Frozen versus fresh embryo transfer in low responders: a systematic review.

IMPORTANCE

Management of low responders is a challenge in the field of assisted reproduction. Several trials comparing frozen versus fresh embryo transfer have been published and are restricted mainly to high and normal responders. Current studies on the suitability of frozen embryo transfer in low responders are limited and yielded mixed results.

OBJECTIVE

To investigate whether cryopreservation of all embryos and subsequent frozen embryo transfer produces better reproductive outcomes compared with fresh embryo transfer in low responders.

EVIDENCE REVIEW: We searched PubMed, Embase, Cochrane Library, Web of Science Core Collection and Scopus databases from inception to December 2025. After de-duplication, titles and abstracts of 4,423 articles were screened, and 154 full-text articles were assessed for eligibility. One randomized controlled trial and 14 nonrandomized studies were included in the systematic review. Data extraction was performed for the primary outcome of live birth rate and secondary outcomes.

FINDINGS: High certainty evidence from 1 randomized controlled trial showed that frozen embryo transfer resulted in a reduction in live birth (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.65-0.94), clinical pregnancy (RR, 0.83; 95% CI, 0.71-0.97) and cumulative live birth rate (RR, 0.86; 95% CI, 0.75-0.99), whereas nonrandomized studies provided very uncertain evidence that there was no significant difference in the 2 groups including live birth rate (RR, 1.00; 95% CI, 0.65-1.55). A lower miscarriage rate favoring fresh embryo transfer was found in women fulfilling the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number criteria (RR, 1.31; 95% CI, 1.11-1.56). Consistent evidence indicated that frozen embryo transfer did not produce significant improvements in other reproductive outcomes.

CONCLUSION AND RELEVANCE: Our results suggested that the "freeze-all" strategy did not produce better reproductive outcomes compared with fresh embryo transfer in low responders. Reproductive outcomes may be improved by performing fresh embryo transfer, which could be explained by a more physiological endometrium or better embryo quality without injury caused by cryopreservation. These findings should be further explored in randomized trials.

TRIAL REGISTRATION: The review protocol was registered at PROSPERO (trial registration number: CRD420251138047, URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251138047). Date of registration: 9 September 2025.