March 18, 2019
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Children conceived through assisted reproductive technology not at increased risk for cancer

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Children conceived through assisted reproductive technology did not demonstrate greater risk for cancer than children in the general population, according to results of a retrospective study published in Human Reproduction.

Results showed no difference in cancer risk between children conceived through assisted reproductive technology (ART) and those conceived naturally by subfertile women.

The findings — based on more than 2 decades of follow-up — provide “reassuring evidence” that cancer risk is not elevated among children conceived as a result of fertility treatments, according to study author Mandy Spaan, PhD student in the department of epidemiology at The Netherlands Cancer Institute.

“We were not surprised that we did not find an increased risk [for] cancer in children born after ART, because some previously published reports had shown comparable results. However, we were very glad that we did not find an increased risk because, currently, 2% to 3% of all children in the Western world are born after ART,” Spaan told HemOnc Today.

The use of ART — in vitro fertilization and intracytoplasmic sperm injection — has increased worldwide during the past 3 decades, but data about the long-term health of children conceived through this method are limited.

Spaan and colleagues evaluated data from 47,690 live-born offspring of women in the OMEGA study, initiated in the Netherlands in 1995, to evaluate cancer risk among women who received ovarian stimulation for ART.

The children (49.2% male; 46% born between 1975 and 1994) included 24,269 conceived using ART; 13,761 conceived naturally; and 9,660 conceived naturally or with the aid of fertility drugs but not through ART.

Researchers used medical records and questionnaires completed by mothers to gather information about conception methods and possible confounders. They also used the Netherlands Cancer Registry to help determine cancer incidence.

During median follow-up of 21 years (interquartile range, 17-25), 231 children in the study developed cancer.

Results showed no increase in overall cancer risk among children conceived through ART compared with children in the general population (standardized incidence ratio = 1.11; 95% CI, 0.9-1.36) or with children conceived naturally from subfertile women (HR = 1; 95% CI, 0.72-1.38).

At age 18 years and thereafter, the HR for cancer among children conceived through ART compared with those conceived naturally was 1.25 (95% CI, 0.73-2.13).

Researchers observed increased cancer risks among children conceived through intracytoplasmic sperm injection (HR = 1.52; 95% CI, 0.81-2.85) and cryopreservation (HR = 1.8; 95% CI, 0.65-4.95), but those differences did not reach statistical significance.

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“The key strength of this study is that this 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,” Spaan told HemOnc Today. “The inclusion of a comparison group of naturally conceived children from subfertile women is important because it is possible that factors related to the underlying subfertility rather than the ART procedure itself are the most important factors for childhood cancer.

“Subfertile couples may already have an increased number of epigenetic defects in their gametes, which come to light through the ART process,” Spaan added. “In this study, we were able to differentiate between the effects of ART and the effects of the underlying subfertility because of the availability of a control group of naturally conceived children from subfertile couples.”

Results showed statistically insignificant increased risks for lymphoblastic leukemia (HR = 2.44; 95% CI, 0.81-7.37) and melanoma (HR = 1.86; 95% CI, 0.66-5.27) among children conceived through ART compared with naturally conceived children.

There is “no reason for concern yet” about these findings, Spaan told HemOnc Today.

“The etiology of childhood cancers is largely unclear,” she said. “However, it has been hypothesized that ART may play a role by inducing epigenetic changes that may increase the risk [for] childhood cancers. Unfortunately, there is no clear explanation ... why risks for leukemia and melanoma were nonsignificantly higher. It is also possible that these are just chance findings.”

The small number of cancer diagnoses, despite the large size of the cohort and long follow-up, served as a limitation to this study. Also, researchers could not identify the method of conception for 12% of the children in this study.

Still, the findings will help physicians better inform couples who are considering fertility treatment, according to study author Flora van Leeuwen, PhD, head of the department of epidemiology at The Netherlands Cancer Institute.

In addition, as more children are born through intracytoplasmic sperm injection and cryopreservation of embryos, more research should focus on whether children born as a result of these techniques demonstrate long-term cancer risk, van Leeuwen said.

“We are currently expanding our study to include more than 30,000 ART-conceived children born in more recent years,” van Leeuwen said in a press release. “It will include children born after [intracytoplasmic sperm injection] and/or embryo cryopreservation of the embryo. We hope this will provide more evidence about the possible long-term risk [for] cancer for these children.”– by John DeRosier

For more information:

Mandy Spaan can be reached at m.spaan@nki.nl

Disclosures: The Dutch Cancer Society and Children Cancer Free funded this study. The authors report no relevant financial disclosures.