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

Min Cheng,Wen-Ling Lee,Chia-Pei Chang,Wen-Hsun Chang,Hsin-Yi Huang,Peng-Hui Wang,Kuan-Hao Tsui,Szu-Ting Yang

doi:10.3390/life10110285

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.

Highlights

Intrauterine adhesion (IUA) is a potentially chronic complication developed by the pathophysiology of trauma to the vascular basal layer of the endometrium, mainly as a result of hysteroscopic surgery, uterine curettage, termination of pregnancy, cesarean section, or genital tuberculosis or other severe inflammation processes [1,2,3,4,5,6,7,8,9]
randomized controlled trials (RCTs) were eligible according to the following inclusion criteria: women undergoing hysteroscopic surgery for benign gynecologic disease, adhesion barrier of hyaluronic acid (HA) gel applied primarily at the end of surgery, and second-look hysteroscopy performed to identify the incidence and severity of IUA
After removing duplications and articles with unrelated topics, a total of 34 studies were reviewed in detail for eligibility; 31 studies were excluded, including 16 articles in review form, 1 observational study, 9 studies with evaluations of secondary intrauterine adhesion, 3 animal studies, 1 study with only one arm, and 1 conference abstract

Summary

Introduction

Intrauterine adhesion (IUA) is a potentially chronic complication developed by the pathophysiology of trauma to the vascular basal layer of the endometrium, mainly as a result of hysteroscopic surgery, uterine curettage, termination of pregnancy, cesarean section, or genital tuberculosis or other severe inflammation processes [1,2,3,4,5,6,7,8,9]. IUA presents a challenge to the endometrial model of scar-free wound healing. The healing process of the endometrium is similar to the classical wound healing process, including three separate, continuous, and overlapping steps: hemostasis/inflammatory, proliferative, and remodeling phases [10,11,12,13,14,15]. Several postulated mechanisms for the loss of scar-free regeneration and repair have been proposed. They include hypoxic injury, unbalanced inflammatory process, decreased angiogenesis, disturbance of immune and molecular mechanisms, unregulated epithelial–mesenchymal transition, aberrant myofibroblast differentiation, bizarre stem cell regeneration, and interrupted normal endometrial cell proliferation [16,17]. IUA is a severe form of disruption of normal endometrial regeneration

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