Evaluation of the effect of delayed blastulation on genetic status and pregnancy outcome of the vitrified-warmed elective single embryo transfer (eSET)

Abstract

Introduction Preimplantation testing for aneuploidy (PGT-A) identifies chromosomally normal embryos with the aim to increase IVF success rate. Trophectoderm biopsy is usually performed on day 5 when the embryos are expanded. A proportion of slower growing embryos that have not reached the expanded blastocyst stage on day 5, or slower developing day 5 morulae are frequently found to have developed to blastocyst stage and expanded by the time of day 6, enable trophectoderm biopsy for chromosome analysis. Blastocyst biopsy with PGT-A increased IVF implantation and delivery. It is not known if prolonging culture of euploid embryos impacts their implantation potential. Material & Methods This is a retrospective analysis of 1,071 IVF patients whom underwent a vitrified-thawed ICSI cycle with PGT-A during January 2016 to July 2017. The rates of full chromosome aneuploidy and segmental (> 10 MB) aneuploidy in trophectoderm biopsies were assessed by Next-generation sequencing-based assay (NGS). No results samples were excluded from the analysis. Aneuploidy rates and pregnancy outcome were compared. Statistical analysis was performed by ANOVA and Chi-square to assess the differences. A total of 5,611 embryos were examined. All embryos were laser hatched at cleavage stage and cultured to day 5/6. 4,222 were biopsied on day 5 and 1,389 were biopsied on day 6. Embryonic ploidy status was examined by analyzing respective trophectoderm cells by NGS (VeriSeq, Illumina). IVF outcome in terms of implantation rates and miscarriage rates were compared between 255 day-5 embryos and 60 day-6 embryos transfers in 315 cycles. Results An average number embryo biopsied per cycle was 6. Day 5 biopsies accounted for 75.2%. The overall aneuploidy rate ranges from 35% ( 42). Aneuploidy rates were higher in day 6 in all individual maternal age group ( 42 yrs 64% vs. 78%, p=0.29. Day 5 biopsy embryos had higher implantation rate (65% vs. 47%, p=0.19) and lower miscarriage rate (1% vs. 7%, p=0.05), than day 6 blastocyst. Delayed blastocyst embryos had an increased in aneuploidy risk, however, the euploid were able to fully developed and successfully implanted achieving a 47% implantation in all combined age group. Conclusions A better understanding on the relationship between embryo delayed development stage and endometrial synchronicity may aid to a higher success rate for cycles achieved only transferrable euploid delayed blastocyst.