Clinical use of monopronucleated zygotes following blastocyst culture and preimplantation genetic screening, including verification of biparental chromosome inheritance

Abstract

In assisted reproduction, embryos derived from monopronucleated (1PN) zygotes are considered abnormal and unsuitable for clinical use. Outcomes of 1PN-derived embryos designated for preimplantation genetic screening (PGS) were analysed. These embryos, especially from intracytoplasmic sperm injection (ICSI), were found to have a low developmental potential; 1PN and 2PN day 5 blastocyst development for IVF was 14.8% versus 36.4% (P < 0.0001), and for ICSI, 6.6% versus 34.0% (P < 0.0001), respectively. With the use of comparative genomic hybridization or next-generation sequencing, PGS was successfully carried out for 74 IVF and 32 ICSI 1PN-derived blastocysts, revealing adjusted abnormality rates of 39.7% and 40.6%, respectively. Additionally, 24 female 1PN-derived blastocysts underwent testing for biparental inheritance, with one ICSI-derived embryo demonstrating paternal only contribution, thus presenting a risk for complete hydatidiform molar pregnancy. Single embryo transfer of 20 IVF and six ICSI 1PN-derived blastocysts with no detectable abnormalities resulted in nine clinical pregnancies. Six have been delivered and three are ongoing, with no anomalies reported to date. The limitation of this study is that pronuclear status was determined through one static observation. The results suggest that 1PN-derived embryos, in which euploidy and biparental inheritance have been established, can provide a source of clinically useful embryos.

Keywords: 1PN; PGS; biparental inheritance; blastocyst; molar pregnancy; preimplantation genetic screening.