Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy

Abstract

Objective To identify factors associated with ovarian reserve (OR) impairment during and immediately after chemotherapy. Design Prospective cohort study. Setting Four university hospitals. Patients Adolescent and young adult females with a new diagnosis of cancer requiring chemotherapy. Interventions None. Main Outcome Measures Participants were followed to assess measures of OR (serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, anti-mullerian hormone (AMH), and antral follicle counts and mean ovarian volume) at 3 month intervals. Changes in OR were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed effects models adjusted for baseline OR, use of alkylating agent, and hormone use. Results 46 women with at least 1 pretreatment and 2 post-treatment study visits were included (mean follow-up 12 months). All measures of OR demonstrated significant changes during chemotherapy. Alkylating agent exposure and baseline OR were associated with the magnitude of impairment acutely, and pretreatment AMH levels were associated with the rate of recovery of AMH post-treatment. In adjusted models, participants with a pretreatment AMH level >2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤2 ng/mL recovered at a rate of 2.6% per month after therapy (p=0.003). Conclusion Baseline OR and alkylating agent exposure effect the magnitude of acute changes in OR from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling.

Ovarian Function after Chemotherapy in Young Breast Cancer Survivors

“…Earlier smaller studies have also reported lower amh levels in cancer survivors than in control subjects 15,[22][23][24][25][36][37][38][39] . In the subgroup of patients with regular menstrual cycles at the time of amh testing, factors with a significant positive effect on serum amh were younger attained age and regular menstrual cycles during chemotherapy; specifically, compared with no loss of menses during treatment, a history of losing and then regaining normal cycles predicted worse outcome.…”

“…We did not have pretreatment measurements of serum amh, which could have been useful for comparison. Dillon et al 38 measured pre-and posttreatment serum amh in young female cancer survivors and demonstrated that pretreatment serum amh was significantly associated with posttreatment serum amh. Similar findings have been reported by other investigators [38][39][40][41][42] , demonstrating that, for patients with reduced ovarian reserve before treatment, chemotherapy moves them further toward a perimenopausal state.…”

“…Dillon et al 38 measured pre-and posttreatment serum amh in young female cancer survivors and demonstrated that pretreatment serum amh was significantly associated with posttreatment serum amh. Similar findings have been reported by other investigators [38][39][40][41][42] , demonstrating that, for patients with reduced ovarian reserve before treatment, chemotherapy moves them further toward a perimenopausal state. In addition, although the ivf live-birth model provides some broad insight into the predicted outcome of ivf for our survivors, the model was not developed specifically for chemotherapytreated patients, and other age-related clinical factors besides ovarian reserve could contribute to the likelihood of ivf success.…”

Anti-Müllerian hormone: determination of ovarian reserve in early breast cancer patients

“…All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy: alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment. Particularly, pretreatment AMH levels were associated with the rate of recovery of AMH after treatment (Dillon et al 2013). …”

“…Recently, Dillon et al (2013) have evaluated factors (FSH, LH, E 2 , inhibin B, and AMH) associated with ovarian reserve impairment during and immediately after chemotherapy. All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy: alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment.…”