Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists

Abstract

CONTEXT: Obesity is responsible for an increased risk of sub-fecundity and infertility. Obese women show poorer reproductive outcomes regardless of the mode of conception, and higher body mass index (BMI) is associated with poorer fertility prognosis. Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, and many women with PCOS are also overweight or obese. EVIDENCE ACQUISITION: The aim of the present narrative review is to describe the mechanisms responsible for the development of infertility and PCOS in women with obesity/overweight, with a focus on the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) as a therapeutic option for obese women with PCOS. EVIDENCE SYNTHESIS: Weight reduction represents the most significant factor affecting fertility and pregnancy outcomes. Current experimental and clinical evidence suggests the presence of an underlying pathophysiological link between obesity, GLP-1 kinetic alterations, and PCOS pathogenesis. Based on the positive results in patients affected by obesity, with or without diabetes, the administration of GLP-1 RA (mainly liraglutide) alone or in combination with metformin has been investigated in women with obesity and PCOS. Several studies demonstrated significant weight loss and testosterone reduction, with mixed results relative to improvements in insulin resistance parameters and menstrual patterns. CONCLUSIONS: The weight loss effects of GLP-1 RA offer a unique opportunity to expand the treatment options available to PCOS patients.