Chemotherapy's Lasting Impact on Male Fertility in Childhood Cancer Survivors

A new study from the Fred Hutchinson Cancer Research Center has found that boys who underwent chemotherapy to treat their cancer—especially alkylating agents and cisplatin—were less likely to father children. While females were relatively less susceptible to the damaging effects of chemotherapy, the authors recommend fertility preservation in young children prior to initiation of treatment.

For their study, published in The Lancet Oncology, the authors analyzed a subset of data that emerged from the Childhood Cancer Survivor Study cohort, which followed 5-year survivors of the most common forms of childhood cancer. The patients were less than 21 years of age when diagnosed during the period between 1970 and 1999 at 27 institutions within the United States and Canada. The authors extracted data on 14 alkylating agents and DNA interstrand crosslinking agents and the doses that were used to treat these children.

A total of 10,938 survivors and 3949 siblings (as controls) were included in the study. After a minimum follow-up of 5 years from cohort entry or age 15 years, 38% (4149) survivors reported having or siring a pregnancy, with 83% (3453) reporting a livebirth. Among the control group, 62% (2445) reported having or siring a pregnancy, with 90% (2201) reporting at least a single live birth. Overall, the authors found that survivors had a significantly lower likelihood of having or siring a pregnancy compared with siblings (male survivors: hazard ratio [HR], 0·63; 95% CI, 0·58-0·68; P < ·0001; female survivors: HR, 0·87, CI, 0·81-0·94; P < ·0001) or of having live birth (male survivors: HR, 0·63; CI, 0·58-0·69; P < ·0001; female survivors: HR, 0·82, CI, 0·76-0·89; P < ·0001).

The culprits? High doses of cyclophosphamide, ifosfamide, procarbazine, and cisplatin in male survivors. In female survivors, only busulfan and lomustine were found responsible. Among women, though, those who tried to get pregnant early were more successful. Those who waited till they were 30 to have kids had a lower probability of conceiving, the study found.

“We’re not saying women have to have kids early but that people need to be aware that this and other studies suggest that even if overall, the impact on fertility is relatively minor, women do seem to be at higher risk of earlier menopause,” said Eric Chow, MD, MPH, lead author of the study, in a statement. “Women who had not yet had kids by age 30 were substantially less likely to have kids than cancer survivors who decided to get pregnant earlier, and also much less likely than siblings who had not had kids by age 30.” Chow, is professor of pediatrics at the University of Washington and medical director of the Cancer Survivorship Program at Seattle Children’s Hospital.

“I think, we as pediatric oncologists still need to do a better job discussing fertility and fertility-preservation options with patients and families upfront before starting cancer treatment,” said Chow. “In particular, all boys diagnosed post-puberty should be encouraged to bank their sperm to maximize their reproductive options in the future.”

The LIVESTONG Foundation has developed an online training program that can help them explain the risks of infertility and provide information on fertility preservation procedures to their young patients and their families.

Parents, too, can play an active role in this part of their child’s care. In an interview with Evidence-Based Oncology, Rajen Mody, MBBS, a pediatric oncologist at the University of Michigan Health System, pointed out that sometimes he finds that parents are more involved with the discussion on fertility preservation than their teenage child who’s undergoing treatment. “Although most parents do want the option, sometimes it may not be practical, especially if treatment needs to be initiated immediately [depending on the diagnosis], because there are some technical challenges associated with this, particularly for girls,” Mody added.

Reference

Chow EJ, Stratton KL, Leisenring WM, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort [published online March 22, 2016]. The Lancet Oncology. doi:http://dx.doi.org/10.1016/S1470-2045(16)00086-3.