41. EARLY EXPERIENCES WITH TESTING FOR ANEUPLOIDY IN PREIMPLANTATION GENETIC TESTING FOR INHERITED DISORDERS

Abstract

Introduction Preimplantation genetic testing (PGT) is divided into three categories based on the indication: PGT-M (Monogenic), PGT-SR (Structural rearrangements) and PGT-A (Aneuploidy). A large study of more than 15000 trophectoderm biopsies found the lowest rate of aneuploidy to be 25% in young women increasing with maternal age to more than 90% ( Franasiak et al., 2014 ). Thus, at least 1 in 4 embryos are expected to be aneuploid, possibly leading to implantation failure, miscarriage or an abnormal fetus. Hence, in theory, selection of euploid embryos should increase pregnancy rates and decrease miscarriage rates, but its application is still a subject of intense international discussion. In our center we do not offer PGT-A, but as our PGT-SR setup is based on Shallow Whole Genome Sequencing, the ploidy status is revealed, and used for prioritizing embryos. Our PGT-M setup (see below) does not detect aneuploidy, why we would expect a higher rate of implantation when performing PGT-SR. We investigated this by looking at clinical outcomes following PGT-SR and PGT-M. Materials and methods PGT-SR was performed by Shallow Whole Genome Sequencing while PGT-M was performed by fragment analysis of short tandem repeats and SNaPshot analysis of the specific mutation when relevant. Embryo ploidy status was obtained and used for prioritizing embryos during PGT-SR combined with morphological assessment. Embryos from the PGT-M group were only subjected to morphological assessment, as ploidy status was available. Single embryo transfer was performed for all transfers in both groups. Positive hCG and ongoing pregnancy rate (OPR) per transfer was used as clinical outcomes. Ongoing pregnancy was defined as detection of an intrauterine gestation with fetal heartbeat at gestational week 8. Data were collected from embryos transferred from 1st January 2017 to1st December 2018. Test of equal proportions where performed using two-proportion Z-test in R version 1.1.453. Results 159 and 27 embryos were transferred in the PGT-M and PGT-SR group, respectively. Mean maternal age was 30.96 in the PGT-M and 32.56 in the PGT-SR group. Positive hCG per transfer were 49.7 % and 48.1 % in the PGT-M and PGT-SR groups, respectively (P = 0.881). OPR per transfer were 34.6 % and 37.0 % in the PGT-M and PGT-SR group, respectively (P = 0.805). Conclusion There are no significant differences between the two groups with respect to positive hCG or OPR. The lack of a statistical difference could not be explained by a difference in mean maternal age, as it was comparable between the two groups. Our current data indicate that aneuploidy screening does not enhance the chance of embryo implantation, but the numbers in the PGT-SR group are low. It is likely, that the slight increase in OPR when performing aneuploidy screening might be statistically significant given a larger dataset.