Barrier agents for adhesion prevention after gynaecological surgery

Review question

This review of trials assessed the effects of barriers agents on pelvic pain, live birth and adhesion formation after pelvic surgery.

Background

A common problem following surgery or infection is the occurrence of adhesions, where two normally separate surfaces stick together. Pelvic adhesions are commonly associated with infection, endometriosis or surgical trauma. During pelvic surgery, strategies to reduce pelvic adhesion formation include placing a synthetic physical barrier between the pelvic structures.

Study characteristics

We included 18 randomised controlled trials (RCTs) of 1262 women undergoing gynaecological surgery. They assessed different types of barrier agents for preventing adhesions and compared them with each other or with no treatment. The data are current to February 2015. Twelve RCTs reported commercial funding; the other studies did not state their source of funding.

Key results

We found no evidence on the effects of barrier agents used during pelvic surgery on either pain or fertility outcomes in women of reproductive age.

Low-quality evidence suggested that oxidised regenerated cellulose (Interceed), expanded polytetrafluoroethylene (Gore-Tex) and sodium hyaluronate with carboxymethylcellulose (Seprafilm) may all be more effective than no treatment in reducing the risk of adhesions following pelvic surgery. There was no conclusive evidence on the relative effectiveness of these interventions. There was no evidence that fibrin sheet was more effective than no treatment. No adverse events directly attributed to the adhesion agents were reported.

Quality of the evidence

The quality of the evidence ranged from very low to moderate. The most common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.

Authors' conclusions: 

We found no evidence on the effects of barrier agents used during pelvic surgery on either pain or fertility outcomes in women of reproductive age.

Low quality evidence suggests that oxidised regenerated cellulose (Interceed), expanded polytetrafluoroethylene (Gore-Tex) and sodium hyaluronate with carboxymethylcellulose (Seprafilm) may all be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. There is no conclusive evidence on the relative effectiveness of these interventions. There is no evidence to suggest that fibrin sheet is more effective than no treatment. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. The most common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.

Read the full abstract...
Background: 

Pelvic adhesions can form as a result of inflammation, endometriosis or surgical trauma. During pelvic surgery, strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene or fibrin sheets between the pelvic structures.

Objectives: 

To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth and postoperative adhesions in women of reproductive age.

Search strategy: 

We searched the following databases in February 2015: the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL) and trial registries. We handsearched relevant journals, conference proceedings and grey literature sources and we contacted pharmaceutical companies for information.

Selection criteria: 

Randomised controlled trials (RCTs) of the use of barrier agents compared with other barrier agents, placebo or no treatment for the prevention of adhesions in women undergoing gynaecological surgery.

Data collection and analysis: 

Two review authors independently assessed trials for eligibility and risk of bias and extracted the data. We calculated odds ratios (ORs) or mean differences (MD) with 95% confidence intervals (CIs) using a fixed effect model. The overall quality of the evidence was assessed using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods.

Main results: 

Eighteen RCTs (1262 women) were included. Six RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (10 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (six RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT) and mixed (one RCT). The sole indication for surgery in three of the RCTs was infertility. Twelve RCTs reported commercial funding; the rest did not state their source of funding.

No studies reported either of our primary outcomes of pelvic pain and live birth.

Oxidised regenerated cellulose (Interceed) versus no treatment at laparoscopy or laparotomy (13 RCTs)

At second-look laparoscopy oxidised regenerated cellulose at laparoscopy was associated with reduced incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, three RCTs, 360 participants, I2 = 75%, very low-quality evidence) and of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, three RCTs, 100 participants, I2 = 36%, low quality evidence).

At second-look laparoscopy no evidence was found of any difference between the groups in the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, one RCT, 271 participants, I2 = 41%, low-quality evidence). However, the incidence of re-formed adhesions was lower in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, six RCTs, 554 participants, moderate-quality evidence).

Expanded polytetrafluoroethylene (Gore-Tex) versus no treatment at gynaecological surgery (one RCT)

The evidence suggested that at second-look laparoscopy expanded polytetrafluoroethylene was associated with a reduction in new adhesion formation (OR 0.17, 95% CI 0.03 to 0.94, one RCT, 42 participants, low-quality evidence).

Expanded polytetrafluoroethylene (Gore-Tex) versus oxidised regenerated cellulose (Interceed) at gynaecological surgery (two RCTs)

One RCT found no difference between the groups at second-look laparoscopy in the incidence of de novo adhesions (OR 0.93, 95% CI 0.26 to 3.41, 38 participants, very low-quality evidence). A second RCT suggested that the expanded polytetrafluoroethylene group had a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants, very low-quality evidence) and a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants, very low-quality evidence). This last finding was sensitive to choice of effect estimate and no longer suggested a difference between the groups when a risk ratio was calculated (RR 0.36, 95% CI 0.13 to 1.01).

Sodium hyaluronate and carboxymethylcellulose (Seprafilm) versus no treatment at gynaecological surgery (one RCT)

Sodium hyaluronate and carboxymethylcellulose was associated with a lower adhesion score (out of 4) at second-look laparoscopy (MD 0.49, 95% CI 0.53 to 0.45, one RCT, 127 participants, moderate-quality evidence).

Fibrin sheet versus no treatment at laparoscopic myomectomy (one RCT)

There was no evidence of a difference between the groups in the incidence of de novo adhesions at second-look laparoscopy (OR 1.20, 95% CI 0.42 to 3.41, one RCT, 62 participants) or in adhesion score (out of 4) (MD 0.14, 95% CI -0.67 to 0.39, one RCT, 48 participants, low-quality evidence).

Fourteen of the 18 RCTs reported adverse events. No events directly attributed to adhesion agents were reported.