SNP microarray-based PGS significantly improves the clinical outcome for translocation carriers

This was a retrospective comparison study of SNP-based preimplantation genetic screening (SNP-PGS) and FISH-based preimplantation genetic diagnosis (FISH-PGD) for 575 couples in total with chromosome translocations, including 169 couples treated by SNP-PGS between October 2011 and August 2012, and 406 couples treated by FISH- PGD between January 2005 and October 2011. In total, 773 blastocysts obtained from 169 couples were biopsied and frozen, embryo transfer was carried out on the balanced embryos. The PGS results and pregnancy outcomes were compared with those of FISH-PGD for 406 translocation carriers with 3,968 embryos biopsied on day 3. Of the 773 biopsied blastocysts, reliable SNP-PGS results were obtained for 717 (92.76%). For Robertsonian translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities, and embryos with abnormalities unrelated to a translocation were 57.80%, 23.39% and 18.81%, respectively. In reciprocal translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities and embryos with abnormalities unrelated to translocation were 35.47%, 52.10% and 12.42%, respectively. There was no significant differences in patient age, basal endocrine level and the average number of retrieved oocytes and good quality day 3 embryos before biopsy in the SNP-PGS group compared with the FISH-PGD group. The number of embryos biopsied in the FISH-PGD group was higher than in the SNP-PGS group. However, the pregnancy rate with successful delivery per oocyte retrieval and the implantation rate were both lower in the FISH-PGD group than in the SNP-PGS group. The spontaneous abortion rate was higher in the FISH-PGD group than in the SNP-PGS group. Affymetrix SNP arrays were performed according to the manufacturer's directions on whole genome amplification product of trophectoderm cells, which were collect from blastocysts biopsy. The results of SNP array were used to determine if the biopsied blastocyst have aneuploidy or unbalanced chromosomes.

本研究为回顾性对比研究，针对共计575对染色体易位携带者夫妇，对比了基于单核苷酸多态性的植入前遗传学筛查（SNP-PGS）与基于荧光原位杂交的植入前遗传学诊断（FISH-PGD）两种技术的应用效果。其中，2011年10月至2012年8月期间，共有169对夫妇接受SNP-PGS治疗；2005年1月至2011年10月期间，共有406对夫妇接受FISH-PGD治疗。
169对夫妇共计获得773枚囊胚，均接受活检并冷冻保存，后续仅对平衡胚胎实施胚胎移植。本研究将SNP-PGS的筛查结果与妊娠结局，与406对染色体易位携带者（于第3天活检3968枚胚胎）的FISH-PGD结果进行对比。
在773枚接受活检的囊胚中，717枚（92.76%）获得了可靠的SNP-PGS检测结果。针对罗伯逊易位（Robertsonian translocation）携带者，正常/平衡胚胎、易位相关异常胚胎、非易位相关异常胚胎的占比分别为57.80%、23.39%及18.81%；针对相互易位（reciprocal translocation）携带者，上述三类胚胎的占比分别为35.47%、52.10%及12.42%。
与FISH-PGD组相比，SNP-PGS组患者的年龄、基础内分泌水平、活检前获卵平均数以及优质第3天胚胎数均无显著差异。FISH-PGD组活检的胚胎数量多于SNP-PGS组，但FISH-PGD组的每取卵周期活产妊娠率及着床率均低于SNP-PGS组，且自然流产率高于SNP-PGS组。
本研究采用Affymetrix公司的SNP芯片，按照厂商说明书对囊胚活检获取的滋养层细胞全基因组扩增产物进行检测，通过SNP芯片结果判断活检囊胚是否存在非整倍体或染色体不平衡情况。