First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis
First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis
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DOI：
10.1093/humrep/der068
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发表时间：
2011-06-01
影响因子：
6.1
通讯作者：
Wells, D.
中科院分区：
文献类型：
--
作者：
Alfarawati, S.;Fragouli, E.;Wells, D.
背景：均衡的染色体重排是植入前遗传诊断（PGD）最常见的适应症之一。尽管在这种情况下已成功地使用了原位杂交（FISH）进行原位杂交（FISH），但这种方法通常限制对重排的染色体的评估。此外，使用基于鱼类的策略，有时有必要创建特定于患者的协议，从而增加等待时间和成本。在当前的研究中，我们探索了两种全面的染色体筛选方法，传统的中期比较基因组杂交（CGH）和微阵列-CGH（ACGH）作为染色体重排的PGD的替代方法。 PGD的循环，用于各种染色体重排（相互或罗伯逊易位或反转）。使用CGH（9例）或ACGH（11例）在各个胚胎阶段进行测试：132个样品中的121个（91.7％）获得了结果。在被诊断的样品中，发现有48.8％的人单独或与其他染色体异常相关的重排相关的异常。对于重排的染色体，另外28.9％的样品是正常/平衡的，但受其他染色体的非整倍性影响。只有22.3％的样品在染色体上正常。在完成治疗周期的15名患者中，有5例在一个或两个周期后怀孕，导致四个健康的出生。每周周期的输送率为21％（每个胚胎转移27％）。结论：这是第一个描述临床应用临床应用的研究，该研究应用于携带反转和易位的患者的极性体，胚泡或滋养剂细胞。使用这些技术，大多数要求PGD进行染色体重排的患者可以使用单一方案进行治疗。另外，检测影响与重排无关的染色体的异常可能有助于选择可行的胚胎进行转移。
BACKGROUND: Balanced chromosomal rearrangements represent one of the most frequent indications for preimplantation genetic diagnosis (PGD). Although fluorescence in situ hybridization (FISH) has been successfully employed for diagnosis in such cases, this approach usually restricts assessment of the chromosomes involved in the rearrangement. Furthermore, with FISH-based strategies, it is sometimes necessary to create patient-specific protocols, increasing the waiting time and costs. In the current study, we explored the use of two comprehensive chromosome screening methods, conventional metaphase comparative genomic hybridization (CGH) and microarray-CGH (aCGH), as alternatives for PGD of chromosome rearrangements.METHODS: The study included 16 patients who underwent 20 cycles of PGD for a variety of chromosome rearrangements (reciprocal or Robertsonian translocations or inversions). Testing was performed at various embryonic stages using CGH (9 cases) or aCGH (11 cases).RESULTS: Results were obtained for 121 out of 132 samples (91.7%). Of the diagnosed samples, 48.8% were found to carry abnormalities associated with the rearrangement, either alone or in combination with other chromosomal abnormalities. A further 28.9% of samples were normal/balanced for the rearranged chromosomes, but affected by aneuploidy for other chromosomes. Only 22.3% of samples were chromosomally normal. Of the 15 patients who completed their treatment cycles, 5 became pregnant after one or two cycles resulting in four healthy births. The delivery rate per cycle was 21% (27% per embryo transfer).CONCLUSIONS: This is the first study to describe the clinical application of comprehensive chromosome screening applied to polar bodies, blastomeres or trophectoderm cells from patients carrying inversions and translocations. Using these techniques, most patients requesting PGD for a chromosome rearrangement can be treated using a single protocol. Additionally, the detection of abnormalities affecting chromosomes unrelated to the rearrangement may assist in the selection of viable embryos for transfer.