Blastocyst formation rate can be predicted by an automatic system independently of the number of oocytes retrieved and the morphology of the embryos on day 3

Abstract

OBJECTIVE: To correlate the different categories provided by an automatic diagnostic test (Eeva) with the blastocyst formation rate and to assess possible confounding factors associated to such correlation. DESIGN: Observational, retrospective, multi-center cohort study. MATERIALS AND METHODS: A total of 3002 embryos from patients undergoing egg donation cycles were imaged with the Eeva System. The Eeva system provides dark-field image and automatic cell-division tracking without the intervention of the embryologist. On Day 3 of development, the system utilizes information on specific division times (defined as P2 and P3) to automatically classify embryos into HIGH, MEDIUM, and LOW according to their probability of becoming a blastocyst. In addition, embryologists classified the same embryos according to standard morphological criteria defined by the Spanish Association of Embryologists (ASEBIR).RESULTS: There was a straight correlation between the Eeva categories and the blastocyst formation rates. More specifically: blastocyst formation rate was 75.20% for embryos categorized as HIGH, 58.50% for embryos categorized as MEDIUM and 51.50% for embryos categorized as LOW. In addition, optimal blastocysts formation rate was 35.7% for HIGH, 27.2% for MEDIUM and 17.3% for LOW. A further logistic regression analysis was developed taking into account possible confounding factors thought as having a potential effect on clinical pregnancy including: number of oocytes retrieved and embryo morphology according to ASEBIR. Results of the model indicate that an embryo labeled as HIGH develops to blastocyst 2.014 times more than an embryo labeled as LOW (Table 1). Analysis of area under the curve revealed values of 0,728 CI95% (0.707-0.749) for blastocyst prediction according to Eeva and of 0.717 CI95% (0.703-0.732) according to ASEBIR classification. When Eeva and ASEBIR were combined the AUC value was of 0.788 (IC95% 0.768-0.808).CONCLUSIONS: This study demonstrates in a large data set that there is a direct link between the Eeva categories and the blastocyst formation rate and quality. Embryos HIGH have a higher probability of becoming a blastocyst than embryos LOW and this is independent of the presented confounding factors. Both classification methods are independent from each other and have similar predictive value. However, when both are combined, the predictive value increases.

Does conventional morphological evaluation still play a role in predicting blastocyst formation?

“…Since the early days of blastocyst culture, many previous studies have investigated the association between conventional morphology assessment and the rates of blastocyst formation [ 28 – 30 ]. However, only a few studies quantitatively evaluated the predictive power [ 16 , 18 ]. Basile et al evaluated the predictive power for blastocyst formation of morphological criteria defined by the Spanish Association of Embryologists (ASEBIR), showing an AUC of 0.717 (CI95%: 0.703–0.732), which is close to the AUC derived from Eeva time lapse system in the same population.…”

“…However, poor-looking day 3 embryos rejected by conventional embryo morphological assessment may also have a chance to develop into blastocysts and it is believed that the associations between morphology and blastocyst formation do not necessarily correlate with blastocyst viability. Nevertheless, data from studies predicting blastocyst formation using conventional morphological assessment and time-lapse microscopy in the same population [ 16 , 18 ], showed that AUCs of conventional embryo morphological assessment for blastocyst formation were close to that of time-lapse microscopy. Especially, in the work of Petersen et al, which compared six time-lapse algorithms in the same study, only two algorithm surpassed an algorithm based on conventional Alpha/ESHRE consensus assessment in terms of predictive power [ 16 ].…”

Does Conventional Morphological Evaluation Still Play a Role in Predicting Blastocyst Formation?

“…Since the early days of blastocyst culture, many previous studies have investigated the association between conventional morphology assessment and the rates of blastocyst formation [28][29][30]. However, only a few studies quantitatively evaluated the predictive power [16,18]. Basile et al evaluated the predictive power for blastocyst formation of morphological criteria de ned by the Spanish Association of Embryologists (ASEBIR), showing an AUC of 0.717 (CI95%: 0.703-0.732), which is close to the AUC derived from Eeva time lapse system in the same population.…”

“…In recent years,'OMICS' technologies [6], and algorithms created through the use of time-lapse microscopy [7] were used to predict the destiny of day 3 embryos during in vitro culture. While 'OMICS' technologies, such as proteomics and metabolomics for non-invasive embryo developmental capacity assessment, are yet to be recommended for routine use [1], time-lapse microscopy has been introduced as a routine clinical practice and showed a capacity to predict the blastocyst formation with AUCs ranging from 0.6-0.8 across different studies [8][9][10][11][12][13][14][15][16][17][18][19]. Unfortunately, novel technologies inevitably require additional cost or equipment and the expense of technologies may limit their widespread use.…”