Abstract: The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown. No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy. There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I² = 0%; very-low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I² = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopy It was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I² = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I² = 0%; low-quality evidence). Implications for clinical practice The quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for research More research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.

Plain-language summary: We searched for studies that randomly compared any treatment versus no treatment, placebo (pretend treatment) or any other intervention. Outcomes were live birth, clinical pregnancy, miscarriage and presence or severity of scar tissue at the second-look procedure. We found 16 studies. Treatments included using a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with the use of membranes of the afterbirth of newborn babies versus device without membranes (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) or device combined with gel versus device (one study; 120 women). From 1273 randomly assigned women, data on 1133 women were available for analysis. In only two studies, all women had difficulty becoming pregnant. Most studies (14/16) were at high risk of bias for at least one reason. As no study reported live births, we also included data on term delivery or ongoing pregnancy, which five studies reported. It was unclear whether there was a difference between anti-adhesion treatment compared to no treatment (two studies; 107 women) or to other treatment (three studies; 180 women) for increasing the chance of a liveborn baby, a term delivery or an ongoing pregnancy. The use of some anti-adhesion therapies (device with or without hormonal treatment or hormonal treatment or gels) (eight studies; 560 women) may diminish the risk of scar tissue formation compared to no treatment. We would expect that out of 1000 women treated by surgery, between 153 and 365 women would develop scar tissue after using gels, compared with 545 women when no treatment was used. The evidence was current to 6 June 2017. The overall quality of the study evidence ranged from very low to low. There were limitations to the studies, for example, a serious risk of bias related to participants and investigators knowing what treatment was given. More research is needed before anti-adhesion treatment can be offered in everyday clinical practice after surgery of the womb in women having difficulty becoming pregnant.