{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:27:21Z","timestamp":1791584841031,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS1269"],"award-info":[{"award-number":["ZR2025MS1269"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031526","name":"Jinan Municipal Health Commission","doi-asserted-by":"publisher","award":["2024210013"],"award-info":[{"award-number":["2024210013"]}],"id":[{"id":"10.13039\/100031526","id-type":"DOI","asserted-by":"publisher"}]}],"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>Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility. Despite a high antral follicle count, advanced-age PCOS patients experience a marked decline in cumulative live birth rates (CLBR) after assisted reproductive technology. The dose-response relationship between total gonadotropin (Gn) dose and CLBR in this population remains poorly defined. This study aimed to quantify the non-linear threshold effect of total Gn dose, characterize the endometrial thickness (EMT) dose-response relationship, and develop a predictive nomogram.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study analyzed 2449 PCOS patients stratified by age quartiles. Univariate and multivariable logistic regression identified predictors of CLBR for the entire cohort and the advanced-age subgroup (\u226535 years). For the advanced-age group, restricted cubic splines (RCS) evaluated non-linear associations between total Gn dose and CLBR; piecewise linear regression identified saturation thresholds. RCS and conditional marginal effects analyzed EMT-CLBR relationships. A nomogram was constructed from multivariable predictors and validated internally with 1000 bootstrap resamples. Model performance was assessed via AUC-ROC, calibration curves, Hosmer-Lemeshow test, and decision curve analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CLBR was significantly lower in the advanced-age group (44.40%) than in younger cohorts (63.90%\u201369.40%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). In the advanced-age subgroup, total Gn dose and EMT independently predicted CLBR. RCS confirmed a non-linear dose-response relationship (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.019), with saturation at 1, 600 IU. Below this threshold, each 100-IU increase was associated with higher odds of CLBR (aOR: 1.059,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.034); above it, no significant association was observed (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.624). EMT showed a stable positive linear association with CLBR (aOR: 1.088,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.016), with predicted CLBR rising from 32.5% at 6\u00a0mm to 66.1% at 22\u00a0mm. The nomogram incorporating age, EMT, transfer type, AFC, and Gn dose demonstrated moderate discrimination (AUC\u00a0=\u00a00.74) and adequate calibration (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.108).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CLBR was substantially lower in advanced-age PCOS patients. A non-linear association between total Gn dose and CLBR was observed, with a plateau at approximately 1, 600 IU, although this finding may reflect confounding by indication. EMT showed a stable positive linear association with CLBR. These findings suggest that moderate stimulation with attention to endometrial preparation may warrant consideration in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1854468","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:37:13Z","timestamp":1779251833000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-linear saturation threshold of gonadotropin dose on cumulative live birth rates in advanced-age women with polycystic ovary syndrome: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yusi","family":"Han","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, 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