Post-thaw embryo culture and the risk of large-for-gestational-age offspring: a retrospective cohort study

Frozen embryo transfer (FET) is widely used due to its safety and effectiveness. However, it has been associated with an increased risk of large for gestational age (LGA) infants. Proposed mechanisms include effects of embryo thawing and post-thaw culture duration on developmental programming. Current evidence remains limited regarding the impact of post-thaw culture on birthweight or LGA risk. A retrospective cohort study conducted in a university affiliated IVF unit including all IVF cycles resulting in singleton live births between 2021 and 2023. Data incorporated maternal characteristics, cycle details, and embryonic data. LGA was defined using national birthweight charts stratified by gestational age and sex. The cohort was classified accordingly: fresh, thawed and transferred and thawed with post-thaw culture ≥ 24 h. A total of 493 singleton births were analyzed. Mean birthweights were comparable across groups: 3192.7 ± 470.4 g (fresh), 3207.5 ± 540.8 g (thawed and transferred) and 3244.9 ± 458.7 g (post-thaw culture) (P > 0.5). LGA rates were also similar: 7.4%,10.6% and 10.1% respectively (P > 0.5). Stratifying by post-thaw culture duration (0, 1, 2, and 3 days), LGA rates were 10.6%, 8.6%, 12.8%, and 5.6% (P > 0.5). Univariate analysis showed no association between LGA and maternal age, parity, number of embryos transferred, endometrial thickness, or treatment group. However, maternal BMI was significantly (P = 0.04) associated with LGA. In a conditional regression analysis, maternal BMI demonstrated a modest association with LGA (P = 0.05). Post-thaw culture duration does not significantly affect LGA risk; however, maternal BMI is a modest predictor. Our study examined whether embryo culture after its thawing affected the infants’ birth weight. We found that post thaw culture did not influence the risk of having a large-for-gestational-age infant. Instead, the mother’s BMI was the main factor associated with larger infants, suggesting that maternal characteristics may have a stronger impact on fetal growth than laboratory culture conditions.

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Journal
Reproductive Health
Published
2026-04-06
DOI
https://doi.org/10.1186/s12978-026-02322-z
Primary Topic
Reproductive Biology and Fertility
Type
article
Field-Weighted Citation Impact
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article

Post-thaw embryo culture and the risk of large-for-gestational-age offspring: a retrospective cohort study

Ranit Hizkiyahu, Yishai Sompolinsky, Yaakov Bentov, M Godin et al.
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Post-thaw embryo culture and the risk of large-for-gestational-age offspring: a retrospective cohort study

Ranit Hizkiyahu, Yishai Sompolinsky, Yaakov Bentov, M Godin, N Vilk Ayalon, A Hershko Klement, M Ketzinel-Gilad, E Esh-Broder, N Omer Vilk, C Adler Lazarovits, R Azulay
article en

Abstract

Frozen embryo transfer (FET) is widely used due to its safety and effectiveness. However, it has been associated with an increased risk of large for gestational age (LGA) infants. Proposed mechanisms include effects of embryo thawing and post-thaw culture duration on developmental programming. Current evidence remains limited regarding the impact of post-thaw culture on birthweight or LGA risk. A retrospective cohort study conducted in a university affiliated IVF unit including all IVF cycles resulting in singleton live births between 2021 and 2023. Data incorporated maternal characteristics, cycle details, and embryonic data. LGA was defined using national birthweight charts stratified by gestational age and sex. The cohort was classified accordingly: fresh, thawed and transferred and thawed with post-thaw culture ≥ 24 h. A total of 493 singleton births were analyzed. Mean birthweights were comparable across groups: 3192.7 ± 470.4 g (fresh), 3207.5 ± 540.8 g (thawed and transferred) and 3244.9 ± 458.7 g (post-thaw culture) (P > 0.5). LGA rates were also similar: 7.4%,10.6% and 10.1% respectively (P > 0.5). Stratifying by post-thaw culture duration (0, 1, 2, and 3 days), LGA rates were 10.6%, 8.6%, 12.8%, and 5.6% (P > 0.5). Univariate analysis showed no association between LGA and maternal age, parity, number of embryos transferred, endometrial thickness, or treatment group. However, maternal BMI was significantly (P = 0.04) associated with LGA. In a conditional regression analysis, maternal BMI demonstrated a modest association with LGA (P = 0.05). Post-thaw culture duration does not significantly affect LGA risk; however, maternal BMI is a modest predictor. Our study examined whether embryo culture after its thawing affected the infants’ birth weight. We found that post thaw culture did not influence the risk of having a large-for-gestational-age infant. Instead, the mother’s BMI was the main factor associated with larger infants, suggesting that maternal characteristics may have a stronger impact on fetal growth than laboratory culture conditions.

Reproductive Health
Hebrew University of Jerusalem (IL), Jerusalem Multidisciplinary College (IL)
Good health and well-being
Openalex Percentile: Top 6%
Reproductive Biology and Fertility
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