From disease prevention to fertility treatment: rethinking the use of mitochondrial donation for oocyte-related infertility in the light of safety and efficacy

Abstract

Maternal spindle transfer (MST) and pronuclear transfer (PNT) raise a number of important ethical and regulatory issues. These IVF procedures that transfer nuclear DNA to enucleated oocytes or zygotes aim to prevent transmitting mitochondrial disease by female carriers of mitochondrial DNA (mtDNA) mutations and enable them to have healthy genetically related children. MST/PNT might also prove effective in treating oocyte-related infertility, but are not permitted in the UK and Australia, unlike MST/PNT for mtDNA disorders. The paper discusses the regulation of MST/PNT for both applications in relation to their risks and efficacy, highlighting the scarcity of clinical data. Based on risk reduction, it has even been proposed to treat oocyte-related infertility first before moving to mtDNA disorders. We argue that a prohibition of MST/PNT for infertility is not justified, neither should it initially be applied only for infertility because of the little evidence yet available regarding its efficacy and potential risks. We propose a staged approach to identify MST/PNT-treatable causes of oocyte-related infertility first, followed by a preclinical study and clinical trial and, if positive, wider application. Importantly, we call for transparency in publishing regular trial results, deeper ethical reflection, and more consistent policies that consider comparable uncertainties in mtDNA disorders and oocyte-related infertility.

Keywords: assisted reproduction; ethics; maternal spindle transfer; mitochondria; mitochondrial DNA disorders; mitochondrial donation; nuclear transfer; oocyte-related infertility; pronuclear transfer; translational research.