Prolonged interval between sibling embryo transfers impairs clinical pregnancy outcomes following assisted reproduction technology

OBJECTIVE: This study investigates the impact of a prolonged time interval between sibling embryo transfers on clinical pregnancy outcomes, utilizing a model that controls for oocyte aging to isolate maternal time-dependent factors. DESIGN: This retrospective, single-center, self-controlled cohort study evaluated patients who underwent at least two distinct embryo transfers utilizing sibling embryos derived from a single oocyte retrieval cycle between January 2013 and June 2024. The exposure group comprised subsequent transfers performed after an interval exceeding 36 months. Clinical outcomes, including implantation, biochemical pregnancy, clinical pregnancy, early miscarriage, and live birth rates, were compared. RESULTS: The final analysis included 2008 cycles from 654 couples (877 initial control cycles and 1131 subsequent exposure cycles). Following logistic regression analyses to adjust for potential confounders, the subsequent transfer group exhibited significantly decreased likelihood of biochemical pregnancy (adjusted odds ratio [OR] 0.60, 95% confidence interval [CI] 0.46-0.77, P < 0.001), clinical pregnancy (adjusted OR 0.49, 95% CI 0.38-0.63, P < 0.001) and live birth (adjusted OR 0.52, 95% CI 0.41-0.66, P < 0.001). To further minimize embryological bias, a highly restricted subgroup analysis was performed on single, good quality day 5 blastocyst transfers utilizing artificial endometrial preparation protocols (144 control vs. 163 exposure cycles). Within this subgroup, the subsequent transfers continued to demonstrate significantly inferior outcomes, with notable reductions in implantation, biochemical pregnancy, clinical pregnancy, and live birth rates (all P < 0.001). CONCLUSION: A prolonged interval (>36 months) between sibling embryo transfers independently and negatively impairs clinical pregnancy outcomes. For patients planning subsequent pregnancies using cryopreserved sibling embryos, it is clinically advisable to proceed with the transfer as early as medically appropriate to mitigate the time-dependent degradation of the reproductive environment.