High-resolution PGT-A results in incidental identification of patients with small pathogenic copy number variants

This study aimed to evaluate whether a high-throughput high-resolution PGT-A method can detect copy number variants (CNVs) that could have clinical implications for patients and their embryos.

A prospective analysis of PGT-A cases was conducted using a high-resolution SNP microarray platform with over 820,000 probes. Cases where multiple embryos possessed the same segmental imbalance were identified, and preliminary PGT-A reports were issued recommending either parental microarray or conventional karyotyping to identify CNVs or translocations.

Analysis of 6080 sequential PGT-A cases led to identification of 41 cases in which incidental findings were observed (0.7%) and parental testing was recommended. All cases, in which parental studies were completed, confirmed the original PGT-A incidental findings. In 2 of the cases, parental studies indicated a pathogenic variant with clinical implications for the associated embryos. In one of these cases, the patient was identified as a carrier of a duplication in chromosome 15q11.2:q11.2 (SNRPN + +), which is associated with autism spectrum disorder. In the second case, the patient was heterozygous positive for an interstitial deletion of 3p26.1:p26.3, which is associated with 3p deletion syndrome and had clinical implications for the patient and associated embryos. In each case, parental studies were concordant with PGT-A findings and revealed the presence of an otherwise unknown CNV.

High-throughput high-resolution SNP array-based PGT-A has the ability to detect previously unknown and clinically significant parental deletions, duplications, and translocations. The use of cost-effective SNP array-based PGT-A methods may improve the effectiveness of PGT by identifying and preventing previously unknown pathogenic CNVs in children born to patients seeking in vitro fertilization.