As reported on Inside Precision Medicine, a large study from Denmark found that children conceived with certain assisted reproductive technologies had a higher relative rate of cancer than children conceived without these treatments. The researchers emphasized that childhood cancer remained uncommon, and the study cannot show that fertility treatment caused the difference.

The findings come from a study published in JAMA. Researchers used national health records to track more than 1 million children born in Denmark from 1996 to 2012. About 37,000 had been conceived using assisted reproductive technology. Children were followed until they developed cancer, died, moved away, turned 20 or the study ended in 2023. The median follow-up was 20 years.

What did the researchers find?

Across the full study group, the rate of cancer was 23.6 cases per 100,000 person-years among children conceived with assisted reproductive technology, compared with 18.3 among children conceived without it. After accounting for other factors, the researchers estimated that the overall relative rate was 26% higher in the assisted-reproduction group.

Person-years combine the number of people studied with the amount of time each person was followed. This measure helps researchers compare rates when participants have different follow-up times.

The researchers also examined three fertility-treatment methods separately:

• In vitro fertilization (IVF): Eggs are fertilized with sperm in a laboratory, and an embryo is placed in the uterus. The study did not find a higher cancer rate linked to conventional IVF.
• Intracytoplasmic sperm injection (ICSI): A single sperm is injected directly into an egg in a laboratory before the resulting embryo is placed in the uterus. ICSI was associated with a 48% higher relative rate of cancer.
• Frozen embryo transfer: An embryo created during fertility treatment is frozen and transferred to the uterus later. This was associated with a little more than twice the relative rate of cancer.

The article reports estimated annual rates of about 41 cases per 100,000 children after frozen embryo transfer and 28 per 100,000 after ICSI, compared with 18 per 100,000 among children conceived without assisted reproductive technology. These figures illustrate that the absolute number of cases was low, even where the relative rate was higher.

What do “relative” and “absolute” risk mean?

A relative increase compares one group’s rate with another’s. A 26% higher relative rate does not mean that 26 out of every 100 children developed cancer. The absolute rate—the number of cases over a given amount of time—remained low in all groups.

The study also reported associations between some treatment methods and certain cancer types, including leukemia, lymphoma, soft-tissue sarcoma and tumors of the central nervous system. Some of those estimates were based on very few cases, so they are uncertain and need further study.

What might explain the findings?

The researchers suggested several possibilities, including changes to embryos during freezing and thawing, laboratory handling, or the hormone treatment sometimes used to prepare the uterus for a frozen embryo transfer. ICSI also differs from natural fertilization because the sperm is selected and injected directly into the egg.

These are possible explanations, not proven causes. The researchers tried to account for parental infertility, which itself may be related to health outcomes, but it can be difficult to separate the effects of infertility from the effects of treatment.

Why more research is needed

The children in this study were born between 1996 and 2012. Fertility-care practices have changed since then, including wider use of frozen embryo transfers and newer ways of freezing embryos. The results may therefore not reflect the risks associated with current treatment methods.

The researchers plan to study more recent births in a Nordic dataset that includes records from Denmark, Sweden and Norway. They hope to compare details such as whether embryos were created using IVF or ICSI, whether frozen transfers used natural or hormone-prepared cycles, and which freezing methods were used.

For people considering fertility treatment, the findings may be useful to discuss with a fertility specialist, but they are not a reason to assume that a child will develop cancer. The study identifies patterns in health records; it does not establish that the treatments caused cancer or predict an individual child’s risk.