As women age, reproductive function undergoes a decline that is gradual in the 30s but much more dramatic in the 40s, resulting ultimately in menopause and complete cessation of the ability to reproduce in the 50s. Although IVF has been a breakthrough technology, which has helped millions of women worldwide achieve a pregnancy, the live birth rates fall steeply between the ages of 35 and 45 (1). There is evidence that this decreased chance to conceive is likely the result of oocyte aneuploidy. Mitochondrial production of ATP is the main source of energy for chromosomal dysjunction, polar body extrusion and subsequent mitoses and cell division related to embryogenesis up to the blastocyst stage. For example, a study by Dalton et al in the mouse has shown very nicely that a spike in ATP occurs at the time of the first polar body extrusion (2) indicating the completion of the first meiotic division. There is evidence that higher levels of oocyte ATP are associated with improved embryogenesis and subsequent implantation (3,4).

One of the main theories for declining mitochondrial ATP production with age was the accumulation of mitochondrial DNA (mtDNA) mutations (5). The mitochondria have their own genome that is distinct from the nuclear genome in the cell. The circular mtDNA is more prone to loss of function mutations because of its lack of protective histones, a deficit of DNA repair enzymes, and the absence of introns (6), the non-coding regions that make up about 90% of nuclear DNA. The absence of intronic sequences alone would make mtDNA 10 times more prone to a functioning mutation. Although mtDNA mutations leading to diminished ATP production with human aging is likely to be a contributing factor to aneuploidy in oocytes and declining pregnancy rates, we believe it is not the main cause.