Abstract STUDY QUESTION Does the type of embryo culture medium affect the birthweight of newborns conceived by ART? SUMMARY ANSWER After fresh embryo transfers, singleton newborns in the G5 and HTF groups exhibited higher birthweight z-scores and increased risks of being large for gestational age (LGA) compared to those in the Cook group. WHAT IS KNOWN ALREADY Current studies have not yet determined whether embryo culture medium affects birthweight, and if such an effect does exist, the significance of embryo culture medium among all the influencing factors is not yet clear. STUDY DESIGN, SIZE, DURATION A retrospective cohort study including 23,403 fresh ET cycles between 1st January 2010 and 31st December 2022 at the reproductive medical center of a university—affiliated hospital was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS We performed a retrospective cohort study including 23,403 fresh ET cycles. Four embryo culture media were analyzed: Cook, G5-PLUS, G5 and HTF. Multiple linear regression analysis was used to evaluate potential associations between embryo culture medium and birthweight z-score. Logistic regression analysis was used to evaluate potential associations between embryo culture medium and the risk of LGA and macrosomia. Random forest models were constructed to conduct significance analysis of all factors that may affect birthweight z-score. MAIN RESULTS AND THE ROLE OF CHANCE The cohort comprised 4453, 8460, 7463 and 3027 singletons in the Cook, G5-PLUS, G5 and HTF groups, respectively. Compared to the Cook group, newborns in the G5 and HTF groups had a higher birthweight z-scores (increased by 0.069 units, P < 0.001, and 0.073 units, P = 0.002, respectively) and a higher risks of LGA (OR: 1.25, 95% CI: 1.12-1.39, P < 0.001; OR: 1.20, 95% CI: 1.05-1.37, P = 0.009, respectively), while newborns in the G5 group also had a higher risk of macrosomia (OR: 1.21, 95% CI: 1.06-1.39, P = 0.006). Of the main factors influencing birthweight, the embryo culture medium had a moderate significance. LIMITATIONS, REASONS FOR CAUTION Due to commercial and regulatory reasons, various culture media were used for different periods, thus resulting in the different number of cases for the four culture media groups. WIDER IMPLICATIONS OF THE FINDINGS Our analysis revealed that the type of embryo culture medium directly affected birthweight z-scores and the risk of LGA and macrosomia in newborns conceived by ART. Consequently, the selection of embryo culture medium shoud be made cautiously. In addition, new embryo culture media require comprehensive safety verification before being marketed. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by National Key Research and Development Program of China [2023YFC2705604] and the National Natural Science Foundation of China [82071721, 82371706 and 82288102]. All authors have no conflicts of interest to report. TRIAL REGISTRATION NUMBER N/A.
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