In the female fetus oocyte numbers peak by 16
weeks of gestation, reaching up to 7 million. They
decrease progressively and at the time of birth a
female will have about 2 million eggs. As she
approaches menarche the woman will have about
500,000. This primordial follicular disappearance
continues throughout reproductive life and
accelerates approximately 10 years prior to the
menopause, by which time the number of eggs
have fallen to a few hundred. If a woman ovulates
one egg per month she will release 12 eggs per
annum. Throughout her reproductive career
(approximately 40 years, from the age of 10 to the
age of 50) she will produce 480 eggs - yet nature
has given her 480,000 eggs to work with.
At all stages of the menstrual cycle there are a
number of small antral follicles present. This
number changes with age, being at its highest in
younger women. As the level of FSH rises at the
beginning of the menstrual cycle more follicles are
recruited and some are then selected for further
development. One follicle, however, will be at the
right condition for development and this “chosen”
follicle will continue to develop till mid cycle
when it ovulates. The quality of the released
oocyte is related to both the age of the woman and
the number of primordial follicles available in the
ovary. Statistically speaking it is more likely for an
egg to be of better quality if it is randomly
“chosen”, for example, out of 100 competing
primordial follicles than if it was randomly
“chosen” out 10 competing primordial follicles.
Follicle stimulating hormone (FSH) is crucial
for follicular development as it is the hormone that
controls the process of recruitment, selection and
finally the full development of the maturing
follicle. The number of primordial follicles
available in the ovary influences the level of FSH.
As the follicles are recruited, however, they secrete
both estrogen and inhibin, which in turn keeps the
level of FSH low. As women age, the number of
recruited follicles decrease. Consequently the
suppression of the FSH level decreases and, as a
result, the level of FSH increases with age in an
attempt to continue to recruit the ever-decreasing
number of eggs within the ovary. The level of FSH
provides a biological marker for ovarian reserve.
The higher the level, the less the ovarian reserve.
Consequently fewer primordial follicles will be
recruited and the situation takes place as described
above, with the “chosen” follicle sought from only
a few competing ones.
Oocyte quality is established early during fetal
life. The first produced oocytes (less susceptible to
non-disjunction) ovulate first and ‘poorer’ oocytes
ovulate later. There is also evidence to suggest
that there is age dependent damage in oocytes due
to gradual increase in intracellular oxidative stress
that also leads to increased frequency of nondisjunction.
It is well documented that there is an
age related reduction in fecundity due to reduction
in pregnancy rate and rise in miscarriage rate. This
is associated with an age related increase in
aneuploidy due to non-disjunction. Age therefore
results in reduction of both quality and quantity of
oocytes. |
