Which set of embryo variables is most predictive for live birth? A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos.
STUDY QUESTION
Which embryo score variables are most powerful for predicting live birth after single embryo transfer (SET) at the early cleavage stage?


SUMMARY ANSWER
This large prospective study of visual embryo scoring variables shows that blastomere number (BL), the proportion of mononucleated blastomeres (NU) and the degree of fragmentation (FR) have independent prognostic power to predict live birth.


WHAT IS KNOWN ALREADY
Other studies suggest prognostic power, at least univariately and for implantation potential, for all five variables. A previous study from the same centre on double embryo transfers with implantation as the end-point resulted in the integrated morphology cleavage (IMC) score, which incorporates BL, NU and EQ.


STUDY DESIGN, SIZE AND DURATION
A prospective cohort study of IVF/ICSI SET on Day 2 (n = 6252) during a 6-year period (2006-2012). The five variables (BL NU, FR, EQ and symmetry of cleavage (SY)) were scored in 3- to 5-step scales and subsequently related to clinical pregnancy and LBR.


PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 4304 women undergoing IVF/ICSI in a university-affiliated private fertility clinic were included. Generalized estimating equation models evaluated live birth (yes/no) as primary outcome using the embryo variables as predictors. Odds ratios with 95% confidence intervals and P-values were presented for each predictor. The C statistic (i.e. area under receiver operating characteristic curve) was calculated for each model. Model calibration was assessed with the Hosmer-Lemeshow test. A shrinkage method was applied to remove bias in c statistics due to over-fitting.


MAIN RESULTS AND THE ROLE OF CHANCE
LBR was 27.1% (1693/6252). BL, NU, FR and EQ were univariately highly significantly associated with LBR. In a multivariate model, BL, NU and FR were independently significant, with c statistic 0.579 (age-adjusted c statistic 0.637). EQ did not retain significance in the multivariate model. Prediction model calibration was good for both pregnancy and live birth. We present a ranking tree with combinations of values of the BL, NU and FR embryo variables for optimal selection of the embryo/s to transfer, providing a revised IMC score. The five embryo variables had similar effects over all age groups.


LIMITATIONS, REASONS FOR CAUTION
Limitations of the present study are those inherent for real-time visual scoring, including risks of inter-observer variation and the hazards of fixed time-point scoring procedures in a dynamic process. The study is restricted to Day-2 transfers.


WIDER IMPLICATIONS OF THE FINDINGS
To our knowledge this is the largest prospective, SET study performed with the explicit aim of constructing an evidence-based embryo score for the ranking and selection of early cleavage stage embryos. In line with previous research, our data suggest that the symmetry of cleavage variable may be omitted when scoring embryos in the early cleavage stage. We suggest that, following validation in other populations, the revised IMC score may be used when international standards for embryo scoring are discussed.


STUDY FUNDING/COMPETING INTEREST
Carl von Linné Clinic, Uppsala and the Department of Women's and Children's Health and the Family Planning Fund in Uppsala, Uppsala University, Uppsala, Sweden financed this study. There are no competing interests to declare.
['Rhenman|A|A|', 'Berglund|L|L|', 'Brodin|T|T|', 'Olovsson|M|M|', 'Milton|K|K|', 'Hadziosmanovic|N|N|', 'Holte|J|J|']
D001757:Blastomeres D004624:Embryo Transfer D047108:Embryonic Development D005260:Female D005307:Fertilization in Vitro D006801:Humans D050498:Live Birth D016015:Logistic Models D015999:Multivariate Analysis D016017:Odds Ratio D011247:Pregnancy D011446:Prospective Studies
prediction embryo transfer embryo score implantation potential embryo morphology