Meiotic determinants of unbalanced gametogenesis in chromosomal inversion carriers.

Abstract

Preimplantation genetic testing for structural rearrangements (PGT-SR) has already been applied in inversion carriers. However, it has not been well clarified which inversion carriers should be recommended for PGT-SR in clinical practice. In this study, we retrospectively analyzed the segregation patterns of inverted loops in 522 blastocysts derived from 145 PGT-SR cycles. Multivariate logistic regression models were applied to identify independent predictors of unbalanced gamete production, while correlation analysis assessed the relationship between the rate of unbalanced embryos and inverted segment length. Among all embryos analyzed, 73 unbalanced embryos (13.98%, 73/522) related to the chromosome inversions originating from 33 carriers (31.43%, 33/105) were identified. Multivariate logistic regression showed neither the carrier's gender nor age affected the production of unbalanced embryos. In contrast, the probability in the pericentric inversion group was significantly higher than that in the paracentric inversion group (p < 0.001), and significant difference was also identified among different chromosomal groups, with groups A (Chr1-3) and C (Chr 6-12) showing higher rates than other groups (p = 0.034). Moreover, we found the haploid autosomal length (HAL) and the ratio of inverted segment size in carriers who produced unbalanced embryos were significantly higher than in those who did not (p < 0.001). Furthermore, our results indicated a positive correlation between Segment size% and the rate of unbalanced embryos (p = 0.042, r = 0.357). In conclusion, carriers of pericentric inversions involving chromosomes from groups A and C are more prone to producing unbalanced embryos. Furthermore, a larger inverted segment size is associated with a higher frequency of unbalanced embryos.