Abstract
Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Obstetrics and Gynecology,Genetics,Reproductive Medicine,General Medicine
Reference11 articles.
1. Romanelli V, Poli M, Capalbo A. Preimplantation genetic testing in assisted reproductive technology. Panminerva Med. 2019;61(1):30–41.
2. Munné S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Fertilization and early embryology: diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8(12):2185–91.
3. Tšuiko O, Dmitrijeva T, Kask K, Tammur P, Tõnisson N, Salumets A, et al. Detection of a balanced translocation carrier through trophectoderm biopsy analysis: a case report. Mol Cytogenet. 2019;12(1):28.
4. Treff NR, Forman EJ, Katz-Jaffe MG, Schoolcraft WB, Levy B, Scott RT Jr. Incidental identification of balanced translocation carrier patients through comprehensive chromosome screening of IVF-derived blastocysts. J Assist Reprod Genet. 2013;30(6):787–91.
5. Snider AC, Darvin T, Spor L, Akinwole A, Cinnioglu C, Kayali R. Criteria to evaluate patterns of segmental and complete aneuploidies in preimplantation genetic testing for aneuploidy results suggestive of an inherited balanced translocation or inversion. F S Rep. 2021;2(1):72–9.