Vitamin D status tracks inflammation perfusion and pregnancy in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by metabolic and inflammatory heterogeneity, but the relative associations of vitamin D status and insulin resistance with inflammatory activation, uterine perfusion, and reproductive outcomes remain unclear. We analyzed a prospective discovery cohort of 580 affected women and 332 controls, followed by multicenter retrospective external validation in 750 additional affected women. Multivariable linear and logistic regression analyses showed that lower serum 25-hydroxyvitamin D was more broadly and consistently associated than the homeostasis model assessment of insulin resistance (HOMA-IR) with inflammatory markers, uterine artery perfusion indices, recurrent pregnancy loss, and live birth. In contrast, associations of HOMA-IR were narrower, mainly involving C-reactive protein and uterine perfusion, and were less stable after mutual adjustment and external validation. These findings suggest that vitamin D status may be a more informative marker than insulin resistance for inflammatory-vascular and reproductive risk stratification in women with PCOS.