Ethical challenges in extending mitochondrial replacement therapy (MRT) for overcoming poor egg quality in older women without mitochondrial diseases.

Recently, eight healthy human offspring were born through mitochondrial replacement therapy (MRT) with pronuclear transfer (PNT), aimed at preventing the transmission of pathological mitochondrial DNA (mtDNA) mutations. These encouraging preliminary results on the safety of MRT, accompanied by some early neonatal findings and ongoing follow-ups, open up the possibility for its broader application in addressing age-related female infertility by enhancing oocyte quality in older women, commonly referred to as ooplasmic donation or ooplasmic transfer. Because female fertility declines sharply with age, and not all women choose to undergo elective egg freezing (oocyte cryopreservation), there will always be a substantial number of older female IVF patients who are unable to conceive with their own oocytes. For such patients, enabling them to conceive genetically related offspring via MRT would be a far more preferable alternative to conventional egg donation, which disrupts the continuity of maternal genetic lineage. However, extending the use of MRT from the prevention of mitochondrial diseases to the treatment of age-related infertility raises numerous ethical issues. A significant challenge lies in balancing the aspirations of infertile older women to have genetically related offspring with the medical risks and ethical concerns associated with the MRT procedure. To navigate these ethical challenges, some policy recommendations are proposed, including (i) MRT should be conducted in clinical trials until its long-term safety is validated, (ii) rigorous patient counseling to ensure informed consent, (iii) stringent regulations to govern egg donation for MRT, and (iv) implementation of an internationally recognized ethical and regulatory framework for MRT.