Preimplantation genetic testing for polygenic diseases: A novel paradigm in embryo selection

Polygenic diseases are caused by a number of independently acting or interacting polymorphic genomic variants in conjunction with environmental factors, and show an increasing global prevalence, posing a significant threat to individual and public health. Given the limited curative prospects for polygenic diseases owing to their complex etiology, preventive strategies have gained paramount importance. Preimplantation genetic testing for polygenic disorders (PGT-P) is an advanced in vitro fertilization technique that screens embryos for genetic susceptibility to polygenic diseases, aiming to reduce the risk of offspring developing conditions such as diabetes, schizophrenia, polycystic ovary syndrome, and certain cancers. This technology calculates polygenic disease risks across sibling embryos relying on the use of a polygenic risk score (PRS) that counts the effects of risk alleles derived from genome-wide association studies. Using PGT-P, each embryo's PRS is computed for any disease or trait of interest, and the euploid embryo with the lowest PRS is prioritized for implantation. As a result, PGT-P may decrease the disease risk for future offspring and provide a novel strategy for embryo ranking, selection, or even discarding. In this review, we systematically summarize the current knowledge regarding PGT-P, detailing its workflow, potential benefits, predictive power, expected risk reduction and significant limitations. We further evaluate its utility and practical implementation in clinical practice and outline critical directions for future research.