Validation of OnePGT in Preimplantation Genetic Testing

Abstract

Background: Chromosomal abnormalities, such as changes in ploidy, aneuploidy, and structural changes, as well as duplication and deletion of microfragments, contribute to reduced implantation rate, pregnancy loss, and congenital disabilities in humans. In this study, we explored the significance of One preimplantation genetic testing (OnePGT) in preimplantation genetic testing (PGT). Methods: In this study, 20 embryos representing seven families undergoing PGT for monogenic disorders (PGT-M) and 11 embryos representing five families undergoing PGT for chromosomal structural rearrangements (PGT-SR) were selected for re-biopsy at our Reproductive Medicine Center. Moreover, blood samples were also obtained from the parents. For monogenic disease (MGD) analysis, 20 embryo samples (7 controls) and parental DNA samples were amplified. A whole-genome library was built and subsequently sequenced to obtain Single Nucleotide Polymorphism (SNP) data of ±2 Mb of the control embryo pathogenic gene loci and SNP data of parental samples. Furthermore, the embryos were screened for carrying any pathogenic gene loci, and the feasibility and accuracy of the OnePGT method relative to the original results in detecting MGDs were analyzed. However, in chromosomal structural rearrangement testing, 11 embryos (4 controls) and parental DNA samples were amplified, and the SNP data of ±2 Mb of chromosomal structural abnormalities were compared to differentiate the carrier embryo from normal ones. Additionally, the aforementioned embryo samples were analyzed for aneuploidy detection, and the accuracy of the aneuploidy detection through OnePGT was compared with the original results, as well as the degree of chimera coincidence. Results: The genetic results of embryos in patients with three MGDs (α-thalassemia, β-thalassemia, and spinal muscular atrophy), reciprocal chromosomal translocation, and Robertsonian translocation detected by the OnePGT method were consistent with those detected by the conventional method. Furthermore, compared to findings from the conventional method, OnePGT exhibited a 100% coincidence rate in distinguishing chromosomal translocation carrying embryos from normal, a 72% coincidence rate in the detection of aneuploidy, and a 50% coincidence rate in chimera. Conclusions: OnePGT is a novel, comprehensive, and effective three-in-one detection method for PGT.