The effect of embryo vitrification duration on frozen-thawed transfer outcomes: the key moderating role of age-a retrospective cohort study of 13,054 cycles.

PURPOSE: To investigate how embryo vitrification duration affects frozen-thawed transfer outcomes, focusing on the interaction between age (at transfer and at freezing) and storage time.

METHODS

This retrospective cohort study included 13,054 first vitrified embryo transfers (2015-2025). Cycles were divided by cryopreservation duration: ≤ 0.5, 0.5-2, 2-5, and > 5 years. Primary outcomes were clinical pregnancy, implantation, and live birth rates; secondary outcomes included biochemical pregnancy, miscarriage, ectopic pregnancy, and multiple pregnancy rates. Multivariate logistic regression adjusted for confounders, followed by age-stratified analyses and interaction tests. Subgroup analyses used age at transfer (ROC cutoff 36 years) and at freezing (cutoff 34.5 years).

RESULTS

Compared to ≤ 0.5 years, the > 5 years group showed lower clinical pregnancy (aOR = 0.757, P = 0.036), implantation (aOR = 0.604, P = 0.001), and live birth rates (aOR = 0.881, P = 0.003). For 2-5 years, only the live birth rate decreased (aOR = 0.875, P = 0.049). Age significantly interacted with freezing duration (P = 0.001). Women aged ≤ 34.5 years at freezing also exhibited a dose-response decline in live birth rates with longer storage.

CONCLUSIONS

Long-term cryopreservation (> 5 years) has an adverse effect on the outcomes of frozen-thawed embryo transfer, but this effect is observed only in younger women (≤ 35 years). In older women (≥ 36 years), the deterioration of the uterine environment may mask the additional risks associated with prolonged cryopreservation. Clinicians should make individualized decisions regarding the use of long-term cryopreserved embryos by considering both the patient's age at the time of transfer and the age of the embryos at the time of cryopreservation.