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后立即冷冻胚胎移植与推迟冷冻胚胎移植：系统评价和荟萃分析。

背景技术在欧洲，冷冻胚胎移植（FET）周期的数量正在稳步增加，现在占每年19万多个周期。在新鲜转移失败后或在全冷冻周期后，将FET推迟至少一个月经周期是标准的临床实践。这种做法的目的是最大程度地减少卵巢刺激对恢复正常排卵周期和子宫内膜容受性的潜在残留负面影响。尽管FET的选择性延期可能会不必要地延迟怀孕时间，但是在不规则排卵周期和功能性囊肿的风险增加之后，立即FET在临床环境中可能效率低下，从而增加了周期取消的风险。目的和理由本综述探讨了在新鲜换胎失败或全冷冻周期失败后，第一个周期（立即FET）的FET时序与第二个或后续周期（推迟的FET）相对于活产率（LBR）的影响。次要终点是植入，妊娠和临床妊娠率（CPR）以及流产率（MR）。搜索方法我们搜索PubMed（MEDLINE）和EMBASE数据库中的MeSH和Emtree术语，以及与FET时序相关的文本单词，直至2020年3月。对于出版年份或随访时间没有限制。纳入标准为年龄在18-46岁之间且有任何IVF / ICSI治疗指征的不育妇女。卵母细胞捐赠的研究被排除在外。包括所有原始研究，但病例报告除外，仅研究协议和摘要。Covidence是一种Cochrane工具，用于对文献进行分类和筛选。使用Robins-I工具评估偏见风险，并使用“建议，评估，发展和评估框架”对证据质量进行评估。结果在4124个搜索结果中，有15项研究被纳入评价。荟萃分析包括对LBR，CPR和MR调整后的优势比（aOR）的研究。所有研究（n = 15）均为回顾性队列研究，涉及总共6,304个立即FET周期和13,851个推迟的FET周期，包括8,019个匹配的对照。十二项非常低至中等质量的研究报告，立即使用和推迟使用的FET的LBR没有差异。两项中等质量的研究报告说，即刻FET使用LBR具有统计学上的显着提高，而一项非常低质量的小规模研究报告说，使用FET延迟可使LBR更好。次要结局发生率的趋势跟随LBR关于FET时序的趋势。荟萃分析显示即时FET（n = 2,076）与延迟FET（n = 3,833）相比具有显着优势，LBR的合并aOR为1.20（95％CI 1.01-1.44），合并的aOR为1.22（95）。 CPR：％CI 1.07-1.39）。对患者的影响这项审查的结果表明，即刻FET与推迟FET相比，LBR和CPR略高。因此，在新鲜转移失败或全冻周期失败后，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的临床实践。但是，由于仅对回顾性队列研究进行了评估，选择偏见的存在是显而易见的，因此证据的质量似乎很低。为了提供有关临床实践和患者咨询的高质量证据，迫切需要包括取消率和取消原因数据在内的随机对照试验。