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

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.