Association of In Vitro Fertilization With Childhood Cancer in the United States

Abstract

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 275 686 children conceived via IVF and a cohort of 2 266 847 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 1 000 000 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.

Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles

“…The added risks have been reported for singleton IVF babies and singletons after fetal reduction having pre-term weights, and large sized babies from frozen embryo procedures. Late onset diseases relating to increased risk of some cancers are being reported 25 26. In vitro embryo cultures and exposures may affect later life developments along with any (epi) genetic modifications provide added risks27 or lead to higher imprinting disorders such as Beckwith-Wiedemann syndrome28–30 30 compared with naturally conceived children.…”

Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group

“…A systematic review and meta-analysis including 16 cohort and 13 case-control studies, showed an increased risk for overall cancer (RR 1.16, 95% CI 1.01-1.32), hematological malignancies (RR 1.39, 95% CI 1.21-1.60) and other solid tumors (RR 1.57, 95% CI 1.14-2.16) when comparing ART offspring to non-ART offspring (Wang et al, 2019). In a later large retrospective study from the United States, including almost 300,000 ART children and above 2 million non-ART controls, there was no difference for overall cancer risk in the first decade of life, yet an association between ART and embryonal tumors, in particular hepatic tumors (HR 2.46, 95% CI 1.29-4.70) (Spector et al, 2019). A recent Danish cohort study, including 37,000 ART children born during 1996 to 2012, showed no association between any type of childhood cancer and any ART treatment or use of any type of fertility drugs in comparison to children born from fertile women.…”

Assessment of Birth Defects and Cancer Risk in Children Conceived via In Vitro Fertilization in the US

“…Data from birth certificates (2004-2013) linked to the SART CORS and the cancer registries were collected in a study of the risk of childhood cancer and IVF. 5 The remaining data (linkages to the birth defects registries, linking or relinking to the cancer registries, and linking to death records) were obtained in the current study of the risk of birth defects in assisted reproductive technology. New York, Texas, Massachusetts, and North Carolina were chosen for the current study because they are large and ethnically diverse, with birth defect registries using the same case definitions and data collected.…”

“…Births conceived with in vitro fertilization (IVF), the ex vivo manipulation of both sexes’ gametes to achieve conception, accounted for 2% of all US births in 2017. 1 , 2 Children born from IVF have been shown to be at greater risk for birth defects 3 and for childhood cancer 4 , 5 compared with children conceived their naturally. A growing body of literature reports an association between birth defects and the development of cancer, but this association has yet to be evaluated among children conceived via IVF.…”