Freeze-all versus fresh embryo transfer strategies in low-prognosis women: an emulated target trial study

How effective is a freeze-all strategy in low-prognosis women, as defined by the Patient-oriented Strategies Encompassing Individualized Oocyte Number criteria, in terms of the cumulative live birth rate in comparison with a fresh embryo transfer strategy?

A target trial was emulated using a retrospective cohort of 2102 women undergoing their first or second cycle of IVF/intracytoplasmic sperm injection (ICSI) at a tertiary reproductive centre. Participants were divided into a freeze-all group (n = 912) and a fresh embryo transfer group (n = 1190). To emulate randomization and control for confounding, propensity score overlap weighting was applied to balance 20 baseline covariates. The primary outcome was cumulative live birth per initiated cycle.

After propensity score overlap weighting, the cumulative live birth rate was lower in the freeze-all group than in the fresh embryo transfer group (40.0% versus 46.7%), with a pooled risk difference of -6.69% (95% CI -7.12% to -6.25%). Live birth (risk difference = -3.94%) and clinical pregnancy (risk difference = -4.05%) rates after the first transfer were also lower in the freeze-all group. Results were consistent across sensitivity analyses. Subgroup analyses indicated that the benefit of fresh transfer was more pronounced in women aged ≥35 years and women with four or more oocytes retrieved.

In low-prognosis women, a fresh embryo transfer strategy was associated with a higher cumulative live birth rate than a freeze-all strategy. These findings support a prognosis-tailored, individualized approach to embryo transfer rather than a uniform policy.