Supplementary file 1_Triglycerides and ovarian response in diminished ovarian reserve: a two-sample mendelian randomization and clinical mediation study.xlsx

Whether triglyceride (TG) plays a causal role in ovarian reserve remains unclear.</p>Methods<p>We performed a bidirectional two-sample Mendelian randomization (MR) analysis using female-specific GWAS data to assess causality between metabolic traits and ovarian reserve markers (AMH, FSH). Findings were validated in a retrospective cohort of 8,851 DOR women undergoing their first IVF/ICSI cycle, using mediation analysis to elucidate pathways to oocyte yield.</p>Results<p>MR revealed that genetically predicted TG was causally associated with lower FSH (IVW β=-0.096, FDR = 5.28×10^-5), with no evidence of reverse causation.

Clinical validation confirmed this association. Mediation analysis uncovered that TG exerted a direct negative effect on oocyte yield, but concurrently lowered FSH, creating a suppression effect that partially counteracted this detriment (indirect effect: β = 0.0073, 95% CI: 0.0029 to 0.0117, p = 0.0021; suppression proportion: 23.6%). TG did not show a causal effect on AMH in MR (IVW OR = 1.035, 95% CI: 0.965-1.111, p = 0.338), and clinical mediation through AMH was not robust.