Maintenance of gestation implicates complex function of multiple endocrine mechanisms, and disruptions of the global metabolic environment prompt profound consequences on fetomaternal well-being during pregnancy and postpartum. Polycystic Ovary Syndrome (PCOS) and gestational diabetes mellitus (GDM) are very frequent conditions which increase risk for pregnancy complications, including early pregnancy loss, pregnancy-induced hypertensive disorders, and preterm labor, among many others. Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug. Although traditional views neglect use of oral antidiabetic agents during pregnancy, increasing evidence of safety during gestation has led to metformin now being recognized as a valuable tool in prevention of IR-related pregnancy complications and management of GDM. Metformin has been demonstrated to reduce rates of early pregnancy loss and onset of GDM in women with PCOS, and it appears to offer better metabolic control than insulin and other oral antidiabetic drugs during pregnancy. This review aims to summarize key aspects of current evidence concerning molecular and epidemiological knowledge on metformin use during pregnancy in the setting of PCOS and GDM. 1. Introduction Infertility currently affects approximately 48.5 million of women aged 20–44 years around the world , with severe implications in their physical and mental well-being . Female fertility entails a complex array of endocrine mechanisms surrounding the integrity of the hypothalamus-pituitary-ovary (HPO) axis, which are especially important in maintenance of a healthy pregnancy, particularly due to the demands of the growing fetus . Many conditions may disrupt this environment, and Polycystic Ovary Syndrome (PCOS)—an endocrine-metabolic disease that encompasses multiple hormonal alterations related to female infertility—stands out mainly due to its high prevalence, affecting 6-7% of women aged 12–45 years , with a worrisome 70% of women estimated to remain undiagnosed . The hallmarks of this gynecoendocrine disease are disruption of ovarian steroidogenesis, giving rise to hyperandrogenemia and insulin resistance (IR) . A complex IR-hyperinsulinemia-hyperandrogenemia cycle involved in the endocrine disruptions in PCOS  leads not only to the typical clinical picture of PCOS—featuring oligoanovulation and hyperandrogenic manifestations—but also to diverse
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Identifier NCT01587378, Metformin to Prevent Late Miscarriage and Preterm Delivery in Women with Polycystic Ovary Syndrome Trial (PregMet2), ClinicalTrials.gov, Bethesda, Md, USA, National Library of Medicine, 2012, http://clinicaltrials.gov/show/NCT01855763.
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