Development of a fertility risk calculator to predict individualized chance of ovarian failure after chemotherapy

J Assist Reprod Genet. 2021 Nov;38(11):3047-3055. doi: 10.1007/s10815-021-02311-0. Epub 2021 Sep 8.

Abstract

Purpose: To develop an innovative machine learning (ML) model that predicts personalized risk of primary ovarian insufficiency (POI) after chemotherapy for reproductive-aged women. Currently, individualized prediction of a patient's risk of POI is challenging.

Methods: Authors of published studies examining POI after gonadotoxic therapy were contacted, and six authors shared their de-identified data (N = 435). A composite outcome for POI was determined for each patient and validated by 3 authors. The primary dataset was partitioned into training and test sets; random forest binary classifiers were trained, and mean prediction scores were computed. Institutional data collected from a cross-sectional survey of cancer survivors (N = 117) was used as another independent validation set.

Results: Our model predicted individualized risk of POI with an accuracy of 88% (area under the ROC 0.87, 95% CI: 0.77-0.96; p < 0.001). Mean prediction scores for patients who developed POI and who did not were 0.60 and 0.38 (t-test p < 0.001), respectively. Highly weighted variables included age, chemotherapy dose, prior treatment, smoking, and baseline diminished ovarian reserve.

Conclusion: We developed an ML-based model to estimate personalized risk of POI after chemotherapy. Our web-based calculator will be a user-friendly decision aid for individualizing risk prediction in oncofertility consultations.

Keywords: Chemotherapy; Fertility preservation; Oncofertility; Primary ovarian insufficiency; Risk calculator.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cancer Survivors
  • Cross-Sectional Studies
  • Female
  • Humans
  • Infertility, Female / chemically induced
  • Infertility, Female / diagnosis*
  • Infertility, Female / epidemiology
  • Models, Statistical*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Ovarian Diseases / chemically induced
  • Ovarian Diseases / diagnosis*
  • Ovarian Diseases / epidemiology
  • Precision Medicine*
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / diagnosis*
  • Primary Ovarian Insufficiency / epidemiology
  • Risk Assessment / methods
  • Surveys and Questionnaires
  • United States / epidemiology