Effect of a Hyaluronan-Enriched Transfer Medium on Live Birth after Frozen Embryo Transfer: A Controlled Study

Hyaluronic acid (HA), a key component of the endometrial extracellular matrix, has been proposed to enhance embryo implantation when added to transfer media. However, its clinical benefit in frozen embryo transfer (FET) cycles remains uncertain. This prospective controlled non-randomized cohort study evaluated the association between HA-enriched transfer medium and reproductive outcomes in a North African IVF center. A total of 692 women undergoing autologous FET with a single frozen–thawed grade 4AA blastocyst were included: 395 in the HA group and 297 in the control group. The primary outcome was clinical pregnancy, defined as the presence of a gestational sac with fetal cardiac activity at 6–8 weeks of gestation. The secondary outcome was miscarriage before 22 weeks. Clinical pregnancy rates were similar between groups (33.1% vs. 34.0%; RR 1.01, 95% CI 0.75–1.37; p = 0.81), as were miscarriage rates (12.1% vs. 11.8%; RR 1.02, 95% CI 0.58–1.78; p = 0.98). Multivariable analysis showed no significant association between HA use and clinical pregnancy (adjusted OR 1.00, 95% CI 0.73–1.37; p = 0.98). Although the confidence intervals exclude a major clinical benefit, the study was not powered to detect modest differences. These findings do not support routine HA use in unselected FET cycles.