Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis
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Endometrial scratching in women undergoing IVF/ICSI : an individual participant data meta-analysis. / van Hoogenhuijze, Nienke E.; Casarramona, Gemma Lahoz; Lensen, Sarah; Farquhar, Cindy; Kamath, Mohan S.; Kunjummen, Aleyamma T.; Raine-Fenning, Nick; Berntsen, Sine; Pinborg, Anja; Mackens, Shari; Inal, Zeynep Ozturk; Ng, Ernest H.Y.; Mak, Jennifer S.M.; Narvekar, Sachin A.; Martins, Wellington P.; Olesen, Mia Steengaard; Torrance, Helen L.; Mol, Ben W.; Eijkemans, Marinus J.C.; Wang, Rui; Broekmans, Frank J.M.
In: Human Reproduction Update, Vol. 29, No. 6, 2023, p. 721-740.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Endometrial scratching in women undergoing IVF/ICSI
T2 - an individual participant data meta-analysis
AU - van Hoogenhuijze, Nienke E.
AU - Casarramona, Gemma Lahoz
AU - Lensen, Sarah
AU - Farquhar, Cindy
AU - Kamath, Mohan S.
AU - Kunjummen, Aleyamma T.
AU - Raine-Fenning, Nick
AU - Berntsen, Sine
AU - Pinborg, Anja
AU - Mackens, Shari
AU - Inal, Zeynep Ozturk
AU - Ng, Ernest H.Y.
AU - Mak, Jennifer S.M.
AU - Narvekar, Sachin A.
AU - Martins, Wellington P.
AU - Olesen, Mia Steengaard
AU - Torrance, Helen L.
AU - Mol, Ben W.
AU - Eijkemans, Marinus J.C.
AU - Wang, Rui
AU - Broekmans, Frank J.M.
N1 - Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.
PY - 2023
Y1 - 2023
N2 - 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 metaanalyses, 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 (ATþET). Treatment-covariate interaction for specific participant characteristics was analyzed in ATþET. 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, ATþET, 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.
AB - 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 metaanalyses, 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 (ATþET). Treatment-covariate interaction for specific participant characteristics was analyzed in ATþET. 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, ATþET, 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.
KW - ART
KW - endometrial injury
KW - endometrial sampling
KW - endometrial scratch
KW - endometrial scratching
KW - frozen embryo transfer
KW - ICSI
KW - individual participant data meta-analysis
KW - IPD
KW - IVF
U2 - 10.1093/humupd/dmad014
DO - 10.1093/humupd/dmad014
M3 - Review
C2 - 37336552
AN - SCOPUS:85172171802
VL - 29
SP - 721
EP - 740
JO - Human Reproduction Update
JF - Human Reproduction Update
SN - 1355-4786
IS - 6
ER -
ID: 397031719