Progress in reproductive endocrinology has resulted in the availability of several options for preserving or permitting fertility in patients about to receive potentially toxic chemotherapy or radiation therapy. For males, cryopreservation of spermatozoa before treatment is an effective method to circumvent the sterilizing effect of therapy. Although pretreatment semen quality in patients with cancer has been shown to be less than that noted in healthy donors, the percentage decline in semen quality and the effect of cryodamage to spermatozoa from patients with cancer is similar to that of normal donors.[66,67,68,69] For those unable to bank sperm, newer technologies such as testicular sperm extraction may be an option. Further micromanipulative technologic advances such as intracytoplasmic sperm injection and similar techniques may be able to render sperm extracted surgically, or even poor-quality cryopreserved spermatozoa from cancer patients, capable of successful fertilization.
Preservation of fertility and successful pregnancies may occur after hematopoietic stem cell transplantation (HSCT), though the conditioning regimens that include TBI, cyclophosphamide, and busulfan are highly gonadotoxic. In a group of 21 females who had received a BMT in the prepubertal years, 12 (57%) were found to have ovarian failure when examined between ages 11 and 21 years, and the association with busulfan was significant. One study evaluated pregnancy outcomes in a group of females treated with BMT. Among 708 women who were postpubertal at the time of transplant, 116 regained normal ovarian function and 32 became pregnant. Among 82 women who were prepubertal at the time of transplant, 23 had normal ovarian function and nine became pregnant. Of the 72 pregnancies in these 41 women, 16 occurred in those treated with TBI and 50% resulted in early termination. Among the 56 pregnancies in women treated with cyclophosphamide without either TBI or busulfan, 21% resulted in early termination. There were no pregnancies among the 73 women treated with busulfan and cyclophosphamide, and only one retained ovarian function.
For childhood cancer survivors who have offspring, there is concern about congenital anomalies, genetic disease, or risk of cancer in the offspring. Children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parents' exposure to mutagenic cancer treatments. A retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female participants of the CCSS showed no significant associations between gonadal radiation or cumulative exposure to alkylating agents and congenital anomalies in offspring. In a report of 2,198 offspring of adult survivors treated for childhood cancer between 1945 and 1975 compared with 4,544 offspring of sibling controls, there were no differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. There was similarly no effect of type of childhood cancer treatment on the occurrence of genetic disease in the offspring. A population-based study of 2,630 live-born offspring of childhood cancer survivors versus 5,504 live-born offspring of the survivors' siblings found no differences in proportion of abnormal karyotypes or incidence of Down syndrome or Turner syndrome between survivor and sibling offspring. Survivors treated with abdominal radiation therapy and/or alkylating agents did not have an increased risk of offspring with genetic disease, compared with survivors not exposed to these agents.[75,76]