Consistent results of non-invasive pre-implantation genetic testing for aneuploidy (niPGT-A) of human embryos using two different techniques for chromosomal analysis

Abstract Research Question Are discordances in niPGT-A results attributable to the technique used for chromosomal analysis? Design A prospective blinded study was performed (September 2018-December 2019). In total 302 chromosomal analyses were performed: 92 TE-PGT-A biopsies and their corresponding spent embryo culture medium (SCM) evaluated by two methods (n=184), negative controls (n=8) and finally, TE and ICM biopsies from TE-aneuploid embryos (n=18). TE analysis were carried out using Veriseq (Illumina®) and SCM by Veriseq (Illumina®) and NICS (Yikon®). Results We obtained genetic results in 96.8% of TE-samples vs 92.4% in both SCM-techniques (p>0.05). The mosaicism rate was higher in SCM regardless the technique used: 30.4% SCM-NICS, 28.3% SCM-Veriseq vs 14.1% TE-biopsies (p 0.05). Considering embryos biopsied on D6 these rates reached up the 92.0% and 86.5%, respectively. Moreover, reanalysing TE-aneuploid embryos, the discrepancies were due to: maternal DNA contamination (55.6%), embryo mosaicism (22.2%), low resolution in SCM-NICS (11.1%) and in both techniques (11.1%). Conclusions This is the first study evaluating the consistency of different chromosomal analyses techniques for niPGT-A. As a conclusion, the diagnostic concordance between PGT-A and niPGT-A seems independent of the technique used. Optimization of culture conditions and medium retrieval constitutes potential targets to improve NIPGT-A reliability.