Non-linear saturation threshold of gonadotropin dose on cumulative live birth rates in advanced-age women with polycystic ovary syndrome: a retrospective cohort study.

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%, P < 0.001). In the advanced-age subgroup, total Gn dose and EMT independently predicted CLBR. RCS confirmed a non-linear dose-response relationship (P = 0.019), with saturation at 1, 600 IU. Below this threshold, each 100-IU increase was associated with higher odds of CLBR (aOR: 1.059, P = 0.034); above it, no significant association was observed (P = 0.624). EMT showed a stable positive linear association with CLBR (aOR: 1.088, P = 0.016), with predicted CLBR rising from 32.5% at 6 mm to 66.1% at 22 mm. The nomogram incorporating age, EMT, transfer type, AFC, and Gn dose demonstrated moderate discrimination (AUC = 0.74) and adequate calibration (P = 0.108).

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.