There was no specific funding for the preparation of these proposed guidelines. Meetings were held opportunistically during scientific conferences and using online communication tools. H.N.C. is a scientific consultant for ESCO, supplier of Miri TL. I.E.A. is a minor shareholder in Unisense Fertilitech, supplier of the EmbryoScope. Full disclosures of all participants are presented herein. The remaining authors have no conflict of interest.

The goal of embryo selection models is to select embryos with the highest reproductive potential, whilst minimizing the rejection of viable embryos. Ultimately, any embryo selection model must be tested on clinical outcome. We therefore retrospectively tested a published blastocyst prediction model on a large combined set of transferred embryos with known clinical outcome. The model was somewhat effective in that we found a relative increase of 30% for implantation in the model-selected group of embryos. There was, however, a concomitant large rejection of embryos from our test cohort, which actually resulted in pregnancy. This hypothetical experiment highlights the limitations of predicting blastulation only. Crucially, it illustrates that both sensitivity and specificity are important parameters when developing embryo selection models for prospective clinical use.

The purpose of this retrospective time-lapse data analysis from transferred preimplantation human embryos was to identify early morphokinetic cleavage variables that are related to implantation and live birth following in vitro fertilization (IVF). All embryos were monitored from fertilization check until embryo transfer for a minimum of 44 hours. The study was designed to assess the association between day 2 embryo morphokinetic variables with implantation and live birth based on Known Implantation Data (KID). The kinetic variables were subjected to quartile-based analysis. The predictive ability for implantation and live birth was studied using receiver operator characteristic (ROC) curves. Three morphokinetic variables, time to 2-cells (t2), duration of second cell cycle (cc2) below one threshold and cc2 above another threshold had the highest predictive value with regards to implantation and live birth following IVF treatment. The predictive pre-transfer information has little divergence between fetal heartbeat and live birth data and therefore, at least for early morphokinetic variables up to the four-cell stage (t4), conclusions and models based on fetal heartbeat data can be expected to be valid for live birth datasets as well. The three above mentioned variables (t2, cc2 below one threshold and cc2 above another threshold) may supplement morphological evaluation in embryo selection and thereby improve the outcome of in vitro fertilization treatments.

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.

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