Clinical utility of polygenic risk scores for embryo selection: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)

Grebe TA; Khushf G; Greally JM; Turley P; Foyouzi N; Rabin-Havt S; Berkman BE; Pope K; Vatta M; Kaur S; ACMG Social; Ethical; Legal Issues Committee

doi:10.1016/j.gim.2023.101052

Ethics and Policy · Reproductive Ethics

Clinical utility of polygenic risk scores for embryo selection: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)

Grebe TA, Khushf G, Greally JM, Turley P, Foyouzi N, Rabin-Havt S, Berkman BE, Pope K, Vatta M, Kaur S, ACMG Social, Ethical, Legal Issues Committee

Published April 2024 Genet Med

DOI 10.1016/j.gim.2023.101052 PMID 38393332

Abstract not indexed.

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The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice

Forzano F et al., 2022 Eur J Hum Genet Free full text on PubMed Central

Polygenic risk score analyses on embryos (PGT-P) are being marketed by some private testing companies to parents using in vitro fertilisation as being useful in selecting the embryos that carry the least risk of disease in later life. It appears that at least one child has been born after such a procedure. But the utility of a PRS in this respect is severely limited, and to date, no clinical research has been performed to assess its diagnostic effectiveness in embryos. Patients need to be properly informed on the limitations of this use of PRSs, and a societal debate, focused on what would be considered acceptable with regard to the selection of individual traits, should take place before any further implementation of the technique in this population.

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Use of preimplantation genetic testing for monogenic defects (PGT-M) for adult-onset conditions: an Ethics Committee opinion

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Preimplantation genetic testing for monogenic diseases for adult-onset conditions is ethically permissible for a range of conditions including when the condition is serious and no safe, effective interventions are available. The Committee strongly recommends that a genetic counselor experienced with PGT-M counsel patients considering such procedures. This document replaces the document titled "Use of preimplantation genetic diagnosis for serious adult-onset conditions: a committee opinion," last published in Fertil Steril 2013;100;54-7.

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Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion

Ethics Committee of the American Society for Reproductive Medicine, 2017 Fertility and sterility

Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. This Opinion sets out the possible rationales for a provider's decision to assist or decline to assist in such transfers. The Committee concludes in most clinical cases it is ethically permissible to assist or decline to assist in transferring such embryos. In circumstances in which a child is highly likely to be born with a life-threatening condition that causes severe and early debility with no possibility of reasonable function, provider transfer of such embryos is ethically problematic and highly discouraged.

Add-Ons and Adjuncts · Preimplantation Genetic Testing

Utility of polygenic embryo screening for disease depends on the selection strategy

Lencz T et al., 2021 eLife Free full text on PubMed Central

Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following polygenic embryo screening for a single disease. A strong determinant of the potential utility of such screening is the selection strategy, a factor that has not been previously studied. When only embryos with a very high PRS are excluded, the achieved risk reduction is minimal. In contrast, selecting the embryo with the lowest PRS can lead to substantial relative risk reductions, given a sufficient number of viable embryos. We systematically examine the impact of several factors on the utility of screening, including: variance explained by the PRS, number of embryos, disease prevalence, parental PRSs, and parental disease status. We consider both relative and absolute risk reductions, as well as population-averaged and per-couple risk reductions, and also examine the risk of pleiotropic effects. Finally, we confirm our theoretical predictions by simulating 'virtual' couples and offspring based on real genomes from schizophrenia and Crohn's disease case-control studies. We discuss the assumptions and limitations of our model, as well as the potential emerging ethical concerns.

Ethics and Policy › Reproductive Ethics › Genetic Testing of Embryos · Assisted Reproduction › Add-Ons and Adjuncts › Preimplantation Genetic Testing · Clinical Guidelines and Standards › Guidelines by Issuing Body › United States Professional Societies

PMID 38393332 38393332 DOI 10.1016/j.gim.2023.101052 10.1016/j.gim.2023.101052 Grebe et al. 2024, Grebe 2024

Cite this article

Grebe, T. A., Khushf, G., Greally, J. M., Turley, P., Foyouzi, N., Rabin-Havt, S., Berkman, B. E., Pope, K., Vatta, M., Kaur, S., ACMG Social, Ethical, & and Legal Issues Committee (2024). Clinical utility of polygenic risk scores for embryo selection: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. https://doi.org/10.1016/j.gim.2023.101052

Clinical utility of polygenic risk scores for embryo selection: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)

Topics

By this author

Problems with Using Polygenic Scores to Select Embryos

Related research

The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice

Use of preimplantation genetic testing for monogenic defects (PGT-M) for adult-onset conditions: an Ethics Committee opinion

Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion

Utility of polygenic embryo screening for disease depends on the selection strategy

Cite this article