Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Abstract

Purpose: This study was undertaken to determine the effect of treatment for childhood cancer on male fertility.

Patients and methods: We reviewed the fertility of male Childhood Cancer Survivor Study survivor and sibling cohorts who completed a questionnaire. We abstracted the chemotherapeutic agents administered, the cumulative dose of drug administered for selected drugs, and the doses and volumes of all radiation therapy from medical records. Risk factors for siring a pregnancy were evaluated using Cox proportional hazards models.

Results: The 6,224 survivors age 15 to 44 years who were not surgically sterile were less likely to sire a pregnancy than siblings (hazard ratio [HR], 0.56; 95% CI, -0.49 to 0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, -0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, -0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, -0.26 to 0.87; third tertile HR, 0.17; 95% CI, -0.07 to 0.41). Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0, a hypothalamic/pituitary radiation dose = 0 Gy, and a testes radiation dose = 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P = .41).

Conclusion: This large study identified risk factors for decreased fertility that may be used for counseling male cancer patients.

Fig 1.

Flowchart of cohort subgroups for male fertility analysis. Long-term follow-up study (LTFU). (*) Includes refusals (n = 1,971) and insufficient data to define participation (n = 81).

Fig 2.

Relationship between summed alkylating agent dose score and the relative risk for siring a pregnancy. (*) Relative risk is adjusted for age at diagnosis, race/ethnicity, marital status, educational attainment, nonalkylating chemotherapy drugs, hypothalamic/pituitary radiation dose, and testicular radiation dose. (†) Referent group = 0 score.