P-159 The role of Embryo transfer medium containing high concentrations of hyaluronic acid on IVF outcome: A systematic review and meta-analysis
Authors: Smith I , Varghese A.C , Jayaprakasan K 
Published: June 2022

Abstract

Study question
Does embryo transfer medium containing high concentrations of hyaluronic acid (HA) increase In Vitro Fertilisation (IVF) success rate?

Summary answer
Embryo transfer medium containing high concentration of HA has increased the live birth (LBR) and clinical pregnancy rate (CPR) whilst decreasing the miscarriage rate.

What is known already
The recent Cochrane systematic review reported low to moderate evidence to support the use of high concentration hyaluronic acid (HA) in the treatment group. Previous studies have also shown no effect of high concentration HA on frozen embryo transfer (FET) rate and have identified the supplementation of the transfer media with HA to have no significance on adverse effect rate.

Study design, size, duration
A literature search was performed on three online databases: Ovid Medline, PsychInfo and Central Cochrane. 1162 citations were retrieved and after screening abstracts and titles 1099 citations were removed and a following 37 removed after screening full texts. This left 26 publications for the review. Bias was assessed for in RCTs using Cochrane collaboration tool of bias and STROBE for observational studies. Meta-analysis was performed using Review manager identifying the risk ratio (RR) and heterogeneity.

Participants/materials, setting, methods
In the review, 6304 participants in the treatment group and, 5965 in the control group were included. The primary outcomes was LBR and secondary outcomes were CPR; miscarriage rate; multiple pregnancy rate; ectopic pregnancy and congenital abnormalities. A subgroup analysis was performed looking into the outcome based on the stage of embryos transferred, the exposure time to the transfer medium and difference between frozen and fresh embryo transfer.

Main results and the role of chance
There was a significant increase in LBR (RR: 1.25; 95% CI 1.17 to 1.33) with use of high concentration HA and this positive effect was seen in both cleavage stage and blastocyst transfer cycles. CPR was also higher (RR: 1.16 (95% CI 1.10 to 1.22), while Miscarriage rate was significantly reduced (RR: 0.75; 95% CI 0.66 to 0.85) in the treatment group. Multiple pregnancy rate were higher in the study group (RR: 1.33; 95% CI: 1.16 to 1.53), although one study had a large influence on these results. The ectopic pregnancy rates (RR: 0.62; 95% CI 0.19 to 1.99) and congenital abnormalities (RR: 0.84; 95% CI 0.37 to 1.92) were similar. On subgroup analysis, the higher LBR was seen only for fresh cycles (RR: 1.2; 95% CI 1.1 to 1.3) but were similar for frozen embryo transfer (RR: 0.99; 95% CI 0.8 to 1.24). Further, LBR were higher in both short (10 minutes) and long exposure (&gt;10 minutes) groups (RR: 1.32; 95% CI 1.19 to 1.45 and RR: 1.23; 95% CI 1.14 to 1.33 respectively.

Limitations, reasons for caution
The high heterogeneity across the studies may increase the risk of bias in the results. Inclusion of observational studies also has an inherent risk of selection bias. The review did not have a restrictive exclusion criterion resulting in inclusion of patients from a large demographic, limiting the specificity of results.

Wider implications of the findings
The data from this review support the use of embryo transfer medium containing high concentration of HA during fresh IVF cycles but not for frozen cycles. However, a large RCT is warranted particularly for selected groups like women of advanced maternal age and those with recurrent implantation failure.

Trial registration number
Not applicable