Diagnostic and prognostic biomarkers in PCOS: Navigating insulin resistance, systemic inflammation, and endometrial...

Polycystic ovary syndrome (PCOS) is a highly prevalent and phenotypically diverse endocrine disorder in which insulin resistance (IR) serves as a central molecular driver of major metabolic and reproductive complications, including infertility, obesity, and increased long-term cardiovascular risk. This review examines the complex pathophysiology of PCOS, emphasizing how chronic systemic low-grade inflammation, gut microbiome dysbiosis, and oxidative stress interact to worsen hyperinsulinemia and hyperandrogenemia. It also highlights the clinical value of emerging diagnostic and prognostic biomarkers to improve risk stratification and patient management. Systemic biomarkers, such as pro-inflammatory cytokines, circulating endotoxemia arising from increased intestinal permeability, and epigenetic regulators including miR-146a, may provide prognostic insight into the trajectory of metabolic deterioration. In parallel, endometrial biomarkers, including the glucose transporter GLUT4, implantation-associated genes such as HOXA10, and inflammatory mediators like TNF-α, can support evaluation of impaired uterine receptivity, prediction of assisted reproductive technology (ART) outcomes, and stratification of miscarriage risk. By mapping key interactions within the gut-immune-metabolic axis and detailing localized endometrial dysfunction, this review proposes a framework for integrating targeted biomarker profiling into clinical practice to enable personalized, biomarker-informed interventions aimed at restoring fertility and metabolic health in patients with PCOS.