BMC Med Inform Decis Mak. 2026 Jul 18. doi: 10.1186/s12911-026-03709-5. Online ahead of print.
ABSTRACT
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.
PMID:42471694 | DOI:10.1186/s12911-026-03709-5
