Updates in diagnosing polycystic ovary syndrome-related infertility.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a condition that affects approximately 13% of reproductive age women and is characterized by androgen excess, menstrual irregularity and altered ovarian morphology. PCOS presents a complex etiology and pathophysiology, which still requires a detailed investigation of biochemical signatures to identify the molecules and mechanisms that govern it. AREAS COVERED: This narrative review summarizes the main molecular alterations found in the ovarian follicular fluid, endometrium and placenta of women with PCOS, and the genotypes potentially associated with the outcome of infertility treatments in PCOS. EXPERT OPINION: PCOS is associated with multiple alterations in growth factors, sex steroid hormones, reactive oxygen species, proinflammatory cytokines and adipokines, which contribute to follicle arrest/ anovulation or suboptimal corpus luteum function, and ultimately to menstrual irregularity and hyperandrogenic symptoms. A panel of PCOS biomarkers should include, besides ovarian products, markers of adipose tissue function, insulin resistance, vascular health, and low-grade chronic inflammation. The effects of ovarian stimulation drugs on infertile women with PCOS are likely to be modified by genetic factors, but the available evidence is heterogeneous; therefore, future studies should evaluate standard treatments and pre-specified outcomes of interest to provide more conclusive answers.

Influence of metformin on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS). METHODS: A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies. RESULTS: Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment. CONCLUSION: We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761).

Influence of n-3 fatty acid supplementation on inflammatory and oxidative stress markers in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD -0·29 (95 % CI -0·56, -0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.

Global DNA methylation in placental tissues from pregnant with preeclampsia: A systematic review and pathway analysis.

Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of gestation) and late- (LOPE, ≥34 weeks of gestation). DNA methylation (DNAm) may help to understand the abnormal placentation in PE. Therefore, we performed a systematic review to assess the role of global DNAm on pathophysiology of PE, focused on fetal and maternal tissues of placenta from pregnant with PE, including EOPE and LOPE. We searched the databases EMBASE, Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Scielo and Google Scholar, and followed the MOOSE guidelines. Moreover, we performed pathway analysis with the overlapping genes from the included studies. Twelve out of 24 included studies in the qualitative analysis considered the classification into EOPE and LOPE. We did not found heterogeneity in the criteria used for diagnosis of PE, and a few studies evaluated whether confounding factors would influence placental DNAm. Fourteen out of 24 included studies showed hypomethylation in placental tissue from pregnant with PE compared to controls. The differences in DNAm are specific to genes or differentially methylated regions, and more evident in EOPE and preterm PE compared to controls, rather than LOPE and term PE. The overlapping genes from included studies revealed pathways relevant to pathophysiology of PE. Our findings highlighted the heterogeneous results of the included studies, mainly focused on North America and China. Replication studies in different populations should use the same placental tissues, techniques to assess DNAm and pipelines for bioinformatic analysis.

The hallmark of pro- and anti-inflammatory cytokine ratios in women with polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrinopathy considered to be the most common metabolic disorder in women of reproductive age. Women with PCOS present with an increased risk of noncommunicable diseases (NCDs), especially low-grade chronic inflammation mediated by proinflammatory cytokines, and insulin resistance. This study aimed to investigate cytokine levels and their ratios in PCOS women compared to a healthy control group. This study evaluated 97 women with PCOS and 99 healthy women as controls. The PCOS diagnosis was performed according to ESHRE/ASRM. Plasma cytokines were evaluated by flow cytometry. We observed lower TNF levels, and decreased TNF/IL-6, TNF/IL-2, and TNF/IL-4 ratios in PCOS patients compared to the control group (p < 0.05). These results indicate an imbalance between pro- and anti-inflammatory cytokines, with prominent counter-regulatory cytokine production. These changes may be important in explaining the phenotypes present in PCOS and to direct better interventions for patients with this syndrome.