Mitochondria-targeted therapeutic strategies in assisted reproduction: challenges and potential solutions.

Abstract

Mitochondria are central to oocyte competence and early embryonic development, with roles that extend beyond energy production to include regulation of redox homeostasis, apoptosis and cellular aging. Mitochondrial dysfunction is increasingly recognized as a key contributor to diminished ovarian reserve, impaired embryo development, and accelerated reproductive aging. Mitochondria-targeted therapeutic strategies, including pharmacological approaches such as Coenzyme Q10, mitoquinone, resveratrol, rapamycin, and NAD+ precursors, as well as mitochondrial replacement techniques such as maternal spindle and pronuclear transfer, have shown promise in preclinical models; however, clinical outcomes remain heterogeneous and often inconclusive. This translational gap likely reflects critical limitations, including variability in therapeutic targets, suboptimal timing of intervention relative to oocyte development, and insufficiently powered or standardized clinical studies. Greater emphasis on well-defined, physiologically justified therapeutic targets, along with the use of physiologically relevant experimental systems, may improve therapeutic precision and efficacy. Rigorous evaluation of safety, particularly for interventions with pleiotropic effects or heritable consequences, remains essential. A more targeted, developmentally informed and systematically validated approach is needed to advance mitochondria-based therapies toward meaningful improvements in reproductive outcomes.