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Ovulation occurs over a period of about 15 minutes and even when
more than one ovum is released, as in a twin pregnancy, the multiple
ovulations
occur very close together in time. Thus ovulation is the one event
in the menstrual cycle with a very precise time frame. The ovulatory
mechanism
produces the two ovarian hormones, oestradiol and progesterone.
The ovum is contained within an ovarian follicle and matures as
the follicle goes
through its rapid growth phase. During this rapid growth phase the
follicle produces increasing amounts of oestradiol. This oestradiol
stimulates the
glands of the cervix to secrete a particular type of mucus ("mucus
with fertile characteristics") which is essential for the sperm
to pass through the
cervix to reach the ovum. Oestradiol also stimulates growth of the
endometrium which lines the body of the uterus, i.e. the womb ("proliferative
phase"). After rupture of the follicle and release of the ovum,
both progesterone and oestradiol are secreted by the corpus luteum
which forms from
the ruptured follicle. The rapid rise in progesterone secretion
strongly counteracts the effect of oestrogen on the cervix and vaginal
epithelium and
thus causes the progesterone change (PC) in the mucus pattern which
occurs near ovulation and defines the Peak day (the last day of
mucus with
fertile characteristics before the change). Progesterone also acts
on the oestrogen-primed endometrium making it suitable for implantation
of the
fertilized ovum ("secretary phase"). In the absence of
pregnancy, secretion of oestradiol and progesterone reaches a maximum
approximately 7 days
after ovulation and then declines. This leads to shedding of the
endometrium as menstrual bleeding 11-16 days after ovulation.
The cyclical changes in ovarian activity are controlled by the
secretion of two hormones by the pituitary gland situated in the
brain, follicle-stimulating
hormone (FSH) and luteinizing hormone (LH). Production of these
two hormones is controlled in turn by an area of the brain called
the
hypothalamus. The hypothalamus acts as a computer, analysing nervous
signals from other areas of the brain including those generated
by the
emotions and by environmental factors, such as stress and nutrition;
it also analyses hormonal signals (oestradiol and progesterone)
generated by the
ovaries and other endocrine glands and transmitted by the blood
stream. The sum total of these effects determines the quality of
the ovarian activity
produced.
Figure 1. Relationship of the hormonal events of a woman's reproductive
cycle to the stamp record. In the pre-ovulatory infertile phase
in a cycle of average length the
woman will observe dryness (green) or an unchanging discharge (yellow).
In an extended pre-ovulatory phase either of the two infertile patterns
may occur at different
times. ER, oestrogen rise. PC, progesterone change. X (on stamp)
= Peak day.
The ovulatory cycle proceeds in a well-ordered series of events
(see Figure 1). During the latter half of the preceding cycle, the
high output of
oestradiol and progesterone by the corpus luteum acting via the
hypothalamus suppresses the production of FSH and LH by the pituitary
gland. The
waning production of oestradiol and progesterone at the end of the
cycle removes this suppression and the FSH levels begin to rise.
The follicles
within the ovaries have a threshold requirement for FSH below which
all remain dormant. Initially, the amounts of FSH reaching the follicles
are
suppressed below this threshold but as the suppression is removed
the FSH levels rise and reach the threshold for a few of the most
sensitive follicles
which include those with the best blood supply. These follicles
begin their rapid growth phase while the remaining follicles whose
thresholds have not
been reached remain in the dormant state. This is an essential mechanism
for conserving follicles so that the initial store at birth lasts
for the
reproductive life span of the individual. This is the recruitment
phase of the ovarian cycle. Once a follicle begins its rapid growth
phase it has only
two outcomes. Either it progresses to its ultimate destiny, ovulation
and the potential production of a new individual, or it fails in
the race to ovulation
and dies in the process of atresia. It cannot return to the original
follicle pool. Several days of growth are required before the growing
follicles
secrete sufficient oestradiol into the blood stream to provide the
signal to the hypothalamus/pituitary that their threshold for FSH
has been reached.
There is also an intermediate level of FSH production which must
be exceeded before a follicle is finally boosted into its full ovulatory
response, and a
maximum level which must not be exceeded otherwise too many follicles
are caused to develop and multiple ovulations occur. The maximum
level is
only 20-30% above the initial threshold so that the FSH must rise
slowly and precise feedback control by the oestrogen produced by
the developing
follicles is essential.
Selection of the follicle which will ovulate is achieved by the
following process. As a follicle develops, its content of granulosa
cells increases and it
produces rapidly increasing amounts of oestradiol and at the same
time its requirements for FSH to maintain its rapid growth diminishes,
that is, its
threshold for FSH decreases. Thus the most advanced follicle quickly
gains the advantage in that it becomes the major producer of oestradiol
and this
reduces FSH production by the pituitary at a rate sufficient to
maintain its own rapid growth but the levels drop below the thresholds
of its less
advanced competitors so that they stop growing and atrese (die).
Only when two or more follicles are exactly equally matched in the
race to
ovulation do multiple ovulations occur. The fall in FSH levels caused
by the rising oestradiol output also turns on a maturing mechanism
within the
dominant follicle which makes it receptive to the second pituitary
gonadotrophin, LH, while its competitors have not reached this stage.
The high oestradiol levels also activate a positive feedback mechanism
in the hypothalamus which causes the pituitary to release a massive
surge of LH. This surge of LH is the trigger which initiates the
ovulatory process and rupture of the follicle (ovulation) occurs
approximately 36 hours after the beginning of the surge or 17 hours
after its peak. Ovarian production of oestradiol reaches a peak
(the pre-ovulatory oestrogen peak) approximately 36 hours before
ovulation and then falls as the ovulatory mechanism progresses.
This fall is an important marker because it signals the end of the
rapid growth phase of that follicle, whether it is proceeding to
ovulation or atresia. The LH surge causes some luteinization of
the follicle before rupture and this leads to the beginning of progesterone
production. Thus a woman monitoring her oestrogen and progesterone
output sees a marked rise in oestrogen production to reach a peak
followed by a fall. She knows that ovulation will occur within 24
hours after identifying the day of the fall and that this is the
most fertile day of her cycle. If ovulation is actually occurring,
i.e. the LH surge has occurred and has triggered the ovulatory process,
she also sees on the day of the fall a small rise in progesterone
output. The actual level of progesterone output associated with
the moment of ovulation can be specified within a small range which
applies to most women, and this, in the presence of an oestrogen
fall, is a very accurate marker for timing ovulation. However, if
the fall happens to signal the end of the rapid growth phase of
a follicle which is not going to ovulate, no rise in progesterone
is seen (anovulatory cycle) or a small rise is seen which is not
progressive (luteinized unruptured follicle). After ovulation, the
ruptured follicle is transformed into the corpus luteum and production
of progesterone increases rapidly (approximately doubling each day)
together with a second rise in oestradiol output. The rise in progesterone
levels causes the progesterone change in the cervical mucus which
allows the Peak day to be calculated. The decrease in the progesterone
levels towards the end of the cycle causes the bleeding - menstruation.
Oestradiol output also falls at the end of the cycle but this fall
is less important in inducing bleeding than the fall in progesterone
output. Bleeding always follows the post-ovulatory rise and fall
in progesterone output but a corresponding rise and fall in oestradiol
output without the production of progesterone, as in anovulatory
ovarian activity, may or may not be followed by bleeding.
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