CoQ10 Treatment to Improve Fertility in Elderly Patients

Over the past 4 decades, because of cultural and social changes, women in the developed world have significantly delayed childbirth. It is well known that fertility decreases with age and that live birth rates in women over the age of 35 are significantly lower both naturally and with assisted reproduction compared to those in women under the age of 35. The decline in live birth rate reflects an increase in oocyte aneuploidy that leads to reduced embryo quality as well as an increased incidence of miscarriages and birth defects, most prominently Down's syndrome (trisomy 21). There is evidence that older infertility patients have abnormal oocyte mitochondrial activity and reduced production of ATP. The meiotic spindle, crucial for normal chromosome segregation, may not be formed properly in the absence of appropriate ATP levels. Altered spindles may result in aneuploid embryos, which implant poorly or not at all.

Coenzyme Q10 (CoQ10) is a vitamin-like antioxidant, essential for proper function of mitochondrial respiratory chain. It has been shown that there is a decrease level of CoQ10 in several tissues with aging (like muscle). We suggest that one possible explanation for altered oocyte mitochondrial function may be diminished CoQ10 substrate availability or utilization as a function of aging. The oocytes, and in fact the pre-granulosa cells which give rise to the granulosa (GC) and cumulus cells (CC), are unique in the body since there is no cell division for many years. Therefore, in older women, the oocytes and GCs in primordial follicles will have been exposed to low levels of radical oxygen species produced by mitochondrial respiration over decades, resulting in possible cumulative damage to mitochondria and DNA. Decreased availability of CoQ10 would contribute to reduced antioxidant activity and decreased ATP production by the mitochondria in the oocyte. In addition, compromised mitochondrial function in GCs can effect steroid hormone production, as steroidogenesis is initiated in the inner mitochondrial membrane. Thus, a vicious circle is created by which decreased CoQ10 bioavailability with advanced age could adversely affect meiosis and further developmental competence of gametes.

In our mice model, we demonstrated mitochondrial dysfunction in oocytes from aged dams. Of importance, we found that many of these mitochondrial abnormalities could be partially or completely corrected by maternal supplementation with CoQ10, translated into significant increase in litter size of old -treated females. We could demonstrate also "normalization" of viability and function of CC (that "nourish" oocyte) by CoQ10 supplementation. The aim of the proposed project is to investigate CoQ10 levels and CC function in women with aging and the potential of CoQ10 treatment to improve follicular function, and as a result, improve oocyte quality. If intra-follicular CoQ10 levels are shown to decrease with maternal aging, nutritional supplementation with CoQ10 can become the future "folic acid" for improving reproductive outcomes in older women and not just those with infertility issues.