Marker For Polycystic Ovary Syndrome Research Articles

Reliability and Agreement of Ultrasonographic Measures of the Ovarian Stroma: Impact of Methodology

Increased ovarian stromal area (SA), stromal-to-ovarian area ratio (S/A), and echogenicity (SEcho) on ultrasonography have been proposed as diagnostic markers for polycystic ovary syndrome. Although several methods to evaluate the stroma exist, their reproducibility has not been defined which limits clinical utility. This study aimed to determine the interrater reliability and agreement of methods to evaluate SA, S/A, and SEcho. Five raters tested 3 methods to obtain SA and S/A, and one to obtain SEcho on 30 ovarian cineloops under two imaging conditions, simulating real-time (free-choice) or offline (fixed-frame) imaging. For SA, Method 1 subtracted follicular area from the ovarian area, Method 2 involved outlining the periphery of the stroma, and Method 3 represented a hybrid approach in which central follicles were subtracted from the outlined stroma. SEcho was scored on a subjective 3-tiered scale. Intraclass correlation coefficients (ICCs) and the coefficient of variation were determined for SA and S/A, and Fleiss' kappa agreement statistics (κ) were determined for SEcho. Interrater reliability of SA was superior using Method 1 (ICC=0.558 and ICC=0.705) versus Method 2 (ICC=0.522 and ICC=0.230) or Method 3 (ICC=0.429 and ICC=0.305) under free-choice and fixed-frame imaging conditions, respectively. Interrater reliability of S/A was also moderate to poor across methods. SEcho was also not reliably assessed across raters (κ=<0.500). Ultrasonographic assessments of the ovarian stroma were associated with moderate to poor reproducibility. Indirect estimates of the ovarian stroma (Method 1) could be optimized to yield a reproducible approach, clarifying the clinical relevance of the stroma.

Investigating Fetuin-A and Paraoxonase-1 Activity as Markers in Polycystic Ovary Syndrome Based on Body Mass Index: A Prospective Case-Control Study.

IntroductionPolycystic ovary syndrome (PCOS) may have an increased risk for the development of systemic and metabolic pathogenesis such as cardiovascular diseases, insulin resistance (IR), diabetes mellitus (DM) and dyslipidemia. However, there is no reliable marker to show the relation. Fetuin-A is an adipokine whereas paraoxonase-1 (PON-1) is a high-density lipoprotein-linked enzyme to demonstrate oxidative stress. This study aimed to evaluate serum fetuin-A and PON-1 levels in infertile PCOS women based on body mass index (BMI).MethodsA prospective case-control study in a university setting was designed. A total of 88 patients admitted to the Giresun University Faculty of Medicine Gynecology Clinic between February and April 2021 were included in the study. The subjects were divided as follows: PCOS-low-BMI (BMI≤25) vs. Controls-low-BMI (BMI≤25) and PCOS-high-BMI (BMI>25) vs. Controls-high-BMI (BMI>25). Those who had at least two criteria of the 2003 Rotterdam Consensus were diagnosed with PCOS. Serum fetuin-A and PON-1 levels were compared.ResultsThe mean levels of fetuin-A were not significantly different in the groups (p=0.955). Serum PON-1 levels were lower in the PCOS group (109.1±61.4 vs. 140.1±80.0; p=0.040), but it lost significance with adjusted values for covariants as age and BMI. Although PON-1 was not significantly different in the PCOS group of BMI<25 kg/m2 subgroup, it was significantly lower in the PCOS group of BMI≥25 kg/m2 subgroup (p=0.820 vs. p=0.048).ConclusionSerum fetuin-A activity did not differ with PCOS. Serum PON-1 might be a promising and research-worthy marker, especially for obese PCOS patients.

Are neutrophil count and neutrophil/lymphocyte ratio useful as markers of polycystic ovary syndrome in early reproductive age?

Necrotizing fasciitis (NF) is often fatal, characterized by extensive necrosis of the subcutaneous tissues and fascia. The present study was aimed to validate the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score as a tool to predict/diagnose NF and to differentiate it from other soft tissue infections depending on the score. A Prospective Observational study was conducted in ESICMC PGI MSR, Medical College Hospital, Rajajinagar, Bengaluru, from Jan 2019 to June 2020. Patients ≥18 years of age with severe soft tissue infections were included in the study. Based on the LRINEC score, the patients were categorised as low (≤5), moderate (6-7) and high risk (≥8) for the prediction of onset or diagnosis of NF. Data analysis was performed using SPSS version 21.0. A total of 55 patients were included in the study. A significant 3 association was observed with age (p=0.042), LRINEC score (p=0.0001), C Reactive Protein (CRP; p=0.0001), haemoglobin (p=0.008), serum Department of XXX, University of XXX, XXX Training and Research Hospital, City, Country sodium levels (p=0.004), serum creatinine (0.001), and amputation (p=0.004). Amputation was done in 5 cases. Only 1 mortality was observed 4Department of XXX, Faculty of XXX, City, Country in LRINEC high risk group with NSSTI. To conclude, LRINEC scoring system showed a better positive predictive value in identifying the onset of NF and risk strategizing of the patients with severe soft tissue infections. This study has aimed to contribute to the literature by investigating the value of inflammatory biomarkers of polycystic ovary syndrome (PCOS) that can be tested via a complete blood count. This retrospectively designed case-control study included 197 women in early reproductive age; who were in the age range of 18-24 years and who were admitted to the gynecology outpatient clinic. A total of 111 PCOS patients; in whom the diagnosis of PCOS was made based on Rotterdam criteria, were included in the study. A control group was formed by including 86 healthy women. All measurements of inflammatory biomarkers were obtained from the complete blood count test results. Of the inflammatory markers; the neutrophil count and the neutrophil/lymphocyte ratio were statistically significantly higher in the PCOS group compared to the control group (p=0.016 and p=0.002, respectively); however, the measured values of other parameters were similar between two groups. To evaluate whether or not the neutrophil count and neutrophil/lymphocyte ratio could be used as a screening tool to exclude PCOS, we constructed a receiver-operating characteristic curve (ROC). The ROC curve for the neutrophil count was 0.60 (p=0.016) and NLR was 0.627 (p=0.002). The neutrophil count and NLR were higher in the PCOS cases compared to the age-matched individuals in the control group. This finding confirms the presence of inflammation in PCOS cases of early reproductive age. However, it has been demonstrated that the diagnostic values of these markers are not strong in distinguishing PCOS patients from healthy individuals.

Resveratrol and Markers of Polycystic Ovary Syndrome: a Systematic Review of Animal and Clinical Studies.

Polycystic ovary syndrome (PCOS) is a common disorder affecting childbearing-age women, and is associated with reproductive and metabolic disturbances. The present study aimed to systematically review current animal studies and randomized placebo-controlled clinical trials (RCT) regarding the effects of resveratrol, a natural polyphenolic compound, on PCOS features. PubMed, Scopus, Web of Knowledge, and Google Scholar were comprehensively searched until December 2020. All original animal articles and RCTs evaluating the effects of resveratrol on PCOS were eligible for the review. Out of 289 initial records, eight animal studies and three RCTs met our inclusion criteria. Most of the included animal studies reported beneficial effects of resveratrol on the histomorphological features, sex hormones and gonadotropins, glycemic control, inflammation, and oxidative stress. Resveratrol also ameliorated ovarian volume, high-quality oocyte rate, high-quality embryo rate, androgens and gonadotropins concentrations, angiogenic factors levels, and endoplasmic reticulum stress in PCOS patients. Upregulation of sirtuin-1 was an examined mechanism proposed for some observed effects of resveratrol. The current literature is limited to conclude the beneficial effects of resveratrol on the management of PCOS. Although, according to the promising results of the animal studies and limited RCTs, resveratrol might be an effective phytochemical in PCOS control, especially regarding hormonal and reproductive abnormalities. More mechanistic studies and RCTs are warranted to obvious whether resveratrol can be prescribed in the clinical situation.

DLK1 and Nesfatin-1 levels and the relationship with metabolic parameters in polycystic ovary syndrome: Prospective, controlled study

Objective:Delta-like 1 (DLK1) is known to inhibit adipocyte differentiation and nesfatin-1 is a neuropeptide that plays a role in the regulation of nutrition and metabolism. We aimed to assess both the levels of DLK1 and nesfatin-1 in polycystic ovary syndrome (PCOS) and determine the association of DLK1 and nesfatin-1 with metabolic parameters.Materials and Methods:Forty-four patients with PCOS and 40 healthy women as the control group were included in this study. Venous blood samples of the participants were collected, and hormonal, metabolic parameters, DLK1 and nesfatin-1 blood levels were determined. Anthropometric parameters were also determined. For a double comparison, the Mann-Whitney U test was used for non-parametric numerical data, and Student’s t-test was used for parametric numerical data. Bivariate correlations were investigated using Spearman’s correlation analysis. The diagnostic performance of the parameters was evaluated using receiver operating characteristic curve analysis.Results:The findings showed that DLK1 and nesfatin-1 levels were lower among the PCOS group, and the differences in these values were found to be statistically significant. A significant negative correlation was found between DLK1 levels and body mass index (BMI), waist/hip ratio, visceral adiposity index (VAI), fasting serum insulin (FSI), homeostasis model of assessment-insulin resistance (HOMA-IR) and triglyceride levels. A significant negative correlation was found between nesfatin-1 levels and BMI, VAI, FSI, HOMA-IR and triglyceride.Conclusion:The findings showed that DLK1 and nesfatin-1 levels were lower in PCOS. Based on this study, DLK1 may be culpable for metabolic disorders in PCOS and can be a novel marker for PCOS in the future.

Characterization of DNA Methylation and Screening of Epigenetic Markers in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder in women, which is characterized by androgen excess, ovulation dysfunction, and polycystic ovary. Although the etiology of PCOS is largely unknown, many studies suggest that aberrant DNA methylation is an important contributing factor for its pathological changes. In this study, we investigated DNA methylation characteristics and their impact on gene expression in granulosa cells obtained from PCOS patients. Transcriptome analysis found that differentially expressed genes were mainly enriched in pathways of insulin resistance, fat cell differentiation, and steroid metabolism in PCOS. Overall DNA methylation level in granulosa cells was reduced in PCOS, and the first introns were found to be the major genomic regions that were hypomethylated in PCOS. Integrated analysis of transcriptome, DNA methylation, and miRNAs in ovarian granulosa cells revealed a DNA methylation and miRNA coregulated network and identified key candidate genes for pathogenesis of PCOS, including BMP4, ETS1, and IRS1. Our study shed more light on epigenetic mechanism of PCOS and provided valuable reference for its diagnosis and treatment.

Age-specific cut-off levels of anti-M\xfcllerian hormone can be used as diagnostic markers for polycystic ovary syndrome

BackgroundThe majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.Methods A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.Main results and the role of chanceTwo optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years.ConclusionsApplication of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.

Replication study of THADA rs13429458 variant with PCOS susceptibility and its related traits in Indian women

Aim The aetiopathogenesis of the multigenic multifactorial endocrinopathy, polycystic ovary syndrome (PCOS) has been explored using linkage, candidate gene and genome-wide association studies. Contradictory reports of replication studies attributed to phenotypic, ethnic and geographic variations are available. In this study, we investigated the association of Han Chinese GWAS polymorphism (rs13429458) in thyroid adenoma-associated gene (THADA) with PCOS susceptibility and its related traits in Indian women. Methods We genotyped rs13429458 of THADA by direct sequencing and investigated its association with PCOS and its related traits in controls (N = 150) and PCOS women (N = 348). All women were extensively phenotyped in terms of anthropometric, hormonal and metabolic parameters. Association of polymorphism with PCOS risk and its related traits was carried out by regression analysis. Results Genotypic and allele frequencies for rs13429458 were not different between controls and PCOS. Women with PCOS carrying variant allele showed significantly reduced fasting glucose levels, and decreased free and bioavailable testosterone and free androgen index. Conclusion To our knowledge, this is the first study to demonstrate that although this polymorphism does not alter PCOS susceptibility, it favorably impacts glucose metabolism and hyperandrogenism in Indian women with PCOS only. This study highlights that genetic predisposition markers for PCOS may differ with ethnicity and phenotypic variations.

The importance of inflammation markers in polycystic ovary syndrome.

This study aimed to examine inflammation markers in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy women. This prospective study was conducted by examining patients who applied to the Near East University Gynecology and Obstetrics Outpatient Clinic between January 2019 and January 2020. A total of 110 PCOS patients with 135 control groups were compared in terms of metabolism, hormonal factors, and inflammation markers. The neutrophil count, neutrophil-lymphocyte ratio (NLR), platelet, platelet-lymphocyte ratio (PLR), platelecrit (PCT), erythrocyte cell distribution width, platelet distribution width, mean platelet volume, and C-reactive protein (CRP) values were found to be statistically significantly higher in patients with PCOS. There was a positive correlation between inflammation markers and serum androgens. Also, a positive correlation was observed between inflammation markers and cardiovascular risk parameters. In receiver operating characteristic curve analysis, the most valuable parameter in distinguishing PCOS patients from healthy controls was serum CRP levels [areas under the curve (AUC)=0.928, 95%CI 0.894-0.963, p<0.001, 92.6% sensitivity, and 82.7% specificity]. Serum CRP, neutrophil count, and PCT and NLR levels are valuable markers that show the inflammatory process in PCOS patients.

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

Investigating oxidized LDL receptor 1 (OLR1) polymorphisms as putative genetic markers for polycystic ovary syndrome

Polycystic ovary syndrome has a perplexing pathophysiology driven by genetic and environmental stimuli wherein the propensity for gynaecological and cardiometabolic complications is well recognized. Oxidized low density lipoprotein is a vital player in inducing endothelial dysfunction and downstream atherosclerotic processes by binding to its receptor oxidized LDL receptor 1 (OLR1). We have undertaken this case-control study to investigate whether common polymorphisms of OLR1 (K167N and 3’UTR C188T) contribute to risk of PCOS development and its related traits. Genotyping of K167N and 3’UTR C188T polymorphisms of OLR1 by direct sequencing and restriction fragment length polymorphism techniques using RsaI, respectively was carried out in 298 women with PCOS and 147 controls. Genotype and genotype-phenotype analysis was performed using additive model with appropriate statistical tests. There were no significant differences in genotypic frequency distributions between PCOS women and controls. However, K167N polymorphism showed significant association with decreased insulin levels and homeostasis model assessment of insulin resistance and increased quantitative insulin sensitivity check index, thereby ameliorating insulin resistance in women with PCOS. Contrastingly, this variant was significantly associated with increased waist-hip ratio, fasting glucose levels coupled with diminished LH levels and LH:FSH ratio in controls. The C188T polymorphism showed significant association with increased LDL only in women with PCOS. Therefore, although we did not detect significant associations of either polymorphism with PCOS susceptibility, our genotype-phenotype analysis showed that they differentially influenced metabolic traits of insulin resistance and dyslipidemia, and gonadotropin-related parameters in controls and women with PCOS. To the best of our knowledge, ours is the first study to highlight that OLR1 could be an important predisposing genetic factor for PCOS-related traits.

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome.

Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values. Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study. Participants (n = 102) aged 38.9 ± 7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT). There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI and cIMT remained directly correlated but to a lesser degree. This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS.

EVALUATING OVARIAN VOLUME AS A SINGLE MARKER FOR POLYCYSTIC OVARY SYNDROME (PCOS) AND METABOLIC DYSFUNCTION

To determine if ovarian volume alone is an adequate marker for Polycystic ovary syndrome (PCOS) and metabolic dysfunction. Tertiary-care based cohort study. Patients age >14 presented for consultation to 4 academic institutions from 1980 to 2010. Markers of hyperandrogenism (HA) included the modified Ferriman-Gallwey score (mFG), free testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) values. Markers of metabolic dysfunction included body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL), triglycerides (TG), hypertension (HTN, defined as ≥ 135/85), and insulin and glucose levels during a 2-hour glucose tolerance test. Women were divided into two groups according to ovarian volume (OV): ≥10 mL (OV≥10) and volume <10 mL (OV<10). Categorical variables were compared using χ2 tests and continuous variables were compared using Student’s t-test or Wilcoxon rank-sum, as appropriate. Spearman’s rank correlation was calculated to correlate OV with antral follicle count (AFC). Seven-hundred eighteen women were included, of which OV≥10 was present in 362 women (50.4%) and OV<10 in 356. There was a positive correlation of OV with AFC (rs =0.54, p<0.0001). The mean ages of women (SD) in OV<10 and OV≥10 women were 30.1(7.3) and 29.1(5.8) years, respectively. (p=0.03). PCOS by Rotterdam criteria was found in 89.4% of the OV≥10 group and 68.0% of the OV<10 (p<0.001). Higher OV was associated with a higher prevalence of HA overall (73.1% vs 58.1%, p <0.001), and with an mFG ≥4 (67.5% vs 54.7%, p=0.001) and elevated free T (30.1% vs 19.1%, p=0.002) specifically. Metabolic parameters including BMI, WC, and 1-hr insulin levels were significantly higher in the OV≥10 group compared to OV<10 women; HTN, HDL, TG and 2-hr glucose values were similar between the groups. Ovarian volume of ≥10 mL, as a single marker, is associated with HA and metabolic dysfunction in PCOS. Given that the measurement of AFC is less precise, particularly in less experienced sites, the use of OV alone decreases the complexity of the evaluation and increases the ability to capture patients with risk for PCOS or metabolic dysfunction.

Insertion/deletion of angiotensin-converting enzyme gene polymorphism as a marker of polycystic ovary syndrome (PCOS) development in South Indian cohort women

Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disease because of the elevated levels of androgen which could lead to anovulation. The angiotensin-converting-enzyme (ACE) is a zinc metallopeptidase that converts angiotensin I to angiotensin II. ACE is bound to the plasma membrane and expressed in many tissues such as ovarian tissues. The renin-angiotensin system (RAS help the production of angiotensin, angiotensinogen, and ACE. Angiotensin II plays a major role in ovulation, steroidogenesis, follicular atresia and hyperandrogenic syndromes such as PCOS. This study aimed to determine the association of ACE polymorphism in PCOS to analyze the distribution allele frequency of insertion or deletion variation in PCOS patients of the South Indian cohort. A total of 430 women with PCOS confirmed based on the Rotterdam criteria and 300 age and sex-matched control samples were studied. PCR technique was used to determine the frequency of polymorphism in the ACE gene. The genotyping distribution of II, DD and ID in PCOS was 4.56%, 30.23%, and 65.11%, respectively, whereas the control group showed 30%, 20%, and 50% for II, DD and ID, respectively. The deletion (D) allele frequency was 62.79% and insertion (I) allele was 37.2 % in PCOS patients, whereas in the control group, it was 45% and 55% for D and I alleles, respectively. This study concludes that the distribution of deletion (D) allele frequency of ACE could be considered as a genetic marker for PCOS in the South Indian cohort.

Dissecting the role of micro-RNAs as a diagnostic marker for polycystic ovary syndrome: a systematic review and meta-analysis

To investigate the clinical diagnostic value and role of micro-RNAs (miRNAs) in the pathogenesis of polycystic ovary syndrome (PCOS). Systematic review and meta-analysis. Not applicable. Patients were women of reproductive age with PCOS and controls. Summary odds ratio was calculated using a random effects model. Association of micro-RNAs with PCOS. An electronic literature search was conducted using PubMed, Scopus, and Google Scholar databases to identify all relevant studies up to May 2019. A random effects model was used to conduct a meta-analysis. Fold change and P values were used to pool effect size. A funnel plot was used to assess publication bias. Quality score was calculated using the QUADAS scale. Subgroup analysis was based on tissue type. Odds ratios, 95% confidence intervals, and P values were estimated using meta-analysis. Metaregression was performed for correlating covariates with effect size. Area under the curve and receiver operating characteristic analysis was done to assess diagnostic performance accuracy of miRNAs in PCOS. Twenty-one studies with a total of 79 miRNAs were included initially. Only three miRNAs (miR-29a-5p, miR-320, miR-93) are reported in more than three studies as of December 2018, so 12 studies were finally included in the quantitative analysis of meta-analysis and 21 studies were involved in the systematic review. The micro-RNAs miR-29a-5p and miR-320 were found to be significantly associated with PCOS. Funnel plot revealed an absence of publication bias for miR-29a-5p and miR-320. Receiver operating characteristic analysis with an area under the curve value of 0.95 proved miR-29a-5p to be the better diagnostic marker of PCOS. Aberrant expression of various miRNAs plays an important role in PCOS pathogenesis. Micro-RNAs hold potential diagnostic value for PCOS. These findings may offer new insights for PCOS pathogenesis research. CRD42018106198.

Relationship between Serum Levels of Anti-Mullerian Hormone, Adiponectin and Oxidative Stress Markers in Patients with Polycystic Ovary Syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Anti-Mullerian hormone (AMH) is a valid indicator of ovarian function and is used for PCOS diagnosis. Some studies have shown that adipokines affect the synthesis of AMH, and therefore they are somehow related in function. The aim of the present study was to determine the relationship between serum levels of AMH, adiponectin and oxidative stress markers in PCOS patients.Materials and MethodsIn this cross-sectional study, PCOS patients and healthy women (80 cases in total) were investigated. Serum levels of AMH, adiponectin, gonadotropins, androgens, total antioxidant capacity (TAC), nitric oxide (NO) and insulin resistance (IR) were measured by standard methods. An independent t test was used to compare the two groups and Pearson correlation coefficient was used to determine the relationship between variables.ResultsThere was a significant difference between the means of AMH (5.16 ± 5.3 vs. 2.44 ± 2.5 ng/mL) (P=0.007) and adiponectin (24.55 ± 9.41 vs. 30.57 ± 14.2 µg/L) (P=0.029) among the PCOS and control groups, respectively. The correlation between AMH and adiponectin in the control group was statistically significant and negative (P=0.028, r=-0.35), while in the PCOS group it was not significant (P=0.11, r=-0.25).ConclusionVarious biochemical and hormonal factors differ between PCOS and healthy women. Different factors can influence AMH and adiponectin levels independently of PCOS in women of reproductive age.

Fructose levels are elevated in women with polycystic ovary syndrome with obesity and hyperinsulinemia.

Are fructose levels altered in women with polycystic ovary syndrome (PCOS)? Elevated serum fructose levels are associated with PCOS in Chinese Han women with overweight/obesity and hyperinsulinemia, and fructose levels are higher in follicular fluids from PCOS patients than from control subjects. Both fructose levels and PCOS are closely linked to obesity and insulin resistance. However, the relationship between fructose and PCOS remains largely unknown. A total of 157 Chinese Han women (67 controls and 90 PCOS patients) were recruited at Shengjing Hospital of China Medical University. To systematically study the relationship between serum fructose levels and PCOS, the study population of control subjects and PCOS patients was divided into overweight/obese and lean subgroups, and hyper-fasting serum insulin (FSI) and normal-FSI subgroups, respectively. Fructose levels were measured in serum samples collected from 80 patients with PCOS (32 lean, 48 overweight/obese) and 59 control subjects (27 lean, 32 overweight/obese) and in follicular fluid samples collected from mature follicles (17-22mm) and matched immature follicles (8-13mm) from 10 patients with PCOS and 8 control subjects. Serum fructose levels were increased in overweight/obese and hyper-FSI PCOS patients compared with the control subjects. Fructose had an area under the curve (AUC) of 79.7% at a cutoff value of 10.13pmol/μl, with a sensitivity of 91.7% and a specificity of 59.3% for the prediction of PCOS in overweight/obese patients. In the hyper-FSI group, fructose had an AUC of 72% at a cutoff value of 10.49pmol/μl, with a sensitivity of 71.1% and a specificity of 64.4% for the prediction of PCOS. There were no differences between fructose, total testosterone, free testosterone or dehydroepiandrosterone sulfate levels with respect to the reliability of predicting PCOS in the overweight/obese or hyper-FSI groups using the method outlined by Hanley and McNeil. Notably, the combination of fructose and total testosterone levels resulted in the highest AUC of 86.0% and high sensitivity (85.4%) and specificity (83.1%) for the prediction of PCOS in overweight/obese patients. The positive predictive value (PPV) and negative predictive value (NPV) were 80.4 and 87.5%, respectively. Similarly, the combination of fructose and total testosterone levels also resulted in a high AUC of 80.2% and moderate sensitivity (73.3%) and high specificity (84.7%) for the prediction of PCOS in hyper-FSI patients. The PPV and NPV were 78.6 and 80.6%, respectively. Furthermore, fructose levels were significantly higher in follicular fluids from PCOS patients than from control subjects, regardless of whether the follicles were mature or immature. It remains unclear whether fructose levels contribute directly to follicular development and the pathogenesis of PCOS or are merely a biomarker of these processes. The results of the present study, together with our previous study, show that monosaccharide status may be a novel marker for PCOS, highlighting the importance of further investigation into the role of monosaccharides, especially fructose, in the pathogenesis of PCOS. This work was supported by the National Natural Science Foundation of China (No. 81671423 and No. 81402130), the National Key Research and Development Program of China (No. 2018YFC1003100), Liaoning Provincial Key Research and Development Program (No. 2018225090), the Fok Ying Tung Education Foundation (No. 151039), Distinguished Talent Program of Shengjing Hospital (No. ME76) and Distinguished Teacher Program of China Medical University (No. QGZ2018079). No competing interests were declared.

Oxidative stress and risk of polycystic ovarian syndrome in women with epilepsy: implications of malondialdehyde and superoxide dismutase serum levels on female fertility

BackgroundEpilepsy is a common neurologic disease and has important implications for women’s fertility, as approximately half of the epileptic women have reproductive disorders. Oxidative stress is a key contributor in the pathogenesis of polycystic ovary syndrome (PCOS) and epilepsy. We aimed to investigate the role of malondialdehyde (MDA) and superoxide dismutase (SOD) serum levels as predictors of PCOS in women with epilepsy (WWE) and to evaluate the possible relationship between oxidative stress and epilepsy characteristics as well as clinicomorphological features of PCOS.Patients and methodsA cross-sectional study enrolled 130 WWE. They were classified to two subgroups; women with PCOS (n=50) and women without PCOS (n=80) according to Rotterdam criteria. Metabolic markers and markers of PCOS were measured. Serum MDA and SOD concentrations were estimated by enzyme-linked immunosorbent assay.ResultsOur results revealed higher levels of MDA and SOD in WWE, in particular, women with PCOS. Moreover, serum MDA and SOD levels were significantly positively correlated with PCOS phenotypes. Linear regression test revealed that Low-density lipoprotein cholesterol (LDL) and luteinizing hormone (LH) were the main predictors of serum MDA levels in PCOS, whereas BMI and LH were the main predictors of serum SOD levels. Regarding antiepileptic medication, there were significantly higher levels of MDA and SOD in patients treated with valproic acid compared with the ones treated with carbamazepine.ConclusionThe high levels of MDA and SOD among WWE, in particular, women with PCOS, were positively correlated with obesity indices and PCOS phenotypes. Thus, we recommended avoid using valproic acid in women during childbearing period.

A Cross Sectional Study on the Status of Inflammatory Markers in Polycystic Ovary Syndrome (Pcos) in Indian Population

Polycystic Ovarian Syndrome (PCOS) is a common disease exclusively seen in women of reproductive age group. World Health Organization reports that Polycystic Ovarian Syndrome approximately affects 5-10% of the reproductive female population worldwide. Women with PCOS have chronic inflammation. This in turn leads to increased incidence of non-communicable diseases like cardiovascular disease and diabetes2. Chronic inflammation in PCOS patients can be identified using serum markers such as C - reactive protein [CRP], Interleukin-6 [IL-6] and Interleukin-18 [IL-18].So the main objective of the study was to assess the status of inflammation in patients with Polycystic Ovary Syndrome (PCOS) and to assess the influence of drugs prescribed for PCOS on inflammation. Patients were divided into three groups as healthy volunteers, newly diagnosed PCOS patients, already on treatment patients for PCOS. High sensitivity CRP (hs-CRP), IL-6 and IL-18 were assessed. There was an increase in the hs-CRP, IL-6 and IL-18 compared to healthy volunteers in both newly diagnosed and already diagnosed groups. But there was no statistical significance (hs-CRP=0.975, IL-6=0.746, IL-18 = 0.148) between them. The mean value has decreased in the already on treatment group as duration of treatment increases. There was no statistical significance between them. There was an inversely proportional relationship between the mean values of inflammatory markers and duration of treatment.

Elevated Serum Mannose Levels as a Marker of Polycystic Ovary Syndrome.

Background: Recent reports have highlighted the role of monosaccharide biosynthesis in the pathogenesis of polycystic ovary syndrome (PCOS), suggesting that these processes may serve as a biomarker in PCOS. Mannose is the main monosaccharide for protein glycosylation in mammals; however, the correlation between mannose and PCOS remains largely unknown.Materials and Methods: A total of 132 Chinese Han women were recruited at Shengjing Hospital of China Medical University. Mannose levels were measured in serum samples collected from 71 patients with PCOS (29 lean, 42 obese) and 61 control subjects (28 lean, 33 obese). Receiver operating characteristics (ROC) curves were prepared to compare the diagnostic performance of mannose and hormonal parameters, individually or in combination. Multivariate logistic regression analysis was used to assess whether serum mannose levels were associated with PCOS after adjusting for other co-variables.Results: We showed that serum mannose levels were significantly increased in PCOS patients compared with control subjects regardless of obese status, and hyperandrogenic PCOS patients had higher serum mannose levels than normo-androgenic PCOS and control subjects. In addition, serum mannose levels were significantly correlated with serum androgen levels. Mannose had an area under the curve (AUC) of 73% at a cutoff value of 225.79 ng/mL with a sensitivity of 66.2% and specificity of 73.8% for predicting PCOS. There were no differences between mannose, total testosterone, free testosterone, or dehydroepiandrosterone sulfate in the reliability of predicting PCOS using the method outlined by Hanley and McNeil. Combining mannose and total testosterone resulted in a higher AUC of 83.3%, and had moderate sensitivity (78.9%) and specificity (77%) for predicting PCOS. The positive and negative predictive values were 80% and 75.8%, respectively. Multivariate logistic regression revealed that higher serum mannose levels were strongly associated with an increased risk of PCOS (P = 0.016; odds ratio, 5.623; 95% confidence interval, 1.371–23.070).Conclusion: Taken together, substantially elevated serum mannose levels are significantly associated with PCOS, highlighting the importance of further research into the role of mannose in the pathogenesis of PCOS.