Hyaluronic acid-based sperm selection and embryo euploidy in human PGT-A cycles: A sibling-oocyte randomized study

Hyaluronic acid (HA)-based sperm selection has been proposed as a physiological strategy to enrich for mature spermatozoa with improved chromatin integrity during intracytoplasmic sperm injection (ICSI). However, whether these biological characteristics translate into improved embryo chromosomal competence remains uncertain. This prospective single-center sibling-oocyte randomized study evaluated the effect of HA-assisted ICSI on embryo euploidy in couples undergoing ICSI with preimplantation genetic testing for aneuploidy (PGT-A). Metaphase II oocytes retrieved within the same cycle were randomly allocated to HA-ICSI or conventional ICSI. The primary outcome was the proportion of euploid embryos among embryos with conclusive PGT-A results. Generalized estimating equations were used to account for embryo clustering within patients, and sperm DNA fragmentation was assessed using TUNEL assay with flow cytometry. Overall, 94 couples undergoing 95 cycles were included, yielding 258 embryos analyzed by PGT-A, including 119 in the HA-ICSI group and 139 in the conventional ICSI group. Euploidy rates were comparable between groups (52.1% vs. 54.7%; p = 0.773). In GEE analyses, sperm selection method was not associated with embryo euploidy (OR 1.20; 95% CI 0.68-2.13; p = 0.52). Fertilization outcomes were also comparable between groups. Most patients exhibited low sperm DNA fragmentation, with 81.1% showing values below 20%. These findings did not demonstrate a measurable advantage of HA-based sperm selection in embryo chromosomal competence in a population predominantly characterized by low sperm DNA fragmentation. However, smaller effects cannot be excluded.