Search

We previously described increased HMGB1 and reduced FOXO1 dependent on CFTR loss of function in cystic fibrosis (CF) and we showed in vitro that HMGB1 was lowered by insulin. Reduced CFTR gene expression has been described in granulosa cells (GC) from PCOS-induced rats. We aimed at studying CFTR and FOXO1 gene expression in GC, HMGB1 concentrations in serum and follicular fluids (FF), and insulin and IL-6 in FF in PCOS women. Thirty PCOS and 36 non-PCOS women (CTRL) undergoing in vitro fertilization were enrolled. CFTR and FOXO1 gene expression were downregulated in PCOS ( p  ≤ .05). HMGB1 was higher in PCOS both in FF ( p  ≤ .05) and in serum ( p  < .005) whereas insulin was lower, and IL-6 was unchanged with respect to controls. 17-β estradiol was higher in PCOS than in CTRL ( p  ≤ .005). HMGB1 correlated negatively with insulin in FF ( p  ≤ .005). The increase in HMGB1 both in FF and in serum, likely reflects both low grade inflammation and insulin sensitivity. IL-6 was unchanged possibly reflecting functions other than inflammation.

Polycystic ovary syndrome (PCOS) is a common female disorder with a pathogenesis still today not completely known. To the present, PCOS is considered more than just a reproductive disorder since several metabolic consequences that could affect women's health during different stages of reproductive and post-reproductive life were reported. The aim of the current review was to evaluate present evidence-based data regarding the pregnancy complications in infertile patients with PCOS. An extensive literature search until February 2018 was performed in PubMed, Medline, the Cochrane Library and Web of Science. Outcomes were classified in: early pregnancy complications, late pregnancy complications, perinatal complications, offspring health and long-term offspring and maternal health. Even if the exact mechanisms involved are still unclear, women with PCOS have an increased risk of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia (PE), premature delivery and caesarean section. Moreover, the offspring of women with PCOS are also at increased risk of congenital anomalies and hospitalization in childhood. Further studies are needed to study the mechanism underlying pregnancy complications in PCOS and to identify any interventions to reduce the risk of obstetric and neonatal risks in women affected by PCOS and in their offspring.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and affects fertility and pregnancy in cases of oligoanovulation. Ovulation induction is often used to treat anovulatory patients with PCOS, but many of these women fail to conceive and resort to assisted reproductive technologies. Alterations in oocyte competence (OC) are considered potential causative factors for subfertility in women with PCOS. In this review we present and critically assess all recent clinical and experimental data regarding OC in women with PCOS. Our analysis demonstrates that the contribution of OC to reproductive potential in women with PCOS varies and largely depends on the PCOS phenotype and comorbidities associated with PCOS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The great majority of studies performed so far concerning women diagnosed with polycystic ovary syndrome (PCOS) have focused on diagnosis, menstrual cycle abnormalities, hirsutism and infertility. Although progress has been made in developing methods for achieving a pregnancy and reducing multiple gestations in women with PCOS, little attention has been paid to pregnancy complications and subsequent child outcomes. This review aims to summarize current knowledge regarding the clinical and pathophysiological features of pregnancy and children in women with PCOS., Methods: A literature search up to April 2015 was performed in PubMed, Medline, the Cochrane Library and Web of Science without language restriction. All articles were initially screened for title and abstract and full texts of eligible articles were subsequently selected. Systematic reviews with meta-analysis were initially included for each specific subject. Recent randomised controlled trials (RCTs), which were not included in the systematic reviews, were also included. In addition to evidence from meta-analyses or RCTs, we used non-randomized prospective, uncontrolled prospective, retrospective and experimental studies. When specific data for patients with PCOS were lacking, results from general population studies were reported., Results: Women with PCOS exhibit a clinically significant increased risk of pregnancy complications compared with controls. Data which were not adjusted for BMI or other confounders demonstrated in PCOS a 3-4-fold increased risk of pregnancy-induced hypertension and pre-eclampsia, a 3-fold increased risk of gestational diabetes and 2-fold higher chance for premature delivery. Features characteristic of PCOS, such as hyperandrogenism, obesity, insulin resistance and metabolic abnormalities, may contribute to the increased risk of obstetric and neonatal complications. Limited available data suggest that offspring of women with PCOS have an increased risk for future metabolic and reproductive dysfunction. Underlying pathophysiological mechanisms of pregnancy complications along with its association with health of offspring remain uncertain. To date, the strategies for prevention and management of pregnancy complications in women with PCOS, and whether long-term health of these women is influenced, and to what extent, by pregnancy and/or pregnancy complications, remain to be elucidated., Conclusions: Women with PCOS show an increased risk of pregnancy complications. Heterogeneous aetiological factors involved in PCOS and associated co-morbidities may all be involved in compromised pregnancy and child outcomes. In women with PCOS, a possible relationship with genetic, environmental, clinical and biochemical factors involved in this complex condition, as well as with pregnancy complications and long-term health for both mother and child, remains to be established., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications. One hundred and fifty nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were serially assayed in all subjects before and throughout pregnancy. Serum low-density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly (P<0.05) higher in PCOS group than in healthy controls at each assessment. Throughout pregnancy, serum LDL and TG levels increased significantly (P<0.05) in both groups, although the change from pre-pregnancy values was significantly (P<0.05) greater in PCOS patients than in healthy controls. A significant (P<0.05) relationship was observed between serum LDL and TG changes and changes in both insulin sensitivity indexes and androgen levels in PCOS patients alone. After adjusting for maternal age, pre-pregnancy BMI and lipid levels, body weight gain, and insulin-resistance markers, serum TG concentrations during pregnancy were directly and independently associated with obstetric complications in both groups, whereas serum LDL levels only in PCOS patients. We can conclude that nonobese PCOS patients had specific changes in lipid profile during pregnancy, and that the lipid pattern typical of PCOS may account for the more frequent adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as insulin resistance and high androgen levels, may mediate this phenomenon., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study evaluated the impact of different phenotypes of polycystic ovary syndrome (PCOS) on early trophoblast invasion and placentation. Pregnant patients with different PCOS phenotypes and healthy pregnant women, matched for age and body mass index, were enrolled. Histological analysis of trophoblastic and decidual tissue and macroscopic and microscopic assessment of the placentas were performed. Implantation-site vessels with endovascular trophoblast differed significantly among PCOS phenotypes. Placental weight, thickness, density and fetal-placental weight ratio were significantly different in the full-blown and non-polycystic ovary (PCO) phenotypes versus the ovulatory and non-hyperandrogenic phenotypes. The incidence of macroscopic placental lesions was only significantly different between controls and the full-blown and non-PCO phenotypes. The overall incidence of microscopic placental lesions was significantly different among PCOS phenotypes and was significantly higher in the full-blown and non-PCO phenotypes than in the ovulatory and non-hyperandrogenic phenotypes. The rates of chorionic villitis and intervillositis were significantly higher in full-blown and non-PCO phenotypes than in ovulatory and non-hyperandrogenic phenotypes. In conclusion, alterations in early trophoblast invasion and placentation observed in PCOS vary widely according to phenotype., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Context: Polycystic ovary syndrome (PCOS) and pregnancy are conditions characterized by an increased low-grade chronic inflammation state. A higher incidence of pregnancy complications has been detected in pregnant PCOS women., Objective: The objective of the study was to test the hypothesis that the low-grade chronic inflammation state typical of PCOS patients persists during gestation and is exacerbated by pregnancy and contributes to the increased risk of obstetric/neonatal complications., Design: This was a prospective controlled clinical study., Setting: The study was conducted at the Academic Department of Obstetrics and Gynecology of the "Pugliese-Ciaccio" Hospital of Catanzaro (Catanzaro, Italy)., Patients: One hundred fifty pregnant PCOS women and 150 age- and body mass index-matched healthy pregnant controls participated in the study., Interventions: INTERVENTIONS included serial clinical, biochemical, and ultrasonographic assessments before and throughout pregnancy., Main Outcome Measures: Serum levels of white blood cell count (WBC), C-reactive protein (CRP), and ferritin were measured., Results: Pregnant women with PCOS had higher WBC, CRP, and ferritin levels at study entry and at all gestational ages than controls. Changes in serum WBC and ferritin levels were significantly higher in PCOS than in controls starting from the 12th week of gestation whereas those in CRP from the 20th week of gestation. By multivariable Cox proportional hazard analysis, in the PCOS group, a significant association with the risk of adverse obstetric/neonatal outcomes was found for WBC [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.64; P = .010], CRP (HR 1.19, 95% CI 1.06-1.34; P = .019), and ferritin levels (HR 1.12, 95% CI 1.03-1.26; P = .011)., Conclusions: In PCOS patients, the low-grade chronic inflammation persists during gestation and is exacerbated by pregnancy, and it is associated with adverse pregnancy outcomes.

The management of oligo-amenorrhea in adolescent patients with polycystic ovary syndrome (PCOS) represents an important and difficult challenge. Metformin and/or oral contraceptives (OCs) are different strategies widely proposed in these patients. The objective of the current review was to provide an overview on the use of metformin and/or OCs for the management of oligo-amenorrhea in adolescents with PCOS underlining their potential risks and benefits in order to help the clinician to choose the best patients' tailored treatment.

The current systematic review with meta-analysis of randomized controlled trials (RCTs) was aimed to evaluate the effects of metformin on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who receive gonadotropins for ovulation induction. After systematic review of electronic databases and websites for registration of RCTs, a total of 7 RCTs reporting data on 1023 cycles were included in the final analysis. Descriptive data showed an overall low studies' quality due to unclear sequence generation and allocation concealment, lack of blinding procedure, incomplete outcome data and several biases and/or confounders. Data synthesis showed that metformin improved live-birth (odds ratio [OR] = 1.94, 95% confidence interval [CI] 1.10 to 3.44; P = 0.020) and pregnancy (OR = 2.25, 95% CI 1.50 to 3.38; P < 0.0001) rates, without significant heterogeneity across the studies (P = 0.230, estimation of inconsistency = 30%; and P = 0.710, estimation of inconsistency = 0%, respectively, for live-birth and pregnancy rates). A significant reduction of cancellation rate was observed after metformin administration (OR = 0.41, 95% CI 0.24 to 0.72, P = 0.002) without significant heterogeneity across the studies (P = 0.500, estimation of inconsistency = 0%). Metformin administration influenced or did not influence other secondary endpoints assessed with a significant heterogeneity. In conclusion, metformin administration increases the live-birth and pregnancy rate in PCOS patients who receive gonadotropins for ovulation induction. Further well designed, blinded, placebo-controlled, and adequately powered RCTs are need to confirm that metanalytic results.

Objective: Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders (PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome (PCOS) are at higher risk of PDDs., Design: Longitudinal case-control study., Patients: Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby., Measurements: Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children's versions of the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) tests were administered., Results: Total AQ-C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ-C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ-C and SQ-C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy non-PCOS controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels., Conclusions: Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone., (© 2012 Blackwell Publishing Ltd.)

Context: Previous experimental and clinical data suggest impaired decidual trophoblast invasion in patients with polycystic ovarian syndrome (PCOS)., Objective: The objective of the study was to test the hypothesis that decidual endovascular trophoblast invasion in pregnant patients with PCOS is impaired and to clarify the potential mechanisms involved., Design: This was an experimental case-control study., Setting: The study was conducted at the academic Departments of Obstetrics and Gynecology and the Unit of Pathology (Italy)., Patients: Forty-five pregnant subjects screened from a wide population of women waiting for legal pregnancy termination were included in the final analysis. Specifically, 15 pregnant patients with PCOS were enrolled as cases and another 30 age- and body mass index (BMI)-matched healthy pregnant women without any feature of PCOS were enrolled as the controls., Intervention: Interventions included the collection of trophoblastic and decidual tissue at the 12th week of gestation., Main Outcome Measures: Clinical, ultrasonographic, and biochemical data as well as the histological analysis of decidual endovascular trophoblast invasion., Results: The rate of implantation site vessels with endovascular trophoblast invasion (ratio between total number of implantation site vessels and total number of vessels with endovascular trophoblast invasion) and the extent of endovascular trophoblast invasion (proportion between immunoreactive areas to cytokeratin 7 and to CD34) were significantly lower in patients with PCOS compared with healthy non-PCOS controls. Endovascular trophoblast invasion data were significantly and indirectly related to the markers of insulin resistance and testosterone concentrations in PCOS patients., Conclusions: Pregnant patients with PCOS patients have impaired decidual trophoblast invasion. Further studies are needed to evaluate the exact mechanisms through which insulin resistance and hyperandrogenemia exert this effect.

Objective: To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF., Design: Parallel, randomized, double-blind, placebo-controlled clinical trial., Setting: Academic departments, general hospital, and IVF centers., Patient(s): One hundred twenty patients with PCOS at high risk for OHSS., Intervention(s): Gonadotropins ovarian stimulation for IVF and metformin (500 mg three times daily) or placebo tablets (three times daily)., Main Outcome Measure(s): The primary end point of the current clinical trial was the rate of OHSS. Anthropometric and reproductive data were evaluated., Result(s): The total OHSS and cancellation rates were significantly reduced in patients treated with metformin. The relative risk for OHSS was of 0.28 (95% confidence interval, 0.11-0.67). With metformin the stimulation length and the total amount of gonadotropins used were significantly increased, whereas the peak E(2) levels were significantly reduced., Conclusion(s): In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles, metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation. REGISTRATION ID NUMBER FROM CLINICALTRIALS.GOV: NCT01233206., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: MicroRNAs (miRNAs) are gene expression regulators. Altered miRNA levels are associated with diabetes, insulin resistance, and inflammation. Insulin resistance and inflammation are both features of Polycystic ovary syndrome (PCOS). The aim of this study was first to assess differences in selected miRNAs (miR-146a, miR-155, miR-320, miR-370, miR-486), involved in insulin sensitivity regulation and inflammation, in women with or without PCOS. Second, to investigate relationships among these miRNAs, insulin, High mobility group box 1 (HMGB1), and IL-6 in follicular fluid (FF), serum 17-beta estradiol (E2), and the number of dominant follicles. Methods: Thirty PCOS and thirty-six non-PCOS women undergoing in vitro fertilization were enrolled. RNA from granulosa cells (GC) and FF was extracted and the specific miRNAs were evaluated using qRT-PCR. HMGB1, insulin, and IL-6 in FF, and serum E2 were assayed using specific kits. Results: MiR-146a, miR-155, miR-486 were upregulated and miR-320 and miR-370 were downregulated in GC from the PCOS patients. In FF, miR-146a, miR-155, and miR-486 showed lower levels in PCOS, whereas miR-320 and miR-370 showed an opposite trend but no significant changes were observed. These miRNAs showed relationships with Body Mass Index (BMI), age, E2, number of dominant follicles, insulin, and HMGB1. Conclusion: In conclusion, the miRNAs analyzed showed changes in PCOS ovaries and had relationships with indices of inflammation and insulin sensitivity within the ovary, providing evidence for new regulatory mechanisms. [ABSTRACT FROM AUTHOR]