Stage and morphology of the competent blastocyst are associated with pregnancy and birth outcomes; a multicenter cohort study

Do stage and morphology of the competent blastocyst associate with initial hCG rise, gestational age, preterm birth, child birth weight, length, and child sex?Higher stage, TE- and ICM-scores associated with higher hCG-rise; ICM- and TE-scores associated with length at birth, and higher stage and TE-score associated with boys.Many studies have focused on the developmental stage and morphology of the blastocysts in order to find biomarkers of competence to improve the efficacy of assisted reproduction technology treatment. In contrast, the associations between blastocyst assessment score parameters (individually or by combined score) and perinatal outcome have only been reported in few and smaller single center studies, and conflicting results have been presented. In the present study, we focused on the in vitro cultured blastocyst leading to a live birth and how the stage and morphology of these competent blastocysts relate to implantation and birth outcomes.Multicenter historical cohort study based on exposure (blastocyst stage (1-6) and morphology (trophectoderm (TE) and inner cell mass (ICM): A,B,C)) and outcome data (serum human chorionic gonadotrophin (hCG), gestational age, preterm birth, child weight, length, and sex) from women undergoing single blastocyst transfer resulting in singleton pregnancy and birth. Data from 16 private and university-based facilities for clinical services and research from 2014 to 2018 was included.7246 women, who underwent ovarian stimulation or Frozen-thawed-Embryo-Transfer with single blastocyst transfer resulting in singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with live birth being included. Initial serum hCG value (IU/L) (11 days after transfer), gestational age (days), preterm birth (\ child weight (grams), length (cm) and sex. The analyses were adjusted for female age, BMI, smoking, center, diagnosis, parity, gestational age and sex.Higher mean initial hCG was consistently positively associated with higher developmental stage (p \lt; 0.001), TE (p \lt; 0.001) and ICM score (p = 0.02); for stage 6, TE (A) and ICM (A): 508.4, 436.5 and 428.5 IU/L, respectively. No differences between blastocyst morphology (stage, TE, ICM), gestational age (mean 276.6 days), preterm birth (8.3\ and birth weight (mean 3461.7 gram) were statistically significant. While stage showed no association with length at birth (mean 51.6 cm), length at birth between blastocysts with a TE score C and a TE score A were statistically significant (mean difference 0.5 cm (0.07;0.83)) as was the length at birth between blastocysts with an ICM score B and C compared to score A, mean differences respectively 0.2 cm (0.02;0.31) and 0.5 cm (0.03;0.87). Stage and TE, but not ICM were associated with the sex of the child. Blastocysts transferred with stage score 5 compared to blastocysts transferred with score 3 had a 33\OR 1.33 (1.08;1.64)). Further, TE score B blastocysts compared to TE score A blastocysts had a 28\OR 0.72 (0.62;0.82)).The assessment scores of the blastocystś stage and morphology were based on subjective evaluation, and information bias may have influenced the results. By adjusting for center, we took the potential variation in scoring between clinics into considerations.Stage and morphology of the competent blastocyst was associated with initial hCG rise suggesting an effect on implantation, which may be used in routine, everyday information to women and couples on the day of blastocyst transfer.j.nr.: VD-2018-282