Ogur Cagri, Kahraman Semra, Griffin Darren Karl, Cinar Yapan Cigdem, Tufekci Mehmet Ali, Cetinkaya Murat, Temel Sehime Gulsun, Yilmaz Alper
Yildiz Technical University, Department of Bioengineering, Istanbul, Turkey; Igenomix Avrupa Laboratories, Istanbul, Turkey.
Istanbul Memorial Hospital, ART and Reproductive Genetics Center, Istanbul, Turkey.
Reprod Biomed Online. 2023 Apr;46(4):713-727. doi: 10.1016/j.rbmo.2022.07.016. Epub 2022 Jul 31.
What factors affect the proportion of chromosomally balanced embryos in structural rearrangement carriers? Is there any evidence for an interchromosomal effect (ICE)?
Preimplantation genetic testing outcomes of 300 couples (198 reciprocal, 60 Robertsonian, 31 inversion and 11 complex structural rearrangement carriers) were assessed retrospectively. Blastocysts were analysed either by array-comparative genomic hybridization or next-generation sequencing techniques. ICE was investigated using a matched control group and sophisticated statistical measurement of effect size (φ).
300 couples underwent 443 cycles; 1835 embryos were analysed and 23.8% were diagnosed as both normal/balanced and euploid. The overall cumulative clinical pregnancy and live birth rates were 69.5% and 55.8%, respectively. Complex translocations and female age (≥35) were found to be risk factors associated with lower chance of having a transferable embryo (P < 0.001). Based on analysis of 5237 embryos, the cumulative de-novo aneuploidy rate was lower in carriers compared to controls (45.6% versus 53.4%, P < 0.001) but this was a 'negligible' association (φ < 0.1). A further assessment of 117,033 chromosomal pairs revealed a higher individual chromosome error rate in embryos of carriers compared to controls (5.3% versus 4.9%), which was also a 'negligible' association (φ < 0.1), despite a P-value of 0.007.
These findings suggest that rearrangement type, female age and sex of the carrier have significant impacts on the proportion of transferable embryos. Careful examination of structural rearrangement carriers and controls indicated little or no evidence for an ICE. This study helps to provide a statistical model for investigating ICE and an improved personalized reproductive genetics assessment for structural rearrangement carriers.
哪些因素会影响结构重排携带者中染色体平衡胚胎的比例？是否有染色体间效应（ICE）的证据？
回顾性评估300对夫妇（198对相互易位、60对罗伯逊易位、31对倒位和11对复杂结构重排携带者）的植入前基因检测结果。通过阵列比较基因组杂交或下一代测序技术分析囊胚。使用匹配的对照组和对效应大小（φ）进行精确统计测量来研究ICE。
300对夫妇进行了443个周期的治疗；分析了1835个胚胎，其中23.8%被诊断为正常/平衡且整倍体。总体累积临床妊娠率和活产率分别为69.5%和55.8%。发现复杂易位和女性年龄（≥35岁）是与可移植胚胎几率较低相关的危险因素（P < 0.001）。基于对5237个胚胎的分析，携带者中累积的新发非整倍体率低于对照组（45.6%对53.4%，P < 0.001），但这是一种“可忽略不计”的关联（φ < 0.1）。对117,033个染色体对的进一步评估显示，与对照组相比，携带者胚胎中单个染色体错误率更高（5.3%对4.9%），尽管P值为0.007，但这也是一种“可忽略不计”的关联（φ < 0.1）。
这些发现表明重排类型、女性年龄和携带者性别对可移植胚胎的比例有显著影响。对结构重排携带者和对照组的仔细检查表明几乎没有ICE的证据。本研究有助于提供一个用于研究ICE的统计模型，并为结构重排携带者提供改进的个性化生殖遗传学评估。
