Cell-Free DNA in the Investigation of Miscarriage.

Emily Colley,Paul Smith,Adam J Devall,Neil V Morgan,Arri Coomarasamy,Susan Hamilton,Siobhan Quenby,Stephanie Allen,Helen Williams

doi:10.3390/jcm9113428

Abstract

Approximately one in four pregnancies result in pregnancy loss, and ~50% of these miscarriages are caused by chromosomal abnormalities. Genetic investigations are recommended after three consecutive miscarriages on products of conception (POC) tissue. Cell-free DNA (cfDNA) has been utilised for prenatal screening, but very little work has been carried out in nonviable pregnancies. We investigated the use of cfDNA from maternal blood to identify chromosomal abnormalities in miscarriage. One hundred and two blood samples from women experiencing a first trimester miscarriage were collected and stored. The mean gestational age was 7.1 weeks (range: 5–11 weeks). In this research, samples without a genetic test result from POC were not analysed. CfDNA was extracted and analysed using a modified commercial genome-wide non-invasive prenatal test. No results were provided to the patient. In 57 samples, cytogenetic results from POC analysis were available. Chromosomal abnormalities were identified in 47% (27/57) of POC analyses, and cfDNA analysis correctly identified 59% (16/27) of these. In total, 75% (43/57) of results were correctly identified. The average cfDNA fetal fraction was 6% (2–19%). In conclusion, cfDNA can be used to detect chromosomal abnormalities in miscarriages where the ‘fetal fraction’ is high enough; however, more studies are required to identify variables that can affect the overall results.

Highlights

Pregnancy loss is the most common complication during pregnancy [1], and is defined as miscarriage
Chromosomal abnormalities were identified by products of conception (POC) analysis in 27/57 (47%) cases
Knowing the genetic result of a pregnancy loss can be applied during counselling patients for the prognosis of future pregnancies

Summary

Introduction

Pregnancy loss is the most common complication during pregnancy [1], and is defined as miscarriage. It is important to identify whether a chromosomal abnormality was the underlying etiology of the pregnancy loss because this may have an indication for the prognosis of future pregnancies. If there is an unbalanced chromosomal rearrangement in the pregnancy loss, it could mean that one of the parents carries a balanced chromosomal rearrangement. This would mean that future pregnancies would be susceptible to the same or other unbalanced rearrangement. In these cases, it is important to obtain blood samples for parental karyotyping for assessment of recurrence risk

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Results

Conclusion