Childhood Chemotherapy Had Little Effect on Female Survivors Becoming Pregnant

Women who were treated with chemotherapy for a childhood cancer still had a good chance of becoming pregnant later in life, according to the results of a new analysis. However, male survivors treated with certain chemotherapy drugs, such as cyclophosphamide or cisplatin, had a decreased likelihood of siring a pregnancy compared with healthy siblings, the study showed.

“Our results should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain,” wrote Eric Chow, MD, of the Fred Hutchinson Cancer Research Center, and colleagues, in Lancet Oncology. “However, women who delay childbearing until later ages and those exposed to very high cumulative doses of alkylating drugs might want to consider earlier consultation with reproductive specialists.”

For this study, Chow and colleagues looked at data from a subset of the Childhood Cancer Survivor Study Cohort. Participants included 10,938 5-year survivors of the most common types of childhood cancer diagnosed between 1970 and 1999, and 3,949 siblings. Survivors exposed to pelvic or cranial radiotherapy were excluded.

With a median follow-up of 8 years or at age 15 years, whichever was later, 38% of survivors reported siring a pregnancy or becoming pregnant, and 83% reported at least one live birth. In comparison, at a median of 10 years follow-up, 62% of siblings reported siring or becoming pregnant and 90% reported at least one live birth. Multivariable analyses indicated that cancer survivors were significantly less likely than their siblings to have sired a pregnancy, become pregnant, or had a live birth.

When the researchers looked more closely at the types of chemotherapy undergone by these survivors, they found that men who had received cyclophosphamide had a 40% lower likelihood of siring a pregnancy (hazard ratio [HR] = 0.60; P < .0001); ifosfamide, a 58% lower likelihood (P = .0069); procarbazine, a 70% lower likelihood (P < .0001); and cisplatin, a 44% lower likelihood (P = .0023).

In contrast, only treatment with busulfan (HR = 0.22; P = .02) or doses of lomustine at 411 mg/m² or greater (HR = 0.41; P = .046) were linked with a lower likelihood of pregnancy among female survivors. Other alkylating and DNA interstrand crosslinking drugs were only associated with a decreased likelihood of pregnancy at very high cumulative doses.

“Nevertheless, female survivors still had a reduced likelihood of these outcomes vs siblings and, in those who had not reported a pregnancy by age 30 years, the likelihood of ever becoming pregnant by age 45 years was even more reduced vs siblings,” the researchers wrote.

The study relied on self-reporting of pregnancy and live birth, the researchers noted, which may affect the interpretation of the findings because as many as 25% of pregnancies can be unrecognized.

“We also did not directly assess gonadal function using laboratory methods, although our results are consistent with studies that used such methods,” the researchers wrote. “Assessment of fertility would ideally also account for other factors, such as marital or cohabitation status, in addition to intention to conceive and duration of time attempting to conceive (usually ≥ 1 year), which might explain some of the differences between survivors and siblings.”