Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials

Abstract

ObjectivesTo identify the efficacy and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery. Data sourcesPubMed, EMBASE, Cochrane Library, Web of science and ClinicalTrials.gov up to November 1, 2023. Study eligibility criteriaRandomized controlled trials reported intrauterine adhesion and fertility outcomes in women using hyaluronic acid following intrauterine surgery. Study appraisal and synthesis methodsThe risk of bias was assessed using criteria per the Cochrane Handbook and the quality of evidence was evaluated using the GRADE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and Stata 14 was used for sensitivity analysis and publication bias analysis. ResultsData from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (Risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2 = 48%) and improve pregnancy rates (Risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2 = 0%). Subgroup analysis was conducted based on factors influencing the effect of hyaluronic acid on the incidence of intrauterine adhesion: It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect in patients undergoing various intrauterine surgeries and with different gynecological medical histories. The protective effect was statistically significant after a follow-up of 6-12 weeks. The trial sequential analysis results indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesion, pregnancy rate, livebirth rate, and miscarriage rate after intrauterine surgery may be inconclusive and necessitate further demonstration through additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. ConclusionsHyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesion and may improve fertility outcomes.