ArticleFrontiers in endocrinology2026
Non-linear saturation threshold of gonadotropin dose on cumulative live birth rates in advanced-age women with polycystic ovary syndrome: a retrospective cohort study.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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 (≥35 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. Results: CLBR was significantly lower in the advanced-age group (44.40%) than in younger cohorts (63.90%-69.40%, Conclusions: 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.
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