Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a prospective multicenter clinical study

作者：Shuo Zhang, Yuan Gao, Xiaohong Wang, Qing Li, Jichun Tan, Bo Liang, Ming Gao, Junping Wu, Xiufeng Ling, Jiayin Liu, Xiaoming Teng, Hong Li, Yun Sun, Weidong Huang, Xianhong Tong, Caixia Lei, Hongchang Li, Jun Wang, Shaoying Li, Xiaoyan Xu, Junqiang Zhang, Wei Wu, Shanshan Liang, Jian Ou, Qiongzhen Zhao, Rentao Jin, Yueping Zhang, Chenming Xu, Daru Lu, Daru Lu, Junhao Yan, Xiaoxi Sun, Kwong Wai Choy, Congjian Xu, Congjian Xu, Zi‐Jiang Chen · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2024.105514 · 被引用次数：14 · 研究领域：Prenatal Screening and Diagnostics、Assisted Reproductive Technology and Twin Pregnancy、Genomic variations and chromosomal abnormalities

BACKGROUND: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) has been widely utilized to select euploid embryos in patients carrying balanced chromosomal rearrangements (BCRs) by chromosome copy number analysis. However, reliable and extensively validated PGT-SR methods for selecting embryos without BCRs in large-cohort studies are lacking. METHODS: In this prospective, multicenter, cohort study, carriers with BCRs undergoing PGT-SR were recruited across 12 academic fertility centers within China. PGT-SR was performed using genome-wide SNP genotyping and haplotyping approach. Parental haplotypes were phased by available genotypes from a close relative or an unbalanced embryo. The karyotypes of embryos were inferred from the haplotypes. Only a single embryo was transferred in each cycle. FINDINGS: Between April 2018 and March 2023, 1298 carriers we randomly enrolled. A total of 7867 blastocysts from 1603 PGT-SR cycles were biopsied, in which 7750 (98.51%) were successfully genotyped and analyzed. Overall, 75.98% (1218/1603) of cycles obtained euploid embryos and 53.15% (852/1603) generated non-carrier embryos. The proportion of carrier and non-carrier embryos was similar in different subgroups. A total of 1030 non-carrier and 439 carrier embryos were transferred, 817 healthy babies were delivered cumulatively. Our results demonstrate that SNP-haplotyping method is highly accurate (sensitivity 95% CI: 98.34%-100%, specificity 95% CI: 96.63%-100...