Mitochondrial replacement therapy for advanced maternal age and diminished ovarian reserve: Efficacy, challenges, and Vietnamese landscape

Mitochondrial replacement therapy (MRT) has emerged as a disruptive frontier in reproductive medicine to address the challenges of advanced maternal age (AMA) and diminished ovarian reserve (DOR). These conditions are primarily driven by mitochondrial dysfunction, which leads to adenosine triphosphate (ATP) depletion, oxidative damage, and increased embryonic aneuploidy. Heterologous techniques, such as maternal spindle transfer (MST) and pronuclear transfer (PNT), have demonstrated high clinical efficacy, with studies reporting fertilization rates up to 88.4% and significantly improved blastocyst formation in patients with poor prognoses. While these methods show promise, autologous strategies utilizing stem cell derived mitochondria offer an alternative to maintain full genetic relatedness and avoid the ethical complexities of "three-parent" embryos. However, MRT remains an investigational procedure globally due to critical safety concerns, including mitochondrial "reversion" where maternal mitochondrial DNA (mtDNA) regains dominance and potential mitonuclear incompatibility. In Vietnam, where infertility affects approximately 7.7% of couples, there is a rising demand for such interventions despite significant gaps in national data and specific regulatory frameworks. Establishing a strategic roadmap that includes a national AMA/DOR database and modernized legal guidelines is essential to ensure the safe and ethical integration of MRT into Vietnam’s clinical landscape.