Promises and pitfalls of preimplantation genetic testing for polygenic disorders
Authors: Roura Jaime , Walker Zachary , Rivera-Cruz Greysha , Reynolds Joel Michael , Hershlag Avner , Altarescu Gheona , Klipstein Sigal , Pereira Stacey , Carmi Shai , Lázaro-Muñoz Gabriel , Lencz Todd , Lathi Ruth Bunker 
Published: July 2024

Objectives: To assess the ethical, legal, and societal implications of preimplantation genetic testing for polygenic disorders (PGT-P).Design: Review of current literature, ethical assessment, and clinical perspectives.Setting: International multidisciplinary expert panel.Patient(s): None.Intervention(s): PGT-P; also known as Polygenic Embryo Screening (PES).Main Outcome Measure(s): Predicted ethical, legal, and societal implications.Results: Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. PGT-P makes use of polygenic risk scores for conditions which are multifactorial and are significantly influenced by environmental and lifestyle factors. These scores are based on genome wide association studies of predominantly European populations. Absolute risk difference is the preferred method of reporting results. If current predictions are accurate, then absolute risk reductions range from about 0.02% to 10.1%, meaning that between 10 and 5,000 IVF patients would need to be tested with PGT-P to prevent one affected offspring from being born, depending on the condition and the number of euploid embryos available from which to select. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations about its potential benefit. The use of PGT-P raises multiple social and ethical concerns, including: the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patient’s unrealistic expectations regarding “healthiest disease-free” embryos. Currently, several professional organizations have position statements recommending that more research is needed prior to clinically offering this technology beyond IRB-approved research protocols.Conclusions: The rapid advancement in genetic technologies has led to unprecedented growth and challenges in the field of reproductive genetics. Healthcare providers and patients would greatly benefit from a scientific and ethical framework to help evaluate novel tests such as PGT-P prior to their incorporation into clinical care. Current evidence lacks long-term outcome data and generalizability. Several professional groups have voiced ethical, social, and pragmatic concerns about introducing PGT-P into clinical practice. Prior to offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P need to be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable prior to the ethical implementation of PGT-P.