TY - JOUR
T1 - Reducing misdiagnosis caused by maternal cell contamination in genetic testing for early pregnancy loss
AU - Volozonoka, Ludmila
AU - Gailite, Linda
AU - Perminov, Dmitrijs
AU - Kornejeva, Liene
AU - Fodina, Violeta
AU - Kempa, Inga
AU - Miskova, Anna
N1 - Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - The analysis of products of conception (POC) is clinically important to establish the cause of early pregnancy loss. Data from such analyses can lead to specific interventions in subsequent natural or assisted conceptions. The techniques available to examine the chromosomal composition of POC have limitations and can give misleading results when maternal cell contamination (MCC) is overlooked. The aim of this study was to develop a protocol for MCC assessment and to formulate POC material handling, testing, and reporting recommendations. Using array comparative genomic hybridization, we tested 86 POC samples, of which 47 sample pairs (DNA extracted from the POC sample and maternal DNA) were assessed for the presence of MCC. MCC was evaluated using an approach we developed, which exploited the genotyping of 14 STR, AMEL, and SRY loci. POC samples showing the clear presence of villi (63.9%) did not contain any signs of the maternal genome and can therefore be reliably tested using conventional methods. The proportion of 46,XX karyotype in the unselected sample batch was 0.39, which fell to 0.23 in visually good samples and was 0.27 in samples having no signs of contamination upon MCC testing. MCC assessment can rescue visually poor samples from being discarded or wrongly genotyped. We demonstrate here that classification based on visual POC material evaluation and MCC testing leads to predictable and reliable POC genetic testing outcomes. Our formulated recommendations covering POC material collection, transportation, primary and secondary processing, as well as the array of pertinent considerations discussed here, can be implemented by laboratories to improve their POC genetic testing practices. We anticipate our protocol for MCC assessment and recommendations will help reduce the misconception regarding the etiology of miscarried fetuses and foster informed decision-making by clinicians and patients dealing with early pregnancy loss.
AB - The analysis of products of conception (POC) is clinically important to establish the cause of early pregnancy loss. Data from such analyses can lead to specific interventions in subsequent natural or assisted conceptions. The techniques available to examine the chromosomal composition of POC have limitations and can give misleading results when maternal cell contamination (MCC) is overlooked. The aim of this study was to develop a protocol for MCC assessment and to formulate POC material handling, testing, and reporting recommendations. Using array comparative genomic hybridization, we tested 86 POC samples, of which 47 sample pairs (DNA extracted from the POC sample and maternal DNA) were assessed for the presence of MCC. MCC was evaluated using an approach we developed, which exploited the genotyping of 14 STR, AMEL, and SRY loci. POC samples showing the clear presence of villi (63.9%) did not contain any signs of the maternal genome and can therefore be reliably tested using conventional methods. The proportion of 46,XX karyotype in the unselected sample batch was 0.39, which fell to 0.23 in visually good samples and was 0.27 in samples having no signs of contamination upon MCC testing. MCC assessment can rescue visually poor samples from being discarded or wrongly genotyped. We demonstrate here that classification based on visual POC material evaluation and MCC testing leads to predictable and reliable POC genetic testing outcomes. Our formulated recommendations covering POC material collection, transportation, primary and secondary processing, as well as the array of pertinent considerations discussed here, can be implemented by laboratories to improve their POC genetic testing practices. We anticipate our protocol for MCC assessment and recommendations will help reduce the misconception regarding the etiology of miscarried fetuses and foster informed decision-making by clinicians and patients dealing with early pregnancy loss.
KW - aneuploidy
KW - early pregnancy loss
KW - genetic testing
KW - maternal cell contamination
KW - Miscarriage
KW - product of conception
UR - http://www.scopus.com/inward/record.url?scp=85092706633&partnerID=8YFLogxK
U2 - 10.1080/19396368.2020.1827081
DO - 10.1080/19396368.2020.1827081
M3 - Article
AN - SCOPUS:85092706633
SN - 1939-6368
VL - 66
SP - 410
EP - 420
JO - Systems Biology in Reproductive Medicine
JF - Systems Biology in Reproductive Medicine
IS - 6
ER -