Anti‐adhesion therapy following operative hysteroscopy for treatment of female subfertility

Jan Bosteels, Steven Weyers, Jenneke Kasius, Frank J Broekmans, Ben Willem J Mol, Thomas M D'Hooghe

Limited observational evidence suggests potential benefit for subfertile women undergoing operative hysteroscopy with several anti-adhesion therapies (e.g. insertion of an intrauterine device (IUD) or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) to decrease intrauterine adhesions (IUAs). To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. We searched the following databases from inception to March 2015: the Cochrane Menstrual Disorders and Subfertility Specialised Register, the Cochrane Central Register of Controlled Trials (2015, Issue 2), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched The Journal of Minimally Invasive Gynecology, and we contacted experts in the field. Randomised comparisons of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth or ongoing pregnancy. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second look, along with their mean adhesion scores or severity. Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) method. We included 11 randomised studies on use of an inserted device versus no treatment (two studies; 84 women) or another inserted device (one study; 162 women), hormonal treatment versus no treatment or placebo (two studies; 131 women), gel versus no treatment (five studies; 383 women) and graft versus no graft (one study; 43 women). The total number of women randomly assigned was 924, but data on only 803 participants were available for analysis. The proportion of subfertile women varied from 0% (one study; 41 women), to less than 50% (six studies; 487 women), to 100% (one study; 43 women); the proportion was unknown in three studies (232 women). Most studies (9/11) were at high risk of bias with respect to one or more methodological criteria.We found no evidence of differences between anti-adhesion therapy and no treatment or placebo with respect to live birth rates (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.46 to 2.13, P value = 0.98, three studies, 150 women; low-quality evidence) and no statistical heterogeneity (Chi(2) = 0.14, df = 2 (P value = 0.93), I(2) = 0%).Anti-adhesion therapy was associated with fewer IUAs at any second-look hysteroscopy when compared with no treatment or placebo (OR 0.36, 95% CI 0.20 to 0.64, P value = 0.0005, seven studies, 528 women; very low-quality evidence). We found no statistical heterogeneity (Chi(2) = 2.65, df = 5 (P value = 0.75), I(2) = 0%). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 6 to 20).No evidence suggested differences between an IUD and an intrauterine balloon with respect to IUAs at second-look hysteroscopy (OR 1.23, 95% CI 0.64 to 2.37, P value = 0.54, one study, 162 women; very low-quality evidence). Implications for clinical practiceThe quality of the evidence retrieved was low or very low for all outcomes. Clinical effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchAdditional studies are needed to assess the effectiveness of different anti-adhesion therapies for improving reproductive outcomes in subfertile women treated by operative hysteroscopy.