子宫内膜搔刮是否能增加胚胎植入和活产的几率？

BACKGROUND

背景

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.

胚胎植入是决定体外受精/单精子注射治疗成功率的关键步骤。有人建议通过子宫内膜搔刮来改善这一过程，但目前还不清楚这一过程是否能增加胚胎植入和活产（LB）的几率，如果能，对哪些人进行子宫内膜搔刮以及如何进行子宫内膜搔刮。

OBJECTIVE AND RATIONALE

目的和依据

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.

这项个体参与者数据荟萃分析（IPD-MA）旨在回答这样一个问题：接受体外受精/卵胞浆内单精子显微注射（IVF/ICSI）的妇女进行子宫内膜搔刮是否会影响胚胎着床的几率，以及这种影响在特定的妇女亚群中是否有所不同。自 2000 年一项偶然发现子宫内膜搔刮后能提高胚胎着床率。但许多随机对照试验（RCT）显示出了相互矛盾的结果。传统的荟萃分析受限于研究内和研究间的高度异质性、研究样本小以及试验的高偏倚风险。此外，一些试验的数据完整性也受到质疑。因此，尽管进行了大量的研究性临床试验和大量的传统荟萃分析，但仍无法就子宫内膜搔刮的临床有效性得出结论。IPD-MA 方法能克服上述许多问题，因为它能提高结果定义的统一性，能过滤掉数据完整性有问题的研究，能更精确地估计真正的治疗效果，这要归功于对参与者特征的调整，而不必做出传统荟萃分析所需的假设，还因为它能进行亚组分析。

SEARCH METHODS

检索方法

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.

通过系统性文献检索确定了有关接受体外受精/卵胞浆内单精子显微注射（IVF/ICSI）女性子宫内膜搔刮的 RCT。我们邀请符合条件的研究的作者为本 IPD-MA 分享原始数据。对研究进行了偏倚风险（RoB）评估和完整性检查。主要研究结果为活产率，以一阶段意向治疗（ITT）作为主要分析。次要分析包括治疗（AT）和接受胚胎移植的妇女子集（AT+ET）。在 AT+ET 中分析了特定参与者特征的治疗与变量交互作用。

OUTCOMES

结果

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.

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）共享了数据。经过数据完整性检查，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）。RoB 被评估为“低”。对搔刮与无搔刮/无手术进行的单阶段 ITT 分析表明，LB 率有所提高（OR  1.29 [95% CI 1.02-1.64]）。AT、ATþET 和低 RoB 敏感性分析结果相似（OR 1.22 [95% CI 0.96-1.54]；OR 分别为 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55]）。治疗与变量交互作用分析表明，治疗与年龄、既往胚胎移植失败次数、治疗类型或不孕原因之间没有交互作用。

WIDER IMPLICATIONS

更广泛的影响

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.

这是首次基于 4000 多名参与者的 IPD 进行的荟萃分析，它表明子宫内膜搔刮可提高接受体外受精/卵胞浆内单精子显微注射的妇女的 LB 率。对年龄、既往胚胎移植失败次数、治疗类型和不孕原因进行的亚组分析无法确定在哪些亚组中子宫内膜搔刮的效果更好或更差。子宫内膜搔刮的时机可能会影响其效果。所以在临床实践中使用子宫内膜搔刮应慎重考虑，即应就证据水平和不确定性向患者提供适当的建议。

参考文献：Nienke E van Hoogenhuijze, Gemma Lahoz Casarramona, Sarah Lensen, Cindy Farquhar, Mohan S Kamath, Aleyamma T Kunjummen, Nick Raine-Fenning, Sine Berntsen, Anja Pinborg, Shari Mackens, Zeynep Ozturk Inal, Ernest H Y Ng, Jennifer S M Mak, Sachin A Narvekar, Wellington P Martins, Mia Steengaard Olesen, Helen L Torrance, Ben W Mol, Marinus J C Eijkemans, Rui Wang, Frank J M Broekmans, Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis, Human Reproduction Update, Volume 29, Issue 6, November-December 2023, Pages 721–740, https://doi.org/10.1093/humupd/dmad014