Copy number variations in spontaneous abortions: a meta-analysis

Area of Science:

• Genetics
• Reproductive Medicine
• Genomic Medicine

Background:

• Spontaneous abortions with euploid karyotypes present a diagnostic challenge.
• Understanding the role of copy number variations (CNVs) in these cases is crucial for reproductive health.

Purpose of the Study:

• To systematically review and analyze CNVs in spontaneous abortions with a euploid karyotype.
• To identify pathogenic CNVs and their potential contribution to pregnancy loss.

Main Methods:

• Systematic review adhering to PRISMA guidelines.
• PubMed database search for articles published between 2006 and 2023.
• Inclusion of studies analyzing CNVs in spontaneous abortions using any detection method.
• Interpretation of CNV pathogenicity based on American College of Medical Genetics and Genomics (ACMG) guidelines.

Main Results:

• Nineteen publications were included, identifying 1425 CNVs in 550 samples from 3953 euploid spontaneous abortions (14% of cases).
• 9% of CNVs were pathogenic, and 7.5% were likely pathogenic.
• Frequent pathogenic CNVs included 22q11.2 deletion/duplication, 16p13.11 deletion, and 15q11.2 deletion/duplication.
• The 22q11.2 deletion emerged as a likely contributor to early embryonic lethality.

Conclusions:

• CNVs are present in a significant proportion of euploid spontaneous abortions.
• While no definitive associations were found, specific CNVs, particularly 22q11.2 deletions, are implicated in early pregnancy loss.
• Further research is needed to elucidate the precise mechanisms by which CNVs contribute to spontaneous abortion.