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Prospective study of automated versus manual annotation of early time-lapse markers in the human preimplantation embryo

Kaser, D J, Farland, L V, Missmer, S A, Racowsky, C,
Hum Reprod. Aug 1. 2017 doi: 10.1093/humrep/dex229

Abstract

STUDY QUESTION: How does automated time-lapse annotation (Eeva) compare to manual annotation of the same video images performed by embryologists certified in measuring durations of the 2-cell (P2; time to the 3-cell minus time to the 2-cell, or t3-t2) and 3-cell (P3; time to 4-cell minus time to the 3-cell, or t4-t3) stages? SUMMARY ANSWER: Manual annotation was superior to the automated annotation provided by Eeva version 2.2, because manual annotation assigned a rating to a higher proportion of embryos and yielded a greater sensitivity for blastocyst prediction than automated annotation. WHAT IS KNOWN ALREADY: While use of the Eeva test has been shown to improve an embryologist's ability to predict blastocyst formation compared to Day 3 morphology alone, the accuracy of the automated image analysis employed by the Eeva system has never been compared to manual annotation of the same time-lapse markers by a trained embryologist. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study of embryos (n = 1477) cultured in the Eeva system (n = 8 microscopes) at our institution from August 2014 to February 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos were assigned a blastocyst prediction rating of High (H), Medium (M), Low (L), or Not Rated (NR) by Eeva version 2.2 according to P2 and P3. An embryologist from a team of 10, then manually annotated each embryo and if the automated and manual ratings differed, a second embryologist independently annotated the embryo. If both embryologists disagreed with the automated Eeva rating, then the rating was classified as discordant. If the second embryologist agreed with the automated Eeva score, the rating was not considered discordant. Spearman's correlation (rho), weighted kappa statistics and the intra-class correlation (ICC) coefficients with 95% confidence intervals (CI) between Eeva and manual annotation were calculated, as were the proportions of discordant embryos, and the sensitivity, specificity, positive predictive value (PPV) and NPV of each method for blastocyst prediction. MAIN RESULTS AND THE ROLE OF CHANCE: The distribution of H, M and L ratings differed by annotation method (P < 0.0001). The correlation between Eeva and manual annotation was higher for P2 (rho = 0.75; ICC = 0.82; 95% CI 0.82-0.83) than for P3 (rho = 0.39; ICC = 0.20; 95% CI 0.16-0.26). Eeva was more likely than an embryologist to rate an embryo as NR (11.1% vs. 3.0%, P < 0.0001). Discordance occurred in 30.0% (443/1477) of all embryos and was not associated with factors such as Day 3 cell number, fragmentation, symmetry or presence of abnormal cleavage. Rather, discordance was associated with direct cleavage (P2

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IVIRMA ) Global Research Alliance is one of the four pillars of IVIRMA Global, the world’s largest company exclusively devoted to human Assisted Reproduction Technology.

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