Interpretable, internally validated prognostic modelling of cumulative clinical pregnancy in women with diminished ovarian reserve

Objective To develop and internally validate an interpretable prognostic model for cumulative clinical pregnancy in women with diminished ovarian reserve (DOR), and to explore, as a hypothesis-generating secondary aim, whether protocol-associated pregnancy rates differ across model-defined baseline-prognosis risk strata. Design Retrospective cohort study. Setting A single tertiary reproductive medicine center. Patients 1,251 oocyte-retrieval cycles in women with DOR (AMH ≤ 1.1 ng/mL) at a single tertiary centre, January 2019–July 2024. Each record is one retrieval cycle; no patient identifier was available. Methods From 37 candidate predictors, random-forest selection (training set only) retained eight; six algorithms were compared for discrimination (AUC, DeLong), calibration (slope, intercept, Brier) and clinical utility (decision-curve analysis), with SHAP for interpretability. Discrimination was further assessed by out-of-time validation (train ≤2022, test 2023–2024). Within model-defined risk strata, protocols were compared (chi-square/Fisher; bootstrap CIs; FDR and Bonferroni correction), with a pre-treatment-variable-only sensitivity analysis. Results A parsimonious logistic regression gave the highest test AUC (0.739, 95% CI 0.688–0.790; Brier 0.200), not significantly better than more complex algorithms (DeLong p>0.10), and held up on out-of-time validation (AUC 0.726). The five most influential predictors (SHAP) were embryo quality, female age, male age, estradiol and AMH. In the exploratory analysis, low-probability cycles showed no protocol differences; among high-probability cycles only one association survived correction (long-acting GnRH-agonist fresh transfer vs HRT frozen transfer; absolute difference +48%, 95% CI 28–67%; FDR p=0.002), persisting in the baseline-only analysis. Conclusions In women with DOR, an interpretable logistic-regression model provided moderate, internally and temporally validated discrimination for cumulative clinical pregnancy at the pre-transfer decision point, though calibration drifted over time and warrants recalibration before use. The single protocol-related association is hypothesis-generating only. The model is best regarded as a pre-transfer prognostic counselling tool, not a basis for protocol selection, and requires prospective external validation. Clinical trial number Not applicable.