Chromosome segregation of human nonhomologous Robertsonian translocations: insights from preimplantation genetic testing

Abstract

Robertsonian translocations (robs) 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 rob carriers and provide information useful in PGT counseling for rob carriers. PGT results were reviewed for 296 couples where a balanced and nonhomologous rob was present in one member of the couple. All embryos had day 5/6 trophectoderm biopsy and SNP-based PGT. The study included 2235 blastocysts, of which 2151 (96.2%) had results. Significantly fewer blastocysts were available for female rob 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). Twenty-one (1%) blastocysts showed 3:0 segregation; these were mostly double trisomies and derived from female carriers. Differences between chromosome complements for male versus female carriers suggest that selection against unbalanced forms may occur during spermatogenesis. Six blastocyst samples showed an unexpected ("noncanonical") 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 rob carriers and patients can be counseled using our estimates for the chance of at least one normal/balanced embryo.

Fig. 1. Proportion (%) of cases with unbalanced segregation products and parental age.

x-axis, age group; y-axis proportion (%) with unbalanced segregation. A Maternal age for female carriers. B Paternal age for maternal carriers. C Maternal age for male carriers. D Paternal age for male carriers. Vertical lines denote 95% confidence intervals.