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Mitochondrial DNA supplementation as an enhancer of female reproductive capacity

St John, Justin C.; Tsai, Te-Sha; Cagnone, Gael L.M.

Current Opinion in Obstetrics and Gynecology: June 2016 - Volume 28 - Issue 3 - p 211–216
doi: 10.1097/GCO.0000000000000265
FERTILITY, IVF AND REPRODUCTIVE GENETICS: Edited by Emre Seli and Juan Antonio García Velasco

Purpose of review There has been increasing interest in developing assisted reproductive technologies to overcome failure at fertilization and early embryonic arrest. Some of the affected patients harbor too few copies of mitochondrial DNA (mtDNA) in their eggs at the time of fertilization, which results in developmental failure.

Recent findings In the last 3–5 years, there has been a drive to overcome mtDNA deficiency through mitochondrial supplementation protocols using autologous populations of mitochondrial DNA so as not to perturb the offspring's genetic identity or mediate a series of side-effects because of the mixing of two distinct populations of mitochondrial DNA. It is evident that there is strict regulation of mitochondrial DNA copy number from the primordial germ cell through to the time when tissues are specified during organogenesis. Supplementation of oocytes can give rise to better quality embryos, enhanced blastocyst rates, and ongoing pregnancies. It utilizes a key mitochondrial DNA replication event that takes place shortly after fertilization to stabilize the embryonic genome.

Summary These findings provide a rationale for undertaking mitochondrial supplementation and propose a mechanism to explain why the process can enhance embryo development. They also take the approach a step closer to clinical practice.

aCentre for Genetic Diseases, Hudson Institute of Medical Research

bDepartment of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia

Correspondence to Justin C. St John, Centre for Genetic Diseases, Hudson Institute of Medical Research, Clayton, Vic 3168, Australia. Tel: +61385722678; fax: +61395947416; e-mail:

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