Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function

BACKGROUND. Various chemotherapy agents, especially of the alkylating category, have been associated with premature ovarian failure but there is no quantitative evidence of chemotherapy-induced ovarian damage in humans. The aim was to quantify the impact of chemotherapy on primordial follicle reserve and stromal function in human ovary with a prospective controlled quantitative histologic and in vitro study. METHODS. Samples from 26 patients who were undergoing ovarian tissue cryopreservation for fertility preservation were assessed histologically and for in vitro estradiol production. Of the 26 patients, 10 had previously received chemotherapy whereas 16 had not (control). There were 17 age-matched patients. Primordial follicle counts and in vitro estrogen production were compared between age-matched control and chemotherapy patients as well as between those who did and did not receive alkylating agents. RESULTS. Patients who received chemotherapy had significantly lower primordial follicle counts than control patients (5.4 +/- 1.32 vs 9.6 +/- 2.2, P = .05). Furthermore patients treated with alkylating regimens had significantly lower primordial follicle counts compared with those who received nonalkylating agents (2.9 +/- 1.1 vs 7.9 +/- 1.6, P < .05) and with those who did not receive any chemotherapy (2.9 +/- 1.1 vs 9.6 +/- 2.2, P < .05). In vitro, ovarian cortical pieces from individuals who were previously exposed to chemotherapy (chemotherapy group) produced significantly less estradiol compared with those who were not (control group). In the chemotherapy group, there was no difference in in vitro estradiol production between those who received alkylating agents and those who did not. CONCLUSIONS. This is the first quantitative evidence of the impact of chemotherapy on ovarian infrastructure, and shows that, whereas alkylating agents can significantly reduce ovarian reserve, both alkylating and nonalkylating regimens may affect ovarian stromal function