We have read the systematic review of Genovese et al.  with interest. Since the same topic has been studied by our study group, we would like to raise some issues.
This systematic review gives a good overview of the most recent evidence on this topic. We believe it is a strength that the authors compared single- and double-layer as clearly as possible by leaving out studies in which locked techniques and endometrial-saving techniques were used since they might interfere with the outcome. Furthermore, almost all included studies were performed in women undergoing a first CS, except for the study of Bamberg et al.  which is good to prevent confounding.
However, in our opinion, it is not right that the authors concluded that “double-layer closure ensures a better healing process of the uterine incision” when no pooling of data has taken place. As far as we are aware, no quantitative data support the statement of Genovese et al.  that double-layer closure after CS is superior to single-layer closure. The fact that several guidelines recommend a specific suture technique is, in our opinion, no reason to not further elaborate on this comparison: the NICE guideline has been updated in March 2021 and now states “as there was no difference between single and double layer closure for the majority of outcomes, the committee agreed that either technique could be used” . The ERASSR recommendation  of double-layer closure (low level of evidence, weak recommendation grade) is based on a higher prevalence of uterine rupture after single-layer closure, reported in a retrospective cohort study published in 2002 in which locked sutures were used , and they also state that more recent evidence does not show superiority of any of the techniques .
To quantitatively support the conclusions of Genovese et al. , we have performed a meta-analysis based on their data to compare single- with double-layer closure and included the same studies, for the outcomes “niche prevalence” (dichotomous outcome, 6 studies of which 4 RCT’s included) [2, 7‒11] and “residual myometrium thickness” (continuous outcome, 4 RCT’s included) . There is no evidence for the superiority of double-layer closure regarding both outcomes, although no figures could be presented in this letter. Niche prevalence was not different between groups (71.8% after single-layer closure vs. 62.1% after double-layer closure, both including the endometrium, RR 1.02, 95% CI: 0.97–1.08, I2 67%, p = 0.42). Residual myometrium thickness was slightly thinner after single-layer closure including the endometrium: weighted mean difference −0.26 mm (95% CI: −0.51 to −0.01, I2 87%, p = 0.05), although the clinical relevance of this difference is of course debatable.
Although the hypothesis of our clinical trial was also that double-layer uterine closure could reduce niche prevalence and related symptoms, based on our systematic review and meta-analysis , we did not prove this in our large RCT the “2Close study” . As stated in Table 2 in the article of Genovese et al. , we found a small difference in niche prevalence in favour of single-layer closure. All other short-term outcomes, including perioperative findings and ultrasound measurements after 3 months, as well as bleeding disorders and quality of life at 9 months follow-up, were not different. Our long-term results at 3 years follow-up will be published soon. We believe that this is enough evidence that single- and double-layer uterine closure can be performed equally, based on safety outcomes, ultrasound findings, and clinical symptoms.
There are, however, some recommendations to make for future studies. Not only other uterine suture factors, for example, inclusion or exclusion of the serosa and decidua but also continuous versus interrupted sutures might be topics of future studies. The level of the uterotomy, correct approximation of the wound edges of the uterotomy, and proper training of residents, and also the use of specific suture material, are additional factors that might contribute to niche development .
Above all, more evidence is needed before solid conclusions can be drawn. For the design of new studies, we advise to perform standardized evaluation of the sonographic scar as has been consented upon among experts . To facilitate implementation, we have also developed an e-learning on how to measure the niche that is freely available . Furthermore, we advise to assess, besides sonographic outcomes, also short- and in particular long-term outcomes including fertility and obstetric outcomes since these are more important for the individual patient. Properly designed studies including long-term clinical outcomes will enable us to develop future preventive strategies for the development of niche-related problems.
Conflict of Interest Statement
Judith Huirne received a grant from ZonMw for the execution of the 2Close trial; she received a grant from PlantTec for the execution of a pilot study (4DryField) to study the effect of adhesion barrier on niche formation and gynaecological complaints. Both funders had no role in the preparation of the currently presented data or the creation of the current manuscript. She received a grant from Samsung and a fee from Olympus, all outside the submitted work. The remaining authors report no conflict of interest.
Sanne I. Stegwee performed the analyses and drafted the first version of the manuscript. Carry Verberkt and Judith A.F. Huirne interpreted the data and critically revised the manuscript. All authors approved the current version to be published.