Nucleation status of Day 2 pre-implantation embryos, acquired by time-lapse imaging during IVF, is associated with live birth

Abstract

The primary purpose of this time-lapse data analysis was to identify the association between the nucleation status of a Day 2 preimplantation embryo and live births following in vitro fertilization (IVF). The retrospective data analysis was based on 2769 transferred embryos from 1966 treatment cycles and utilised only Known Implantation Data (KID) for live births. Nucleation errors (NE) such as micronucleation, binucleation, multinucleation and minor error groups, were annotated in the time-lapse images which were taken every 15 minutes for a minimum of 44 hours post insemination. Further, factors that may impact NE and the relationship of early morphological attributes and morphokinetic variables with NE occurrence were explored. The frequency of NE among the transferred embryos was 23.8%. The reversibility of NE evidenced by their presence at the two-cell stage, but absence at the four-cell stage was 89.6%. Embryos exhibiting nucleation errors at the two-cell stage had significantly lower live birth rates compared to embryos with no nucleation errors, constituting a significant predictor. A Generalized Additive Mixed Model was used to control for confounders and for controlling clustering effects from dual embryo transfers. Increased incidences of NE were observed with increasing age, with delayed occurrence of cell divisions and in oocytes inseminated with surgically retrieved spermatozoa. NE assessment and their impact on live birth provides valuable markers for early preimplantation embryo selection. In addition, the high incidence of reversibility of NE and their possible impact on live birth suggest that incorporating two-cell nuclear status annotations in embryo selection, alongside morphology and morphokinetics, is of value.

Shape of the first mitotic spindles impacts nucleation in human embryos

“…4a). This modi cation process is supported by other studies that reported 73-89% of multiple nuclei at the 2-cell stage became mononuclei at the 4-cell stage by using time-lapse monitoring 9,41 . In our study, there was also a severe reduction in the frequency of the multinuclear type between the 2-and 4-cell stages (Fig.…”

“…A live-cell imaging study using time-lapse confocal microscopy showed that the frequency of multinucleation at the 2-cell stage was 78% in human embryos 8 . Embryos with multiple nuclei at the 2-cell stage have lower blastocyst developmental rate and live birth rates than those with normal nuclei 9 ; thus, nuclear errors are used as a deselection biomarker for embryo transfer 8, [10][11][12][13] .…”

Shape of the first mitotic spindles impacts multinucleation in human embryos

“…A live-cell imaging study using time-lapse confocal microscopy showed that the frequency of multinucleation at the 2-cell stage was 78% in human embryos 9 . Although multinucleated embryos transferring could lead to birth of babies, embryos with multiple nuclei at the 2-cell stage have lower blastocyst developmental rate and live birth rates than those with normal nuclei 10 ; thus, nuclear errors can be used as a deselection biomarker for embryo transfer 9,[11][12][13][14] .…”