Frumkin Tsvia, Peleg Sagit, Gold Veronica, Reches Adi, Asaf Shiri, Azem Foad, Ben-Yosef Dalit, Malcov Mira
Wolf PGD Stem Cell Lab, Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Genetic Institute, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
J Assist Reprod Genet. 2017 Aug;34(8):1095-1100. doi: 10.1007/s10815-017-0954-y. Epub 2017 May 29.
The aim of the study is to report a case of non-diagnosed complex chromosomal rearrangement (CCR) identified by preimplantation genetic screening (PGS) followed by preimplantation genetic diagnosis (PGD) which resulted in a pregnancy and delivery of healthy offspring.
A 29-year-old woman and her spouse, both diagnosed previously with normal karyotypes, approached our IVF-PGD center following eight early spontaneous miscarriages. PGS using chromosomal microarray analysis (CMA) was performed on biopsied trophectoderm. Fluorescence in situ hybridization (FISH), as well as re-karyotype, were performed on metaphase derived from peripheral blood of the couple. Subsequently, in the following PGD cycle, a total of seven blastocysts underwent CMA.
A gain or loss at three chromosomes (3, 7, 9) was identified in six out of seven embryos in the first PGS-CMA cycle. FISH analysis of parental peripheral blood samples demonstrated that the male is a carrier of a CCR involving those chromosomes; this was in spite of a former diagnosis of normal karyotypes for both parents. Re-karyotype verified the complex translocation of 46,XY,t (3;7;9)(q23;q22;q22). Subsequently, in the following cycle, a total of seven blastocysts underwent PGD-CMA for the identified complex translocation. Two embryos were diagnosed with balanced chromosomal constitution. A single balanced embryo was transferred and pregnancy was achieved, resulting in the birth of a healthy female baby.
PGS employing CMA is an efficient method to detect unrevealed chromosomal abnormalities, including complicated cases of CCR. The combined application of array CGH and FISH technologies enables the identification of an increased number of CCR carriers for which PGD is particularly beneficial.
本研究旨在报告一例通过植入前基因筛查（PGS）及随后的植入前基因诊断（PGD）鉴定出的未被诊断的复杂染色体重排（CCR）病例，该病例最终成功妊娠并分娩出健康后代。
一名29岁女性及其配偶，双方此前均被诊断为核型正常，在经历了8次早期自然流产后前来我们的体外受精 - 植入前基因诊断中心。对活检的滋养外胚层进行了基于染色体微阵列分析（CMA）的PGS。对这对夫妇外周血来源的中期细胞进行了荧光原位杂交（FISH）以及重新核型分析。随后，在接下来的PGD周期中，共有7个囊胚接受了CMA检测。
在第一个PGS - CMA周期的7个胚胎中，有6个在三条染色体（3、7、9）上出现了增减情况。对父母外周血样本的FISH分析表明，男性是涉及这些染色体的CCR携带者；尽管之前诊断父母双方核型均正常。重新核型分析证实为46,XY,t(3;7;9)(q23;q22;q22)的复杂易位。随后，在接下来的周期中，共有7个囊胚针对鉴定出的复杂易位进行了PGD - CMA检测。两个胚胎被诊断为染色体组成平衡。移植了一个平衡的胚胎并成功妊娠，最终分娩出一名健康的女婴。
采用CMA的PGS是检测未发现的染色体异常的有效方法，包括复杂的CCR病例。阵列比较基因组杂交（array CGH）和FISH技术的联合应用能够识别出更多的CCR携带者，对于这些携带者，PGD特别有益。
