Identification of chromosomal rearrangements by next-generation sequencing in blastocysts derived from couples with balanced translocations

Abstract

Introduction Reciprocal translocations are one of the most common abnormalities in chromosomal structure. Couples with a balanced translocation have an increased risk for infertility and recurrent pregnancy loss. The present study aims to evaluate the ability of next-generation sequencing (NGS) to detect unbalanced chromosomal rearrangements in blastocysts derived from couples with balanced reciprocal translocations. Material & Methods First, the performance of NGS (VeriSeq, Illumina, USA) for unbalanced rearrangement detection was determined. Whole-genome amplification (WGA) products from trophectoderm biopsy samplesof 12 couples with a balanced reciprocal translocation previously analyzed by aCGH (24Sure+array, Illumina, USA) were reanalyzed by NGS. Second, a retrospective study was performed in a private ART clinic in Thailand between January to December 2017. A total of 70 embryos of 10 different couples with a balanced reciprocal translocation were analyzed by NGS and the pregnancy outcomes for couples with normal/balanced embryos available for transfer were followed up. Results NGS was 95.8% concordancefor detecting unbalanced chromosomal rearrangement with aCGH, and 99.7% for overall analyzed chromosomes. We found that NGS can detect segmental aneuploidies as small as 5 Mb in size. Results of 70 embryos revealed 30% normal/balanced embryos. 17.1% of embryos were found to be aneuploid balanced embryos and 2.9% of embryos were mosaic balanced embryos. Imbalanced segmental aneuploidies were detected in 50% of embryos, 47.1% of the imbalances were related to parental translocation while 2.9% of them were not related to parental translocation. Seven couples had normal/balanced embryos available for transfer, 57.1% (4/7) of them had clinical pregnancies as indicated by an intrauterine gestational sac with fetal heartbeat visualized by ultrasound examination at 3 months after embryo transfer. Conclusions Our results demonstrated that NGS hasa high resolution to detect imbalanced segmental rearrangements. The accurate detection of NGS for imbalanced segmental and whole chromosome aneuploidies might improve the IVF success rate and increase thechances of having a healthy child for translocation carriers.