All postpubertal boys newly diagnosed with cancer should be encouraged to bank their sperm to preserve fertility prior to initiation of chemotherapy, one of the largest studies of pregnancy and livebirth in cancer survivors not exposed to gonadal or cranial radiation has found.1

In contrast to women survivors of childhood cancer, who have a good chance of conceiving with newer chemotherapeutic agents, male survivors are significantly less likely to have children, especially if treated with regimens that contain high-dose cisplatin or alkylating agents.

The study is the first to examine “a broad range of commonly used chemotherapy drugs, given at varying doses,” which allowed Eric J. Chow, MD, of Fred Hutchinson Cancer Research Center in Seattle, WA, and colleagues “to establish more precise dose thresholds associated with reduced likelihood of siring a pregnancy or livebirth for male and female survivors of childhood cancer.”

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Using data from a subset of the Childhood Cancer Survivor Study (CCSS) cohort, the study team examined the effect of chemotherapeutic agents on pregnancies and livebirths occurring between the ages of 15 and 44 years in 10 938 survivors and 3949 sibling comparators. Excluded were those who had received radiotherapy to the pelvis or the brain.

A total of 79% of survivors were treated with chemotherapy, 54% of whom had received at least 1 alkylating or similar DNA interstrand crosslinking drug. Cumulative doses of 14 drugs were examined: busulfan, carboplatin, carmustine, chlorambucil, chlormethine, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, lomustine, melphalan, procarbazine, temozolomide, and thiotepa.

Among male survivors, those who received cumulative upper tertile doses of cyclosphosphamide (≥ 7412 mg/m²; P < .0001), ifosfamide (≥ 53 000 mg/m², P = .0069), procarbazine (≥ 5060 mg/m²; P < .0001), and cisplatin (≥488 mg/m²; P = .0023) had a “significantly decreased likelihood of siring a pregnancy compared with those not exposed to each drug,” they reported. Among female survivors, only busulfan, at any dose, and lomustine (≥ 411 mg/m²) “were associated with significantly decreased pregnancy.”

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Compared with same-sex siblings, “the cumulative incidence at age 44 years of having or siring a pregnancy or livebirth was significantly lower for both male and female survivors,” the study authors wrote. By age 45 years, 70% of women cancer survivors had become pregnant, compared with more than 80% of siblings; for men, this was 50%, compared with 80% for siblings.