Improving Sperm Oxidative Stress and Embryo Quality in Advanced Paternal Age Using Idebenone In Vitro—A Proof-of-Concept Study

Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm from men aged >40 years and older CBAF1 mice (12-18 months), were treated with 5 µM and 50 µM of idebenone and intracellular and superoxide ROS concentrations assessed. Following in vitro fertilization (IVF), embryo development, blastocyst differentiation, DNA damage and cryosurvival, pregnancy and implantation rates and fetal and placental weights were assessed. Five µM of idebenone given to aged human and mouse sperm reduced superoxide concentrations ~20% (<i>p</i> < 0.05), while both 5 and 50 µM reduced sperm intracellular ROS concentrations in mice ~30% (<i>p</i> < 0.05). Following IVF, 5 µM of idebenone to aged sperm increased fertilization rates (65% vs. 60%, <i>p</i> < 0.05), blastocyst total, trophectoderm and inner cell mass cell numbers (73 vs. 66, 53 vs. 47 and 27 vs. 24, respectively, <i>p</i> < 0.01). Treatment with idebenone also increased blastocyst cryosurvival rates (96% vs. 78%, <i>p</i> < 0.01) and implantation rates following embryo transfer (35% vs. 18%, <i>p</i> < 0.01). Placental weights were smaller (107 mg vs. 138 mg, <i>p</i> < 0.05), resulting in a larger fetal to placental weight ratio (8.3 vs. 6.3, <i>p</i> = 0.07) after sperm idebenone treatment. Increased sperm ROS concentrations associated with advanced paternal age are reduced with the addition of idebenone in vitro, and are associated with improved fertilization rates, embryo quality and implantation rates after IVF.