Increased childhood leukemia risk with embryo transfer vs. natural conception
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Key takeaways:
- Frozen embryo transfer vs. natural conception was tied to increased acute lymphoblastic leukemia risk.
- Children born from 2010 to 2015 after fresh embryo transfer vs. natural conception had higher leukemia risk.
Children conceived via fresh or frozen embryo transfer may have increased risk for acute lymphoblastic leukemia compared with children conceived naturally, according to cohort study results published in JAMA Network Open.
“Compared with children conceived naturally, children born after medically assisted reproduction have an increased risk of adverse perinatal outcomes, including preterm birth, low birth weight and fetal growth anomalies,” Paula Rios, MD, PhD, from the EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, French National Health Insurance, and colleagues wrote. “However, little is known about the medium-term and long-term effects of fertility treatments on child health.”
Rios and colleagues conducted a nationwide birth cohort study using the French National Mother-Child Register data to identify 8,526,306 children (mean age, 6.4 years; 51.2% boys) born in France from 2010 to 2021. Researchers compared cancer risk overall and by cancer type among children conceived via assisted reproductive technologies (ART), such as fresh embryo transfer, frozen embryo transfer or artificial insemination, and those conceived naturally.
Overall, 3.1% of children were conceived with ART: 1.6% via fresh embryo transfer, 0.8% via frozen embryo transfer and 0.7% via artificial insemination. During a median follow-up period of 6.7 years, 9,256 children had cancer. Of those with cancer, 165 were conceived by fresh embryo transfer, 57 with frozen embryo transfer and 70 with artificial insemination.
Overall cancer risk did not differ between children conceived naturally and those conceived via fresh embryo transfer (HR = 1.12; 95% CI, 0.96-1.31), frozen embryo transfer (HR = 1.02; 95% CI, 0.78-1.32) or artificial insemination (HR = 1.09; 95% CI, 0.86-1.38). Leukemia was the most diagnosed cancer type, accounting for 29.4% of all cancer cases. Most leukemia cases were acute lymphoblastic leukemia, of which 39 children were conceived via fresh embryo transfer, 20 via frozen embryo transfer and 16 via artificial insemination.
Compared with children conceived naturally, acute lymphoblastic leukemia risk was significantly higher for children conceived by frozen embryo transfer (HR = 1.61; 95% CI, 1.04-2.5). In analyses restricted to children born from 2010 to 2015, after a median follow-up of 9.4 years, children conceived by fresh embryo transfer had a significantly increased risk for leukemia compared with children conceived naturally (HR = 1.42; 95% CI, 1.06-1.92).
“Our findings do not provide evidence of an increased risk of other types of childhood cancer among children born after medically assisted reproduction,” the researchers wrote. “Based on 19 exposed case patients, the nonsignificantly increased risk of central nervous system tumors after artificial insemination reported here warrants further investigation.”
In a related commentary, Marie Hargreave, PhD, senior researcher at the Danish Cancer Institute, Denmark, noted that these findings are the latest among several studies that report increased leukemia risk among children born to mothers using ART.
“More large high-quality studies are needed to corroborate the accumulating evidence of increased cancer risk among children after ART and to investigate what aspects of ART may confer higher risk,” Hargreave wrote. “With an increasing number of children being born after ART use, this risk becomes progressively easier to investigate as more childhood cancer cases become available for study. Likewise, the increasing number of children being born after these procedures highlights the imperativeness and importance of these studies.”