UNDERLYING RISK FOR A PARENTAL BALANCED CHROMOSOME REARRANGEMENT IDENTIFIED THROUGH PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY USING SNP MICROARRAY ANALYSIS WITH INFORMATICS

To determine the rate of parental balanced chromosome rearrangements identified following preimplantation genetic testing for aneuploidy (PGT-A) with embryo results suggestive of a parental rearrangement and to assess any correlation between the number of embryos with an abnormality involving the same chromosomes and the likelihood of confirming a parental rearrangement. Retrospective study of all trophectoderm (TE) biopsy samples received between April 2014-February 2020 that were suggestive of a parental rearrangement due to a pattern of deletions/duplications and/or aneuploidy involving the same chromosome(s) and parental origin. TE biopsies were performed at in vitro fertilization (IVF) centers and shipped to a single reference laboratory for PGT-A using Illumina CytoSNP-12b microarrays and bioinformatics which determine parental origin of each chromosome. For cases with results suggestive of a parental rearrangement, clinics were contacted, and parental chromosome analysis was suggested. Fifty-seven flagged cases were identified with a total of 228 TE samples. The average number of TE samples tested per case was 7 (range 2-23). Clinics provided follow up on 49 cases, 44 of which pursued chromosome analysis. A chromosome rearrangement was confirmed in 37 patients (84.1%) including 35 translocations and 2 inversions. For all cases, parental origin was consistent with the prediction based on embryo results (29 paternal and 8 maternal). Broken down by the number of TE results suggestive of a parental rearrangement: 16 cases had 5 or more suggestive results with a parental rearrangement confirmed in 13 (81.3%); 14 cases had 3-4 suggestive results with a parental rearrangement confirmed in 13 (92.9%); 14 cases had 1-2 suggestive results with a parental rearrangement confirmed in 11 (78.6%). In this study, 84.1% of patients with PGT-A results suggestive of a parental rearrangement were confirmed to carry a translocation or inversion. While having 3 or more embryos with suggestive results correlated to a very high rate of a confirmed parental translocation or inversion (81.3%-92.9%), high confirmation rates (78.6%) were also seen in cases with only 1 or 2. The ability to determine parental origin of abnormalities on PGT-A can be used to identify possible patterns in embryo results, suggest partner-specific karyotype analysis, and may allow for the option of PGT for structural rearrangements in future IVF cycles.