Short- and long-term outcomes of postoperative intrauterine application of hyaluronic acid gel: a meta-analysis of randomized controlled trials

Goal

To systematically assess 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.

Information source

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

Study selection methods

We selected medical subject headings and relevant terms from other articles to search the database. The following intervention was selected: HA gel or related derivatives versus placebo in randomized controlled trials (RCTs). The following outcomes were selected: rate and severity of AUI after intrauterine operations and pregnancy rate. After full-text screening, 12 articles were included in the final analysis. Study quality and risk of bias were assessed with the Cochrane tool.

Tabulation, integration and results

Data from 12 articles involving 1579 patients were extracted and analyzed by two independent reviewers. According to the meta-analysis, HA gel could reduce the risk of IUA (relative risk[RR]= 0.50; 95% confidence interval [CI] 0.37 to 0.67; P=0.005; I2= 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilation and curettage (D&C) (RR=0.42; 95% CI 0.30-0.59; P= 0.86;I2= 0) or hysteroscopic surgery (RR = 0.55, 95% CI 0.38–0.80; P = 0.007; I2= 66%). Sensitivity analysis showed that heterogeneity could be significantly improved by deleting one study. The severity of the IUA (mean difference[MD]= -0.92; 95% CI -1.49 to -0.34; P2= 89%) was lower in the intervention group. Subgroup and sensitivity analyzes did not significantly improve heterogeneity. When studies are ranked by volume of HA gel, 10 mL (RR=0.40; 95% CI 0.27-0.60; P=0.96; I2= 0) and 5 mL (RR = 0.34; 95% CI 0.14–0.82; P = 0.36; I2= 0) were effective in the treatment of IUA. In contrast, HA gel 2= 71%; p = 0.05). Pregnancy rate was also improved by using HA gel (RR=1.39; 95% CI 1.13–1.72; P=0.37, I2= 0).

Conclusion

HA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A larger volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Additionally, HA gel can increase the pregnancy rate after intrauterine surgery. However, these findings should be interpreted with caution due to the insufficient quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are needed to verify these findings in the future.