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

Authors: Nienke E van Hoogenhuijze; Gemma Lahoz Casarramona; Sarah Lensen; Cindy Farquhar; Mohan S Kamath; Aleyamma T Kunjummen; Nick Raine-Fenning; +14 Authors

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

Abstract

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.

Keywords

Visual Analog Scale, Pregnancy Rate, Supplementary Data, endometrial scratch, multiple pregnancy, adverse event, intracytoplasmic sperm injection, Review, Medical Procedures, single embryo transfer, sensitivity analysis, systematic review, Pregnancy, randomized controlled trial (topic), Birth Rate, numeric rating scale, Embase, endometrial sampling, Medline, risk assessment, forceps, General Medicine, clinical practice, Intention to Treat Analysis, publication, spontaneous abortion, IVF, RG Gynecology and obstetrics, ectopic pregnancy, Sperm Injections, Intracytoplasmic/methods, Female, frozen embryo transfer, infertility, in vitro fertilization, post hoc analysis, Live Birth, Infertility, Female, Art, ART, Human, Infertility, Female/therapy, Fever, Endometriosis, 610, Gestational Age, Fertilization in Vitro, endometrial scratching, Fertilization in Vitro/methods, ICSI, endometrial injury, live birth, smoking, Humans, Sperm Injections, Intracytoplasmic, Embryo Transfer/methods, embryo transfer, data analysis software, pregnancy outcome, abdominal pain, therapy effect, bleeding, Embryo Transfer, individual participant data meta-analysis, IPD, Frozen embryo transfer (FET), RG, disease duration, secondary analysis, gynecological and obstetric catheter, meta analysis

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
18
Top 10%
Top 10%
Top 10%
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