Preimplantation genetic testing (PGT) enhances embryo selection by detecting aneuploidies and genetic disorders, yet its reliance on invasive embryo biopsy raises concerns regarding cost, ethical implications, diagnostic limitations, and the potential risk of embryo damage. Since the discovery of cell-free DNA (cfDNA) in blastocoel fluid (BF) and spent culture medium (SCM) in 2013, research has focused on developing non-invasive PGT (niPGT) methods as an alternative to biopsy. These approaches may lower procedure costs and eliminate biopsy-associated risks, though challenges remain due to the possibility of maternal DNA contamination and uncertainties about the origin of cfDNA. This review evaluated the effectiveness of niPGT using cfDNA from BF and SCM through a systematic search in PubMed, Scopus, and the Cochrane Library up to June 2025. From 97 identified articles, 16 met the inclusion criteria: one investigated BF, 14 examined SCM, and one studied both. While BF-based niPGT demonstrated low amplification and concordance rates with trophectoderm (TE) and whole blastocysts (WB), SCM-based analysis achieved moderate to high amplification success, though concordance with TE and WB varied widely (20–100%). Overall, SCM appears to be the more promising cfDNA source for niPGT, but current methods are not yet sufficiently reliable to replace conventional PGT. Further refinement of protocols and technologies is required before niPGT can be applied in clinical practice.
Γεωργία Μ. Σεργίου (2025) studied this question.