BACKGROUND In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation. OBJECTIVE AND RATIONALE This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR). SEARCH METHODS We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. OUTCOMES Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01–1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07–1.39) for CPR. WIDER IMPLICATIONS The results of this review indicate a slightly higher LBR and CPR in immediate versus postponed FET. Thus, the standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. However, as only retrospective cohort studies were assessed, the presence of selection bias is apparent, and the quality of evidence thus seems low. Randomised controlled trials including data on cancellation rates and reasons for cancellation are highly needed to provide high-grade evidence regarding clinical practice and patient counselling.

中文翻译：

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IVF/ICSI 后立即与推迟冷冻胚胎移植：系统评价和荟萃分析

背景在欧洲，冷冻胚胎移植 (FET) 周期的数量正在稳步增加，目前每年已超过 190 000 个周期。标准的临床实践是在新鲜移植失败或全部冷冻周期后将 FET 推迟至少一个月经周期。这种做法的目的是尽量减少卵巢刺激对恢复正常排卵周期和子宫内膜容受性的可能残留负面影响。尽管选择性延迟 FET 可能会不必要地延迟妊娠时间，但在临床环境中，即刻 FET 可能效率低下，因为不规则排卵周期的风险增加和功能性囊肿的存在，增加了周期取消的风险。目的和理由 本综述探讨了在新鲜移植失败或全冷冻循环后第一个周期（立即 FET）与第二个或后续周期（延迟 FET）的 FET 时间对活产率 (LBR) 的影响。次要终点是植入率、妊娠率和临床妊娠率（CPR）以及流产率（MR）。搜索方法 我们在 PubMed (MEDLINE) 和 EMBASE 数据库中搜索了 MeSH 和 Emtree 术语，以及截至 2020 年 3 月的与 FET 时间相关的文本词。发表年份或随访时间没有限制。纳入标准是年龄在 18-46 岁的不育女性，有任何接受 IVF/ICSI 治疗的指征。排除了有关卵母细胞捐赠的研究。除病例报告外，所有原始研究均被纳入，仅研究方案和摘要。Covidence 是一种 Cochrane 工具，用于对文献进行分类和筛选。偏倚风险使用 Robins-I 工具进行评估，证据质量使用建议分级、评估、开发和评估框架进行评估。结果 在 4124 条搜索结果中，15 项研究被纳入审查。报告 LBR、CPR 和 MR 调整优势比 (aOR) 的研究纳入荟萃分析。所有研究（n = 15）均为回顾性队列研究，共涉及 6,304 个立即 FET 周期和 13,851 个延迟 FET 周期，包括 8,019 个匹配对照。12 项质量极低到中等质量的研究报告了立即与延迟 FET 的 LBR 没有差异。两项中等质量的研究报告了立即 FET 的 LBR 在统计学上显着增加，一项非常低质量的小型研究报告了延迟 FET 更好的 LBR。次要结局发生率的趋势遵循 LBR 关于 FET 时间的趋势。荟萃分析显示，与延迟 FET (n = 3,833) 相比，即刻 FET (n = 2,076) 具有显着优势，LBR 的汇总 aOR 为 1.20 (95% CI 1.01–1.44)，汇总 aOR 为 1.22 (95 % CI 1.07–1.39) 用于 CPR。更广泛的影响 本次审查的结果表明，与延迟 FET 相比，即刻 FET 的 LBR 和 CPR 略高。因此，在新鲜移植失败或全冷冻周期后将 FET 推迟至少一个月经周期的标准临床实践可能不是最佳临床实践。然而，由于只评估了回顾性队列研究，选择偏倚的存在是显而易见的，因此证据的质量似乎很低。非常需要随机对照试验，包括取消率和取消原因的数据，以提供有关临床实践和患者咨询的高级证据。