Timing of blastocyst development is the sole predictor of positive pregnancy outcome in advanced maternal age patients following single euploid blastocyst transfer

Abstract

Improving embryo quality and selection is imperative to achieve a shorter time to pregnancy and successful live birth outcome, specifically for women of advanced maternal age (AMA). Preimplantation genetic testing for aneuploidy (PGT-A) allows for selection of euploid embryos, beneficial for this older population that are at increased risk for oocyte aneuploidy. The purpose of this study was to identify effective predictors of reproductive outcomes for AMA patients in conjunction with a euploid single embryo transfer (SET). Retrospective cohort study. AMA patients (≥ 38 years; n=847) underwent routine oocyte retrieval, ICSI, blastocyst biopsy, PGT-A and subsequent euploid SET at a single large infertility clinic. Patients presented with various infertility diagnoses and without significantly compromised ovarian reserve. Reproductive outcomes were divided into three groups; successful live birth (n=504), positive implantation followed by pregnancy loss (ultrasound ± FHT; n=81) and negative/biochemical (negative, or rise and subsequent direct fall of βhCG; n=262). Statistical analyses included Chi Square test for independence and ANOVA where appropriate, with significance at P<0.05. Maternal age at oocyte retrieval was significantly associated with the likelihood of an embryo transfer, as the percent of aneuploid-only cycles increased significantly with age; 38-40 years (20%), 41-42 years (46%), 43+ years (76%; P<0.0001). Reproductive outcomes following euploid SET were not associated with any of the following: maternal age at oocyte retrieval (mean 40.0 years), total number of oocytes retrieved, total number of MII oocytes, number of blastocysts available for biopsy, % euploid blastocysts, or the inner cell mass (ICM) and trophectoderm grade. Pregnancy outcomes following euploid SET were only significantly associated with the timing of blastocyst development and the appearance of the ICM (P<0.0001). Euploid blastocysts that resulted in negative/biochemical outcomes were significantly over-represented by slower blastocyst development (52.3%) compared to those with live birth (37.5%) and pregnancy loss (38.3%) (P<0.0001). Remarkably, no differences were observed between successful live birth and positive implantation followed by pregnancy loss for any parameters analyzed. Interestingly, a second euploid SET for AMA patients with prior pregnancy loss resulted in 58.3% successful live births (n=36), comparable to the overall first SET live birth rate (59.5%; ns). The timing of blastocyst development and the appearance of the ICM was the sole predictor of positive pregnancy in AMA patients following a euploid SET, and thus should be highly considered for euploid blastocyst selection to achieve the fastest time to pregnancy. Further investigations are essential to identify potential predictors of euploid pregnancy loss, and the stochastic occurrence of this adverse outcome.