medwireNews: A French cohort study has found a significantly increased risk for leukemia in children born after fresh or frozen embryo transfer (ET) relative to those conceived naturally.
“This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART [assisted reproduction technology],” write Paula Rios (French National Agency for Medicines and Health Products Safety, Saint-Denis) and team in JAMA Network Open.
They note, however, that the overall cancer risk was not significantly higher with use of ARTs versus natural conception.
The author of a related commentary says that although this research question has been addressed previously, “[t]he major limitations of studies published to date include small sample sizes, leading to imprecise risk estimates, and self-reported retrospectively collected data, leading to potential recall bias.”
Marie Hargreave (Danish Cancer Institute, Copenhagen) continues: “The study by Rios et al is the largest to date based on high-quality registry data and thus adds great value to the published literature.”
Drawing on the French National Mother-Child Register (EPI-MERES), the researchers collated data for 8,526,306 children born in France during 2010–2021, 3.1% of whom were born following use of medically assisted reproduction, including 1.6% after fresh ET, 0.8% after frozen ET, and 0.7% after artificial insemination.
Over a median follow-up of 6.7 years, there were 9256 incidences of cancer, but there was no significant difference in the overall risk for cancer between children conceived naturally and those born after fresh ET, frozen ET, or artificial insemination.
But analysis by tumor type showed a significantly increased risk for acute lymphoblastic leukemia (ALL) among children conceived after frozen ET compared with those conceived naturally, with a hazard ratio (HR) of 1.61 and an adjusted risk difference of 23.2 per million person–years.
Furthermore, analyses restricted to children born between 2010 and 2015 revealed a significantly higher risk for leukemia after fresh ET versus children born without use of ARTs, at an HR of 1.42 and an adjusted risk difference of 19.7 per million person–years.
Rios and colleagues say that the association was observed in the restricted but not the overall analysis “probably as a result of more homogeneous follow-up between children born after fresh ET or [frozen] ET and better coverage of the age range corresponding to the incidence peak of leukemia (2-6 years).”
Hargreave wonders “why the authors did not report a common estimate for ART (including both fresh ET and [frozen] ET),” but adds that “if these associations are confirmed, they suggest that factors related to both ART types […] may confer the observed risk.”
She says that “[m]ore large high-quality studies are needed (1) to corroborate the accumulating evidence of increased cancer risk among children after ART and (2) to investigate what aspects of ART may confer higher risk.”
The commentator believes that the increasing number of children being born after ART use will make it “progressively easier” to evaluate the risks “as more childhood cancer cases become available for study,” but the rising numbers also highlight “the imperativeness and importance of these studies.”
She concludes: “Until then, it should be considered whether the accumulating evidence to date is enough to put fertility treatment on the still short list of modifiable risk factors for leukemia in children.”
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JAMA Netw Open 2024; 7: e249429
JAMA Netw Open 2024; 7: e249435