AUTHOR=Gómez-Elías Matías D. , Luque Guillermina M. , Oscoz-Susino Natalia , Novero Analía G. , Briski Olinda , Kásparas Inés , Steeman Tomás J. , Stival Cintia , Lavolpe Mariano , Julianelli Vanina , Geller Marisa , Attie Martín , Vassena Rita , Krapf Darío , Buffone Mariano G. 

TITLE=Increased reproductive outcomes after optimized sperm preparation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1596421

DOI=10.3389/fcell.2025.1596421

ISSN=2296-634X

ABSTRACT=A key factor to the success of in vitro fertilization (IVF) is the preparation of human sperm, a critical step that directly impacts the efficacy of the procedure. This proof-of-concept study evaluated the effect of HyperSperm, a novel sperm preparation technique designed to enhance sperm function, on fertilization, embryo development, and pregnancy outcomes in both a mouse model and a first-in-human trial following IVF. In mice, HyperSperm treatment significantly increased hyperactivated motility (p < 0.05), leading to improved fertilization and blastocyst development (p < 0.05), as well as higher implantation rates (p < 0.05) and larger litter sizes (p < 0.05). Offspring displayed normal growth and fertility. In human sperm samples from normozoospermic men, HyperSperm exhibited a high safety profile, with motility, acrosome reaction, viability, and DNA fragmentation comparable to controls. A first-in-human, prospective, single-center, split-oocyte study in 10 couples undergoing IVF with donated oocytes demonstrated similar fertilization rates between HyperSperm and control groups (p = 0.425), but significantly higher usable blastocyst rates in the HyperSperm arm (43.8% vs. 67.9%, p = 0.0122). Morphokinetic parameters were comparable between groups. These results suggest that HyperSperm enhances sperm hyperactivation, a hallmark of capacitation, leading to improved embryo development in both mice and humans. This technique represents a promising approach to optimizing sperm preparation in assisted reproduction, warranting further clinical investigation.