Unbalanced translocation rate according to gender of carriers and types of chromosomal rearrangement in pgt-sr based on next-generation sequencing (ngs)

Couples with chromosomal structural rearrangements have an increased risk of having unbalanced embryos which results in poor reproductive outcomes. PGT-SR allows these couples to select normal or balanced embryos. The rate of transferrable embryos is varying according to the couples. In this study, we aimed to evaluate the proportion of unbalanced embryos in NGS setting according to the types of structural rearrangement and the gender of carriers. This retrospective study conducted in all PGT-SR cycles performed between January 2021 and December 2022. PGT-SR was performed on 2,237 embryos from 608 cycles of 333 couples: 239 Reciprocal translocation (REC-T), 56 Robertsonian translocation (ROB-T), 21 Inversion (INV). Couples were divided into female carrier group (357 cycles, 1,305 embryos) and male carrier group (251 cycles, 932 embryos). The rate of unbalanced embryos was compared according to the types of rearrangement in each group. The unbalanced embryo rate and sporadic aneuploid (diagnosed as aneuploid but balanced for structural rearrangement) were compared according to the maternal age. NGS-based PGT-SR was performed using Veriseq NGS (Illumina, San Diego, USA) platform. The results were analyzed by BlueFuse Multi v4.3 software (Illumina). The rate of unbalanced embryos after NGS-based PGT-SR was significantly higher in female carrier group than in male carrier group (58.5% vs 48.0% respectively, p<0.001). According to the types of rearrangement, the rate of unbalanced embryos was significantly higher in REC-T (64.2% female, 58.2% male, p<0.02) than ROB-T (45.5% Female, 17.1% male, p<0.001) and INV-T (18.4% female, 18.9% male, p>0.05). Interestingly enough, the unbalanced embryo rate was very low in male carrier of ROB-T. Paternally derived translocations led to lower rate of unbalanced embryos in ROB-T (45.5% maternal vs. 17.1% paternal, p<0.001) than in REC-T (64.2% maternal vs. 58.2% paternal, p<0.02). In contrast to the translocation carriers, the inversion carriers had significantly lower rate of unbalanced rearrangement. Regardless of the female age, the unbalanced embryos rate was relatively constant (mean rate: 58.5%, <35 years: 58.6%; 35–37 years: 58.6%; 38–40 years: 56.3%; and >40 years: 54.1% in female carriers and mean rate: 48.0%, <35 years: 45.2%; 35–37 years: 51.3%; 38–40 years: 47.6%; and >40 years: 50.0% in male carriers. In this study, reciprocal translocation carrier, especially female carriers, were found to have a higher risk of having unbalanced embryos than ROB-T and INV. Although the unbalanced embryo rate can be predicted according to the gender and type of the rearrangements in couples with chromosomal structural rearrangements, the feasibility of getting transferrable embryo from PGT-SR would be heavily dependent upon the age of female due to aneuploidy of other chromosomes.