A Rapid NGS-Based Preimplantation Genetic Testing for Chromosomal Abnormalities in Day-3 Blastomere Biopsy Allows Embryo Transfer Within the Same Treatment Cycle.

Yinghui Ye,Sijia Lu,Jieliang Ma,Long Cui,Fan Jin

doi:10.3389/fgene.2021.636370

Abstract

Nowadays, most of the preimplantation genetic testing (PGT) is performed with a strategy of comprehensive chromosome screening and trophectoderm biopsy. Nevertheless, patients with ovarian insufficiency may not have competent blastocysts. In the present study, we aimed to establish the value of multiple annealing and looping-based amplification cycle (MALBAC)-based next-generation sequencing (NGS) for PGT in day-3 embryos. A total of 94.3% (1168/1239) of embryos yielded informative results, and the overall embryo euploid rate was 21.9% (256/1168). Overall, 225 embryos were transferred in 169 cycles with a clinical pregnancy rate of 49.1% (83/169). The live birth and implantation rates were 47.3% (80/169) and 44.4% (100/225), respectively. Double embryos transfer showed higher clinical pregnancy and live birth rates compared with single embryo transfer, but the implantation rates were similar (44.2% vs. 44.6%, P > 0.05). The euploid rate for reciprocal translocations (16.1%) was significantly lower than that for Robertsonian translocations (28.0%, P < 0.01) and inversions (28.0%, P < 0.01). However, higher percentages of embryos with de novo abnormalities were observed with Robertsonian translocations (23.3%, P < 0.01) and inversions (30.5%, P < 0.01) than with reciprocal translocations (11.6%). We demonstrated that NGS for PGT on day-3 embryos is an effective clinical application, particularly for patients with a diminished ovarian reserve and limited embryos.

Highlights

Preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are effective approaches for selecting euploid embryos for transfer to lower the risks of implantation failure and miscarriage in the clinical treatment of in vitro fertilization (IVF)
The majority of PGT is performed with a strategy of genetic testing with comprehensive chromosome screening (CCS) methods to evaluate the genetic abnormalities of all 23 chromosome pairs and trophectoderm (TE) biopsy at the blastocyst stage (Coonen et al, 2020)
Single embryo transfer was performed in 113 cycles, and two embryos were transferred in 56 cycles, resulting in a clinical pregnancy rate of 49.1% (83/169)

Summary

Introduction

Preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are effective approaches for selecting euploid embryos for transfer to lower the risks of implantation failure and miscarriage in the clinical treatment of in vitro fertilization (IVF) (Munné et al, 2006; Hodes-Wertz et al, 2012; Rapid NGS-PGT Strategy for BlastomereForman et al, 2013; Christodoulou et al, 2017). Several randomized controlled trials verified that FISH cannot truly improve IVF outcomes (Mastenbroek et al, 2011; Rubio et al, 2013) since de novo abnormalities may be ignored if they occur in any undetected chromosomes (Ye et al, 2011). Another aspect related to unfavorable PGT results is that cleavage-stage embryos have a higher chance of being mosaic for aneuploidies (Vanneste et al, 2009; Mertzanidou et al, 2013); the PGT results may not be representative of the genuine genetic status of the embryos. There is still a lack of large-scale clinical data to fully verify these outcomes

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