Chemotherapy-induced Ovarian Damage Research Articles

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

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. 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. 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. 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.

Effect of paclitaxel on primordial follicular reserve in mice

Premature ovarian failure and infertility are long-term consequences of chemotherapy in young women. Because primordial follicular cells in the ovary cannot regenerate, destruction of these cells results in ovarian dysfunction and premature ovarian failure. Histologic studies of chemotherapy-induced ovarian damage showed loss of primordial follicles and ovarian volume (1). Paclitaxel is an anticancer agent widely used in patients with carcinoma of the ovary, breast, and lung. In addition, promising results have been reported in patients with germ cell tumors and non-Hodgkin lymphomas, which occur frequently in young patients. Paclitaxel damages healthy mature oocytes (2) and affects short-term reproductive potential in a dose-dependent manner (3). However, a search of the MEDLINE database of the U.S. National Library of Medicine (1980 to 2000) found no study that evaluated the potential effect of paclitaxel on the primordial follicle reserve in healthy ovaries. The aim of our study was to evaluate the dose-related effects of paclitaxel on primordial follicle reserve in young mice.

The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease.

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.