Treatment with cytotoxic
chemotherapy and
radiotherapy is associated with significant gonadal damage in men and women.
Alkylating agents such as
cyclophosphamide and
procarbazine are the most common agents implicated. The vast majority of men receiving
procarbazine-containing regimens for the treatment of
lymphomas become permanently infertile.
Cisplatin-based
chemotherapy for
testicular cancer results in temporary
azoospermia in most men, with a recovery of spermatogenesis in about 50% after 2 years and in 80% after 5 years. There is also evidence of Leydig cell impairment in a proportion of these men, although the clinical significance of this is not clear. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia occurring following as little as 0.1 Gy and permanent
infertility after fractionated doses of 2 Gy and above. Cytotoxic-induced
premature ovarian failure is age- and
drug-dependent and ensues in approximately half of women treated with
procarbazine-containing
chemotherapy for
lymphomas. High-dose
chemotherapy, total body irradiation, and irradiation at an ovarian dose above 6 Gy usually result in permanent ovarian failure. The course of ovarian function after
chemotherapy is variable, and late recovery occurs in some patients. Several methods of preserving gonadal function during potentially sterilizing treatment have been considered. Currently, sperm banking remains the only proven method in men, although hormonal manipulation to enhance the recovery of spermatogenesis and cryopreservation of testicular germ cells are possibilities for the future. Transposition of the ovaries to allow better shielding during
radiotherapy is of use in some women, and the prospect of cryopreservation and
reimplantation of ovarian tissue is promising.