Today's special report in the New England Journal of Medicine raises serious concerns about the ethics and benefits of a new service called "embryo select based on polygenic score" (or ESPS). This allows patients who are undergoing in vitro fertilization to choose embryos for their children with the aim of having healthier, smarter children.A multinational research team outlines the weaknesses of ESPS. They warn that patients, IVF clinicians, and others may mistakenly believe that ESPS can be more effective and safer than it actually is. Because the same gene can influence many traits, ESPS that is designed to select one trait may lead to unintentional selection for adverse traits. They warn that ESPS could alter the demographics of the population, increase socioeconomic inequalities, and devalue some traits.Researchers call for the Federal Trade Commission's enforcement of standards for responsible communication regarding ESPS if it is not discontinued. The authors call for society-wide discussion about ethical use of this technology and whether regulation should be adopted.The prediction of individual health and other outcomes using genome-wide association studies are called polygenic scores. In adults, polygenic scores can partially predict these outcomes. However, the predictive power of these scores is greatly reduced when embryos are compared to each other, as the authors explain."Polygenic scores have been weak predictors of most adult outcomes, particularly for social and behavioral traits, and it is not clear what factors will affect their predictive power in the context of embryo selectivity," stated Patrick Turley, assistant professor of economics at USC Dornsife College of Letters, Arts and Sciences and coauthor of the paper. "Polygenic scores were designed to function in a different environment than an IVF clinic. These poor predictors can be used to select embryos.Turley and his colleagues compared the risk of developing a variety of diseases by calculating the difference between selecting an embryo from ESPS or choosing one randomly from 10 viable embryos. ESPS has a very low absolute risk reduction in most cases. These estimates are also extremely uncertain and the background variation can overwhelm the effects of ESPS.AdvertisementMany companies have partnered with IVF clinics in order to offer ESPS to patients who wish to select an embryo that has a lower chance of developing as an adult. This includes those with diabetes, heart disease, inflammatory bowel diseases, Alzheimer's disease, schizophrenia, and cancer. One company offers ESPS to help select embryos based on their expected educational attainment, household income, and cognitive ability. Another company founder has not ruled it out that ESPS may be offered in certain countries to people with a high cognitive ability or skin color.Drawbacks to ESPSIn order for ESPS to be effective, polygenic scores must give at least moderately accurate predictions about whether the resulting individuals will possess a particular trait. Although the genome-wide association studies that produce polygenic scores can sometimes show large or moderate differences in actual outcomes among people with high and low polygenic scores, these differences are only based on a small sample of people from different families. Turley and his colleagues point out that ESPS often involves comparing members from the same family. This significantly lowers the predictive power for polygenic scores.Genomewide association studies with people of similar ancestry are also conducted for statistical purposes. Existing studies have not included enough people of European ancestry for many reasons. Therefore, polygenic scores that are constructed today won't be as predictive of people with other ancestries.Assessments of the predictive power and similarity of polygenic scores often assume that the environment for the generations that were enrolled in the genome-wide association study as well as the one that will be born through ESPS are very similar. However, ESPS may not be able to predict the future of an embryo that has been selected.AdvertisementEven if ESPS's limited effectiveness is communicated to patients accurately, widespread usage of ESPS poses other risks. Researchers warn that ESPS may worsen existing health problems and other disparities. ESPS is largely available only to those who are wealthy, and it currently predicts the outcomes best for people with European ancestry. ESPS could also increase prejudice and discrimination, signaling that people with certain traits are less valuable than others.Michelle N. Meyer, an assistant professor of bioethics at Geisinger Health System and coauthor of the special report, stated that some countries have authorities that determine which traits embryos can test for. The United States has a strong ethical and legal tradition that views reproductive decisions as private individual choices. The FTC should establish in the short-term what constitutes adequate evidence to support claims regarding the expected benefits and information disclosure of ESPS.Researchers also recommend that professional medical associations develop policies and guidelines in this area, and that companies demonstrate that the information they provide diverse customers is accurate, complete, and well-understood.They say that society needs to have a conversation about whether existing legal frameworks are sufficient to provide accurate information about ESPS, and if there should be limits to ESPS use.Daniel J. Benjamin, the corresponding author, is a professor at UCLA Anderson School of Management, and David Geffen School of Medical. He said that many individual reproductive decisions can have devastating societal consequences. These decisions can affect population demographics and inequalities, as well as devalue the traits they are deemed to be harmful.This research was supported in part by the National Institutes of Health and Open Philanthropy.
