A comparison of morphokinetic models and morphological selection for prioritizing euploid embryos: a multicentre cohort study

Abstract

Study question: Are morphokinetic models better at prioritizing a euploid embryo for transfer over morphological selection by an embryologist?

Summary answer: Morphokinetic algorithms lead to an improved prioritization of euploid embryos when compared to embryologist selection.

What is known already: PREFER (predicting euploidy for embryos in reproductive medicine) is a previously published morphokinetic model associated with live birth and miscarriage. The second model uses live birth as the target outcome (LB model).

Study design, size, duration: Data for this cohort study were obtained from 1958 biopsied blastocysts at nine IVF clinics across the UK from January 2021 to December 2022.

Participants/materials, setting, methods: The ability of the PREFER and LB models to prioritize a euploid embryo was compared against arbitrary selection and the prediction of four embryologists using the timelapse video, blinded to the morphokinetic time stamp. The comparisons were made using calculated percentages and normalized discounted cumulative gain (NDCG), whereby an NDCG score of 1 would equate to all euploid embryos being ranked first. In arbitrary selection, the ploidy status was randomly assigned within each cycle and the NDGC calculated, and this was then repeated 100 times and the mean obtained.

Main results and the role of chance: Arbitrary embryo selection would rank a euploid embryo first 37% of the time, embryologist selection 39%, and the LB and PREFER ploidy morphokinetic models 46% and 47% of the time, respectively. The AUC for LB and PREFER model was 0.62 and 0.63, respectively. Morphological selection did not significantly improve the performance of both morphokinetic models when used in combination. There was a significant difference between the NDGC metric of the PREFER model versus embryologist selection at 0.96 and 0.87, respectively (t = 14.1, P < 0.001). Similarly, there was a significant difference between the LB model and embryologist selection with an NDGC metric of 0.95 and 0.87, respectively (t = 12.0, P < 0.001). All four embryologists ranked embryos similarly, with an intraclass coefficient of 0.91 (95% CI 0.82-0.95, P < 0.001).

Limitations, reasons for caution: Aside from the retrospective study design, limitations include allowing the embryologist to watch the time lapse video, potentially providing more information than a truly static morphological assessment. Furthermore, the embryologists at the participating centres were familiar with the significant variables in time lapse, which could bias the results.

Wider implications of the findings: The present study shows that the use of morphokinetic models, namely PREFER and LB, translates into improved euploid embryo selection.

Study funding/competing interest(s): This study received no specific grant funding from any funding agency in the public, commercial or not-for-profit sectors. Dr Alison Campbell is minor share holder of Care Fertility. All other authors have no conflicts of interest to declare. Time lapse is a technology for which patients are charged extra at participating centres.

Trial registration number: N/A.

Keywords: embryo ranking; embryo selection; morphokinetics; non-invasive embryo assessment; ploidy; time lapse.