Abnormal poc results after single euploid blastocyst transfer exposes the prevalence of contributing fetal chromosomal mosaicism

Preimplantation genetic testing for aneuploidy (PGT-A) performed on a small biopsy of trophectoderm (TE) cells allows for the identification of embryonic chromosome numeration. Biological accuracy of PGT-A testing is determined by the concordance rate between the biopsied TE cells and the chromosome constitution of the blastocyst itself. The aim of this study was to examine abnormal products of conception (POC), following single euploid blastocyst transfer, in an effort to characterize limitations of PGT-A testing. Next generation sequencing (NGS) based PGT-A testing from January 2017 to December 2021 contributed to 3,992 single euploid blastocyst transfers (mean maternal age = 35.8±3.8 years), resulting in 2,597 (65.1%) healthy live births. When possible, POCs were collected from clinical pregnancy losses (after confirmation of a fetal pole and heart tone) for fetal karyotype and/or single nucleotide polymorphism microarray analyses. In total, only 22 abnormal POC results (0.6%) were reported following these 3,992 single euploid blastocyst transfers. The abnormal POC results are outlined in the included table. With exception of the female triploid conceptions, two thirds of these abnormal POCs (n=12; 67%) confirmed the presence of fetal mosaicism, involving chromosomes 2, 3, 4, 6, 8, 9, 13, 18, 21 and X. Single euploid blastocyst transfer offers infertile couples the fastest path to a successful live birth. On examination of abnormal POCs, the vast majority were identified as fetuses with either female triploidy or mosaic aneuploidy, both considered limitations of PGT-A testing. Fetal chromosomal mosaicism can occur at any time point during embryonic development, including post-implantation and the early stages of pregnancy. Only a very small number of abnormal POCs resulted in uniform fetal aneuploidies, reflecting the high concordance of TE biopsy testing for identification of blastocyst chromosome constitution.