Natural Compared With Artificial Cycle Endometrial Preparation for Frozen Embryo Transfer: A Systematic Review and Meta-analysis.

Abstract

To compare live-birth rates between natural cycle and artificial cycle endometrial preparation protocols in women undergoing frozen embryo transfer. A comprehensive literature search was conducted through July 2025 across PubMed, EMBASE, Cochrane Library, ClinicalKey, ProQuest, Cumulative Index to Nursing and Allied Health Literature Plus, ClinicalTrials.gov , and World Health Organization International Clinical Trials Registry Platform. Search terms combined "frozen embryo transfer," "endometrial preparation," "natural cycle," and "artificial cycle" with no language restrictions during search phase. Only randomized controlled trials comparing natural cycle with artificial cycle preparation in women aged 18-45 years undergoing frozen embryo transfer were included. Studies were required to report live-birth rate or clinical pregnancy rate. Of 824 records identified, 45 full-text articles were assessed, and 11 randomized controlled trials (9,955 women) met inclusion criteria. Review Manager 5.4 was used for meta-analyses. Data were extracted independently by two reviewers using standardized forms. Risk of bias was assessed with the Cochrane Risk of Bias Tool 2.0. Natural cycle preparation demonstrated significantly higher live-birth rates (41.5% vs 39.2%; risk ratio [RR] 1.11, 95% CI, 1.03-1.19, P =.007; moderate-quality evidence), corresponding to 43 more live births per 1,000 women and a number needed to treat of 23. Modified natural cycle showed significant benefit (RR 1.11, 95% CI, 1.01-1.23, P =.03), whereas true natural cycle showed no significant difference (RR 1.08, 95% CI, 0.95-1.23, P =.21). Natural cycle was associated with lower miscarriage rates (13.4% vs 17.5%; RR 0.76, 95% CI, 0.67-0.87, P <.001; moderate-quality evidence). Natural cycle endometrial preparation, particularly modified natural cycle with human chorionic gonadotropin trigger, is associated with higher live-birth rates compared with artificial cycle preparation, although true natural cycle showed no significant difference. PROSPERO, CRD420251090016.