Consistent associations of BMI with ovarian response and pregnancy loss risk across PCOS, DOR, and tubal factor infertility: a complete-case mediation analysis of 8,923 IVF cycles

To investigate whether body mass index (BMI) affects in vitro fertilization (IVF) outcomes through consistent pathways across different infertility etiologies. A retrospective cohort study with mediation analysis. A reproductive medicine center in China. Of 11,524 eligible women (PCOS n = 2,881; DOR n = 4,354; tubal factor infertility n = 4,289), 8,923 with complete data for mediation analysis were included (PCOS n = 2,507; DOR n = 2,425; tubal factor n = 3,991); outcome analyses included 6,708, 4,182, and 6,523 women for clinical pregnancy, pregnancy loss, and live birth, respectively. None. Primary outcome was oocyte yield. Secondary outcomes included clinical pregnancy, miscarriage, and live birth. Mediating variable was basal follicle-stimulating hormone (FSH). BMI was associated with a small indirect effect on oocyte yield via FSH (proportion mediated: 5.31–8.21%). The direction of this indirect association was similar across cohorts, but the magnitude was small and confidence intervals were wide, particularly in the DOR cohort. For reproductive outcomes, obesity was significantly associated with a higher risk of pregnancy loss (OR=1.60, 95% CI: 1.02–2.53, P=0.041; NNH=19), showed a non-significant trend toward lower live birth rates (OR=0.77, P=0.078); however, the live birth analysis had only 5.3% power and was therefore inconclusive. No association was observed with clinical pregnancy. These associations were consistent across PCOS, DOR, and tubal factor cohorts. The live birth finding should be considered exploratory and hypothesis-generating. BMI showed consistent associations with IVF outcomes across distinct infertility etiologies. The FSH-related indirect association with oocyte yield was small and similar in direction across cohorts, but its clinical relevance remains uncertain. More importantly, obesity was consistently associated with increased pregnancy loss risk regardless of infertility cause. The live birth analysis was underpowered and inconclusive; therefore, no clinical recommendation can be made for live birth based on this study.