The Assessment of Methods for Preimplantation Genetic Testing for Aneuploidies Using a Universal Parameter: Implications for Costs and Mosaicism Detection

Abstract

Abstract Preimplantation genetic testing for aneuploidies (PGT-A) is used to increase live birth rates following in vitro fertilization. The assessment of different testing methods to date has relied on non-universal parameters, e.g., sensitivity, specificity that must be individually stipulated for each study, typically performed using arbitrarily selected cell lines. Here we present a robust approach that is based on assessment of the median noise in a large dataset of routine clinical samples. Raw sequencing data obtained during PGT-A testing of 973 trophectoderm biopsies was used for comparison of two methods, VeriSeq PGS (Illumina) and AB-PGT™ (AB Vector). Three times less median noise was a feature of the AB-PGT™ method; thereby, allowing the number of multiplexed samples per sequencing run to be increased from 24 with VeriSeq PGS to 72 with AB-PGT™ effectively reducing price per sample without compromising data quality. The improvement is attributed to a novel SuperDOP™ whole genome amplification technology, combined with a simplified AB-PGT™ protocol. We show that the median noise level associated with a large dataset of biopsies is a simple, universal metric for assessment of PGT-A methods which has implications for other screening methods, detection of mosaicisms and the improvement of fertility clinic practices.