Application of array comparative genomic hybridization (aCGH) for identification of chromosomal aberrations in the recurrent pregnancy loss

Abstract

Spontaneous abortion occurs in 8–20% of recognized pregnancies and usually takes place in the first trimester (7–11 weeks). There are many causes of pregnancy loss, but the most important (about 75%) is the presence of chromosomal aberrations. We present the results of oligonucleotide array application in a cohort of 62 miscarriage cases. The inclusion criteria for the study were the loss after 8th week of pregnancy and the appearance of recurrent miscarriages. DNA was extracted from trophoblast or fetal skin fibroblasts. In the 62 tested materials from recurrent miscarriages, the detection rate was 56.5% (35/62). The most commonly found were aneuploidies (65%) (chromosomal trisomy 14, 16, 18, 21, and 22), Turner syndrome, and triploidy (17.1%). Other chromosomal abnormalities included pathogenic and likely pathogenic structural aberrations: 1) pathogenic: deletion 7p22.3p12.3 and duplication 9p24.3p13.2 inherited from the normal father, deletion 3q13.31q22.2 and deletion 3q22.3q23 of unknown inheritance and duplication of 17p12 inherited from father with foot malformation; 2) likely pathogenic variants: deletion 17p13.1 inherited from normal mother, deletion 5q14.3 of unknown inheritance and de novo deletion 1q21.1q21.2. Among these aberrations, six CNVs (copy number variants) were responsible for the miscarriage: deletion 7p22.3p12.3 and duplication 9p24.3p13.2, deletion 3q13.31q22.2 and deletion 3q22.3q23, and deletion 17p13.1 and deletion 1q21.1q21.2. Other two findings were classified as incidental findings (deletion 5q14.3 and 17p12 duplication). Our research shows that 17% of the aberrations (6/35 abnormal results) that cannot be identified by the routine kariotype analysis are structural aberrations containing genes important for fetal development, the mutations of which may cause spontaneous abortion.

Post-implantation analysis of genomic variations in the progeny from developing fetus to birth

“…The study conducted by Kowalczyk et al has revealed that up to 17.1% of small aberrations cannot be identified through conventional chromosome analysis. These aberrations include genes important for fetal development, and their mutations could cause spontaneous abortion [ 20 ]. However, there is a dearth of published research on DNMs that vary from the fetus to the newborn.…”

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples

“…Foetal chromosomal abnormalities have been recognized as a major cause of EPLs [ 4 ]. Several methods have been used for the detection of chromosomal abnormalities with different detection rates [ 17 , 18 , 19 , 20 , 21 ]. Using a combination of QF-PCR and MLPA analyses, the chromosomal abnormality rate in our study was 56.25%, which agrees with the majority of previously published data.…”

Investigating the “Fetal Side” in Recurrent Pregnancy Loss: Reliability of Cell-Free DNA Testing in Detecting Chromosomal Abnormalities of Miscarriage Tissue

“…A Samsung machine (Samsung) with a 9 MHz frequency probe was used. Crown rump length (CRL) measurement was obtained by a two-dimensional ultrasound (2DUS) on the midsagittal plane according to the International Society Ultrasound in Obstetrics and Gynecology (ISUOG) Practice Guidelines [ 12 ].…”

“…Notably, the prevalence of abnormalities in women with two losses has been observed to be higher than that in women with three or more losses [ 5 , 6 , 7 , 9 ]. Not surprisingly, according to the recent European Society of Human Reproduction and Embryology (ESHRE) guideline on RPL, genetic analysis of miscarried tissue has the benefit of providing the patient with a reason for the pregnancy loss and may help to determine whether further investigations or treatments are required [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Identifying the cause of RPL is important, not only for its prognostic implications, but also for satisfying a couple’s desire to know the reason underlying their pregnancy loss.…”