Bidirectional Mediation Effects of Body Mass Index and Inflammatory Markers on Assisted Reproductive Outcomes in Women With Polycystic Ovary Syndrome

Abstract

Objective To evaluate the bidirectional mediation effects of body mass index (BMI) and inflammatory markers (neutrophil‐to‐lymphocyte ratio [NLR], systemic immune‐inflammation index [SII], platelet‐to‐lymphocyte ratio [PLR]) on assisted reproductive technology (ART) outcomes in women with polycystic ovary syndrome (PCOS). Design A historical cohort study. This analysis is exploratory and hypothesis‐generating rather than confirmatory. Setting Department of Reproductive Medicine, Nanjing Women's Hospital of Nanjing Medical University, China. Population A total of 966 women with PCOS undergoing ART, categorized by BMI: underweight ( n = 38), normal weight ( n = 547), overweight ( n = 282), and obesity ( n = 99). Methods Multivariable regression, restricted cubic splines, and bidirectional causal mediation analysis using the Quasi‐Bayesian approach with 1000 simulations were performed. Main Outcome Measures Number of oocytes retrieved, high‐quality embryos, available embryo rate, and clinical pregnancy outcomes. Results Oocytes retrieved decreased from 14.50 (IQR 12.00–20.75) in underweight to 12.00 (IQR 9.00–16.00) in obese women ( p < 0.001). High‐quality embryos declined from 4.00 (IQR 0.25–6.00) to 1.00 (IQR 0.00–3.50) across BMI categories ( p < 0.001). All inflammatory markers showed consistent negative dose–response relationships with available embryo rate (all p < 0.001). NLR mediated 9.2% (95% CI: 2.3%–20.0%) of BMI's effect on high‐quality embryos. BMI mediated 26.6% (95% CI: 13.3%–62.3%) of NLR's effect on high‐quality embryos and 58.6% (95% CI: 5.6%–528.4%) on available embryos. SII and PLR showed minimal mediation effects (< 5%). Conclusions These findings are exploratory and hypothesis‐generating. In this single‐centre cohort of women with PCOS, higher BMI and higher peripheral inflammatory indices were associated with fewer oocytes retrieved and fewer high‐quality embryos, and BMI and NLR appeared to lie on shared, bidirectionally related pathways, with the larger share attributable to BMI.