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The aims of the research were (i) to compare the clinical outcome of IVF using follicular-phase depot gonadotropin-releasing hormone (GnRH) agonist (depot agonist) protocol and GnRH antagonist protocol in patients with repeated IVF failure (RIF), (ii) to discover the optimal ovarian stimulation protocol for this group of low prognosis patients. 801 RIF patients with normal ovarian reserve receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) were included in this retrospective study. Among them, 492 patients were treated with the depot agonist protocol, and the remaining 309 patients with the antagonist protocol. Multivariable logistic regression analysis was used to find the predictor(s) of the chance of live birth. Higher live birth rate (LBR) and clinical pregnancy rate (CPR) in fresh embryo transfer (ET) cycles were associated with the use of depot agonist compared with the antagonist protocols (44.81% vs. 27.27%, 54.64% vs. 34.93%, respectively; both p < 0.01) and depot agonist protocol was a strong predictor of live birth (OR = 2.182, 95% CI 1.355–3.514, p < 0.01). The CPR in thawed ET cycles was not significantly different between the two groups (38.12% vs. 45.26%, p > 0.05). A higher cumulative live birth rate (CLBR) was achieved in the depot agonist group (46.59% vs. 35.21%, p < 0.01). Beneficial endometrial receptivity in the depot agonist protocol contributed to a higher LBR in fresh ET cycles, rendering this protocol the preferred option in the treatment of RIF patients. [ABSTRACT FROM AUTHOR]