No Increase in Cancer Among Children Conceived by IVF

Nancy A. Melville

February 11, 2019

The first generation of children conceived through assisted reproductive technology (ART) — including in vitro fertilization (IVF) — show no increased risk of cancer compared with the general population or those conceived using other fertility methods, in the largest study of its kind in which offspring were followed from birth for a mean of 21 years.

"Our study is the first one to compare long-term cancer risk in ART-conceived children both with the general population and with naturally conceived offspring from subfertile women while adjusting for confounders," say the authors of the study, which was published online February 4 in Human Reproduction.

"These results provide reassuring evidence that children conceived as a result of fertility treatments do not have an increased risk of cancer after a median follow-up of 21 years," added lead author Flora van Leeuwen, PhD, head of the Department of Epidemiology at The Netherlands Cancer Institute, Amsterdam, in a press statement from the European Society of Human Reproduction and Embryology, which publishes the journal.

"They will enable physicians to better inform couples considering fertility treatment about its long-term safety for their children," she said.

Assisted Reproduction "Significantly" Differs From Natural Conception

Although IVF and other related assisted reproduction techniques such as intracytoplasmic sperm injection (ICSI) are considered highly safe, each phase of the procedure, including stimulation of multiple follicles, the process of oocyte retrieval and sperm preparation, culture of embryos, cryopreservation of sperm, oocytes and embryos, and embryo transfer, is substantially different from natural conception.

An estimated 6 million children worldwide have been born as a result of such techniques, and there have been some concerns about the potential ill effects on health. For example, a meta-analysis published in 2013 suggested an overall increased risk of cancer, but other studies have shown no such increased risk of cancer.

And another recent study suggested potential increased vascular aging among children conceived by ART, as reported by Medscape Medical News, however, the study was very small.

For a more comprehensive look at the issue, van Leeuwen and colleagues turned to the OMEGA cohort, a large study of subfertile women in the Netherlands, providing data on the oldest generation of Dutch children conceived through ART.

The data, from 12 Dutch IVF clinics and two fertility clinics between 1980 and 2001, were compared with figures from the general population from the Netherlands cancer registry between 1989 and 2016.

In total, the study involved 47,690 children, including 24,269 conceived using ART, 13,761 conceived naturally, and 9660 conceived naturally or with the assistance of fertility drugs but not ART.

Overall, 231 cases of cancer were identified.

After adjusting for factors including age and causes of subfertility, rates of cancer were found to be no higher among children conceived through ART compared with the general population (standardized incidence ratio [SIR], 1.11) or naturally conceived children born to subfertile women (hazard ratio [HR], 1.00).

Among children who had reached age 18 years or older, the HR of cancer among ART-conceived versus naturally conceived individuals was 1.25.

Of those specifically conceived by ICSI or cryopreservation of embryos, the risk of cancer was slightly higher (HR, 1.52 and 1.80, respectively) but did not reach significance in either case.

The authors add that because the number of cancers in the ICSI or cryopreservation groups were small, "the findings may be due to chance and must be interpreted with caution."

"Only three earlier studies investigated cancer risk in children born after ICSI and/or cryopreservation of embryos; no significantly increased risks were found," they note.

More Work Needed, Especially for ICSI, Cryopreservation of Embryos

Although the median overall follow-up time was 21 years (range, 17-25 years), the follow-up was 20 years for ART-conceived children (range, 17-23 years) and a bit longer, 24 years, for naturally conceived children (range, 20-30 years).

Important study limitations include the fact that cancer in children and young adults is generally rare and therefore the number of cases was small. Furthermore, some potential confounders such as gestational age, birth weight, or parental cause of subfertility were missing in "a substantial proportion" of the cohort and had to be imputed.

Strengths, however, include the relatively long study follow-up and the inclusion of births to subfertile women, the authors underscore.

"This study, with a median follow-up of 21 years, is especially important because it includes a comparison group of naturally conceived children born to subfertile women; these women are different from the general population and it is possible that difficulty in conceiving could be a factor that influences the risk of cancer in their offspring," van Leeuwen said.

Although the findings are reassuring, "as ever more children are born through ICSI and cryopreservation of embryos, the long-term cancer risk should be investigated in larger numbers of children born as a result of these techniques," she added.

The research team is meanwhile pushing ahead with an expansion of the study to include more than 30,000 ART-conceived children born in more recent years.

"[The study] will include children born after ICSI and/or cryopreservation of the embryo," van Leeuwen said. "We hope this will provide more evidence about the possible long-term risk of cancer for these children."

The authors have reported no relevant financial relationships.

Human Reprod. Published online February 4, 2019. Full text

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