Synergistic effect of transfer of blastocyst and embryo vitrification on birth weight: a retrospective cohort study

Does the synergistic interaction between blastocyst-stage embryo transfer and vitrification in assisted reproductive technology increase the risk of adverse neonatal outcomes, specifically elevated birth weight z-scores and a higher incidence of clinically concerning large for gestational age (LGA) or macrosomia in offspring?

In this cohort study, multivariable regression analyses were conducted to examine the association between embryo transfer strategies (fresh versus frozen; cleavage versus blastocyst stage) and the birth weight z-score of singletons, as well as the incidence of LGA and macrosomia among 42,190 singleton live births from the Center for Reproductive Medicine at Peking University Third Hospital between 2012 and 2022.

Compared with cleavage-stage embryo transfer, newborns resulting from blastocyst-stage transfers had significantly higher birth weight z-scores (P < 0.001), LGA (P < 0.001) and macrosomia (P = 0.013). Frozen embryo transfer (only vitrified-warmed) was associated with increased birth weight z-scores (P = 0.001), LGA (P = 0.004) and macrosomia (P = 0.007), compared with fresh embryo transfers. A significant synergetic effect of blastocyst transfer and vitrified-warmed transfer concerning the LGA was found (relative excess risks due to interaction = 0.24; 95% CI 0.06 to 0.42; P = 0.022 for multiplicative interaction term) on the additive and multiplicative scales.

Blastocyst stage and embryo vitrification were associated with elevated birth weight z-scores and an increased likelihood of LGA, with evidence of a synergistic effect. These findings support the importance of personalized clinical decision-making in the use of vitrified-warmed cleavage-stage transfer, particularly in the absence of clear medical indications.