ISSN 2330-717X

Report Sounds Alarm On Efficacy, Safety, Ethics Of Embryo Selection With Polygenic Scores

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A special report published in the New England Journal of Medicine raises serious questions about the benefits, risks and ethics of a new service — which the authors call “embryo selection based on polygenic scores,” or ESPS — that allows in vitro fertilization patients to select embryos with the goal of choosing healthier and even smarter children.

The multinational team of researchers describes the limitations of ESPS and warns of the risk that patients and even in vitro fertilization (IVF) clinicians may form the impression that ESPS is more effective and less risky than it is. The authors highlight that since the same gene often influences many different traits, ESPS designed to select for one trait can lead to the unintentional selection of adverse traits. They also warn about the potential of ESPS to alter population demographics, exacerbate socioeconomic inequalities and devalue certain traits.

If ESPS continues to be available to IVF patients, the researchers call on the Federal Trade Commission to develop and enforce standards for responsible communication about the service. The authors also call for a societywide conversation about the ethical use of the technology and whether it should be regulated.

Polygenic scores are predictions of individual health and other outcomes derived from genomewide association studies. Polygenic scores have been shown, in adults, to partially predict those outcomes. As the authors explain, however, their predictive power is significantly reduced when comparing embryos to one another.

“Polygenic scores are already only weak predictors for most individual adult outcomes, especially for social and behavioral traits, and there are several factors that lower their predictive power even more in the context of embryo selection,” said Patrick Turley, assistant research professor of economics at the USC Dornsife College of Letters, Arts and Sciences and co-first author of the paper. “Polygenic scores are designed to work in a different setting than an IVF clinic. These weak predictors will perform even worse when used to select embryos.”

Turley and colleagues modeled, for several diseases, the expected difference in the future individual’s risk for the disease between using ESPS to select an embryo versus choosing an embryo at random among 10 viable embryos. In most cases, the absolute risk reduction from ESPS is very small. Moreover, these estimates are extremely uncertain, so much so that the effect of ESPS is swamped by background variation.

Multiple companies are now working with IVF clinics to offer ESPS to patients who want to select an embryo with a lower chance than other embryos of developing, as an adult, diabetes, cancer, heart disease, inflammatory bowel disease, Alzheimer’s disease and schizophrenia. One company also offers ESPS for selecting embryos according to their predicted educational attainment, household income and cognitive ability. The founder of another company has not ruled out someday offering ESPS in some countries for skin color or above-average cognitive ability.

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