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Article: Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis

TitleEndometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis
Authors
Issue Date19-Jun-2023
PublisherOxford University Press
Citation
Human Reproduction Update, 2023, v. 6 How to Cite?
Abstract

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.


Persistent Identifierhttp://hdl.handle.net/10722/331786
ISSN
2023 Impact Factor: 14.8
2023 SCImago Journal Rankings: 4.074

 

DC FieldValueLanguage
dc.contributor.authorVan Hoogenhuijze, Nienke E-
dc.contributor.authorLahoz, Casarramona Gemma-
dc.contributor.authorLensen, Sarah-
dc.contributor.authorFarquhar, Cindy-
dc.contributor.authorKamath, Mohan S-
dc.contributor.authorKunjummen, Aleyamma T-
dc.contributor.authorRaine-Fenning, Nick-
dc.contributor.authorBerntsen, Sine-
dc.contributor.authorPinborg, Anja-
dc.contributor.authorMackens, Shari-
dc.contributor.authorInal, Zeynep Ozturk-
dc.contributor.authorNg, Ernest H Y-
dc.contributor.authorMak, Jennifer S M-
dc.contributor.authorNarvekar, Sachin A-
dc.contributor.authorMartins, Wellington P-
dc.contributor.authorSteengaard, Olesen Mia-
dc.contributor.authorTorrance, Helen L-
dc.contributor.authorMol, Ben W-
dc.contributor.authorEijkemans, Marinus J C-
dc.contributor.authorWang, Rui-
dc.contributor.authorBroekmans, Frank J M-
dc.date.accessioned2023-09-21T06:58:54Z-
dc.date.available2023-09-21T06:58:54Z-
dc.date.issued2023-06-19-
dc.identifier.citationHuman Reproduction Update, 2023, v. 6-
dc.identifier.issn1355-4786-
dc.identifier.urihttp://hdl.handle.net/10722/331786-
dc.description.abstract<p>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.</p><p>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.</p>-
dc.languageeng-
dc.publisherOxford University Press-
dc.relation.ispartofHuman Reproduction Update-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleEndometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis-
dc.typeArticle-
dc.identifier.doi10.1093/humupd/dmad014-
dc.identifier.volume6-
dc.identifier.eissn1460-2369-
dc.identifier.issnl1355-4786-

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