Abstract
Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine disorder that affects 11%-13% of women worldwide, with profound implications for fertility and long-term metabolic health. Here we identify four reproducible subtypes-PCOS with hyperandrogen, with obesity, with high-sex hormone-binding globulin and with high-luteinizing hormone-anti-Müllerian hormone-through unsupervised clustering of 9 clinical variables in 11,908 affected women, validated across 5 international cohorts. Prospective 6.5-year follow-up and in vitro fertilization treatment data revealed distinct reproductive and metabolic trajectories: hyperandrogenic PCOS showed the highest risk of second trimester pregnancy loss and dyslipidemia incidence; PCOS with obesity exhibited the most severe metabolic complications, lowest live birth rates and highest PCOS remission rate; PCOS with high-sex hormone-binding globulin demonstrated favorable reproductive outcomes and the lowest incidence of diabetes and hypertension; and PCOS with high-luteinizing hormone-anti-Müllerian hormone had the greatest risk of ovarian hyperstimulation and the lowest PCOS remission rate. These findings advance understanding of PCOS heterogeneity and provide a framework for subtype-based risk stratification and personalized management.