Evaluation of preimplantation genetic testing for chromosomal structural rearrangement by a commonly used next generation sequencing workflow.

OBJECTIVES: To evaluate the applicability of a commonly used next generation sequencing workflow in detecting unbalanced meiotic segregation products for reciprocal translocation and inversion carriers.

STUDY DESIGN: All preimplantation genetic testing treatment cycles performed for reciprocal translocation or inversion carriers from 2012 to April 2017 were included. Three hundreds and forty-two archived whole genome amplified DNA, which had previously analyzed by array comparative genomic hybridization (aCGH), were retrospectively analyzed by next generation sequencing (NGS). Concordance on overall diagnosis and segmental aneuploidies related to the translocation/inversion breakpoints between aCGH and NGS were determined.

RESULTS: Retrospective analysis of 287 blastomere biopsies and 55 trophectoderm (TE) biopsies showed that the concordance rate on the overall diagnosis between aCGH and NGS on abnormal samples was 100% (266/266), irrespective to the type of biopsy. The concordance rates of normal biopsies were 98.4% (61/62) on blastomere and 78.6% (11/14) on TE biopsies. NGS detected a de novo segmental aneuploidy on one blastomere biopsy and three possible low level mosaic aneuploidies on 3 TE biopsies, which were previously concluded as euploid by aCGH. Using the karyotype of reciprocal translocation/inversion carriers, size of anticipated segmental aneuploidies could be calculated and be used to predict the applicability of NGS before proceeding to treatment.

CONCLUSION: This is the first report to evaluate the applicability of a commercial NGS-based workflow for preimplantation testing for reciprocal translocations/inversions. Our study demonstrated that NGS can diagnose unbalanced translocation/inversion products with the same efficiency as aCGH. The applicability of NGS, with respect to individual karyotype, can be predicted before proceeding to treatment.