COMMENTARY

Cancer in Children Born Through IVF: Is the Risk Real?

Peter Kovacs, MD, PhD

Disclosures

June 20, 2019

Assisted Reproduction and Cancer

Each year, the 1-2 million in vitro fertilization (IVF) treatments performed worldwide result in 8 million children.[1] The safety of fertility treatments has been evaluated from the early days of assisted reproduction technology (ART), and reports about the risk for cancer among children conceived through ART have been conflicting.[2,3]

A recent study[4] assessed the risk for cancer among the offspring of subfertile women seen in fertility clinics in the Netherlands. Of 47,690 live-born children, 231 (93 conceived with ART and 138 conceived without ART) were diagnosed with cancer during a median of 21 years of follow up.

The study's findings included the following:

  • The overall cancer risk was not increased among ART-conceived children compared with naturally conceived children from subfertile women or in the general population.

  • The risk for cancer was not increased among the offspring of mothers exposed to fertility drugs compared with naturally conceived offspring.

  • A slight but nonsignificant increased risk for cancer was observed among children conceived by intracytoplasmic sperm injection or cryopreservation.

  • The risks for lymphoblastic leukemia and melanoma were nonsignificantly increased for ART-conceived children compared with naturally conceived children.

Viewpoints

Conflicting reports have been published with respect to cancer risk among children born through ART.[2,3] These reports are typically limited by the low numbers of cancers involved, short follow-up periods, and the use of inappropriate comparison groups.

This study used a large cohort of ART-exposed women and a long follow-up period, and compared outcomes with the general population as well as with a cohort of subfertile women who did not undergo ART. This allowed the study of the role of fertility drug exposure and in vitro manipulations alone after controlling for subfertility.

There are plausible reasons to be concerned about cancer in children born through ART. During ART, embryos are kept outside the female reproductive tract for a few days, which may affect their epigenetic programming.[5] Differences in epigenetic programming could influence the activity of various genes that may impact the health of the offspring.

This study cohort underwent ART treatments between 1983 and 2000. ART treatments have changed significantly since that time. Extended embryo culture to the blastocyst stage has become more widespread. Longer in vitro culture may further alter gene methylation, and therefore it will be important to compare outcomes with cleavage versus blastocyst stage transfer. Cryopreservation of embryos, oocytes, and even ovarian tissue is increasingly used. Some trends for higher cancer risk were observed in this study after frozen embryo transfer, but the number of cases was too small to analyze subgroups.

This study did not find an increased cancer risk in children conceived after ART or after fertility drug exposure, but as new technologies are introduced and the number of treatment cycles increases, further studies will be needed to confirm their safety.

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