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Objective <p>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.</p> Design <p>Retrospective cohort study.</p> Setting <p>A single tertiary reproductive medicine center.</p> Patients <p>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.</p> Methods <p>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.</p> Results <p>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&gt;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.</p> Conclusions <p>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.</p> Clinical trial number <p>Not applicable.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月18日

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  • Huimei Wu,
  • Qianyi Huang,
  • Yu Long,
  • Li Jiang,
  • Lidan Liu

摘要

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.