Authors
Xiaoju Wan, Min Yu, Xingwu Wu, Zhihui Huang, Jun Tan
Published in
Frontiers in endocrinology. Volume 17. Pages 1914533. Epub Sep 15, 2026.
Abstract
Diminished ovarian reserve (DOR) impairs assisted reproduction. Whether triglyceride (TG) plays a causal role in ovarian reserve remains unclear.
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.
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.
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.
PMID:
42812276
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.
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