Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials

Abstract

Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced development of intrauterine instruments, more intrauterine diseases can be successfully cured by hysteroscopic surgery. Among these, submucosal myoma is one of the best examples. Submucosal myomas are often related to abnormal bleeding, anemia, and possible infertility or miscarriage. However, submucosal myoma after hysteroscopic myomectomy may be complicated by IUA in various grades of severity, and its incidence and prevalence might be nearly one-quarter to one-third of patients, suggesting an urgent need for efforts to decrease the risk of developing IUA after hysteroscopic myomectomy. Many strategies have been reported to be useful for this purpose, and intrauterine application of anti-adhesive gels, such as polyethylene oxide–sodium carboxymethylcellulose (PEO-NaCMC) or auto-crosslinked hyaluronic acid (ACHA), has become increasingly popular in routine clinical practice. This meta-analysis is aimed at investigating the effect of ACHA on the primary prevention of IUA formation after hysteroscopic myomectomy. A pooled analysis of three studies (hysteroscopic surgeries for fibroids, polyps, and septum) including 242 women showed that using PEO-NaCMC or ACHA gel decreased the IUA rate with an odds ratio (OR) of 0.364 (95% confidence interval (CI) 0.189–0.703, p = 0.03). Pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction of the development of IUA postoperatively (OR 0.285, 95% CI 0.116–0.701, p = 0.006). All of this suggests that the use of ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA, although more evidence is needed.

Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision

“…Our previous findings demonstrated that crosslinked hyaluronic acid gels are highly recommended for the prevention of intrauterine adhesions [ 86 ]. A pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction in the development of IUA postoperatively (OR 0.285, 95% CI 0.116–0.701, p = 0.006) [ 148 ]. All this suggests that using ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA.…”

“…A barrier can be achieved by two strategies; one uses agents and the other is physical or mechanical. Agents act as a barrier, can be solid form, liquid form (hydroflotation agents) or gel form, and the components include polyethylene oxide–sodium carboxymethylcellulose gel and crosslinked hyaluronic acid (CHA) gels [ 71 , 81 , 82 , 96 , 97 , 98 , 99 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 120 , 148 , 149 , 154 , 155 , 156 ]. Physical or mechanical barriers include intrauterine suitable balloon catheters, Foley balloon catheters, Malecot catheters, silicone sheets, and intrauterine devices (IUD) [ 73 , 103 , 104 , 105 , 106 , 107 , 108 ].…”

Bioprinting of a Blue Light-Cross-Linked Biodegradable Hydrogel Encapsulating Amniotic Mesenchymal Stem Cells for Intrauterine Adhesion Prevention

“… 19 Currently, hydrogels based on natural materials such as chitosan, gelatin, and hyaluronic acid have been used to prevent adhesion. 20 − 22 Due to their poor mechanical properties and rapid degradation, they are not yet able to achieve satisfactory treatment outcomes. In order to improve the physical properties of natural polymers and enhance their resistance to enzyme attacks, 23 light-activated materials play an increasingly important role in three-dimensional (3D) bioprinting technology.…”

“…Prior research suggests that a GelMA hydrogel has good biological and adjustable physical properties, which allows cell proliferation and diffusion in GelMA hydrogel-based materials. 22 , 24 Collagen is the main component of the extracellular matrix (ECM), which is widely used in the field of biomaterials because of its good physical and chemical properties. 25 − 27 However, a pure collagen hydrogel has a single structure, simple properties, and poor mechanical properties.…”

Special Issue “Reproductive Health Concerns for Women”

“…Women treated with HA gels have a statistically significant lower incidence of IUAs than non-treated women (13% vs. 39%), and additionally, women receiving the HA gel treatment have a significantly reduced severity of IUA than women in the no-HA treatment group [7]. In the current special issue, based on the positive benefits of application of HA as a preventive strategy for patients after hysteroscopic myomectomy [7], a systematic review and meta-analysis was conducted to investigate the effect of HA on the primary prevention of IUA formation after hysteroscopic myomectomy [8]. A pooled analysis of three randomized controlled trials shows a statistically significant reduction in the development of IUA postoperatively, with an odd ratio (OR) of 0.29, and a 95% confidence interval (CI) of 0.12~0.70, suggesting that the use of HA gel in patients after hysteroscopic myomectomy can significantly reduce de novo IUA [8].…”