1. A Novel Ovarian Reserve Monitoring Algorithm for Patients at Risk of Ovarian Injury from Gonadotoxic Therapy

Abstract

Background

Adolescent and young adult cancer survivors are at risk of infertility due to the gonadotoxic effects of treatment. Although ovarian function testing (OFT) is an essential aspect of fertility care, there is currently no standard of care for monitoring reserve after gonadotoxic therapy. At our institution, we measure AMH and FSH at 12-, 18-, and 24-months post-therapy for early detection of DOR (diminished ovarian reserve) and POI (premature ovarian insufficiency) to avoid delays in referral for assisted reproductive technologies (ART). The primary objective of this study is to assess whether a novel ovarian reserve monitoring algorithm enables early detection of DOR and POI after gonadotoxic therapy to improve reproductive outcomes.

Methods

In this IRB-approved observational cohort study at University of Colorado Hospital, we evaluated the algorithm to (1) identify survivors at risk of DOR and POI due to gonadotoxic therapy and (2) minimize time from treatment to ART. Group A (n=106) consisted of a retrospective cohort of survivors who completed therapy between October 1, 2016, and September 31, 2019, with AMH and FSH evaluated at 12, 18, and 24 months post-treatment completion (n=27). Group B (n=418) included survivors who completed cancer therapy after September 31, 2019, assessed prospectively at similar time points (n=64). AMH and FSH values, along with time since treatment, were analyzed to determine if the algorithm enables early detection of DOR before POI. Ovarian status was categorized as normal, diminished, impending POI, or POI. Time from treatment to diagnosis of DOR and POI was compared between the prospective group and historical controls using the log-rank test.

Results

Demographics between groups A and B were similar. OFT within 36 months after completing cancer treatment was performed in only 17.4% (91/524) of patients, and AMH was rarely tested before 2019. At the 24-month follow-up, the prospective group had a higher prevalence of normal ovarian reserve (44.3% [27/61] vs. 17% [4/23], p=0.05) compared to the retrospective group. Time from treatment to diagnosis of DOR or POI was shorter in Group B, although not significantly due to the small sample size (8.2 months in group A [n=19] vs. 6.1 months in group B [n=24], p=0.7).

Conclusions

Results suggests that patients followed under the fertility preservation program since 2019 have received more frequent monitoring and earlier OFT with increased use of AMH testing to detect changes before significant decline. The ovarian reserve monitoring algorithm allows early detection of DOR and POI after gonadotoxic therapy, potentially improving reproductive outcomes.