Obesity and reproductive health: Pathophysiological mechanisms and emerging interventions

Abstract

This review examines the multifaceted relationship between obesity and human reproduction, emphasizing the molecular, cellular, and systemic mechanisms by which excessive adiposity impairs fertility in both women and men. We synthesized findings from epidemiological, experimental, and clinical studies to explore how obesity influences hormonal balance, gametogenesis, and treatment outcomes in assisted reproduction. Mechanistic pathways, including insulin resistance, mitochondrial dysfunction, oxidative and endoplasmic reticulum stress, were critically analyzed. In women, obesity disrupts ovulation, oocyte maturation, and hormonal regulation, primarily through insulin resistance, altered adipokine secretion, and mitochondrial and ER stress. In men, obesity compromises spermatogenesis, testosterone production, and sperm quality via hormonal imbalance, oxidative stress, and inflammation. These disruptions lead to poorer outcomes in fertility treatments, including decreased oocyte quality and live birth rates. However, interventions such as weight reduction, pharmacological therapies (metformin, GLP-1 agonists), and bariatric surgery significantly improve reproductive outcomes. Obesity exerts profound, bidirectional effects on reproductive health through metabolic and molecular disturbances. Comprehensive management integrating lifestyle, pharmacological, and surgical strategies offers a promising route to restore fertility in obese individuals. Recognizing obesity as a critical determinant of reproductive potential highlights the need for integrated metabolic and reproductive care.