Zhang Shuo, He Yaqiong, Lu Yao, Huang Yi, Huang Jiaan, Niu Yichao, Zhang Yueping, Du Yanzhi, Sun Yun, Zhang Ting, Wei Zhe
Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
J Hum Genet. 2025 Sep 16. doi: 10.1038/s10038-025-01402-5.
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.
用于结构重排的植入前基因检测（PGT-SR）已应用于倒位携带者。然而，在临床实践中，对于哪些倒位携带者应推荐进行PGT-SR尚未明确。在本研究中，我们回顾性分析了来自145个PGT-SR周期的522个囊胚中倒位环的分离模式。应用多因素逻辑回归模型确定不平衡配子产生的独立预测因素，同时进行相关性分析以评估不平衡胚胎率与倒位片段长度之间的关系。在所有分析的胚胎中，鉴定出73个与来自33名携带者（31.43%，33/105）的染色体倒位相关的不平衡胚胎（13.98%，73/522）。多因素逻辑回归显示，携带者的性别和年龄均不影响不平衡胚胎的产生。相比之下，臂间倒位组的概率显著高于臂内倒位组（p<0.001），不同染色体组之间也存在显著差异，A组（1-3号染色体）和C组（6-12号染色体）的比率高于其他组（p=0.034）。此外，我们发现产生不平衡胚胎的携带者的单倍体常染色体长度（HAL）和倒位片段大小比率显著高于未产生不平衡胚胎的携带者（p<0.001）。此外，我们的结果表明片段大小百分比与不平衡胚胎率之间存在正相关（p=0.042，r=0.357）。总之，涉及A组和C组染色体的臂间倒位携带者更容易产生不平衡胚胎。此外，较大的倒位片段大小与较高频率的不平衡胚胎相关。
