Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations

Research question: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next -generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)?Design: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 x whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 x WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. Results: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis.Conclusions: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.