Improved clinical utility of preimplantation genetic testing through the integration of ploidy and common pathogenic microdeletions analyses.

This article focuses on the development and validation of a novel integrated preimplantation genetic testing (PGT) approach that simultaneously detects chromosomal ploidy abnormalities and common pathogenic microdeletions (MDs) in human embryos. Using targeted next-generation sequencing (NGS) and a probabilistic bioinformatic model, the method accurately identifies ploidy status (haploid, diploid, triploid) and six clinically relevant MD syndromes, expanding the diagnostic scope beyond standard PGT for aneuploidy (PGT-A). Validation on embryo biopsies demonstrated high sensitivity and specificity, and clinical application revealed cases of triploidy and a pathogenic 22q11.21 microdeletion in embryos previously classified as euploid, highlighting the potential of this approach to improve embryo selection and understanding of genetic causes of implantation failure and miscarriage. The study emphasizes the importance of incorporating parental DNA analysis to distinguish true MDs from inherited loss of heterozygosity and notes limitations in detecting certain MD regions due to population haplotype structures.