Extended embryo culture and cumulative live birth in patients with limited embryos

Among IVF/ICSI patients with only 2-4 Day 3 embryos, which embryo culture strategy is associated with the highest cumulative live birth rate (CLBR): cleavage-stage transfer, blastocyst-stage transfer, or a mixed strategy?

This retrospective cohort study included 5758 first IVF/ICSI cycles performed between January 2016 and May 2022. Patients were divided into 3 groups according to embryo culture strategy: cleavage group (all embryos transferred/frozen at Day 3, n = 1859), blastocyst group (all embryos cultured to Day 5, n = 529), and mixed group (1-2 best cleavage embryos transferred or cryopreserved, with the remainder cultured, n = 3370). The primary outcome was CLBR per oocyte retrieval cycle. Confounders were adjusted using multivariable logistic regression. In addition, a doubly robust approach combining inverse probability weighting (IPW) with regression adjustment was performed as a sensitivity analysis.

Compared with the cleavage-stage group, the blastocyst-stage group had a significantly lower CLBR after one oocyte retrieval cycle (adjusted odds ratio (aOR) 0.243, 95% CI 0.185-0.319 in logistic regression; aOR 0.345, 95% CI 0.271-0.437 in IPW). In contrast, the mixed group showed no significant difference in CLBR after adjustment (aOR 0.924, 95% CI 0.795-1.075 in logistic regression; aOR 0.978, 95% CI 0.867-1.103 in IPW).

For IVF patients with limited Day 3 embryos, a full blastocyst-stage strategy was associated with a substantially lower cumulative chance of live birth, whereas a mixed strategy did not improve CLBR compared with the cleavage-stage strategy after adjustment. These findings suggest that preserving transfer opportunities may be more important than further in vitro selection in this population.