Fertility 'reassurance' for most chemotherapy-treated female childhood cancer survivors

By Shreeya Nanda

Both female and male chemotherapy-treated survivors of childhood cancer have an increased risk of impaired fertility, but results suggest that the risk in women is limited to those given specific chemotherapy drugs.

"[O]ur findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few", say Eric Chow (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA) and co-researchers.

They report on the reproductive outcomes of 10,938 participants of the Childhood Cancer Survivor Study who had survived for at least 5 years following a diagnosis of cancer prior to the age of 21 years, compared with 3949 siblings. All cancer survivors had received chemotherapy, but not direct or scatter radiation to the brain or pelvis.

During a median follow-up of 8 years for survivors and 10 years for siblings, 38% of survivors reported having or siring a pregnancy, compared with 62% of siblings.

And multivariable analysis, adjusting for self-reported ethnicity and year of birth, showed that the probability of having or siring a pregnancy was significantly reduced for survivors versus siblings, with hazard ratios of 0.87 and 0.63 for female and male survivors, respectively.

This was also the case for having a livebirth - female survivors were 0.82 times less likely to have at least one livebirth compared with siblings, while male survivors had a 0.63 times reduced likelihood of their partner having a livebirth.

Among male survivors, the probability of siring a pregnancy was significantly lower for patients who received high cumulative doses of cyclophosphamide, ifosfamide, procarbazine and cisplatin (≥7412 mg/m², ≥53,000 mg/m², ≥5060 mg/m² and 488 mg/m², respectively) than for those not exposed to any of these drugs.

By contrast, in female survivors, treatment with any dose of busulfan and a high cumulative dose of lomustine (≥411 mg/m²) was associated with a significantly reduced likelihood of becoming pregnant relative to survivors not exposed to either drug.

In light of the similar findings for livebirths, the investigators reiterate that female survivors can be reassured by their results.

"Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer", they conclude in The Lancet Oncology.

In an accompanying comment, Richard Anderson (The University of Edinburgh, UK) and W Hamish Wallace (Royal Hospital for Sick Children, Edinburgh, UK) write that "[t]his important result further focuses attention on how best to develop strategies for the protection of fertility in young patients with cancer."

For male survivors, they advocate the importance of awareness of the risk of fertility loss associated with alkylating agents and cisplatin and pretreatment referral to fertility services.

And although agreeing that "the data are generally more positive" for girls and young women, Anderson and Wallace believe that the findings "emphasise the need for accurate identification of the relatively small proportion who are at high risk, to avoid subjecting those at low risk to what might be invasive procedures."

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