Reply. The role of endometrial scratching in IVF/ICSI: a critical appraisal of individual participant data meta-analysis (2024)

Search for other works by this author on:

Article history

Sir,

We would like to thank Aktoz (2024) for their kind words regarding our work (van Hoogenhuijze et al., 2023), as well as for taking the time and energy to further discuss the scientific content and its interpretation. After the many randomized controlled trials and other studies that had been conducted on endometrial scratching—all with slightly different methods and inclusion criteria—the scientific and clinical community had become divided on its relevance. With our individual participant data (IPD) meta-analysis, we therefore aimed to align all these trials and extract as much information as possible in order to give the best balanced assessment of the value of endometrial scratching for patients in the IVF/ICSI treatment path.

The first point raised by Aktoz (2024) is the discussion on how strongly we believe that endometrial scratching improves chances of live birth, based on the odds ratios (ORs) of around 1.25 but confidence intervals with lower limits close to 1.0 and a few just below 1.0. While statistical significance is a definition with a sharp yes/no cutoff, in reality, we believe that it should rather be viewed as the spectrum from ‘less likely a true difference’ to ‘very likely a true difference’ that it is. On this spectrum, our point-estimates for the ORs were all similar, the 95% confidence intervals became wider with smaller sample sizes (as expected in statistics), and the lower limits of the 95% confidence intervals were also similar in all analyses. These data support that there is a good chance that endometrial scratching indeed improves live birth rates, but of course with taking caution of the lower confidence interval limits that show that endometrial scratching may also have a more limited or a nil effect. Nevertheless, chances are 97.5% that the effect of scratching is larger than the lower limit of the confidence interval. We therefore believe we have rightly attenuated our conclusion by stating that scratching may improve live birth rates, and we have highlighted the uncertainties multiple times in our discussion by stating that it cannot be ruled out that scratching has no or even a negative effect. We also clearly stated caution by highlighting the unknowns (e.g. biological plausibility, optimal timing) and what has not yet been researched (e.g. effect of repeated scratching), and expressed that implementation in clinical practice should take these unknowns into consideration in deciding whether to implement this technique.

We would like to thank Aktoz (2024) for drawing our attention to the second point, which we think is mostly a different interpretation of the meaning of ‘in line with’. In our discussion, we state that ‘the overall results of this IPD-MA are in line with previous conventional meta-analyses; the most recent being the Cochrane update’—even though the Cochrane review (Lensen et al., 2021) reported no significant improvements after scratching but a positive trend. What we aimed to express is that the Cochrane’s (and other meta-analyses’) ORs and confidence intervals are all in the same area on the spectrum of statistical significance. In other words, the confidence intervals overlap and the point-estimates of the ORs fall within each other’s confidence intervals. Thus, while the conclusions of the various scientific works are different, the results do not contradict each other and are, in fact, ‘in line’ with each other.

The last point of Aktoz (2024) is regarding the inclusion of the aggregate data (AD) from the randomized controlled trial by Metwally et al. (2022), which we included in an additional two-stage intention-to-treat IPD + AD analysis (Fig.3 of van Hoogenhuijze et al., 2023). We agree that in Fig.3, we could have highlighted better that the trial by Metwally et al. is different from the other trials in that they did not yet share their IPD. While the main one-stage analysis and all other analyses were performed solely on the 13 trials that shared IPD, we decided to also include a separate two-stage analysis with Metwally et al.’s trial as they did agree to share IPD in the future but could not do so at that moment in time. Therefore, we were interested to estimate if and how this study would affect the study results if it were included in the IPD analysis. We did not receive any other agreements for future participation, otherwise we would have included those trials as well. We could not assess this trial for Risk of Bias (RoB) as it was not published yet at the time of submission—we only included full-text publications in the RoB, as it is very hard to determine this based on a conference abstract. We agree with Aktoz (2024) that including Metwally’s results this way is suboptimal as the study could not be assessed as thoroughly as the other trials and obtaining IPD could have led to slightly different numbers of events, but given their willingness to participate in the future and given that it is the second-largest trial that seems to be performed according to current scientific standards, it was thought even less optimal to not include them in any of the analyses.

All in all, we agree with Aktoz (2024) that even though our point-estimates suggest a positive impact from endometrial scratching on the chance of live birth, careful consideration should be applied when implementing it in clinical practice given the uncertainties regarding scratching method and timing. Proper counseling of couples that could have an indication for endometrial scratching is therefore key in order to achieve a well-shared decision. We would like to thank Aktoz (2024) again for deepening the discussion on our results and on endometrial scratching in general: only through this can we progress science and improve patient care.

Conflict of interest

N.v.H. has received honorarium for presentations from Merck and Organon. F.B. has received a speaking fee for a lecture from Besins healthcare, reports a grant from Merck, and participation on advisory boards for Merck and Ferring.

References

© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com

Email alerts

See also

Citing articles via

More from Oxford Academic