The Significance of Hyaluronic Acid in Fertility Treatments: Current Evidence and Future Directions

A BSTRACT The etiological factors of infertility include endocrine dysfunctions, oxidative stress, genetic predisposition, environmental influences, and unexplained reproductive anomalies. Recent research clearly highlighted the significant role of oxidative stress in female infertility, particularly its impact on oocyte viability and embryonic development. Reactive oxidative stress contributes to poor fertilization outcomes, recurrent implantation failure, and pregnancy loss. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has been widely studied in the context of reproductive medicine, especially in assisted reproductive technologies (ART). HA is an important component of the extracellular matrix (ECM) and plays a role in oocyte maturation, sperm selection, embryo implantation, and endometrial receptivity. The incorporation of HA-enriched embryo transfer media (HETM) has been proven to improve implantation rates, clinical pregnancy rates, and live birth outcomes, especially in patients who have previously failed in-vitro fertilization (IVF). Furthermore, HA-mediated sperm selection techniques, such as Physiological Intracytoplasmic Sperm Injection (PICSI), enhance the fertilization potential by selecting sperm with intact deoxyribonucleic acid (DNA) integrity. Although promising results have been obtained, the efficacy of HA in ART remains to be explored. While some studies suggest improved embryo adhesion and better clinical pregnancy rates, others suggest that the benefit is minimal in non-selected patient populations. Future randomized controlled trials are needed to establish standardized protocols for the application of HA in ART. This review discusses the mechanistic role of HA in reproductive biology and its clinical implications in optimizing ART success.