Hyaluronic Acid Enriched Medium for Embryo Transfer: A Systematic Review and Meta-analysis

This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated whether the use of hyaluronic acid (HA)-enriched medium for embryo transfer (ET) improves live birth rates in in-vitro fertilization (IVF) cycles. A comprehensive search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov was conducted up to December 2024, without language restrictions, and only RCTs comparing HA-enriched to standard ET media were included. Risk of bias was assessed using the Cochrane tool, meta-analyses were performed using a random-effects model with the Mantel-Haenszel method, sensitivity analyses excluded studies at high risk of bias, and evidence quality was evaluated with GRADE. Of 450 records identified, 24 studies were eligible, of which 20 were included in the meta-analysis, and most studies had a high risk of bias. Eleven studies reported live birth outcomes, with 2,026 versus 2,037 participants and 803 versus 697 live births in the HA-enriched and standard medium groups, respectively. The relative risk (RR) for live birth was 1.14 (95% CI: 0.99-1.31; p=0.07), with moderate heterogeneity (I2=54%), and sensitivity analysis showed an RR of 1.06 (95% CI: 0.85-1.31; p=0.62). Clinical pregnancy rates were initially higher with HA-enriched medium (RR=1.17; 95% CI: 1.05-1.29; p=0.004), but this effect disappeared in sensitivity analysis (RR=1.05; p=0.53), and pregnancy loss showed no significant difference between groups. Previous studies had suggested a potential benefit of HA-enriched ET medium on live birth outcomes; however, in the present analysis no significant difference in live birth rates was observed between HA-enriched and standard ET media. Overall evidence quality was rated as very low due to high risk of bias, inconsistency, and imprecision, and current evidence does not support a clear benefit of HA-enriched ET medium, although ongoing trials may further clarify its role.