Study question What is the optimal time post oocyte retrieval (POR) to undertake intracytoplasmic sperm injection (ICSI) in order to maximise subsequent pregnancy and live birth outcomes? Summary answer Delaying ICSI for 5 hours or more POR may compromise subsequent clinical pregnancy and live birth rates. What is known already It is often challenging to perform ICSI at a set timing POR, especially in ART clinics with a heavy workload. However, the degree of flexibility in ICSI timing remains unclear in the literature. Some articles have reported detrimental impacts by delaying ICSI on the subsequent treatment outcomes (Pujol et al 2018), while others reported no evidence of adverse effects caused by different ICSI timings (Vandenberghe et al 2021). Therefore, we aimed to explore a “safety time window” for ICSI procedures to enable flexibility in workflow arrangement without compromising pregnancy outcomes. Study design, size, duration A systematic review and meta-analysis were performed according to PRISMA guidelines, with protocol registered with PROSPERO (ID: CRD42022296838). The studies were searched for in PubMed, MEDLINE, EMBASE and the Cochrane Library on 16 December 2021, using (“subfertile” OR “sub-fertile” OR “infert*” OR “fertility treatment” OR “women” OR “female” OR “couple”) AND (“ICSI” OR “intracytoplasmic sperm injection” OR “intra-cytoplasmic sperm injection”) AND (“timing” OR “time interval”) AND (“pregnancy” OR “fertili*” OR “birth”) NOT (Review [Publication Type]). Participants/materials, setting, methods Two independent reviewers systematically evaluated each study on patient, intervention, comparison, and outcome (PICO). The Newcastle-Ottawa scale was used for risk of bias assessment in non-randomised trials and observational studies. Further screening was performed separately by the two independent reviewers, with differences mediated by the third reviewer. Data extraction was performed according to Cochrane methods. Clinical pregnancy or live birth data were synthesised from eligible studies depending on availability of raw data in corresponding subgroups. Main results and the role of chance A total of 605 records were hit in the search. After initial exclusion according to PICO, 30 articles were included for further screening for eligibility. For meta-analysis, 4 retrospective cohort studies were eventually included for clinical pregnancy rate assessment while 2 for live birth rate analysis. Due to different groupings in ICSI timing amongst these studies, a series of comparisons on ICSI timings with a cut-off at an hourly increment were set up to pool data from the 4 included studies where applicable. Clinical pregnancy rates were comparable when ICSI was performed (a) 2+ hours (n = 6448, Relative Risk or RR = 1.031, 95% CI 0.964-1.102) in reference to < 2 hours POR (n = 2336), (b) 3+ hours (n = 5101, RR = 1.005, 95% CI 0.945-1.069) in reference to < 3 hours POR (n = 3465), and (c) 4+ hours (n = 3192, RR = 1.017, 95% CI 0.956-1.082) in reference to < 4 hours POR (n = 5374). However, clinical pregnancy rates were significantly compromised when ICSI was performed at 5+ hours (n = 2335, RR = 1.103, 95% CI 1.036-1.175) in reference to < 5 hours POR (n = 7169). Similarly, live birth rate was also significantly reduced when ICSI was performed 5+ hours (n = 2335, RR = 1.155, 95% CI 1.070-1.246) in reference to < 5 hours POR (n = 7169). Limitations, reasons for caution All studies included for meta-analysis were retrospective with heterogeneity. There were various groupings amongst studies due to the wide range of ICSI timings POR, which limits data pooling and subsequent comparisons. A future well designed randomised controlled trial is warranted for further analysis based on better quality evidence. Wider implications of the findings Our results indicate 5 hours POR should be considered the maximum time limit to perform ICSI. This finding, supported by statistics with improved power through meta-analysis, offers valuable guidance to busy clinics. This information could both improve pregnancy outcomes and allow better workflow arrangements without compromising them. Trial registration number not applicable

中文翻译：

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P-203 寻找取卵后胞浆内精子注射的最佳时机：系统评价和荟萃分析

研究问题 取卵后 (POR) 进行胞浆内单精子注射 (ICSI) 以最大限度地提高随后的妊娠和活产结果的最佳时间是什么时候？总结答案 将 ICSI 延迟 5 小时或更长时间 POR 可能会影响随后的临床妊娠率和活产率。已知情况 在设定的 POR 时间执行 ICSI 通常具有挑战性，尤其是在工作量很大的 ART 诊所。然而，ICSI 时间安排的灵活性程度在文献中仍不清楚。一些文章报告了延迟 ICSI 对后续治疗结果的不利影响（Pujol 等人 2018），而另一些文章则报告没有证据表明不同 ICSI 时间会引起不利影响（Vandenberghe 等人 2021）。所以，我们旨在探索 ICSI 程序的“安全时间窗口”，以便在不影响妊娠结局的情况下灵活地安排工作流程。研究设计、规模、持续时间 根据 PRISMA 指南进行系统评价和荟萃分析，方案在 PROSPERO 注册（ID：CRD42022296838）。这些研究于 2021 年 12 月 16 日在 PubMed、MEDLINE、EMBASE 和 Cochrane 图书馆中检索，使用（“subfertile”或“sub-fertile”或“infert*”或“fertility treatment”或“women”或“female”或“夫妇”）和（“ICSI”或“胞浆内精子注射”或“胞浆内精子注射”）和（“时间”或“时间间隔”）和（“怀孕”或“受精*”或“出生”）不是（查看 [出版物类型]）。参与者/材料、设置、方法 两名独立的评审员系统地评估了每项关于患者的研究，干预、比较和结果（PICO）。纽卡斯尔-渥太华量表用于非随机试验和观察性研究中的偏倚风险评估。进一步的筛选由两位独立评审员分别进行，差异由第三位评审员调解。根据Cochrane方法进行数据提取。根据相应亚组中原始数据的可用性，从符合条件的研究中综合临床妊娠或活产数据。主要结果及机会的作用 共检索到605条记录。根据 PICO 初步排除后，30 篇文章被纳入进一步筛选资格。对于荟萃分析，最终纳入了 4 项回顾性队列研究用于临床妊娠率评估，而 2 项用于活产率分析。由于这些研究中 ICSI 时间的不同分组，设置了一系列以每小时增量为截止值的 ICSI 时间比较，以便在适用的情况下汇集来自 4 个纳入研究的数据。当进行 ICSI 时，临床妊娠率具有可比性 (a) 2 小时以上（n = 6448，相对风险或 RR = 1.031，95% CI 0.964-1.102）2 小时 POR (n = 2336), (b) 3+ 小时 (n = 5101, RR = 1.005, 95% CI 0.945-1.069) 参考 < 3 小时 POR (n = 3465)，和 (c) 4+ 小时 (n = 3192, RR = 1.017, 95% CI 0.956-1.082) 4 小时 POR (n = 5374)。然而，当在 5 小时以上进行 ICSI 时（n = 2335，RR = 1.103，95% CI 1.036-1.175），临床妊娠率显着降低，参考＜1.036-1.175。5 小时 POR (n = 7169)。相似地，当 ICSI 进行 5 小时以上时，活产率也显着降低（n = 2335，RR = 1.155，95% CI 1.070-1.246），参考 <<; 5 小时 POR (n = 7169)。局限性，谨慎的原因 所有纳入荟萃分析的研究都是回顾性的，具有异质性。由于 ICSI 时间 POR 的范围广泛，研究中有各种分组，这限制了数据汇集和随后的比较。未来设计良好的随机对照试验有必要根据质量更好的证据进行进一步分析。研究结果的更广泛含义 我们的结果表明 5 小时 POR 应被视为执行 ICSI 的最大时间限制。这一发现得到了通过荟萃分析提高的统计数据的支持，为繁忙的诊所提供了有价值的指导。这些信息既可以改善妊娠结果，又可以在不影响它们的情况下进行更好的工作流程安排。试用注册号不适用