Anti-adhesion barrier gels following operative hysteroscopy for treating female infertility: a systematic review and meta-analysis

Abstract

The aim of this study was to assess the effects of any anti-adhesion barrier gel used after operative hysteroscopy for treating infertility associated with uterine cavity abnormalities. Gynecologists might use any barrier gel following operative hysteroscopy in infertile women for decreasing de novo adhesion formation; the use of any barrier gel is associated with less severe de novo adhesions and lower mean adhesion scores. Nevertheless, infertile women should be counseled that there is at the present no evidence for higher live birth or pregnancy rates. There is a lack of data for the outcome miscarriage. Preclinical studies suggest that the use of biodegradable surgical barriers may decrease postsurgical adhesion formation. Observational studies in the human report conflicting results. We searched the Cochrane Menstrual Disorders and Subfertility Specialized Register (10 April 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), MEDLINE (1950 to 4 April 2013), EMBASE (1974 to 4 April 2013), and other electronic databases of trials including trial registers, sources of unpublished literature, and reference lists. We handsearched the Journal of Minimally Invasive Gynecology (from 1 January 1992 to 13 April 2013); we also contacted experts in the field. We included the randomized comparisons between any anti-adhesion barrier gel versus another barrier gel, placebo, or no adjunctive therapy following operative hysteroscopy. Primary outcomes were live birth rates and de novo adhesion formation at second-look hysteroscopy. Secondary outcomes were pregnancy and miscarriage rates, mean adhesion scores, and severity of adhesions at second-look hysteroscopy. Two authors independently assessed eligible studies for inclusion and risk of bias, and extracted data. We contacted primary study authors for additional information or other clarification. Five trials met the inclusion criteria. There is no evidence for an effect favoring the use of any barrier gel following operative hysteroscopy for the key outcomes of live birth or clinical pregnancy (risk ratio (RR) 3.0, 95 % confidence interval (CI) 0.35 to 26, P = 0.32, one study, 30 women, very low quality evidence); there were no data on the outcome miscarriage. The use of any gel following operative hysteroscopy decreases the incidence of de novo adhesions at second-look hysteroscopy at 1 to 3 months (RR 0.65, 95 % CI 0.45 to 0.93, P = 0.02, five studies, 372 women, very low quality evidence). The number needed to treat to benefit is 9 (95 % CI 5 to 33). The use of auto-cross-linked hyaluronic acid gel in women undergoing operative hysteroscopy for fibroids, endometrial polyps, or uterine septa is associated with a lower mean adhesion score at second-look hysteroscopy at 3 months (mean difference (MD) -1.44, 95 % CI -1.83 to -1.05, P < 0.00001, one study, 24 women; this benefit is even larger in women undergoing operative hysteroscopy for intrauterine adhesions(MD -3.30, 95 % CI -3.43 to -3.17, P < 0.00001, one study, 19 women). After using any gel following operative hysteroscopy, there are more American Fertility Society 1988 stage I (mild) adhesions (RR 2.81, 95 % CI 1.13 to 7.01, P = 0.03, four studies, 79 women). The number needed to treat to benefit is 2 (95 % CI 1 to 4). Similarly there are less' moderate or severe adhesions' at second-look hysteroscopy (RR 0.25, 95 % CI 0.10 to 0.67, P = 0.006, four studies, 79 women). The number needed to treat to benefit is 2 (95 % CI 1 to 4) (all very low quality evidence). There are some concerns for the non-methodological quality. Only two trials included infertile women; in the remaining three studies, it is not clear whether and how many participants suffered from infertility. Therefore, the applicability of the findings of the included studies to the target population under study should be questioned. Moreover, only one small trial studied the effects of anti-adhesion barrier gels for the key outcome of pregnancy; the length of follow-up was, however, not specified. More well-designed and adequately powered randomized studies are needed to assess whether the use of any anti-adhesion gel affects the key reproductive outcomes in a target population of infertile women.

Keywords: Adhesion prevention; Barrier gel; Infertility; Meta-analysis; Operative hysteroscopy; Systematic review.

Fig. 1

Intrauterine adhesions

Fig. 2

Study flow diagram

Fig. 3

Risk of bias summary: review authors’ judgments about each risk of bias item for each included study

Fig. 4

Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies

Fig. 5

Any anti-adhesion gel versus no gel, outcome 2: incidence of de novo adhesions at second-look hysteroscopy

Fig. 6

Any anti-adhesion gel versus no gel, outcome 3: pregnancy

Fig. 7

Auto-cross linked hyaluronic acid gel versus no gel, outcome 5.1: mean adhesion score AFS 1988 at 3 months in women with myomas, polyps, or uterine septa

Fig. 8

Auto-cross linked hyaluronic acid gel versus no gel, outcome 5.2: mean adhesion score AFS 1988 at 3 months in women with intrauterine adhesions

Fig. 9

Any anti-adhesion gel versus no gel, outcome 5.3: AFS 1988 stage I (mild) adhesions at second-look hysteroscopy

Fig. 10

Any anti-adhesion gel versus no gel, outcome 5.3: AFS 1988 stage II (moderate) adhesions at second-look hysteroscopy

Fig. 11

Any anti-adhesion gel versus no gel, outcome 5.3: AFS 1988 stage III (severe) adhesions at second-look hysteroscopy

Fig. 12

Any anti-adhesion gel versus no gel, outcome 5.3: AFS 1988 stage II (moderate) or stage III (severe) adhesions at second-look hysteroscopy