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.

中文翻译：

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透明质酸凝胶术后宫内应用的短期和长期结果：随机对照试验的荟萃分析

客观的

系统评价透明质酸（HA）凝胶及其衍生物在宫腔粘连（IUA）术后预防中的作用，并评估透明质酸凝胶是否能提高妊娠率。

数据源

2022 年 2 月 2 日，在 PubMed、Cochrane、Scopus、Web of Science 和 Embase 中进行了结构化搜索。

研究选择方法

我们从其他文章中选择医学主题词和相关术语进行数据库搜索。选择了以下干预措施：随机对照试验 (RCT) 中的 HA 凝胶或相关衍生物对比安慰剂。选择以下结果：宫内手术后 IUA 的发生率和严重程度以及妊娠率。全文筛选后，12篇文章被纳入最终分析。使用 Cochrane 工具 (www.training.cochrane.org/handbook) 评估研究质量和偏倚风险。

制表、积分和结果

来自 1579 名患者的 12 篇文章的数据由 2 位独立评审员提取和分析。根据荟萃分析，HA 凝胶可降低 宫内手术后IUA 的风险（风险比 [RR]，0.50；95% 置信区间 [CI]，0.37–0.67；p = .005； I ² = 59%） . 亚组分析显示 HA 凝胶对接受刮宫术 (RR, 0.42; 95% CI, 0.30–0.59; p = .86; I ²  = 0) 或宫腔镜手术 (RR, 0.55; 95% CI，0.38–0.80；p = .007；I ²  = 66%）。敏感性分析表明，去除一项研究可以显着改善异质性。IUA 的严重程度（平均差 = –0.92；95% CI，–1.49 至 –0.34；p <.00；I²  = 89%）在干预组中较低。亚组和敏感性分析没有显着改善异质性。当研究按 HA 凝胶的体积分类时，10 mL（RR，0.40；95% CI，0.27–0.60；p = .96； I ²  = 0）和 5 mL（RR，0.34；95% CI，0.14 –0.82；p = .36； I ²  = 0) 对治疗 IUA 有效。相比之下，HA 凝胶 <5 mL 不足以预防 IUA（RR，0.66；95% CI，0.43–1.01；p = .02； I ²  = 71%；p = .05）。使用 HA 凝胶也提高了妊娠率（RR，1.39；95% CI，1.13–1.72；p = .37， I ²  = 0）。

结论

HA 凝胶有助于预防 IUA 并降低宫内手术后 IUA 的严重程度。根据该分析，建议使用更大体积（≥5 mL）的 HA 凝胶来预防 IUA。此外，HA凝胶可以增加宫内手术后的妊娠率。然而，由于一些样本量相对较小且样本异质性的随机对照试验质量不足，因此应谨慎解释这些结论。未来需要大型 RCT 来验证这些结论。