Is there an advantage in scoring early embryos on more than one day?

Abstract

Background: This study was undertaken to determine what characteristics should be recorded on which days to build a predictive model for selection of Day 3 embryos.

Methods: Embryos failing to form a clinical sac or that formed a viable fetus (to > or =12 weeks), and transferred singly (n = 269) or in pairs (n = 1326) were scored for early cleavage and pronuclear status on Day 1, and cell number, fragmentation, and symmetry on Days 2 and 3, with number of nuclei per blastomere also recorded on Day 2. Seven candidate models were identified using a priori clinical knowledge and univariate analyses. Each model was fit on a training-set and evaluated on a test-set with resampling, with discrimination assessed using the area under the ROC curve (AUC) and calibration assessed using the Hosmer-Lemeshow statistics.

Results: Models built using Day 1, 2 or 3 scores independently on the 30 resampled data sets showed that Day 1 evaluations provided the poorest predictive value (median AUC = 0.683 versus 0.729 and 0.725, for Day 2 and 3). Combining information from Day 1, 2 and 3 marginally improved discrimination (median AUC = 0.737). Using the final Day 3 model fitted on the whole dataset, the median AUC was 0.732 (95% CI, 0.700-0.764), and 68.6% of embryos would be correctly classified with a cutoff probability equal to 0.3.

Conclusions: Day 2 or Day 3 evaluations alone are sufficient for morphological selection of cleavage stage embryos. The derived regression coefficients can be used prospectively in an algorithm to rank embryos for selection.

Figure 1

8-Cell human embryos on Day 3 of culture with varying degrees of fragmentation and asymmetry, as reflected by the numerical scores on the images corresponding to the cell number, fragmentation score and asymmetry scores, respectively, as defined in Table I. The arrows in (D) point to examples of fragmentation; bar = 25 µm.

Figure 2

The probability of achieving a viable pregnancy to at least 12 weeks of gestation according to patient age.

Figure 3

The AUCs and the goodness of fit P-values fit for the seven putative models. (A) AUCs of the training set. (B) AUCs of the test set. (C) P-values of the training set. (D) P-values of the test set. A logistic regression model is considered to be acceptable if the P-value is greater than the P = 0.05 threshold (horizontal dashed lines in B and D).

Figure 4

Calibration plot of the observed proportion of embryos developing into fetuses at 12 weeks versus the prediction probability calculated using the whole dataset and the final Day 3 model. Prediction probabilities were grouped into six equal fixed sets.

Figure 5

Distributions of probabilities associated with developing a fetus or not developing a fetus.