Array-based comparative genomic hybridization is more informative than conventional karyotyping and fluorescence in situ hybridization in the analysis of first-trimester spontaneous abortion

Abstract

BackgroundArray-based comparative genomic hybridization (aCGH) is a new technique for detecting submicroscopic deletions and duplications, and can overcome many of the limitations associated with classic cytogenetic analysis. However, its clinical use in spontaneous abortion needs comprehensive evaluation. We used aCGH to investigate chromosomal imbalances in 100 spontaneous abortions and compared the results with G-banding karyotyping and fluorescence in situ hybridization (FISH). Inconsistent results were verified by quantitative fluorescence PCR.ResultsAbnormalities were detected in 61 cases. aCGH achieved the highest detection rate (93.4%, 57/61) compared with traditional karyotyping (77%, 47/61) and FISH analysis (68.9%, 42/61). aCGH identified all chromosome abnormalities reported by traditional karyotyping and interphase FISH analysis, with the exception of four triploids. It also detected three additional aneuploidy cases in 37 specimens with ‘normal’ karyotypes, one mosaicism and 10 abnormalities in 14 specimens that failed to grow in vitro.ConclusionsaCGH analysis circumvents many limitations in traditional karyotyping or FISH. The accuracy and efficiency of aCGH in spontaneous abortions highlights its clinical usefulness for the future. As aborted tissues have the potential to be contaminated with maternal cells, the threshold value of detection in aCGH should be lowered to avoid false negatives.

Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study

“…The overall detection rate of clinically significant chromosomal abnormalities was 55.1% (295/535), and the rate of VOUS was 2.8%, which is in accordance with previous studies (6,7,9,15). We also compared the frequency and distribution of chromosomal abnormalities between patients with SA and RM.…”

Effects of subtelomeric copy number variations in miscarriages

“…Also, while conventional cytogenetic techniques are allowed in the detection of chromosomal abnormalities that are 45 Mb, they do not detect chromosomal abnormalities smaller than 5 Mb [16]. It is reported that the use of fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe hybridization (MLPA) and comparative genomic hybridization (CGH) methods are required in the investigation of these abnormalities [4,22]. This study was performed to detect subtelomeric chromosomal abnormalities that cannot be identified by conventional cytogenetic methods, to determine frequencies of these abnormalities in miscarriages samples and to adapt prenatal diagnostic applications of MLPA method in miscarriage samples.…”

Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges

“…Whole-chromosome aneuploidies are the most common etiology. [4][5][6][7][8][9][10][11] Fetal chromosomal abnormalities account for approximately 8-10% of intrauterine fetal demises occurring after 20 weeks of gestation and/or stillbirths occurring in the second or third trimester. 9,12 The etiologic analysis of pregnancy loss can provide important information for medical management, reproductive counseling, and supportive patient care.…”

“…The superior diagnostic power of CMA compared with karyotyping is well established in the pediatric and prenatal literature; however, exploration of the use of this technology for studying POC samples has been somewhat limited to date. 9,10,12,14,15,18,[20][21][22][23][24][25][26][27][28] Specifically, CMA is a particularly attractive technology for use in the study of POC samples because it is performed using extracted cellular DNA, significantly improving the likelihood of obtaining a result. Unlike karyotype analysis, CMA can even be performed on DNA extracted from formalin-fixed and paraffin-embedded tissues (FFPE), a process that is undergone by nearly every POC sample subjected to histopathological evaluation.…”