Clinical application progress and prospects of non-invasive preimplantation genetic testing (niPGT): A review

Abstract

Preimplantation genetic testing (PGT) is a critical tool in reproductive medicine for selecting genetically healthy embryos, thereby reducing the risk of congenital disabilities. However, conventional PGT relies on invasive embryo biopsy, which carries risks of embryo damage and diagnostic challenges related to mosaicism. Non-invasive preimplantation genetic testing (niPGT), which analyzes embryonic cell-free DNA (cfDNA) from spent culture medium or blastocoel fluid, has emerged as a promising and safer alternative. This review provides a comprehensive overview of the principles, clinical applications, challenges, and future prospects of niPGT. Although some initial studies have indicated a correlation between niPGT for aneuploidy and the overall embryo or inner cell mass, its potential as an embryo sorting tool is hindered in clinical practice by the lack of reliability in its results. This issue could result in inaccurate assessments of viable embryos. Key challenges hindering its widespread adoption include low cfDNA yield leading to amplification failure, maternal and exogenous DNA contamination, the diagnostic dilemma of embryonic mosaicism, and a profound lack of standardized laboratory protocols. Future progress in the field will depend on technological innovations in cfDNA analysis, the integration of multi-omics data with artificial intelligence for comprehensive embryo assessment, and, most critically, large-scale clinical validation through randomized controlled trials. Establishing standardized guidelines and robust ethical frameworks is imperative for the responsible transition of niPGT from a promising research method to a reliable clinical tool.