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. 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. 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. 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.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute to subfertility and poor reproductive outcomes in affected women. OBJECTIVE AND RATIONALE: The aim of this review was to determine whether there is sufficient evidence to support that endometrial function is altered in women with PCOS, whether clinical features of PCOS affect the endometrium, and whether there are evidence-based interventions to improve endometrial dysfunction in PCOS women. SEARCH METHODS: An extensive literature search was performed from 1970 up to July 2020 using PubMed and Web of Science without language restriction. The search included all titles and abstracts assessing a relationship between PCOS and endometrial function, the role played by clinical and biochemical/hormonal factors related to PCOS and endometrial function, and the potential interventions aimed to improve endometrial function in women with PCOS. All published papers were included if considered relevant. Studies having a specific topic/hypothesis regarding endometrial cancer/hyperplasia in women with PCOS were excluded from the analysis. OUTCOMES: Experimental and clinical data suggest that the endometrium differs in women with PCOS when compared to healthy controls. Clinical characteristics related to the syndrome, alone and/or in combination, may contribute to dysregulation of endometrial expression of sex hormone receptors and co-receptors, increase endometrial insulin-resistance with impaired glucose transport and utilization, and result in chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities in women with PCOS. Among several interventions to improve endometrial function in women with PCOS, to date, only lifestyle modification, metformin and bariatric surgery have the highest scientific evidence for clinical benefit. WIDER IMPLICATIONS: Endometrial dysfunction and abnormal trophoblast invasion and placentation in PCOS women can predispose to miscarriage and pregnancy complications. Thus, patients and their health care providers should advise about these risks. Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.

Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus. Because many women with polycystic ovary syndrome (PCOS) are insulin resistant, metformin was introduced in clinical practice to treat these patients also. Moreover, metformin's effect has other targets beside its insulin-sensitizing action. The present review was aimed at describing all evidence-based and potential uses of metformin in PCOS patients. In particular, we will analyze the uses of metformin not only for the treatment of all PCOS-related disturbances such as menstrual disorders, anovulatory infertility, increased abortion, or complicated pregnancy risk, hyperandrogenism, endometrial, metabolic and cardiovascular abnormalities, but also for the prevention of the syndrome.

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS). Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries. A significant (P < 0.05) difference in flow-mediated dilation (14.3 ± 1.9% vs. 18.1 ± 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 ± 0.09 mm vs. 0.39 ± 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 ± 0.4 pmol/liter vs. 0.5 ± 0.2 pmol/liter for PCOS patients and controls, respectively). In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function.

Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up.