Biomarker For Polycystic Ovary Syndrome Research Articles

Bioinformatics Analysis of ceRNA Network Related to Polycystic Ovarian Syndrome.

Introduction Polycystic ovary syndrome (PCOS) is caused by the hormonal environment in utero, abnormal metabolism, and genetics, and it is common in women of childbearing age. A large number of studies have reported that lncRNA is important to the biological process of cancer and can be used as a potential prognostic biomarker. Thus, we studied lncRNAs' roles in PCOS in this article. Methods We obtained mRNAs', miRNAs', and lncRNAs' expression profiles in PCOS specimens and normal specimens from the National Biotechnology Information Gene Expression Comprehensive Center database. The EdgeR software package is used to distinguish the differentially expressed lncRNAs, miRNAs, and mRNAs. Functional enrichment analysis was carried out by the clusterProfiler R Package, and the lncRNA-miRNA-mRNA interaction ceRNA network was built in Cytoscape plug-in BiNGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively. Results We distinguished differentially expressed RNAs, including 1087 lncRNAs, 14 miRNAs, and 566 mRNAs in PCOS. Among them, 410 lncRNAs, 11 miRNAs, and 185 mRNAs were contained in the ceRNA regulatory network. The outcomes from Gene Ontology (GO) analysis showed that the differentially expressed mRNAs (DEMs) were mainly enriched in response to the maternal process involved in female pregnancy, morphogenesis of embryonic epithelium, and the intracellular steroid hormone receptor signaling pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis data showed that DEMs were primarily enriched in pathways related to the TGF-β signaling pathway, Type I diabetes mellitus, and glycolysis/gluconeogenesis. In addition, we chose NONHSAT123397, ENST00000564619, and NONHSAT077997 as key lncRNAs due to their high bearing on PCOS. Conclusion ceRNA networks play an important role in PCOS. The research indicated that specific lncRNAs were related to PCOS development. NONHSAT123397, ENST00000564619, and NONHSAT077997 could be regarded as potential diagnostic mechanisms and biomarkers for PCOS. This discovery might provide more effective and more novel insights into the mechanisms of PCOS worthy of further exploration.

3 CpG Methylation Biomarkers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Blood Samples.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women that seriously interferes with patient's metabolic and reproductive functions. The current diagnostic criteria for PCOS are expert-based and still disputed. Previous studies have identified changes in DNA methylation in peripheral blood of women with PCOS, but their diagnostic potential for PCOS remains to be studied. The present study aimed to identify potential methylation biomarkers for the diagnosis of PCOS in blood. Methylation profiling of peripheral blood was downloaded from a public database, Gene Expression Omnibus (GEO), including 30 PCOS patients (diagnosed with the revised 2003 Rotterdam consensus criteria) and 30 age-matched healthy women recruited from Centre of Reproductive Medicine, Linyi People's Hospital, Shandong, China. Weighted gene co-expression network analysis (WGCNA) was utilized to identify PCOS-related co-methylation CpG sites (co- MPs). Functional enrichment analysis was performed on the localized genes of PCOS-related co- MPs. The least absolute shrinkage and selection operator (LASSO) regression was used to screen out CpG methylation signatures for PCOS diagnosis, and receiver operating characteristic (ROC) analysis was conducted to evaluate their diagnostic accuracy. To assess the accuracy of the combination of the investigated indicators, multivariate ROC analysis was performed on the predicted probability values obtained using binary logistic regression on the methylation levels of selected CpGs. Seven co-methylation modules were obtained, among which the turquoise module is the most relevant to PCOS, containing 194 co-MPs. The genes that these co-MPs located in were mainly associated with the immune-related pathway. According to LASSO regression, three Co- MPs (cg23464743, cg06834912, cg00103771) were identified as potential diagnostic biomarkers of PCOS. ROC analysis showed an AUC (area under curve) of 0.7556 (sensitivity 60.0%, specificity 83.3%) for cg23464743, 0.7822 (sensitivity 70.0%, specificity 80.0%) for cg06834912, and 0.7611 (sensitivity 63.3%, specificity 83.3%) for cg00103771. The diagnostic accuracy of the combination of these 3 indicators presented to be higher than any single one of them, with the AUC of 0.8378 (sensitivity 73.3%, specificity 93.3%). The combination of 3 CpG methylation signatures in blood was identified with a good diagnostic accuracy for PCOS, which may bring new insight into the development of PCOS diagnostic markers in the future.

CircASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a kind of endocrine disorder which is prevalent in adult women, so exploring more biomarkers for PCOS is imperative. Recently, circular RNA and microRNA are confirmed to be related with PCOS development. Whether circular RNA ASPH (circASPH) is involved in PCOS need to be studied further. We utilized RT‐qPCR to measure the expression levels of circASPH, miR‐375 and MAP2K6 in PCOS patients and normal group. The effects of circASPH and miR‐375 on KGN cells proliferation and apoptosis were observed by CCK‐8 assay, EdU incorporation assay and apoptosis assay, separately. Then Dual‐luciferase reporter assay was carried out to verify the circASPH/miR375 axis and miR375/MAP2K6 axis. The interaction between circASPH and MAP2K6 were detected with the support of RT‐qPCR and Western blot. We found circASPH and MAP2K6 were both over‐expressed in PCOS patients, while miR‐375 was in the opposite direction. Moreover, miR‐375 was negatively regulated by circASPH, while MAP2K6 was positively regulated by circASPH. In addition, circASPH directly targeted miR‐375, which targeted MAP2K6. More than that, the knockdown of circASPH repressed KGN cells proliferation and enhanced apoptosis, while the silence of miR‐375 reversed the above effects. In conclusion, circASPH promotes KGN cells proliferation through miR‐375/MAP2K6 axis in PCOS, and they are thought‐provoking biomarkers for PCOS diagnosis and therapy.

Assessment of Serum Irisin in Overweight And Obese Patient with Polycystic Ovary Syndrome

Background and Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 10–15 % of women in reproductive age. The objective was to evaluate the effect of irisin in the etiology of obese patient with PCOS. Study Design and Methods: The study design its a case control study. This study involved fifty obese ladies (50) with confirmed diagnosis of PCOS. The second group served as control group and included forty apparently normal (non-polycystic ovary) obese ladies (40). The following main parameters were measured: Fasting serum levels of total Cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein– cholesterol, glycohaemoglobin (HbA1c%), Insulin , Testosterone, FSH, serum LH and Irisin. Results: The median serum Irisin was significantly higher among PCOS cases (119.1 ng/ml) compared to healthy controls (74.7 ng/ml). The median serum FSH was significantly higher among PCOS cases (6.52 ng/ml ) compared to controls (4.72 ng/ml). Serum LH was obviously higher among PCOS cases (6.88 ng/ml) compared to controls (6.08 ng/ml). The mean pulse rate, blood WBC count and serum VLDL were significantly higher (71.6/min, 8.3 mg/dl and 22.5 mg/dl respectively) in cases with PCOS compared to controls (67.5/min, 7.2 mg/dl and 18.5 mg/dl respectively). Conversely, the serum HDL was significantly lower among PCOS cases (43.8 mg/dl) compared to controls (48.4 mg/dl), serum testosterone showed statistically non-significant differences. Conclusion: Data of the present study showed that serum Irisin was significantly higher among PCOS cases. These findings suggest important role of irisin as a biomarker for PCOS and an important factor in the development of PCOS.

Identification of Potential Biomarkers of Polycystic Ovary Syndrome via Integrated Bioinformatics Analysis.

Polycystic ovary syndrome (PCOS) is a life-long reproductive, endocrine, and metabolic disorder that affects up to 17% of women of reproductive age. However, the effect of granulosa cells (GCs) transcriptome changes on oocyte capacity and follicular development in patients with PCOS has not been elucidated. This study aims to analyze transcriptome changes in GCs of PCOS from different perspectives and explore potential biomarkers for the diagnosis and treatment of PCOS. The gene expression profiles of GSE34526 and GSE107746 were obtained from the GEO database. Differentially expressed genes (DEGs) and key signaling pathways were identified. Gene Set Enrichment Analysis (GSEA) revealed that Toll-like receptors, NOD-like receptors, and NOTCH signaling pathways were obviously enriched in GCs of PCOS. We further analyzed DEGs from three aspects: transcription factors (TFs), secreted proteins, and follicular development. Compared with normal GCs, the DEGs encoding TFs and secretory proteins in GCs of PCOS remarkably changed. Besides, HAS2 and CBLN1, which are highly expressed in preovulatory follicular GCs and may trigger ovulation, were significantly decreased in GCs of PCOS. This study found candidate genes and signaling pathways in PCOS, providing new insights and foundations for the etiology of PCOS. Besides, HSA2 and CBLN1 may be potential therapeutic biomarkers for ovulation disorders in PCOS.

Serum Trace Elements in Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome (PCOS) is reported to be associated with certain trace elements. However, previous data are inconsistent and potentially biased due to small sample sizes. The potential utility of trace element levels for screening of PCOS remains to be established. The aim of this meta-analysis was to investigate the potential relationships between PCOS and serum levels of zinc (Zn), copper (Cu), magnesium (Mg), iron (Fe) and ferritin. We carried out a literature search of PubMed, EMBASE, and Web of Science for relevant cross-sectional/case-control studies published prior to October 2019. Random-effect models were used to estimate the overall standard mean differences (SMDs) between PCOS and healthy control subjects. The screening value of potential microelement biomarkers for PCOS was assessed using the receiver operating characteristic (ROC) curve. Twenty-one studies featuring 2,173 women with PCOS and 1,897 healthy women were selected for analysis. Our results showed that Cu and ferritin levels were significantly higher in women with PCOS than healthy controls, with SMDs of 0.52 [95% confidence interval (CI): 0.38–0.67, I2 = 47.6%] and 1.05 (95% CI: 0.25–1.86, I2 = 97.0%), respectively. The serum ferritin concentration was distinguished as a potential biomarker for PCOS based on the high area under ROC curve value of 0.71 (95% CI: 0.57–0.86). Although we did not identify a statistical association between serum Zn concentration and PCOS overall, the concentration of Zn in PCOS women with insulin resistance (IR) was lower than that in healthy women (SMD = −0.89, 95% CI: −1.73 to −0.06). Furthermore, the concentrations of Mg (SMD = 0.31, 95% CI: −0.32–0.94, I2 = 95.4%) and Fe (SMD = −0.59, 95% CI: −1.29–0.12, I2 = 97.2%) were not statistically significant between the PCOS and control groups. We generated hypothetical pathways for associations among serum Cu, ferritin and PCOS. The serum concentrations of both Cu and ferritin were significantly higher in women with PCOS, and ferritin was identified as a potential early indicator for PCOS screening. Further studies are essential to determine the specific underlying mechanisms.

Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome

ABSTRACT Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (TUG1), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of TUG1 in PCOS remains unclear. Herein, TUG1 expression was assayed in granulosa cells (GCs) of 100 patients with PCOS and 100 control participants. Receiver operating characteristic (ROC) curve analysis was conducted to determine the diagnostic value of TUG1 in PCOS. TUG1 expression was also silenced in KGN cells to explore the role of TUG1 in cellular proliferation, apoptosis, cell-cycle progression, autophagy, and steroidogenesis. We found that TUG1 levels were dramatically increased in the PCOS group compared with those of the control group; this increased expression was related to a rising antral follicle count (R = 0.209, P < 0.001 versus control). The ROC curve indicated a significant separation between PCOS group and the control group (AUC: 0.702; 95% CI: 0.630–0.773; P < 0.001). TUG1 showed a predominantly nuclear localization in human GCs. TUG1 knockdown reduced cellular proliferation, and promoted MAPKs pathway-dependent apoptosis and P21-dependent autophagy, but may not affect cell-cycle progression. TUG1 knockdown increased aromatase expression and oestradiol biosynthesis. Our results indicate that increased TUG1 expression in PCOS GCs may contribute to excessive follicular activation and growth, and may disrupt the selection of dominant follicle. Our study shows that TUG1 can be used as a diagnostic biomarker for PCOS.

Visfatin and SREBP-1c mRNA Expressions and Serum Levels Among Egyptian Women with Polycystic Ovary Syndrome

Background: Obesity and insulin resistance are common features accompanying polycystic ovary syndrome (PCOS). Aim: To analyze the impact of obesity on the expression of the visfatin and sterol regulatory element-binding protein (SREBP)-1c genes among a group of Egyptian women with PCOS, and to assess their suitability as PCOS biomarkers. Subject and methods: Seventy healthy women (control group) (35 nonobese and 35 obese) and 140 women with PCOS (70 nonobese and 70 obese) were enrolled in this study. The visfatin and SREBP-1c genes' expression analyses were performed via real-time polymerase chain reaction. Serum visfatin and SREBP-1c protein levels were measured with ELISA kits. Results: Among PCOS patients, upregulation of visfatin and SREBP-1c expression was observed. We did not identify significant differences between the obese and nonobese PCOS patients nor between obese and non-obese controls. The mRNA expression levels of both genes were significantly positively correlated with their serum protein levels, as well as with fasting serum insulin levels, homeostatic model assessments of insulin resistance (HOMA-IR), luteinizing hormone (LH) ratios, LH/follicular stimulating hormone ratios, total testosterone, and free androgens. We observed significant negative correlations between visfatin and SREBP-1c expression levels and sex hormone binding globulin levels in all studied groups. Receiver operating characteristic curve analyses revealed that combining the visfatin and SREBP-1c expression data increased the sensitivity (95.92%) and specificity (93.2%) for PCOS diagnoses. Conclusion: Upregulation of visfatin and SREBP-1c was observed among PCOS patients. These genes may play a role in the pathogenesis of PCOS independent of obesity. Combined visfatin and SREBP-1c analyses could be used as a noninvasive biomarker for PCOS.

Protein Network Studies on PCOS Biomarkers With S100A8, Druggability Assessment, and RNA Aptamer Designing to Control Its Cyst Migration Effect.

The prevalence of polycystic ovary syndrome (PCOS) has been gradually increasing among adult females worldwide. Laparoscopy drilling on ovary is the only available temporary solution with a high incidence of reoccurrence. S100A8 with S100A9 complex is believed to facilitate the cyst migration in PCOS condition. The high evident protein interaction network studies between PCOS biomarkers, cancer invasion markers, and the interactors of S100A8 confirm that this protein has strong interaction with other selective PCOS biomarkers, which may be associative in the immature cyst invasion process. Through the network studies, intensive structural and pathway analysis, S100A8 is identified as a targetable protein. In this research, the non-SELEX in silico method is adapted to construct RNA Library based on the consensus DNA sequence of Glucocorticoid Response Element (GRE) and screened the best nucleotide fragments which are bound within the active sites of the target protein. Selected sequences are joined as a single strand and screened the one which competitively binds with minimal energy. In vitro follow-up of this computational research, the designed RNA aptamer was used to infect the MCF7 cell line through Lipofectamine 2000 mediated delivery to study the anti-cell migration effect. Wound Scratch assay confirms that the synthesized 18-mer oligo has significant inhibition activity toward tumor cell migration at the cellular level.

Association between polycystic ovary syndrome and the vaginal microbiome: A case-control study.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Some evidence suggests that dysbiosis of the gut microbiota could be associated with PCOS clinical parameters, but little is known for the association between vaginal microbiome and PCOS. To determine differences in the vaginal microbiome between women with PCOS and healthy control women. In this case-control study, the women with newly diagnosed PCOS (n=39) and healthy controls (n=40) were included from the hospital and maternal and child health centre, respectively. The vaginal swabs were collected, and microbiome structures were identified by 16S rRNA gene sequencing. The screening values for potential bacteria biomarker for PCOS were assessed by receiver operating characteristic (ROC) curve method. There was significant difference in vaginal bacterial structures between PCOS and healthy control women. The vaginal bacterial species in the PCOS group were more diverse than the control group (Simpson index for PCOS group vs. control group: median 0.49 vs. 0.80, P=.008; Shannon index: median 1.07 vs. 0.44, P=.003; Chao1 index: median 85.12 vs. 66.13, P<.001). The relative abundance of Lactobacillus crispatus in the PCOS group was significantly lower than controls (P=.001), and the relative abundance of Mycoplasma and Prevotella was higher than controls (P<.001, P=.002, respectively). The Mycoplasma genus could be a potential biomarker for PCOS screening, as ROC analysis showed that the area under the curve (AUC) for the relative abundance of Mycoplasma was 0.958 (95% CI: 0.901-0.999). Subgroup analyses also showed these associations would not change among the women with the same BMI level and vagina cleanliness grading. In the vaginal microbiome, the Mycoplasma genus was associated with PCOS. Further research is required to explore causal correlations between PCOS and the vaginal microbiome.

Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization

ObjectiveCXCL14 (C-X-C motif chemokine ligand-14) is a chemokine released by active brown fat, showing protective effects against insulin resistance in experimental models. Polycystic ovary syndrome (PCOS) in adolescent girls is...

Progress in diagnosis and therapy of polycystic ovary syndrome

The etiology of polycystic ovary syndrome(PCOS) is unknown, which is closely related to insulin resistance and hyperinsulinemia. There are several controversies on PCOS diagnosis because of its diversity and heterogeneity in clinical manifestations. PCOS biomarkers have become a research hotspot. The methods of treatment include lifestyle interventions and improving metabolic dysfunction, hyperandrogenism, and reproduction abnormality. This article reviews the latest research progress in the morbidity characteristics, diagnostic criteria, and the therapy of PCOS. Key words: Polycystic ovary syndrome; Diagnosis; Therapy

Plasma Levels of miR-27a, miR-130b, and miR-301a in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder in women of reproductive age. There is adequate evidence that suggests several microRNAs (miRNAs) are of great importance for PCOS. It seems that dysregulated expression of miR-27a, miR-130b, and miR-301a are associated with PCOS. The aim of this study was to investigate whether plasma levels of these miRNAs are different between patients with PCOS and healthy controls. Fifty-three women with a definite diagnosis of PCOS, and 53 healthy controls were enrolled. MiRNAs expression levels in plasma were evaluated by real-time PCR. The diagnostic values of each miRNA were calculated by the receiver operating characteristic (ROC) curve and areas under the curves (AUC). The main clinical characteristics were not significantly different between the two groups. The circulating plasma expression levels of miR-27a and miR-301a had a significant increase (P = 0.0008 and P <0.0001, respectively) but miR-130b expression level decreased in the patient group (P <0.0001). The AUC for miR-27a, miR-130b, and miR-301a were 0.71, 0.77, and 0.66, respectively. A positive exponential was observed for miR-27a and miR-301a in multiple logistic regression. Changes in the plasma expressions of the studied miRNAs are likely to be associated with PCOS phenotypes. MiR-27a has a potential to serve as a diagnostic biomarker of PCOS.

Metabolic alterations associated with polycystic ovary syndrome: A UPLC Q-Exactive based metabolomic study

BackgroundThe polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder syndrome of women in reproductive age. Metabolomic studies of the follicular fluid can reveal the potential metabolic pathways related to PCOS. The objection of this study was to explore the changes of metabolites in the follicular fluid of PCOS. MethodsWe collected follicular fluid samples of 35 patients with PCOS and 33 controls without PCOS for metabolomic analysis with UPLC Q-Exactive. The identified metabolites were annotated with KEGG and HMDB to determine the disturbances of metabolic pathways in PCOS. Based on the regression model, we conducted the ROC analysis to find the biomarker of PCOS in the follicular fluid. ResultsMetabolomic analysis identified 21 differential metabolites in PCOS, which revealed that the Vitamin B6 metabolism, phenylalanine metabolism and carnitine synthesis were the key changed pathways. We found that 7β-Hydroxycholesterol was potential biomarker of PCOS based on the ROC analysis. ConclusionWe identified metabolic alterations and biomarker in the follicular fluid of PCOS, providing novel ways for the diagnosis and treatment of PCOS.

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.

Diagnostic Value of Anti-Müllerian Hormone as a Biomarker for Polycystic Ovary Syndrome: A Meta-Analysis Update

Objective: A previous meta-analysis carried out on the predictive ability of anti-Müllerian hormone (AMH) for polycystic ovary syndrome (PCOS) showed that independent AMH may be a useful initial diagnostic test for PCOS. The aims of this study were to update the meta-analysis and to evaluate the diagnostic efficacy of AMH when it replaces polycystic ovary morphology (PCOM) in the Rotterdam criteria. Methods: Two independent reviewers searched PubMed, Cochrane Library, and the Web of Science databases systematically to identify relevant articles by using the key words "anti-Müllerian hormone" and "polycystic ovary syndrome." The deadline for manuscript inclusion was July 31, 2018. A random effects model was used and subgroup analysis and meta regression were performed to identify possible sources of heterogeneity. The methodologic quality of each study was assessed by QUADAS-2 and funnel plot asymmetry test. Results: According to the inclusion criteria, 29 studies were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for AMH alone detecting PCOS were 0.76 (95% confidence interval [CI] 0.71 to 0.81), 0.86 (95% CI 0.82 to 0.90) and 20 (95% CI 12 to 33), respectively. When AMH replaces polycystic ovary morphology (PCOM) for the diagnosis of PCOS, the pooled sensitivity, specificity, and DOR rose to 0.93 (95% CI 0.89 to 0.96), 0.99 (95% CI 0.95 to 1.00), and 1,634 (95% CI 217 to 12,324), respectively. The area under the summary receiver-operating characteristic curve for AMH alone and for AMH replacing PCOM detecting PCOS were 0.88 (95% CI 0.85 to 0.91) and 0.97 (95% CI 0.95 to 0.98), respectively, which was found to be significantly different (Z = 4.89, P<.01). Conclusion: When AMH replaces PCOM in the Rotterdam criteria, the diagnostic efficacy for polycystic ovary syndrome is better. Abbreviations: AMH = anti-Müllerian hormone; AUC = area under the summary receiver operating characteristic curve; BMI = body mass index; CI = confidence interval; DOR = diagnostic odds ratio; HA = hyperandrogenism; IBC = Immunotech-Beckman Coulter; NLR = negative likelihood ratio; OA = oligo-anovulation; PCOM = polycystic ovary morphology; PCOS = polycystic ovary syndrome; PLR = positive likelihood ratio; QUADAS = the Quality Assessment of Diagnostic Accuracy Studies; SENS = sensitivity; SPEC = specificity.

Identification of potential metabolic biomarkers of polycystic ovary syndrome in follicular fluid by SWATH mass spectrometry

BackgroundPolycystic ovary syndrome (PCOS) is a complex disorder associated with multiple metabolic disturbance, including defective glucose metabolism and insulin resistance. The altered metabolites caused by the related metabolic disturbance may affect ovarian follicles, which can be reflected in follicular fluid composition. The aim of this study is to investigate follicular fluid metabolic profiles in women with PCOS using an advanced sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry.Materials and methodsNineteen women with PCOS and twenty-one healthy controls undergoing IVF/ET were recruited, and their follicular fluid samples were collected for metabolomic study. Follicular fluid metabolic profiles, including steroid hormones, free fatty acids, bioactive lipids, and amino acids were analyzed using the principal component analysis (PCA) and partial least squares to latent structure-discriminant analysis (PLS-DA) model.ResultsLevels of free fatty acids, 3-hydroxynonanoyl carnitine and eicosapentaenoic acid were significantly increased (P < 0.05), whereas those of bioactive lipids, lysophosphatidylcholines (LysoPC) (16:0), phytosphingosine, LysoPC (14:0) and LysoPC (18:0) were significantly decreased in women with PCOS (P < 0.05). Additionally, levels of steroid hormone deoxycorticosterone and two amino acids, phenylalanine and leucine were higher in the PCOS patients (P < 0.05).ConclusionWomen with PCOS display unique metabolic profiles in their follicular fluid, and this data may provide us with important biochemical information and metabolic signatures that enable a better understanding of the pathogenesis of PCOS.

Associations of different molecular forms of antimüllerian hormone and biomarkers of polycystic ovary syndrome and normal women

To study different antimüllerian hormone (AMH) isoforms in women with polycystic ovary syndrome (PCOS) and healthy regularly cycling women and to investigate whether levels of AMH isoforms combined with baseline characteristics can predict PCOS. Cross-sectional study. Fertility clinic. Eighty-eight women with PCOS and 24 age- and body mass index (BMI)-matched normal control subject women recruited from April 2010 to February 2013. AMH isoforms were analyzed in biobanked serum samples collected at Holbaek Fertility Clinic, Denmark. All study participants went through a baseline examination including gynecologic history, objective examination, transvaginal ultrasound, and blood sampling. Each woman was characterized by measurement of total T, free T, SHBG, A, DHEAS, FSH, LH, E2, PRL, TSH, serum insulin, plasma glucose, and C-peptide. None. Serum levels of three different AMH isoforms. Levels of AMH measured with each of three AMH ELISAs were significantly higher in women with PCOS compared with control women. The ratio between AMH isoforms showed significant associations with metabolic parameters (BMI, SHBG, C-peptide, cholesterols, triglycerides, and the modified homeostasis-model assessment). Prediction of PCOS showed a high precision with areas under the receiver operating characteristic curve of 97% when AMH measurements were combined with androgens and BMI. Three ELISAs detecting different parts of the AMH molecule all detected significantly higher levels in women with PCOS compared with control women. The relative distribution of AMH isoforms did not differ between women with PCOS and control women. AMH isoforms alone and in combination with baseline characteristics predicted PCOS with close to 100% area under the receiver operating characteristic curve.

ACOG Committee Opinion No. 773: The Use of Antimüllerian Hormone in Women Not Seeking Fertility Care.

Antimüllerian hormone is produced by the granulosa cells surrounding each oocyte in the developing ovarian follicle. The production and serum levels of antimüllerian hormone at any given time are reflective of a woman's ovarian reserve, and multiple studies have demonstrated that antimüllerian hormone levels decline across the reproductive lifespan. Data exist to support the use of antimüllerian hormone levels for the assessment of ovarian reserve in infertile women and to select ovarian stimulation protocols in this population; however, using serum antimüllerian hormone levels for fertility counseling in women without a diagnosis of infertility is not currently supported by data from high-quality sources. The obstetrician-gynecologist should exercise caution when considering the predictability of serum antimüllerian hormone levels in any population of women with a low prevalence of infertility, including reproductive-aged women who either have never tried to become pregnant or have become pregnant previously without assistance. Based on the current information, a single serum antimüllerian hormone level assessment obtained at any point in time in a population of women with presumed fertility does not appear to be useful in predicting time to pregnancy and should not be used for counseling patients in this regard. At this time, routine antimüllerian hormone testing for prediction of pregnancy loss is not recommended. More data are needed to determine the utility of antimüllerian hormone as a predictor of time to menopause, a biomarker for polycystic ovary syndrome, or a predictor of future menses in women who have received gonadotoxic therapy.

ACOG Committee Opinion No. 773 Summary: The Use of Antimüllerian Hormone in Women Not Seeking Fertility Care.

Antimüllerian hormone is produced by the granulosa cells surrounding each oocyte in the developing ovarian follicle. The production and serum levels of antimüllerian hormone at any given time are reflective of a woman's ovarian reserve, and multiple studies have demonstrated that antimüllerian hormone levels decline across the reproductive lifespan. Data exist to support the use of antimüllerian hormone levels for the assessment of ovarian reserve in infertile women and to select ovarian stimulation protocols in this population; however, using serum antimüllerian hormone levels for fertility counseling in women without a diagnosis of infertility is not currently supported by data from high-quality sources. The obstetrician-gynecologist should exercise caution when considering the predictability of serum antimüllerian hormone levels in any population of women with a low prevalence of infertility, including reproductive-aged women who either have never tried to become pregnant or have become pregnant previously without assistance. Based on the current information, a single serum antimüllerian hormone level assessment obtained at any point in time in a population of women with presumed fertility does not appear to be useful in predicting time to pregnancy and should not be used for counseling patients in this regard. At this time, routine antimüllerian hormone testing for prediction of pregnancy loss is not recommended. More data are needed to determine the utility of antimüllerian hormone as a predictor of time to menopause, a biomarker for polycystic ovary syndrome, or a predictor of future menses in women who have received gonadotoxic therapy.