Experts Question Whether It’s Okay to Test Embryos for Common Diseases

Scientists said they can predict the risk of common diseases, such as breast cancer and diabetes, in in vitro-fertilized embryos by combining “molecular and statistical techniques,” but ethicists and other experts are sounding the alarm over the clinical use of such technologies.

Among 10 couples who underwent in vitro fertilization (IVF), results from whole-genome reconstruction using the parental genome sequences and embryo genotyping were 97% to 99% accurate at sites relevant to polygenic risk scoring (PRS), reported Akash Kumar, MD, PhD, of MyOme in Menlo Park, California, and colleagues.

“Our approach enabled the prediction of both rare and common variants in embryo genomes,” they wrote in Nature Medicine. With these data, the researchers generated a single PRS for each of the 110 embryos included in the study.

Predictions using day-5 trophectoderm biopsies (99.0-99.4%) were more accurate than those from day-3 blastomere biopsies (97.2-99.1%), the researchers noted.

In one couple who had a family history of breast cancer, the researchers predicted 13 out of 20 total euploid embryos would carry a pathogenic BRCA1 variant. Predicted genetic risk for breast cancer varied by 15-fold across the embryos, with odds ratios ranging from 0.35 for a non-BRCA1 carrier with low PRS, to 5.35 for a BRCA1 carrier with high PRS.

“For those who keep brushing off polygenic embryo screening [PES] as something that is not going to work and we should not pay attention to, this is another development that suggests that it can have utility,” said Gabriel Lázaro-Muñoz, PhD, JD, of Harvard Medical School in Boston, who was not involved in the study.

“With the decreasing cost of sequencing and genotyping, this may become available at a relatively accessible price for people who have the means to access IVF,” he told MedPage Today in an email. “Most importantly, this means that we need to start addressing the ethical and social implications of PES now.”

Kumar and team addressed several limitations related to preimplantation genetic testing (PGT). “PRSs have limited effectiveness in non-European populations,” they noted, since people of color have historically been excluded from genetics research, and “foremost is the risk of unequal access to this technology for families due to either cost of IVF or limitations in cross-ancestry performance of polygenic models.”

However, these limitations may have been “severely understated” by Kumar and colleagues, said Josephine Johnston, LLB, MBHL, and Lucas Matthews, PhD, of the Hastings Center in Garrison, New York, in a corresponding editorial.

They pointed to a 2017 study that showed PRSs from genome-wide association studies with mostly people of European ancestry yielded highly inaccurate results, and in one example “inaccurately predicted Africans to be shorter than Europeans.”

Johnston and Matthews also took issue with the study authors describing unequal access as a foremost concern. “This concern reveals an underlying assumption that PGT for common diseases is of substantial clinical value and that the primary injustice will be the lack of access for those unable to afford it,” they wrote. “Indeed, a more pressing justice concern is that PRS-informed PGT may further de-emphasize environmental and social determinants of common diseases, drawing public attention away from structural solutions to health and disability challenges and toward individual responsibility for managing disease risk.”

The study examined the risks associated with 12 common diseases, including various cancers, atrial fibrillation, coronary artery disease, Crohn’s disease, lupus, and type 1 and type 2 diabetes. For diseases such as colorectal cancer and type 2 diabetes, non-genetic factors such as physical activity and diet also play a role in disease risk.

The study also tested embryos for aneuploid, finding that 42 of 110 embryos had one or more aneuploid chromosomes, while the other 68 were euploid.

In a separate commentary, Norbert Gleicher, MD, of the Center for Human Reproduction in New York City, and colleagues suggested that the assumptions underlying genetic testing for aneuploidy are flawed. “Chromosomal testing of embryos and pregnancies has relied on two assumptions that are no longer tenable: first, that normal humans are universally euploid because anything else would automatically indicate disease; and second, that a small sample of DNA can represent the complete organism,” they wrote.

The fetus can self-correct after being tested for aneuploidy, Gleicher and colleagues noted. They added that a recent randomized trial found no difference in live birth rates between women who underwent conventional IVF with and without PGT for aneuploidy.

In the U.S., there are no regulations surrounding PGT testing. There are a number of loopholes that allow companies to sell genetic tests, and companies can market these tests directly to consumers considering IVF, Lázaro-Muñoz said. That gives prospective parents “the impression that PES gives them a ‘choice’ about their future child’s health, when the reality is that there is not enough evidence about clinical utility,” he added.

“I worry that ranking embryos introduces significant bias, implies that certain lives are more worth living than others, and may unduly influence potential parents’ decisions about which embryos to select if not given enough context and adequate counseling when making these decisions,” he said.