Yang Lan, Tang Ye, Lu Mudan, Yang Yuefen, Xiao Jianping, Wang Qiaoxia, Yang Canfeng, Tao Hehua, Xiang Jingying
Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
Department of Laboratory Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
Acta Obstet Gynecol Scand. 2016 Dec;95(12):1433-1440. doi: 10.1111/aogs.13026.
Labor-intensive karyotyping is used as the reference standard diagnostic test to identify copy number variants (CNVs) in the fetal genome after recurrent pregnancy loss. Our aim was to present and evaluate a novel molecular assay called CNVplex that could potentially be used as an alternative method to conventional karyotyping for diagnosing fetal chromosomal abnormalities associated with recurrent pregnancy loss.
Using karyotyping as the reference standard, CNVplex was performed to identify fetal chromosomal abnormalities in the chorionic villus samples from 76 women experiencing at least two pregnancy losses. Its diagnostic accuracy, sensitivity, and specificity were evaluated to detect aneuploidies associated with recurrent pregnancy loss. Turnaround time and costs of CNVplex were also measured.
Diagnostic accuracy of CNVplex in aneuploidies that are associated with recurrent pregnancy loss was 1.0 (95% CI 0.94-1.0), sensitivity was 100% (95% CI 0.89-1.0), and specificity was 100% (95% CI 0.875-1.0). Diagnostic accuracy of CNVplex was similar to that of karyotyping. Both karyotyping and CNVplex assay detected 27 autosomal trisomies, three 45,X monosomies, and three polyploidies. CNVplex also detected additional novel structural abnormalities of the fetal genome. Compared with karyotyping, CNVplex significantly (p = 0.001) reduced the waiting time by 13.98 days (95% CI 13.88-14.08) and the cost by US $241 (95% CI 234.53-247.47).
CNVplex is a novel effective assay for diagnosing fetal chromosomal abnormalities associated with recurrent pregnancy loss. In the routine clinical work-up of recurrent pregnancy loss, diagnostic accuracy of CNVplex is comparable to that of conventional karyotyping but it requires less waiting time and has lower cost.
在复发性流产后，采用劳动密集型的核型分析作为参考标准诊断测试来识别胎儿基因组中的拷贝数变异（CNV）。我们的目的是介绍并评估一种名为CNVplex的新型分子检测方法，该方法有可能作为传统核型分析的替代方法，用于诊断与复发性流产相关的胎儿染色体异常。
以核型分析作为参考标准，对76名经历至少两次流产的女性的绒毛样本进行CNVplex检测，以识别胎儿染色体异常。评估其诊断准确性、敏感性和特异性，以检测与复发性流产相关的非整倍体。还测量了CNVplex的周转时间和成本。
CNVplex对与复发性流产相关的非整倍体的诊断准确性为1.0（95%可信区间0.94 - 1.0），敏感性为100%（95%可信区间0.89 - 1.0），特异性为100%（95%可信区间0.875 - 1.0）。CNVplex的诊断准确性与核型分析相似。核型分析和CNVplex检测均检测到27例常染色体三体、3例45,X单体和3例多倍体。CNVplex还检测到胎儿基因组其他新的结构异常。与核型分析相比，CNVplex显著（p = 0.001）减少了13.98天的等待时间（95%可信区间13.88 - 14.08），成本降低了241美元（95%可信区间234.53 - 247.47）。
CNVplex是一种诊断与复发性流产相关的胎儿染色体异常的新型有效检测方法。在复发性流产的常规临床检查中，CNVplex的诊断准确性与传统核型分析相当，但所需等待时间更短且成本更低。
