Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials

Abstract

Objective: To systematically evaluate the role of hyaluronic acid (HA) gel and its derivatives in the postoperative prevention of intrauterine adhesions (IUA) and to assess whether HA gel could improve the pregnancy rate.

Data sources: A structured search was performed in PubMed, Cochrane, Scopus, Web of Science, and Embase on February 2, 2022.

Methods of study selection: We chose medical subject headings and relevant terms from other articles for the database search. The following intervention was selected: HA gel or related derivatives vs placebo in randomized controlled trials (RCTs). The following outcomes were selected: the rate and severity of IUA after intrauterine operations and pregnancy rate. After the full-text screening, 12 articles were included in the final analysis. The study quality and risk of bias were assessed with the Cochrane tool (www.training.cochrane.org/handbook).

Tabulation, integration, and results: Data from 12 articles on 1579 patients were extracted and analyzed by 2 independent reviewers. According to the meta-analysis, HA gel could decrease the risk of IUA (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.37-0.67; p = .005; I² = 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilatation and curettage (RR, 0.42; 95% CI, 0.30-0.59; p = .86; I² = 0) or hysteroscopic surgery (RR, 0.55; 95% CI, 0.38-0.80; p = .007; I² = 66%). The sensitivity analysis showed that heterogeneity could be improved significantly by removing one study. The severity of IUA (mean difference = -0.92; 95% CI, -1.49 to -0.34; p <.00; I² = 89%) was lower in the intervention group. Subgroup and sensitivity analyses did not significantly improve the heterogeneity. When the studies are classified by the volume of HA gel, 10 mL (RR, 0.40; 95% CI, 0.27-0.60; p = .96; I² = 0) and 5 mL (RR, 0.34; 95% CI, 0.14-0.82; p = .36; I² = 0) were effective in treating IUA. In contrast, HA gel <5 mL was not sufficient to prevent IUA (RR, 0.66; 95% CI, 0.43-1.01; p = .02; I² = 71%; p = .05). The pregnancy rate was also improved by the use of HA gel (RR, 1.39; 95% CI, 1.13-1.72; p = .37, I² = 0).

Conclusion: HA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A greater volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Moreover, HA gel can increase the pregnancy rate after intrauterine surgery. However, these conclusions should be interpreted with caution because of the inadequate quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are required to verify these conclusions in the future.

Keywords: Hyaluronic acid gel; Intrauterine adhesion; Meta-analysis.