For the millions of women undergoing IVF who produce only a small number of eggs, the choice between transferring embryos fresh or after freezing carries outsized consequences. A dominant assumption in modern reproductive medicine — that freeze-all strategies improve outcomes by allowing uterine recovery — may not apply universally, and this systematic review offers the clearest evidence yet that low responders represent a critical exception.
This review, published in Fertility and Sterility, synthesized evidence from 15 studies encompassing one randomized controlled trial and 14 nonrandomized studies, identified through a comprehensive search of five major databases covering literature through December 2025. The pivotal finding comes from the single RCT, rated as high-certainty evidence: frozen embryo transfer was associated with a statistically significant reduction in live birth rate (RR 0.79; 95% CI 0.65–0.94), clinical pregnancy rate (RR 0.83), and cumulative live birth rate (RR 0.86) compared with fresh transfer in low responders. The nonrandomized studies, rated as very low certainty, showed no significant difference between approaches, illustrating the hazard of relying solely on observational data in this population.
The broader freeze-all literature has been shaped predominantly by studies in normal and high responders, where freezing reduces hyperstimulation risk and allows endometrial synchronization. Extrapolating those benefits to low responders appears biologically questionable: women producing few follicles generate lower circulating estrogen during stimulation, meaning their endometrial environment may already be less supraphysiological and more receptive at the time of fresh retrieval. Cryopreservation introduces additional embryo attrition risk — a factor disproportionately costly when only one or two embryos exist. This review is limited by having only one high-quality RCT, and the original trial's sample characteristics deserve scrutiny before broad clinical translation. Still, the signal is directionally clear and practically significant: the freeze-all paradigm likely does not confer the same advantage in poor responders and may actively reduce cumulative success rates.