Reproductive Physiological Phenomena Clinical Trial
Official title:
THE EFFECT OF COQ10 SUPPLEMENTATION ON FOLLICULAR CELLS' BIOLOGY/PROPERTIES IN ELDERLY IVF PATIENTS
Delaying first childbirth is a progressive trend in the developed societies. Several theories tried to explain the reproductive aging, in purpose to hasten it. One of the theories include mitochondrial dysfunction with aging. In this study we will investigate the potential of treating elderly IVF patients with CoQ10, a mitochondrial stimulator, to improve follicle cells' properties.
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03286517 -
Link Between the Sensitivity of Kisspeptin Signalling and Pubertal Onset in Boys.
|
Phase 3 |