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Updated: Jun 4, 2025
FISH for Pre-implantation Genetic Diagnosis
Published on: February 23, 2011
Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a
Shuo Zhang1, Yuan Gao2, Xiaohong Wang3
1Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, 200032, China.
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%, respectively), and can be applied universally to different BCR types. Moreover, the clinical outcomes were comparable between the carrier and non-carrier embryo groups.
Interpretation:
This study demonstrates the effectiveness of preimplantation genetic genome-wide SNP-genotyping and haplotyping method, resulting in the delivery of more babies with a normal karyotype.
Funding:
This study was funded by the National Key Research and Development Program of China (2022YFC2703200, 2021YFC2700600, 2021YFC2700500), National Natural Science Foundation of China (82201807, 82171639, 82071717). Shanghai Science and Technology Innovation Action Plan Program (18411953800), and the Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2022YQ075).
