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

Abstract

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 (β): −127.97 g, 95% CI: −234.46 to −21.47, P = 0.019) and blastocysts with TE grade C (β: −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 (β: −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. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by National Key R&D Program of China (2018YFC1003000), National Natural Science Foundation of China (81771533 to Y.P.K. and 31200825 to L.S.) and Innovative Research Team of High-level Local Universities in Shanghai (SSMU-ZLCX20180401), Shanghai Sailing Program(21YF1423200) and the Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong university School of Medicine (JYZZ117). The authors declare no conflict of interest in this present study. TRIAL REGISTRATION NUMBER N/A

Blastocyst quality and perinatal outcomes of frozen-thawed single blastocyst transfer cycles

“…Therefore, we performed this retrospective cohort study that restricted maternal age and BMI to specific ranges ( 12 , 20 ) in a single tertiary academic medical center to investigate further the correlation between blastocyst quality, each morphologic characteristic, and a range of perinatal outcomes, including the incidence of PTD, the likelihood of a male neonate, birthweight and birth defects.…”

Correlation between an annotation-free embryo scoring system based on deep learning and live birth/neonatal outcomes after single vitrified-warmed blastocyst transfer: a single-centre, large-cohort retrospective study

“…iDAScore did not correlate with basic neonatal outcomes such as malformation, birth weight, gestational age, and male sex rates. Previous studies suggested that blastocyst morphology, including the inner cell mass and trophectoderm, and morphokinetics correlate with sex [ 21 , 41 ], birthweight [ 42 , 43 ], and congenital anomalies [ 44 ]. However, the correlation between blastocyst quality and neonatal outcomes remains controversial.…”

Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen–thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology

“…BW differences have been shown before to be related to variations in growth trajectories emerging as early as the first trimester and continuing with greater EFW in the midtrimester 25 . Previous studies also showed the impact of both maternal cardiovascular profile and embryo quality on embryo/fetal growth, which we believe would be promising research areas 26,27 .…”

“…BW differences have been shown before to be related to variations in growth trajectories emerging as early as the first trimester and continuing with greater EFW in the midtrimester 25 . Previous studies also showed the impact of both maternal cardiovascular profile and embryo quality on embryo/fetal growth, which we believe would be promising research areas 26,27 . The choice of using the Hadlock formula 17 for calculation of EFW in our model was supported by the results of a previous study 28 , comparing 70 models of EFW extracted from 45 publications, in which it was deemed the most accurate model with the lowest Euclidean distance and highest proportion of absolute mean error ≤ 10%.…”