ESPE Yearbook of Paediatric Endocrinology

J Cancer Surviv. 2021; 15: 259–272. https://pubmed.ncbi.nlm.nih.gov/32844376/

Long-term treatment effects are possible reasons for reduced fertility and adverse pregnancy outcomes in childhood cancer survivors (CCS) (1). This observational study reports perinatal and health outcomes of offspring born to CCS using assisted reproductive technologies (ART). CCS were almost 2-fold more likely to use ART compared to the general population (4.6% vs. 2.6%).

Among offspring born to CCS, multiple sibling births and low birth weight were significantly more common following ART than after spontaneous conception. The high prevalence of multiple sibling births after ART in CCS was similar to the 34% reported in the general population. ART did not increase the prevalence of childhood cancer or congenital malformations in offspring born to CCS. A mildly increased prevalence of moderate preterm births (32 to 37 gestational weeks) in the offspring of CCS was detected. The differences in perinatal outcomes were completely explained by differences in multiple sibling birth and other known confounders.

Patients included in this study were treated between 1980 and 1999, before the implementation of the guidelines for fertility preservation. Only few patients cryopreserved oocytes/sperm prior to cancer treatment. Most CCS (58.7%) were treated in the 1980s, with higher doses of radiation and alkylating agents than used now. These findings appear particularly reassuring for current patients treated with less toxic protocols. The results are also reassuring because only a mild increase of moderate preterm birth was demonstrated in survivor offspring and most medical consequences occur in severely preterm infants.

In this study, the prevalence of childhood cancer and congenital malformations, whether conceived by ART or spontaneous conception, was not higher in CCS offspring than in the general population. A meta-analysis published in 2013, had reported a slightly elevated overall cancer risk in children born after ART. Fertility impairment and potential epigenetic defects in the gametes, rather than the ART procedure itself, were supposed to be the main predisposing factors (2).

The study has some limitations. The recruitment based on previous surveys identifying CCS with biological children (required by the German Society for Pediatric Oncology and Hematology to reduce the study burden for survivors) potentially caused a selection bias. The questionnaire-based setting reduces data accuracy by recall bias. Moreover, factors as maternal age, body mass index, infections or other maternal diseases, which clearly influence pregnancy outcome and perinatal events, were not analyzed.

Reference: 1. van Dorp W E, et al. Reproductive function and outcomes in female survivors of childhood, adolescent, and young adult cancer: a review. J Clin Oncol. 2018; 36: 2169–80.2. Hargreave M, et al. Fertility treatment and childhood cancer risk: a systematic metaanalysis. Fertil Steril. 2013; 100: 150–61.