PGT as Quality Control for ART methods

Abstract

Between 20% to 80% of ART generated embryos are chromosomally abnormal, increasing with advancing maternal age, embryo dysmorphism but also caused by iatrogenic factors. Aneuploidy has been shown to increase with advancing maternal age but not mosaicism. Mosaicism was extensively investigated using FISH on entire embryos showing that it occurs through post-zygotic malsegregation and increases with cleavage-stage dysmorphism, but not with advancing maternal age. With newer PGT molecular techniques, biopsied cells from a TE biopsy are analyzed as a group, and not individually. Mosaicism was barely detectable from TE biopsies with some molecular techniques such as aCGH, qPCR, or SNP arrays but with the advent of Next Generation Sequencing (hr-NGS), which has a higher dynamic range and offer much higher resolution, we can now detect mosaicism in TE biopsies at a 20- 80% abnormal cell range or is 1/5 to 4/5 abnormal cells. We recently showed that chromosome abnormalities in egg donors, a group of patients quite homogeneous, are ART-induced ranging from 20% in some centers to 60% in others. Several reasons for these changes were investigated, and we found differences between doctors of the same center, pointing to hormonal stimulation and/or other treatment related factors. One being investigated is differences between follicular size of eggs retrieved. On the other hand, changes in Ph, Temperature, volatile compounds, and culture media have been reported to affect chromosome abnormalities. As such, PGT can be used as a faster QC method to determine best practices and methods instead of waiting for pregnancy outcome, while selecting good prognosis embryos even within a sub-optimal ART set up.