Advanced trophectoderm quality increases the risk of a large for gestational age baby in single frozen-thawed blastocyst transfer cycles

STUDY QUESTION: Does trophectoderm (TE) quality affect birthweight after single frozen-thawed blastocyst transfer? SUMMARY ANSWER: Transfer of single blastocyst with advanced TE quality was associated with higher birthweight and increased risk of a large for gestational age (LGA) baby. WHAT IS KNOWN ALREADY: Transfer of blastocysts with advanced TE quality results in higher ongoing pregnancy rates and a lower miscarriage risk. However, data on the relationship between TE quality and birthweight are still lacking. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study at a tertiary-care academic medical center included 1548 singleton babies born from single frozen-thawed blastocyst transfer from January 2011 to June 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Babies were grouped into four groups according to embryo expansion (Stages 3, 4, 5 and 6), three groups according to inner cell mass (ICM) quality (A, B and C), and three groups according to TE quality (A, B and C). Main outcomes included absolute birthweight, Z-scores adjusted for gestational age and gender, and adverse neonatal outcomes. Multivariable linear and logistic regression analyses were performed to investigate the association of neonatal outcomes with expansion stage, ICM quality and TE quality. MAIN RESULTS AND THE ROLE OF CHANCE: As TE quality decreased, birthweight (3468.10 +/- 471.52, 3357.69 +/- 522.06, and 3288.79 +/- 501.90 for A, B and C, respectively, P = 0.002), Z-scores (0.59 +/- 1.07, 0.42 +/- 1.04, and 0.27 +/- 1.06 for A, B and C, respectively, P = 0.002) and incidence of LGA (28.9%, 19.7% and 17.4% for A, B and C, respectively, P = 0.027) decreased correspondingly. After adjusting for confounders, compared with the Grade A group, blastocysts with TE Grade B (standardized coefficients (b): -127.97 g, 95% CI: -234.46 to -21.47, P = 0.019) and blastocysts with TE grade C (beta: -200.27 g, 95% CI: -320.69 to -79.86, P = 0.001) resulted in offspring with lower birthweight. Blastocysts with TE grade C brought babies with lower Z-scores than TE Grade A (beta: -0.35, 95% CI: -0.59 to -0.10, P = 0.005). Also, embryos with TE Grade B (adjusted odds ratio (aOR):0.91, 95% CI: 0.84 to 0.99, P = 0.033) and embryos with TE Grade C (aOR : 0.89, 95% CI: 0.81 to 0.98, P = 0.016) had lower chance of leading to a LGA baby than those with TE Grade A. No association between neonatal outcomes with embryo expansion stage and ICM was observed (all P> 0.05). LIMITATIONS, REASONS FOR CAUTION: The retrospective design, lack of controlling for several unknown confounders, and inter-observer variation limited this study. WIDER IMPLICATIONS OF THE FINDINGS: The study extends our knowledge of the down-stream effect of TE quality on newborn birthweight and the risk of LGA.