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oai:figshare.com:article/33770680 2026-09-15T04:25:12Z category_658 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Triglycerides and ovarian response in diminished ovarian reserve: a two-sample mendelian randomization and clinical mediation study.xlsx Xiaoju Wan (14297048) Min Yu (120607) Xingwu Wu (12232805) Zhihui Huang (2541538) Jun Tan (46388) Cell Metabolism assisted reproductive technology diminished ovarian reserve lipid metabolism mediation analysis Mendelian randomization triglycerides Background<p>Diminished ovarian reserve (DOR) impairs assisted reproduction. 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. Despite impacting oocyte yield, TG did not independently predict clinical pregnancy or live birth; age and AMH remained dominant.</p>Conclusion<p>This study provides genetic evidence for a causal role of TG in lowering FSH and identifies a suppression pathway through which TG affects oocyte yield. These findings provide additional insight into the relationship between lipid metabolism and ovarian reserve, and highlight TG as a potential modifiable factor worthy of further investigation.</p> 2026-09-15T04:25:12Z Dataset Dataset 10.3389/fendo.2026.1914533.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Triglycerides_and_ovarian_response_in_diminished_ovarian_reserve_a_two-sample_mendelian_randomization_and_clinical_mediation_study_xlsx/33770680 CC BY 4.0