicators for MS. This study aimed to evaluate the predictive potential of non-traditional lipid parameters and the TyG index to identify MS in PCOS. This cross-sectional study included 134 women diagnosed with PCOS (50 patients with comorbid MS and 84 patients without MS). Biochemical indices were collected, and triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, non-HDL-C, TyG, and TyG-BMI indices were calculated. Logistic regression analysis was used to compare and determine the association of the six parameters with MS, and the receiver operating characteristic (ROC) curve was used to evaluate the performance of each parameter in identifying MS in the PCOS population. After adjusting for age and body mass index (BMI), TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI were associated with MS (all P<0.05). The odds ratios were 4.075 (0.891, 1.107), 3.121 (1.844, 5.282), 3.106 (1.734, 5.561), 2.238 (1.302, 3.848), 13.422 (4.364, 41.282), and 1.102 (1.056, 1.150), respectively. TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI are effective predictors of MS in PCOS, and their cut-off values can be used for the early detection of MS. TyG-BMI had the strongest performance in predicting MS (area under the curve 0.905, 95% CI 0.855-0.956), and its optimal critical value for predicting MS was 202.542. TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C, TyG, and TyG-BMI are novel, clinically convenient and practical markers for the early identification of MS risk in PCOS patients.