Association of in Vitro Fertilization with Childhood Cancer in the United States

Importance: In vitro fertilization (IVF) is associated with birth defects and imprinting disorders. Because these conditions are associated with an increased risk of childhood cancer, many of which originate in utero, descriptions of cancers among children conceived via IVF are imperative. Objective: To compare the incidence of childhood cancers among children conceived in vitro with those conceived naturally. Design, Setting, and Participants: A retrospective, population-based cohort study linking cycles reported to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System from January 1, 2004, to December 31, 2012, that resulted in live births from September 1, 2004, to December 31, 2013, to the birth and cancer registries of 14 states, comprising 66% of United States births and 75% of IVF-conceived births, with follow-up from September 1, 2004, to December 31, 2014. The study included 275686 children conceived via IVF and a cohort of 2266847 children, in which 10 births were randomly selected for each IVF birth. Statistical analysis was performed from April 1, 2017, to October 1, 2018. Exposure: In vitro fertilization. Main Outcomes and Measures: Cancer diagnosed in the first decade of life. Results: A total of 321 cancers were detected among the children conceived via IVF (49.1% girls and 50.9% boys; mean [SD] age, 4.6 [2.5] years for singleton births and 5.9 [2.4] years for multiple births), and a total of 2042 cancers were detected among the children not conceived via IVF (49.2% girls and 50.8% boys; mean [SD] age, 6.1 [2.6] years for singleton births and 4.7 [2.6] years for multiple births). The overall cancer rate (per 1000000 person-years) was 251.9 for the IVF group and 192.7 for the non-IVF group (hazard ratio, 1.17; 95% CI, 1.00-1.36). The rate of hepatic tumors was higher among the IVF group than the non-IVF group (hepatic tumor rate: 18.1 vs 5.7; hazard ratio, 2.46; 95% CI, 1.29-4.70); the rates of other cancers did not differ between the 2 groups. There were no associations with specific IVF treatment modalities or indication for IVF. Conclusions and Relevance: This study found a small association of IVF with overall cancers of early childhood, but it did observe an increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility. Continued follow-up for cancer occurrence among children conceived via IVF is warranted.