Age- and AMH-based prediction of mature oocyte yield in oncofertility is well calibrated overall, but substantial underestimation is more frequent in hematologic malignancies
- 1University of Genova, Dipartimento di Neuroscienze- Riabilitazione- Oftalmologia- Genetica e Scienze Materno-Infantili (DINOGMI Department) , ,
- 2AOM – IRCCS Ospedale Policlinico San Martino, SSD Physiopathology of Human Reproduction , ,
- 3University of Genova, BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV) , ,
Abstract
Introduction: age and ovarian reserve markers are commonly used in clinical practice to predict ovarian response to controlled stimulation for assisted reproductive techniques in infertile patients. In oncofertility, some reports suggest the predictive performance of these markers may be lower in specific subgroups. We evaluated the performance of a prespecified age + log(AMH) model for predicting metaphase-II (MII) oocyte yield in women undergoing oocyte cryopreservation before gonadotoxic treatment.
Methods: This retrospective single-center cohort study included consecutive oocyte cryopreservation cycles performed before gonadotoxic treatment between January 2015 and January 2025. MII yield was modelled using negative-binomial regression with age and log-transformed AMH as predictors. Regression coefficients were estimated in the current cohort. Model performance was assessed using calibration measures and patient-level bootstrap internal validation, with all cycles from the same woman kept together during resampling. Analyses were performed overall and by cancer type. Threshold-based underestimation analyses and the incremental value of antral follicle count (AFC) were also explored.
Results: A total of 179 oocyte cryopreservation cycles performed in 167 women were included. The model showed good overall calibration using aggregated out-of-bootstrap predictions, with calibration-in-the-large of 0.00 (95% CI −0.08 to 0.09) and calibration slope of 0.98 (95% CI 0.80 to 1.15). Mean prediction error was −0.10 MII (95% CI −0.97 to 0.80), indicating minimal average directional bias. Mean absolute error was 4.12 MII (95% CI 3.53 to 4.76), and root mean squared error was 5.94 MII (95% CI 4.92 to 7.00). Substantial underestimation, defined as observed MII yield exceeding predicted yield by more than 4 MII, was more frequent in hematologic malignancies than in solid tumors (31.8% [14/44] vs 12.6% [17/135]; risk difference +19.2 percentage points, 95% CI + 4.4 to +34.1; Fisher’s exact p=0.006). This finding remained consistent in the one-cycle-per-woman sensitivity analysis. Adding AFC did not improve predictive performance in the complete-case analysis.
Conclusion: age and AMH are useful tools for counseling regarding the expected mature oocyte yield, including in our subset of oncofertility patients. As we found substantial underestimation of mature oocyte yield to be more frequent in hematologic malignancies, the results should be interpreted cautiously in this subgroup.
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BibTeX
@article{massarotti2026amhbased,
title = {{Age- and AMH-based prediction of mature oocyte yield in oncofertility is well calibrated overall, but substantial underestimation is more frequent in hematologic malignancies}},
author = {Claudia Massarotti and Sara Stigliani and Paola Scaruffi and Fausta Sozzi and Andrea Amaroli and Paola Anserini},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1940599},
url = {https://europepmc.org/article/PMC/PMC13671969},
note = {CC BY},
}
RIS
TY - JOUR
TI - Age- and AMH-based prediction of mature oocyte yield in oncofertility is well calibrated overall, but substantial underestimation is more frequent in hematologic malignancies
AU - Claudia Massarotti
AU - Sara Stigliani
AU - Paola Scaruffi
AU - Fausta Sozzi
AU - Andrea Amaroli
AU - Paola Anserini
PY - 2026
DA - 2026/10/02
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1940599
UR - https://europepmc.org/article/PMC/PMC13671969
AB - Introduction: age and ovarian reserve markers are commonly used in clinical practice to predict ovarian response to controlled stimulation for assisted reproductive techniques in infertile patients. In oncofertility, some reports suggest the predictive performance of these markers may be lower in specific subgroups. We evaluated the performance of a prespecified age + log(AMH) model for predicting metaphase-II (MII) oocyte yield in women undergoing oocyte cryopreservation before gonadotoxic treatment. Methods: This retrospective single-center cohort study included consecutive oocyte cryopreservation cycles performed before gonadotoxic treatment between January 2015 and January 2025. MII yield was modelled using negative-binomial regression with age and log-transformed AMH as predictors. Regression coefficients were estimated in the current cohort. Model performance was assessed using calibration measures and patient-level bootstrap internal validation, with all cycles from the same woman kept together during resampling. Analyses were performed overall and by cancer type. Threshold-based underestimation analyses and the incremental value of antral follicle count (AFC) were also explored. Results: A total of 179 oocyte cryopreservation cycles performed in 167 women were included. The model showed good overall calibration using aggregated out-of-bootstrap predictions, with calibration-in-the-large of 0.00 (95% CI −0.08 to 0.09) and calibration slope of 0.98 (95% CI 0.80 to 1.15). Mean prediction error was −0.10 MII (95% CI −0.97 to 0.80), indicating minimal average directional bias. Mean absolute error was 4.12 MII (95% CI 3.53 to 4.76), and root mean squared error was 5.94 MII (95% CI 4.92 to 7.00). Substantial underestimation, defined as observed MII yield exceeding predicted yield by more than 4 MII, was more frequent in hematologic malignancies than in solid tumors (31.8% [14/44] vs 12.6% [17/135]; risk difference +19.2 percentage points, 95% CI + 4.4 to +34.1; Fisher’s exact p=0.006). This finding remained consistent in the one-cycle-per-woman sensitivity analysis. Adding AFC did not improve predictive performance in the complete-case analysis. Conclusion: age and AMH are useful tools for counseling regarding the expected mature oocyte yield, including in our subset of oncofertility patients. As we found substantial underestimation of mature oocyte yield to be more frequent in hematologic malignancies, the results should be interpreted cautiously in this subgroup.
SN - 2234-943X
ER -