In vitro fertilization (IVF), a common type of assisted reproductive technology (ART), seems to be a solution to subfertile couples worldwide, with over 8 million children conceived since its first success in 1978.1 Early safety of ART was observed closely given the controversial evidence on the risk of certain types of cancer among children conceived through ART.2,3 The largest study of childhood cancer in IVF-conceived children was conducted by researchers from the University of Minnesota and the results were recently published in JAMA Pediatrics.4
“A population-based retrospective study suggests modest excess risk for embryonal — especially hepatic tumors — in children conceived with IVF”, stated Robert W. Rebar, MD, an associate editor of the New England Journal of Medicine, who reviewed the study report recently published by Prof. Logan Spector.
In this study, researchers compared the incidence of childhood cancers among children conceived in vitro with those conceived naturally. The final dataset compared 275,686 IVF-conceived children with randomly matched 2,266,847 naturally conceived children.
During a mean follow-up of 4.5 years, the overall risk of cancer was not increased among IVF group (321 cases) compared with naturally conceived children (2,014 cases) from subfertile women or in the general population (252 and 193 per 1,000,000 person-years, respectively; HR=1.2; 95% CI: 1.00–1.36). The incidence rate of embryonal tumors was higher in the IVF group than the non-IVF group, mostly due to a higher rate of hepatic tumors (18.1 vs. 5.7; HR=2.46; 95% CI: 1.29–4.70). However, the rates of other cancers did not differ between the two groups.
The risk for cancer was not associated with specific IVF treatment modalities nor indication for IVF.
“For the few cancers to be associated with IVF, the absolute risk was still extremely rare,” said Prof. Spector, a lead study author and a principal investigator from the University of Minnesota, United States. “Due to the nature of our study, we could not distinguish between IVF itself versus the parents’ underlying infertility,” he emphasized with regards to the increased risk of hepatic cancer. He further explained that such increase may be due at least in part to advanced maternal age and other health factors that lead women to try IVF initially.
Another study recently published in Human Reproduction confirmed no overall increase in the risk of cancer in IVF-conceived children.5 In this nationwide historical cohort study with prospective median follow-up of 21 years, including all live-born offspring from women treated with subfertility treatments, researchers observed 231 cancers. These findings showed no difference in the cancer risk in IVF group compared with naturally conceived children (HR=1.00; 95% CI: 0.72–1.38).5
Overall, the existing evidence is reassuring to parents who have had children through IVF or who are considering conceiving a child using this technique. Yet continued follow-up for cancer occurrence among children conceived via IVF is recommended.
1. Fauser BC. Towards the global coverage of a unified registry of IVF outcomes. Reprod Biomed Online. 2019;38(2):133–137.
2. Källén B, Finnström O, Nygren KG, et al. In vitro fertilization in Sweden: child morbidity including cancer risk. Fertil Steril. 2005;84(3): 605-610.
3. Reigstad MM, Larsen IK, Myklebust TÅ, et al. Risk of cancer in children conceived by assisted reproductive technology. Pediatrics. 2016;137(3):e20152061.
4. Spector LG, Brown MB, Wantman E, et al. Association of in vitro fertilization with childhood cancer in the United States. JAMA Pediatr. 2019;173(6):e190392.
5. Spaan M, van den Belt-Dusebout AW, van den Heuvel-Eibrink MM, et al. Risk of cancer in children and young adults conceived by assisted reproductive technology. Hum Reprod. 2019;34(4):740-50.