Biop-C enables genome-wide detection of balanced and unbalanced rearrangements in preimplantation human embryos

ABSTRACT: Preimplantation genetic testing for structural rearrangements (PGT-SR) is critical for embryo selection. Most advanced PGT-SR platforms rely on sequence- or marker-based analysis near chromosomal breakpoints, which is costly, labor-intensive, and time-consuming. As a result, clinical practice often defaults to using PGT-A, a platform that cannot detect balanced rearrangements affecting the offspring's reproductive potential. In this study, we introduce Biop-C, a Hi-C–based technique enabling the comprehensive detection of both unbalanced and balanced translocations, including Robertsonian ones, as well as copy number variations (CNV). By developing custom algorithms for translocation detection, we achieved high accuracy in embryo and biopsy samples. We show that using machine-learning-based approaches allows detecting CNVs using low-coverage Hi-C without control euploid human embryos, which are typically unavailable. In a cohort of 88 samples for translocation detection and 78 samples for CNV detection, Biop-C correctly identified over 86% of detected translocations, and 83% of these calls were concordant with the refined reference. Additionally, Biop-C confirmed the aneuploid status in 84% of embryos, with no embryos initially classified as euploid by standard PGT being misclassified as aneuploid. For CNVs, Biop-C detected 72% of reference CNVs, and 95% of all identified CNVs were true positives. Notably, Biop-C identified an unbalanced translocation in an embryo derived from a couple with a previously undiagnosed parental translocation, demonstrating its diagnostic value. We had 36 samples derived from patients carrying balanced chromosomal rearrangements, we identified 4 balanced translocations in samples classified as These findings establish Biop-C as a powerful PGT-SR approach for distinguishing between normal and balanced embryos, with significant implications for embryo selection and genetic counseling in IVF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311964 | GEO | 2025/12/08

REPOSITORIES: GEO