The literature search yielded 879 potentially relevant reports (Fig. 1). Subsequently, the titles of these manuscripts were examined, resulting in 222 potentially eligible publications. The abstracts of these studies were then examined and eventually 96 manuscripts that could provide data to answer the research question were identified. The full text of these studies was examined thoroughly, resulting in the inclusion of 40 publications, that represent 39 RCTs [5, 8, 11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45, 47, 48] (one report [46] contained post-hoc analyses of a previously published RCT [41] (Table 1). It should also be noted that Liu et al., [29] included four groups in their study (intervention and no intervention during the follicular and the luteal phase of the cycle preceding IVF) and therefore, we analyzed the follicular and the luteal phase arms of the study separately. Characteristics of the reports included in the systematic review appear in Tables 1 and 2. Eligible studies were published between 2008 and 2022. Randomization method was reported in 34 of the publications included, while allocation concealment method was reported in 19 of the studies included (Table 1). Most studies did not state clearly if the participants or those involved in the analysis were blinded to the type of intervention. Only 3 studies were reported to be single-blind and 3 were reported to be double-blind. Financial support was declared in 20 studies (Table 1). The largest study published so far on this issue was by Lensen et al. in 2019 [5]. The risk of bias assessment of the eligible studies is presented in Table 3. Overall, 9 studies [11,12,13, 15, 16, 23, 27, 28, 37] were deemed to be at high risk of bias (Supplementary Figures 1 & 2).
Fig. 1
Table 3 Risk of Bias assessment of included studies (using RoB-2)Meta-analysisLive birthA significantly higher probability of live birth was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (risk ratio-RR: 1.12, 95% CI: 1.05– 1.20; fixed effects model; heterogeneity: I2=46.30%, 28 studies, 29 datasets, 7425 patients; low certainty; NNT: 30) (Fig. 2). Publication bias did not seem to be present (p=0.727). A sensitivity analysis excluding studies at high risk of bias [13, 15, 16, 23, 27, 37] did not materially change the results obtained (RR: 1.13, 95% CI: 1.05-1.21; fixed effects model; heterogeneity: I2=29.87%, 22 studies, 23 datasets; moderate certainty; NNT: 28) (Supplementary Figure 3).
Fig. 2
Forest plot presenting the risk ratio of live birth between women who had endometrial scratching prior to their embryo transfer and those who had a placebo/sham procedure or no intervention
Ongoing pregnancyA higher, but not significantly so, probability of ongoing pregnancy was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.07, 95% CI: 0.98– 1.18; fixed effects model; heterogeneity: I2=27.44%, 11 studies, 11 datasets, 4515 patient; low certainty) (Fig. 3). Publication bias did not seem to be present (p=0.494). A sensitivity analysis excluding studies at high risk of bias did not materially change the results obtained (RR: 1.07, 95% CI: 0.97-1.18; fixed effects model; heterogeneity: I2=0.00%, 8 studies, 8 datasets; moderate certainty) (Supplementary Figure 4).
Fig. 3
Forest plot presenting the risk ratio of ongoing pregnancy between women who had endometrial scratching prior to their embryo transfer and those who had a placebo/sham procedure or no intervention
Clinical pregnancyA significantly higher probability of clinical pregnancy was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.12, 95% CI: 1.06– 1.18; fixed effects model; heterogeneity: I2=47.48%, 37 studies, 38 datasets, 8804 patients; low certainty; NNT: 27) (Fig. 4). Publication bias did not seem to be present (p=0.514). A sensitivity analysis excluding studies at high risk of bias did not materially change the results obtained (RR: 1.12, 95% CI: 1.05-1.19; fixed effects model; heterogeneity: I2=21.88%, 21 studies, 22 datasets; moderate certainty; NNT: 25) (Supplementary Figure 5).
Fig. 4
Forest plot presenting the risk ratio of clinical pregnancy between women who had endometrial scratching prior to their embryo transfer and those who had a placebo/sham procedure or no intervention
Cumulative live birthA higher, but not significantly so, probability of cumulative live birth was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.11, 95% CI: 0.99–1.24; fixed effects model; heterogeneity: I2=0%, 2 studies, 1298 patients; very low certainty) (Supplementary Figure 6). Publication bias could not be assessed due to the small number of available studies.
MiscarriageNo significant difference in the probability of miscarriage was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 0.89, 95% CI: 0.75–1.06; fixed effects model; heterogeneity: I2=0%, 24 studies, 25 datasets, 2568 patients; low certainty) (Supplementary Figure 7). Publication bias did not seem to be present (p=0.432).
Ectopic pregnancyNo significant difference in the probability of ectopic pregnancy was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.02, 95% CI: 0.46– 2.27; fixed effects model; heterogeneity: I2=0%, 8 studies, 9 datasets, 1219 patients; very low certainty) (Supplementary Figure 8). Publication bias did not seem to be present (p=0.148).
Multiple pregnancyNo significant difference in the probability of multiple pregnancy was present in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.11, 95% CI: 0.92–1.35; fixed effects model; heterogeneity: I2=25.68%, 17 studies, 18 datasets, 1974 patients; low certainty) (Supplementary Figure 9). Publication bias did not seem to be present (p=0.482).
Adverse events PainFive studies [4, 8, 19, 36, 44] reported pain in the endometrial scratching group with VAS scores ranging from 3.5 to 6.4. Only one study (158 patients) provided VAS scores both in the endometrial scratching group and the control group (sham procedure) indicating higher pain scores (6.42, SD (2.35) vs 1.82, SD (1.52); P < 0.001) in women who had the endometrial scratching [19].
BleedingIn patients allocated to endometrial scratching, bleeding was reported in a proportion of them in four studies [5, 8, 33, 42], while in further 8 studies [13, 19, 23, 29, 38, 39, 41, 43] no patients experienced bleeding after endometrial scratching The remaining studies did not report on this adverse event.
InfectionIn patients allocated to endometrial scratching no infections were observed in 11 studies [5, 8, 13, 19, 23, 29, 38, 39, 41,42,43], while the remaining studies did not report on this adverse event.
DizzinessIn patients allocated to endometrial scratching, dizziness was not observed in 10 studies [8, 13, 19, 23, 29, 38, 39, 41,42,43] while in a single study [5] 7 out of 690 patients (~1%) who underwent endometrial scratching experienced this adverse event.
FeverIn patients allocated to endometrial scratching, fever was not observed in 10 studies [5, 13, 19, 23,
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