In Vitro Fertilization Associated With Small Increase in Childhood Cancer Risk

Baby in hospital
Baby in hospital
In vitro fertilization was shown to have a small but significant association with the development of childhood cancers.

In vitro fertilization (IVF) was shown to have a small but significant association with the development of childhood cancers, according to study results published in JAMA Pediatrics. While children conceived in vitro had a higher rate of embryonal cancers specifically, this may be attributed to underlying fertility rather than IVF itself.

Previous studies have associated IVF with birth defects and imprinting disorders, which are both associated with increased risk for childhood cancer. The investigators of this retrospective cohort study sought to understand the association of IVF with childhood cancers by comparing the incidence of cancer among children conceived with IVF vs those conceived naturally.

The study included 275,686 children conceived in vitro and a comparison cohort of 2,266,847 children randomly selected from the population (10 natural births for every 1 IVF birth). Data from the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System from January 2004 through December 2012 were linked to birth and cancer registries of 14 US states. The primary study outcome was the incidence of cancer diagnosed in the first decade of life. Statistical models were created for combined childhood cancers as well as for individual cancers, including embryonal tumor classes. Because of the large study population, most comparisons were significant even if differences were small.

Compared with children conceived naturally, children conceived in vitro had a lower mean birth weight and a shorter mean gestation period. Children conceived using IVF had 321 cases of recorded childhood cancers, while children conceived naturally reported 2042 cancer cases. The overall cancer rate for the IVF group was 251.9/1,000,000 person-years vs 192.7/1,000,000 person-years for the non-IVF group (hazard ratio [HR], 1.17; 95% CI, 1.00-1.36).

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When controlling for individual cancers, embryonal tumors were detected at a higher rate in the IVF group compared with the non-IVF group, mainly driven by rate of hepatic tumors (18.1 vs 5.7/1,000,000 person-years, respectively; HR, 2.46; 95% CI, 1,29-4.70). The incidence rates of other cancers were similar in both groups. Furthermore, the investigators did not observe any significant differences in the rate of combined or individual cancers with different IVF treatment modalities or indications for IVF.

Limitations to the study included unmeasured confounders associated with the data sets, including income, medical insurance status, and prenatal care access. The investigators could not account for non-IVF infertility treatments among the IVF cohort, and the person-time data may be overestimated as there was no way to detect when children moved out of state or died after infancy.

“An association of conception by IVF with childhood cancer is small and limited to rare tumors; however, continued follow-up for cancer occurrence among children conceived via IVF is warranted,” stated the researchers.

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Spector LG, Brown MB, Wantman E, et al. Association of in vitro fertilization with childhood cancer in the United States [published online April 1, 2019]. JAMA Pediatr. doi:10.1001/jamapediatrics.2019.0392