Polygenic Embryo Screening: Ethical Considerations and Recommendations for Clinical Practice On behalf of the Ethics and Good Clinical Practice Group and the Genetics Group of the Spanish Fertility Society

Abstract

Recent advances in Next-Generation Sequencing (NGS) technologies at the embryonic level have made Whole Genome Sequencing (WGS) a feasible tool for embryo analysis. These findings have enabled the development of Polygenic Risk Scores (PRS), which aggregate information from hundreds or thousands  of Single Nucleotide Polymorphisms (SNPs) to estimate an individual’s relative risk of developing a given condition compared with the general population.

When PRS are applied at the embryonic stage, the approach is referred to as Polygenic Embryo Screening (PES) or, more specifically, Preimplantation 
Genetic Testing for Polygenic Disorders (PGT-P)

PGT-P provides a measure of each embryo’s relative genetic susceptibility compared with the general population. These estimates rely on statistical models  that weigh the contribution of each SNP according to its frequency and estimated disease association. However, interpreting PRS at the embryonic level is  challenging. Polygenic risk is probabilistic; thus, an embryo with a high PRS may never develop the disease, while an embryo with a low PRS is not risk-free.

PGT-P raises important ethical concerns, including the need for adequate counseling, realistic patient expectations, issues of distributive justice, the impact  of environmental and social determinants of health, and the potential exacerbation of health inequities.

The main objective of this document, prepared by the Ethics and Good Clinical Practice Interest Group of the Spanish Fertility Society (SEF), is to provide guidance to researchers, clinicians, embryologists, regulators, and professional societies as they make decisions regarding the implementation of this emerging technique, with particular emphasis on its ethical implications.