Mosaic embryos are not the only option for transfer in 90% of PGT-A cases

Abstract

Objectives The increased sensitivity of NGS for routine PGT-A has allowed the accurate classification of embryo biopsies as mosaic. Correspondingly, there is now a proportion of clinical cases in which there are no euploid embryos and at least one other mosaic for transfer consideration. This presents unique challenges to clinical decision makers about whether to transfer mosaic embryos. An increasing number of studies report normal live births after the transfer of mosaic embryos, but nonetheless, the issue of knowingly transferring an embryo with a detected abnormality is an ethically fraught issue. To the best of our knowledge however no studies have yet, in a sufficiently large cohort, audited the extent to which clinicians encounter this predicament and the extent to which it is related to maternal age. The objective of this study was therefore to address these two questions. Method Retrospective analysis of whole genome NGS PGT-A cases (Dec2015-Oct2017, Cooper Genomics). Re-biopsy, gender only and donor egg (age unknown) cases were excluded. Results 6,615 cases involving 27,396 biopsies were reviewed (table below) with the above categories in mind and in 4 age categories. The no euploid (1 or more mosaic) group constitutes 10.8% of the total and does not change significantly with maternal age. The one euploid (1 or more mosaic) group constitutes 10.1% of the total and reduces with maternal age, from 11.43% of cases associated with maternal age below 35, down to 6.10% of cases of patients over 40. Conclusions We found that 10-11% of cases only have a mosaic embryo available for transfer, and a further 10% of cases only have 1 euploid embryo and a further mosaic embryo available for double embryo transfer or a subsequent frozen embryo transfer. In these cases, clinical and genetic counselling involvement would be required to aid in decision making as to whether a mosaic embryo is to be transferred. Conversely, 80% of cases wouldn't present such a predicament with, 21% of cases only having aneuploid embryos reported and 59% of cases having one or more euploid embryos available (excl. our 1 euploid and 1 or more mosaic group). While the incidence of overall euploidy vs aneuploidy is clearly an age-related phenomenon on both an individual embryo and per case basis, the incidence of our two sub groups (each 10-11% of the total) does not appear to vary significantly with age with the possible exception of the “1 euploid and at least 1 mosaic” category in the over 40 age group. This suggests that the frequency of our two sub groups in question are more related to errors of mitosis (post-zygotic) than meiosis. It is important that we continue to monitor pregnancies and live birth outcomes where mosaic embryos are transferred to gather more information regarding those which are more likely to result in live births and low levels of pregnancy loss.