Differential Rates of Change in Measures of Ovarian Reserve in Young Cancer Survivors across the Reproductive Lifespan

Context: Recent studies have examined level and rate of change of anti-Müllerian hormone (AMH) for predicting time to menopause. Limited prospective, longitudinal data exists evaluating measures of ovarian reserve (MOR) in cancer survivors. Purpose: Determine the rate of change of MOR in survivors (15 to 39 years) compared with similar-aged controls and compared with late reproductive-aged controls (40 to 50 years). Design: Prospective cohort. Setting: Quaternary university hospital. Participants: Survivors at least 1 year from therapy completion, similar-aged controls, and late reproductive-aged controls. Interventions: Annual visits with early follicular-phase hormone analysis and ultrasound. Main Outcome Measure: Changes in AMH and antral follicle count (AFC) were modeled using random effects linear regression. Results: Cancer survivors (170) and 135 similar-aged controls had annual visits for an average of 38 months; 71 late reproductive-aged controls were followed for an average of 24 months. In models adjusted for body mass index, time since cancer therapy (for survivors), and exogenous hormone use, the geometric mean AMH and AFC levels were lower in the survivors than similar-aged controls at all ages. After age 24.5 AMH and AFC declined in both groups at rates that were similar (P = 0.78 for AMH, P = 0.37 for AFC). Late reproductive-aged controls declined at a much more precipitous rate of 30% per year for AMH and 16% per year for AFC (P < 0.01 compared with survivors). Conclusions: Although survivors had lower levels of AMH and AFC at the time of enrollment, the rate of change of AMH and AFC is not significantly different than similar-aged controls.