Chromosome segregation of human non-homologous Robertsonian translocations: insights from preimplantation genetic testing

Abstract

Robertsonian translocations (RTs) are associated with a high risk for unbalanced segregations. Preimplantation Genetic Testing (PGT) offers an early opportunity to evaluate segregation patterns and selection against chromosome imbalances. The objective of this study was to evaluate the chromosome complements in blastocysts for male and female RT carriers and provide information useful in PGT counseling for RT carriers. PGT results were reviewed for 296 couples where a balanced and non-homologous RT was present in one member of the couple. All embryos had day 5/6 trophectoderm biopsy and SNP-based PGT. The study included 2,235 blastocysts, of which 2,151 (96.2%) had results. Significantly fewer blastocysts were available for female RT carriers (mean 4.60/IVF cycle) compared to males (5.49/cycle). Male carriers were more likely to have blastocysts with a normal/balanced chromosome complement; 84.8% versus 62.8% (P < 0.00001). Male carriers had fewer blastocysts with monosomy (60/152, 39.5%) compared to female carriers (218/396, 55.1%) (P = 0.001). 21 (1%) blastocysts showed 3:0 segregation; these were mostly double trisomies and derived from female carriers. Differences between chromosome complements for males versus female carriers suggest that selection against unbalanced forms may occur during spermatogenesis. Six blastocyst samples showed an unexpected (“non-canonical”) combination of trisomy and monosomy One case of uniparental disomy was identified. For female carriers, there was no association between unbalanced segregation and parental age but for male carriers, there was an inverse association. PGT is a highly beneficial option for RT carriers and patients can be counseled using our estimates for the chance of at least one normal/balanced embryo.