Hum. Reprod. Advance Access originally published online on June 2, 2009
Human Reproduction 2009 24(9):2104-2113; doi:10.1093/humrep/dep198
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Is there an advantage in scoring early embryos on more than one day?
1 Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, ASB 1+3, Rm 082, Boston, MA 02115, USA 2 Decision Systems Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA 3 Division of Biomedical Informatics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA 4 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
5 Correspondence address. Tel: +1-617-732-5455; Fax: +1-617-975-0825; E-mail: cracowsky{at}partners.org
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 
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.
Key words: embryo morphology/embryo score/evaluation day/implantation potential/prediction
Submitted on November 25, 2008; resubmitted on April 30, 2009; accepted on May 6, 2009.