Mediating role of the systemic immune-inflammation index in obesity-induced glycolipid dysmetabolism and compromised IVF/ICSI outcomes in polycystic ovary syndrome: A retrospective cohort study

This study aims to investigate the mediating role of the systemic immune-inflammation index (SII) in the relationship between obesity-related glycolipid indices and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in women with polycystic ovary syndrome (PCOS). A total of 598 women diagnosed with PCOS according to the Rotterdam criteria and undergoing their first IVF/ICSI cycle at the Reproduction Medicine Center, Taizhou People's Hospital Affiliated with Nanjing Medical University, Jiangsu, China between January 2021 and December 2023 were included. Key exposures included obesity-related metabolic indices (e.g., triglyceride to high-density lipoprotein ratio [TG/HDL], homeostasis model assessment of insulin resistance [HOMA-IR]) and the SII. The primary outcome was the live birth rate per initiated cycle. Associations were evaluated using multivariate generalized linear models, and causal mediation analysis was performed to quantify the proportion of the effect mediated by the SII. Higher TG/HDL, total cholesterol to HDL ratio (TC/HDL), low-density lipoprotein to HDL ratio (LDL/HDL), and HOMA-IR levels showed dose-dependent negative correlations with oocyte yield, fertilization rate, embryo quality, and live birth rate (all P < .05). An elevated SII was an independent predictor of a reduced live birth rate (β = -0.08, P = .008) and mediated 8.8% to 10.7% of the adverse effects of dyslipidemia (via TC/HDL and LDL/HDL) on live birth. This study shows that the SII is statistically linked to and potentially mediates the connection between metabolic dysfunction and poor IVF/ICSI outcomes in PCOS. Integrated strategies targeting both metabolism and inflammation may optimize fertility success in this population.