Time-lapse algorithms and morphological selection of day-5 embryos for transfer: a preclinical validation study

Abstract

Objective: To determine the agreement between published time-lapse algorithms in selecting the best day-5 embryo for transfer, as well as the agreement between these algorithms and embryologists.

Design: Prospective study.

Setting: Private in vitro fertilization center.

Patient(s): Four hundred and twenty-eight embryos from 100 cycles cultured in the EmbryoScope.

Intervention(s): None.

Main outcome measure(s): Interalgorithm agreement as assessed by the Fleiss kappa coefficient.

Result(s): Of seven published algorithms analyzed in this study, only one of the 18 possible pairs showed very good agreement (κ = 0.867); one pair showed good agreement (κ = 0.725), four pairs showed fair agreement (κ = 0.226-0.334), and the remaining 12 pairs showed poor agreement (κ = 0.008-0.149). Even in the best-case scenario, the majority of algorithms showed poor to moderate kappa scores (κ = 0.337-0.722) for the assessment of agreement between the embryo(s) selected as "best" by the algorithms and the embryo that was chosen by the majority (>5) of embryologists, as well as with the embryo that was actually selected in the laboratory on the day of transfer (κ = 0.315-0.802).

Conclusion(s): The results of this study raise concerns as to whether the tested algorithms are applicable in different clinical settings, emphasizing the need for proper external validation before clinical use.

Keywords: Agreement; algorithm; embryologist; morphokinetics; time-lapse.