Ethical Challenges with Comprehensive, Integrated, and Universal Preimplantation Genetic Testing Platforms Utilizing...

Recent advances in preimplantation genetic testing (PGT) and whole genome amplification technologies have resulted in the development of comprehensive platforms that integrate multiple types of PGT utilizing whole genome sequencing (PGT-WGS). These platforms combine PGT-A, PGT-M, PGT-SR, and PGT-P into a single universal genetic screening system for IVF embryos. Leveraging cutting-edge computing and artificial intelligence technologies, PGT-WGS allows simultaneous screening for aneuploidies, monogenic disorders, chromosomal structural rearrangements, and polygenic disease risks using a single trophectoderm biopsy from a blastocyst-stage embryo. The popularization of Newborn Genomic Sequencing (NBSeq) for the early diagnosis and treatment of rare genetic disorders will likely promote extensive uptake of PGT-WGS among IVF patients because many prospective parents will rationalize that "prevention is better than cure." While this technology platform provides the opportunity to select the "best and healthiest" IVF embryo based on the optimal genetic profile, it also raises profound ethical issues. Due to commercial interests, profit-driven private fertility clinics will likely advocate for extensive, indiscriminate, and non-judicious use of universal PGT-WGS in the future, regardless of appropriate medical indications, such as family history of genetic diseases, recurrent miscarriages, or repeated IVF failures. This concern is amplified by findings from large randomized clinical trials, which have repeatedly demonstrated that the broad application of PGT-A does not significantly improve IVF success rates, which can be extrapolated to PGT-WGS in the future. There are also concerns about the lack of evidence for the usefulness and effectiveness of the PGT-P component of PGT-WGS. Moreover, the identification of recessive monogenic disease gene loci in a significant number of IVF embryos via PGT-WGS may cause unnecessary confusion and distress to some ill-informed patients. Hence, the ethical implications of the potential widespread, indiscriminate, and non-judicious use of universal PGT-WGS will be examined, focusing on its possible harms and the need for balanced and comprehensive patient counseling.