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 OUTCOMES Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants.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：

---

接受 IVF/ICSI 的女性子宫内膜刮擦：个体参与者数据荟萃分析


背景 在 IVF/ICSI 治疗中，胚胎植入的过程是成功率限制步骤。有人建议子宫内膜刮擦可以改善这一过程，但目前尚不清楚这种手术是否会增加植入和活产 （LB） 的机会，如果是这样，为谁增加，以及如何进行抓挠。客观和基本原理 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 的机会，以及这种影响在特定女性亚组中是否不同。在 2000 年偶然发现后，子宫内膜刮擦被认为可以改善胚胎着床。已经进行了大量随机对照试验 （RCT），结果相互矛盾。传统的meta分析受到研究内和研究间异质性高、研究样本小和许多试验的高偏倚风险的限制。此外，一些试验的数据完整性也受到质疑。因此，尽管有大量的 RCT 和大量的常规荟萃分析，但无法得出关于子宫内膜搔抓的临床疗效的结论。IPD-MA 方法能够克服其中的许多问题，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，由于调整了参与者的特征，并且不必在传统的荟萃分析中做出必要的假设，因此能够更精确地估计真实的治疗效果，并且因为它允许进行亚组分析。检索方法 一项系统的文献检索确定了关于接受 IVF/ICSI 的女性子宫内膜刮擦的 RCT。 邀请符合条件的研究的作者分享本 IPD-MA 的原始数据。评估研究的偏倚风险 （RoB） 并进行完整性检查。主要结局是 LB，以一期意向治疗 （ITT） 为主要分析。二次分析包括接受治疗 （AT） 和接受胚胎移植 （AT+ET） 的女性亚群。在 AT+ET 中分析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 名参与者） 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，我们纳入了 13 项 RCT（12 项已发表，1 项未发表），涉及 4112 名参与者。10/13 项 RCT 的 RoB 评估为“低”。划痕与无划痕/假手术的一期 ITT 分析显示 LB 率改善 （比值比 （OR） 1.29 [95% CI 1.02–1.64]）。AT、AT+ET 和低 RoB 敏感性分析产生了相似的结果 （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]）。治疗-协变量相互作用分析显示，没有证据表明与年龄、既往胚胎移植失败的数量、治疗类型或不孕原因存在相互作用。更广泛的影响 这是第一项基于 4000 多名参与者的 IPD 的荟萃分析，它表明子宫内膜搔抓可能会改善接受 IVF/ICSI 的女性的 LB 率。年龄、既往胚胎移植失败次数、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。子宫内膜搔抓的时间可能对其有效性产生影响。 在临床实践中应谨慎考虑子宫内膜搔抓的使用，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。