{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:50Z","timestamp":1789448570606,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diminished ovarian reserve (DOR) impairs assisted reproduction. Whether triglyceride (TG) plays a causal role in ovarian reserve remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR revealed that genetically predicted TG was causally associated with lower FSH (IVW \u03b2=-0.096, FDR\u00a0=\u00a05.28\u00d710\n                      <jats:sup>-5<\/jats:sup>\n                      ), 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: \u03b2 = 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\u00a0=\u00a01.035, 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1914533","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:26:20Z","timestamp":1789446380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Triglycerides and ovarian response in diminished ovarian reserve: a two-sample mendelian randomization and clinical mediation study"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoju","family":"Wan","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwu","family":"Wu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Huang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12958-024-01321-8","article-title":"Analysis of single-cell RNA sequencing in human oocytes with diminished ovarian reserve uncovers mitochondrial dysregulation and translation deficiency","volume":"22","author":"Li","year":"2024","journal-title":"Reprod Biol Endocrinol RB&E"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa513","article-title":"Anti-M\u00fcllerian hormone and ovarian reserve: Update on assessing ovarian function","volume":"105","author":"Moolhuijsen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1186\/s12864-023-09728-0","article-title":"Diminished ovarian reserve causes adverse ART outcomes attributed to effects on oxygen metabolism function in cumulus cells","volume":"24","author":"Zhang","year":"2023","journal-title":"BMC Genomics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s12958-024-01298-4","article-title":"Identify high-risk DOR women\u2009\u2264\u200935 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts","volume":"22","author":"Teng","year":"2024","journal-title":"Reprod Biol Endocrinol RB&E"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315426","article-title":"Ovarian reserve disorders, can we prevent them? 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