title: Novel rapid molecular diagnosis of fetal chromosomal abnormalities associated with recurrent pregnancy loss.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Laboratory Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Mudan
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Family Planning, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Yuefen
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Family Planning, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Qiaoxia
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Canfeng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Hehua
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Prenatal Diagnosis Center, Wuxi Maternal and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007621:Karyotyping; D060885:Multiplex Polymerase Chain Reaction; D011247:Pregnancy; D012680:Sensitivity and Specificity
keywords: Aneuploidy; CNVplex; fetal chromosome abnormalities; karyotyping; recurrent pregnancy loss