Research in context
Evidence before this study
We searched PubMed from 1966 up until June 1, 2015, for English-language publications, with the keywords “childhood cancer”, “survivor”, “fertility”, “pregnancy”, “birth”, “ovary”, and “sperm”. We additionally examined the bibliographies of selected references. Most of the previous literature, including analyses from the Childhood Cancer Survivor Study, included large numbers of individuals exposed to radiotherapy with known effects on gonadal function (ie, radiation to the gonads or the hypothalamic–pituitary axis). We identified only a few analyses (most with sample sizes <50) that specifically examined the effects of newer chemotherapeutic drugs, such as ifosfamide and cisplatin, in survivors of childhood cancer who were not exposed to such radiotherapy.
Added value of this study
This is one of the largest studies of pregnancy and livebirth in cancer survivors of any age who were not exposed to gonadal or cranial radiation. Importantly, our study features a broad range of commonly used chemotherapy drugs, given at varying doses, which allowed us to establish more precise dose thresholds associated with reduced likelihood of siring a pregnancy or livebirth for male and female survivors of childhood cancer. Our findings show an association between risk and exposure to cisplatin, a finding not consistently reported in survivors of childhood cancer. Female survivors can be reassured by the result that chemotherapy-specific effects in women who did not receive any radiotherapy to the pelvis or brain were generally few in relation to these reproductive outcomes, except with exposure to the highest cumulative doses.
Implications of all the available evidence
Counselling of patients and families about fertility preservation before initiation of cancer therapy is important. In particular, sperm banking should be encouraged for all newly diagnosed pubertal men, since this is a proven method of fertility preservation. The association of risk with cisplatin exposure should be investigated further, given the increase in use of that drug in many contemporary paediatric treatment protocols.