Fertility Treatment and Childhood Cancer Risk: What’s the Link?

The risk of childhood cancer may be increased in children born after the use of frozen embryo transfer, according to the findings of a recently published retrospective cohort study.

In order to investigate the relationship between various fertility treatments and childhood cancer risk, study authors used Danish population-based registry data and the Danish Infertility Cohort to obtain data on children born in Denmark between January 1, 1996 and December 31, 2012 (n=1,085,172) that had linked information regarding maternal infertility and use of fertility drugs or assisted reproductive technology. In the follow-up period (1996 to 2015), 2217 children were reported to be diagnosed with cancer. 

Using this data, the study authors sought to evaluate the risk of cancer in children born after exposure to different types of fertility treatments compared with those born to fertile women. Exposures included fertility drugs (clomiphene, gonadotropins, gonadotropin-releasing hormone analogs, human chorionic gonadotropin, progesterone, and estrogen) as well assisted reproductive technology (in vitro fertilization, intracytoplasmic sperm injection, and frozen embryo transfer). Hazard ratios as well as incidence rate differences for childhood cancer were calculated.

Findings of the study revealed that, of all types of fertility treatment examined, the only one that significantly increased the risk of cancer in children was frozen embryo transfer. The study authors reported incidence rates of childhood cancer to be 17.5 per 100,000 children born to fertile women (n=910,291) compared with 44.4 per 100,000 children born following frozen embryo transfer use (n=3356), within a 12.2 million person-years follow-up period (mean: 11.3 years). Additionally, an incidence rate difference of 26.9 (95% CI: 2.8, 51.0) per 100,000 and a hazard ratio (HR) of 2.43 (95% CI: 1.44, 4.11; n=14 cancer cases) were reported. 

The authors commented that this elevated risk of childhood cancer was mostly caused by an increased risk of leukemia (incidence rate: 14.4 per 100,000; incidence rate difference: 10.1 [95% CI: −4.0, 24.2] per 100,000; HR: 2.87 [95% CI: 1.19, 6.93]; n=5 cancer cases) as well as sympathetic nervous system tumors (HR: 7.82 [95% CI: 2.47, 24.70]; n<5 cancer cases). 

“Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined,” the study authors concluded. 

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