BACKGROUND In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as ‘low’ for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02–1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96–1.54]; OR 1.25 [95% CI 0.99–1.57]; OR 1.26 [95% CI 1.03–1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.

中文翻译：

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接受 IVF/ICSI 的女性子宫内膜刮伤：个体参与者数据荟萃分析

背景技术在IVF/ICSI治疗中，胚胎植入过程是成功率的限制步骤。有人建议子宫内膜刮擦可以改善这一过程，但尚不清楚该手术是否会增加着床和活产 (LB) 的机会，如果是的话，为谁进行，以及如何进行刮擦。目的和理由 这项个体参与者数据荟萃分析 (IPD-MA) 旨在回答接受 IVF/ICSI 的女性子宫内膜刮擦是否会影响 LB 机会的问题，以及这种影响在特定女性亚组中是否不同。2000 年偶然发现子宫内膜刮擦术后，有人提出可以改善胚胎植入。已经进行了大量的随机对照试验（RCT），结果却相互矛盾。传统的荟萃分析受到研究内和研究间异质性高、研究样本小以及许多试验的高偏倚风险的限制。此外，多项试验的数据完整性也受到质疑。因此，尽管进行了大量的随机对照试验和大量的传统荟萃分析，但仍无法得出子宫内膜刮擦的临床有效性的结论。IPD-MA 方法能够克服其中许多问题，因为它可以提高结果定义的一致性，可以过滤掉存在数据完整性问题的研究，通过对参与者特征进行调整，可以更准确地估计真实的治疗效果，而不是必须在传统荟萃分析中做出必要的假设，并且因为它允许进行亚组分析。搜索方法 系统的文献搜索确定了关于接受 IVF/ICSI 的女性子宫内膜刮擦的随机对照试验。合格研究的作者受邀分享本次 IPD-MA 的原始数据。研究评估了偏倚风险 (RoB) 并进行了完整性检查。主要结局是 LB，以一阶段意向治疗 (ITT) 作为主要分析。二次分析包括治疗组 (AT) 和接受胚胎移植的女性子集 (AT+ET)。在 AT+ET 中分析了特定参与者特征的治疗-协变量相互作用。结果 在 37 项已发表和 15 项未发表的 RCT（7690 名受试者）中，15 项 RCT（14 项已发表，1 项未发表）共享数据。经过数据完整性检查后，我们纳入了代表 4112 名参与者的 13 项 RCT（12 项已发表，1 项未发表）。10/13 RCT 的 RoB 被评估为“低”。划痕与无划痕/假手术的一阶段 ITT 分析显示 LB 率有所改善（比值比 (OR) 1.29 [95% CI 1.02–1.64]）。AT、AT+ET 和低 RoB 敏感性分析得出相似的结果（OR 1.22 [95% CI 0.96–1.54]；OR 1.25 [95% CI 0.99–1.57]；OR 1.26 [95% CI 1.03–1.55]，分别）。治疗协变量相互作用分析显示，没有证据表明与年龄、先前失败的胚胎移植次数、治疗类型或不孕原因之间存在相互作用。更广泛的影响 这是第一个基于 4000 多名参与者的 IPD 的荟萃分析，它表明子宫内膜刮擦可能会提高接受 IVF/ICSI 的女性的 LB 率。对年龄、先前失败的胚胎移植次数、治疗类型和不孕原因的亚组分析无法确定子宫内膜刮擦表现更好或更差的亚组。子宫内膜刮擦的时机可能会影响其有效性。在临床实践中应谨慎考虑使用子宫内膜刮擦术，这意味着应就证据水平和不确定性向患者提供适当的咨询。