Genetic analysis of first‐trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH

Abstract

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.

Análise citogenética em material de abortamento espontâneo

“…The detection of approximately 55% of abnormalities in miscarriage material, without previous selection, is in accordance with data from the literature 4,11 . In a study conducted in China, Zhang et al 4 assessed 115 miscarriage materials and concluded that 61% presented chromosome abnormalities, 90% of which were numerical and 10% of which were structural, underscoring that polymerase chain reaction and comparative genomic hybridization are useful techniques for cases in which there is no cell growth in growth medium or when there is contamination by maternal cells 11 .…”

“…In a study conducted in China, Zhang et al 4 assessed 115 miscarriage materials and concluded that 61% presented chromosome abnormalities, 90% of which were numerical and 10% of which were structural, underscoring that polymerase chain reaction and comparative genomic hybridization are useful techniques for cases in which there is no cell growth in growth medium or when there is contamination by maternal cells 11 . The rate of cell growth failure mentioned in the literature ranges from 10% to 15%, which is in accordance with the rate found in this study (10.7%).…”

“…A great part of first trimester miscarriages are due to chromosomopathies 11 . Chromosome abnormalities were observed in 55.4% of miscarriage materials assessed in this study, thus confirming previous data from the literature, which has shown that 45% to 70% of all first trimester miscarriages are caused by chromosome abnormalities [12][13][14][15] .…”

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

“…9,12 The etiologic analysis of pregnancy loss can provide important information for medical management, reproductive counseling, and supportive patient care. 4,13,14 Although fetal karyotyping has been used for many years to evaluate samples of products of conception (POCs), there are two primary limitations to this method. First, cytogenetic analysis requires live cells, which requires culture.…”

“…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.…”