Department of Gynaecology & Reproductive Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Medicine, Utrecht University, Utrecht, the Netherlands.
Hum Reprod Update. 2023 Nov 2;29(6):721-740. doi: 10.1093/humupd/dmad014.
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.
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.
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.
Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data.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.
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.
在体外受精/卵胞浆内单精子注射（IVF/ICSI）治疗中，胚胎着床过程是成功率的限制步骤。子宫内膜搔刮术被认为可以改善这一过程，但尚不清楚该操作是否增加了着床和活产（LB）的机会，如果有，是针对哪些人，以及如何进行刮搔。
本项个体参与者数据荟萃分析（IPD-MA）旨在回答以下问题：在接受 IVF/ICSI 的女性中进行子宫内膜搔刮是否会影响 LB 的机会，以及这种效果在女性的特定亚组中是否不同。2000 年偶然发现子宫内膜搔刮术可以改善胚胎着床后，它被认为可以改善胚胎着床。已经进行了许多随机对照试验（RCT），但结果相互矛盾。常规荟萃分析受到高内和间研究异质性、小样本量以及许多试验存在偏倚风险的限制。此外，还对一些试验的数据完整性提出了质疑。因此，尽管进行了许多 RCT 和大量常规荟萃分析，但仍无法得出关于子宫内膜搔刮术临床有效性的结论。采用 IPD-MA 方法可以克服许多这些问题，因为它可以提高结果定义的一致性，可以筛选出数据完整性有问题的研究，通过调整参与者特征来更精确地估计真实的治疗效果，而无需进行常规荟萃分析中必需的假设，并且可以进行亚组分析。
系统文献检索确定了在接受 IVF/ICSI 的女性中进行子宫内膜搔刮的 RCT。邀请符合条件的研究的作者分享本 IPD-MA 的原始数据。对研究进行了风险偏倚（RoB）评估和完整性检查。主要结局是 LB，主要分析为意向治疗（ITT）的一次性分析。次要分析包括治疗分析（AT）和接受胚胎移植（AT+ET）的女性亚组。对特定参与者特征的治疗协变量交互作用在 AT+ET 中进行了分析。
在 37 篇已发表和 15 篇未发表的 RCT 中（7690 名参与者），有 15 项 RCT（14 篇已发表，1 篇未发表）分享了数据。经过数据完整性检查，我们纳入了 13 项 RCT（12 篇已发表，1 篇未发表），代表 4112 名参与者。10/13 项 RCT 的 RoB 评估为“低”。与不刮搔/假手术相比，搔刮组的 LB 率有所提高（比值比（OR）1.29 [95%置信区间 1.02-1.64]）。治疗分析、AT+ET 分析和低 RoB 敏感性分析均得出相似的结果（OR 1.22 [95%置信区间 0.96-1.54]；OR 1.25 [95%置信区间 0.99-1.57]；OR 1.26 [95%置信区间 1.03-1.55]）。治疗协变量交互作用分析未发现与年龄、既往胚胎移植失败次数、治疗类型或不孕原因的交互作用证据。
这是第一项基于超过 4000 名参与者的 IPD 的荟萃分析，它表明子宫内膜搔刮术可能会提高接受 IVF/ICSI 的女性的 LB 率。对于年龄、既往胚胎移植失败次数、治疗类型和不孕原因的亚组分析，未能确定子宫内膜搔刮术表现更好或更差的亚组。子宫内膜搔刮术的时间可能在其有效性中起作用。在临床实践中使用子宫内膜搔刮术应谨慎考虑，这意味着应向患者提供关于证据水平和不确定性的适当咨询。
