Children born after fresh and frozen embryo transfers at increased leukemia risk than children conceived naturally: JAMA

A new cohort study published in JAMA Network Open provides reassuring findings on this front, suggesting that offspring of MAR procedures are not at a significantly higher risk of developing cancer compared to those conceived naturally.

In the cohort study of 8 526 306 children, there was no difference in the overall risk of cancer among children born after fresh embryo transfer (ET), frozen embryo transfer (FET), or artificial insemination (AI) and children conceived naturally. However, an increased leukemia risk was observed among children born after fresh ET (especially those with the longest follow-up) and among children born after FET (particularly acute lymphoblastic leukemia).

"These findings suggest that leukemia risk among children conceived by frozen embryo transfer or fresh embryo transfer should be further monitored," the researchers wrote.

Cancer is the foremost cause of death among children worldwide. Treatments used for MAR are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. Paula Rios, French National Health Insurance, Saint-Denis, France, and colleagues aimed to assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally.

For this purpose, the researchers searched the French National Mother-Child Register (EPI-MERES) for all live births in France between 2010 and 2021 (followed up until June 30, 2022). The EPI-MERES was built from comprehensive French National Health Data System data.

Using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth, the risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or artificial insemination and children conceived naturally.

The study included 8 526 306 children with a mean age of 6.4 years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation.

The study revealed the following findings:

• There were 3.1% of children born after MAR, including 1.6% after fresh ET, 0.8% after FET, and 0.7% after AI.
• A total of 9256 case-patients with cancer were identified over a median follow-up of 6.7 years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively.
• The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12), FET (HR, 1.02), or AI (HR, 1.09).
• The risk of acute lymphoblastic leukemia was higher among children born after FET (20 case-patients; HR 1.61; risk difference [RD], 23.2 per million person-years) compared with children conceived naturally.
• Among children born between 2010 and 2015, leukemia risk was higher among children born after fresh ET (45 case-patients; HR, 1.42; adjusted RD, 19.7 per million person-years).

The study findings suggest that children born after FET or fresh ET had an increased leukemia risk compared with children conceived naturally. There is a need to monitor this risk, although resulting in a limited number of cases, given the continuous increase in the use of ART.

Reference:

Rios P, Herlemont P, Fauque P, et al. Medically Assisted Reproduction and Risk of Cancer Among Offspring. JAMA Netw Open. 2024;7(5):e249429. doi:10.1001/jamanetworkopen.2024.9429