Diagnostic utility of microarray testing in pregnancy loss

Rosenfeld, Jill A.; Tucker, Megan; Escobar, Luis; Neill, Nicholas J.; Torchia, Beth S.; McDaniel, Lisa D.; Schultz, Roger A.; Chong, Karen; Chitayat, David

doi:10.1002/uog.14866

Cited by 59 publications

(77 citation statements)

References 44 publications

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“…VOUS were obtained in 2.8% of our cases, which is consistent with the frequency reported in other studies (6,7,14). However, we checked all the reference genes involved in these VOUS and none of them are known to play a key role in embryonic development or to be associated with fetal death.…”

Section: Discussionsupporting

confidence: 91%

“…Although attempts have been made over many years to identify human lethal CNVs, so far, little is known about the association between a specific CNV and miscarriage. The prevalence of the 22q11.2 microdeletion was 0.19% (1/535), which is consistent with the frequency reported in previous studies on miscarriage (0.05-0.8%) (6,13,14), and notably higher than the incidence of 22q11.2 microdeletion in the general population (0.013% of live births) (24). We identified submicroscopic pathogenic genomic imbalances in 2.2% (12/535) of our cases.…”

Section: Discussionsupporting

confidence: 91%

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

Wang¹,

Cheng

Meng³

et al. 2016

Clinical Genetics

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Chromosomal microarray analysis (CMA) has been used routinely in pediatric and prenatal genetic diagnosis in clinical practice, but it has rarely been applied to miscarriage analysis. In this study, we conducted a prospective study to evaluate the feasibility of CMA for genetic diagnosis of first-trimester miscarriage specimens. We successfully analyzed 551 fresh miscarriage specimens using single-nucleotide polymorphism (SNP) array. Among the specimens, 2.9% (16/551) had significant maternal cell contamination and were excluded from the study. Clinically significant chromosomal abnormalities were identified in 295 (55.1%) cases, including 214 (40%) with aneuploidy, 40 (7.5%) with polyploidy, 19 (3.6%) with partial aneuploidy, 12 (2.2%) with pathogenic microdeletion/microduplication, and 10 (1.9%) with uniparental isodisomy (isoUPD). Variants of uncertain significance were obtained in 15 cases (2.8%). Notably, isoUPD involving a single chromosome (chromosome 22) and two recurrent copy number variations, 22q11.2 microdeletion and 7q11.23 microdeletion, were identified as probably to be associated with miscarriage. The frequency and distribution of genetic aberrations in the spontaneous abortion group was not significantly different from those in the recurrent miscarriage group. Our study suggests SNP array is a reliable, robust, and high-resolution technology for genetic diagnosis of miscarriage in clinical practice.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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

Wang¹,

Cheng

Meng³

et al. 2016

Clinical Genetics

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“…[1,2] It is estimated that chromosomal abnormalities, in the majority of cases aneuploidies, account for 50–70% of miscarriages of less than 10 week’ gestation in the general reproductive population [3–9]. In the presence of recurrent pregnancy loss (RPL), it is important to distinguish between parental genetic abnormalities and embryo chromosomal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

“…Miscarried embryo chromosomal abnormalities are mostly de novo in origin. Nevertheless, in specific cases, chromosomal characterization of miscarriage tissues can identify familial chromosomal rearrangements that may predispose couples to RPL [1]. Even in those cases of de novo chromosomal abnormalities, being aware of such information may provide couples with an explanation for the loss.…”

Section: Introductionmentioning

confidence: 99%

“…To overcome these limitations, scientists have started conducting genetic chromosomal microarray testing [1,6,16]. This test allows to perform chromosome analysis on DNA extracted from direct fetal samples without the need for live dividing cells and it can detect quantitative chromosomal abnormalities significantly below the resolution of about 10 megabases (Mb) of the conventional karyotyping [18–20].…”

Section: Introductionmentioning

confidence: 99%

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The chromosome analysis of the miscarriage tissue. Miscarried embryo/fetal crown rump length (CRL) measurement: A practical use

et al. 2017

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ObjectiveTo investigate whether miscarried embryo/fetal crown rump length (CRL) measurement may yield a practical application for predicting a conclusive result at the cytogenetic analysis of miscarriage tissue. Our study might help in improving the cytogenetic method, the results of which may be affected by maternal cell contamination (MCC). In particular, we aimed at establishing whether the miscarried embryo/fetal CRL measurement shows accuracy in predicting the possibility of MCC and the scan cut-off value useful to this purpose and, as a result, suggest a multi-step procedure for the genetic ascertainment.MethodsWomen experiencing at least two miscarriages of less than 20 weeks size at the Pregnancy Loss Unit at Fondazione Policlinico A. Gemelli underwent a scan before surgery. The CRL value was recorded. After the dilatation and courettage (D&C) procedure, miscarriage tissue was processed through the proposed multi-step procedure before performing oligo-nucleotide-based and SNP (single nucleotide polymorphisms)-based comparative genomic hybridization (CGH+SNP) microarray analysis.Results63 women and 63 miscarriages met the criteria. By using the Receiving Operator Characteristic (ROC) curves, CRL showed an AUC of 0.816 (95%CI:0.703–0.928,p<0.001). A CRL≥24.5 mm cut-off value showed a higher positive likelihood ratio (5.27) but, conversely, a higher negative likelihood ratio (0.64) in predicting the possibility of MCC. Microarray analysis was successful in the totality of cases in which the embryo/fetal origin of miscarriage tissues was proven.ConclusionsThe 24.5 mm CRL value emerges as the most suitable cut-off enabling the identification of cases in which the embryo-fetal component can be isolated in the absence of MCC and the chromosomal array provide informative results.

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Interventions for investigating and identifying the causes of stillbirth

Wojcieszek

Shepherd

Middleton

et al. 2018

Cochrane Database of Systematic Reviews

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There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes.Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials.

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Diagnostic utility of microarray testing in pregnancy loss

Abstract: Objectives

Cited by 59 publications

References 44 publications

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

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

The chromosome analysis of the miscarriage tissue. Miscarried embryo/fetal crown rump length (CRL) measurement: A practical use

Interventions for investigating and identifying the causes of stillbirth

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