Meiotic segregation of Robertsonian translocations ascertained in cleavage-stage embryos-implications for preimplantation genetic diagnosis
Meiotic segregation of Robertsonian translocations ascertained in cleavage-stage embryos-implications for preimplantation genetic diagnosis
复制标题
DOI：
10.1093/humrep/der080
复制
发表时间：
2011-06-01
影响因子：
6.1
通讯作者：
Scriven, P. N.
中科院分区：
文献类型：
--
作者：
Bint, S. M.;Ogilvie, C. Mackie;Scriven, P. N.
背景技术背景：本研究的目的是确定13/14和14/21罗伯逊易位携带者胚胎中减数分裂分离产物的发生率，并评估荧光原位杂交（FISH）技术检测单细胞的预测价值，为PGD的决策提供更多的信息。在这项前瞻性队列研究中，使用基因座特异性FISH探针确定卵裂期胚胎裂解卵裂球细胞核中易位染色体的拷贝数。Logistic回归分析，控制易位类型，女性年龄和生育状况，用于计算女性和男性杂合子的不平衡分离产物的比值比（OR）。主要的诊断指标是测试结果的预测值。结果：女性携带者产生不平衡易位产物胚胎的可能性是男性携带者的4倍（OR 3.8，95%可信区间2.0-7.2，P < 0.001）。在来自女性或男性杂合子的胚胎中检测的染色体异常的患病率估计分别为43%或28%，而正常检测结果的预测值估计为93- 100%或96-100%，异常检测结果的预测值估计为79%或57%。女性携带者每对夫妇的活产率为58%，男性携带者为50%。结论：对于女性携带者，使用FISH的PGD可以降低因易位而流产的风险或因14/21罗伯逊易位而患唐氏综合症的风险。由于染色体不平衡的发生率相对较低，预测值较低，因此使用FISH对男性携带者进行PGD不太可能。
BACKGROUND: The aim of this study was to ascertain the prevalence of meiotic segregation products in embryos from carriers of 13/14 and 14/21 Robertsonian translocations and to estimate the predictive value of testing single cells using the fluorescence in situ hybridization (FISH) technique, to provide more information for decision-making about PGD.METHODS: In this prospective cohort study, the copy number of translocation chromosomes in nuclei from lysed blastomeres of cleavage-stage embryos was ascertained using locus-specific FISH probes. Logistic regression analysis, controlling for translocation type, female age and fertility status, was used to calculate the odds ratio (OR) of unbalanced segregation products for female and male heterozygotes. The primary diagnostic measure was the predictive value of the test result. The primary outcome measure was the live birth rate per couple.RESULTS: Female carriers were four times more likely than male carriers to produce embryos with an unbalanced translocation product (OR 3.8, 95% confidence interval 2.0-7.2, P < 0.001). The prevalence of abnormality for the chromosomes tested in embryos from female or male heterozygotes was estimated to be 43 or 28%, respectively, while estimates of the predictive value were 93-100 or 96-100% for a normal test result and 79 or 57% for an abnormal test result. The live birth rate per couple was 58% for female carriers and 50% for male carriers.CONCLUSIONS: For female carriers, PGD using FISH could reduce the risk of miscarriage from either translocation or the risk of Down syndrome from the 14/21 Robertsonian translocation. PGD using FISH for male carriers is unlikely to be indicated given the relatively low prevalence of chromosome imbalance and low predictive value.