About Clomiphene (Serophene and Clomid)
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Brief Review of Ovarian
Function
Women are born with a limited reserve of oocytes, and this supply
diminishes continuously during their life reaching critical numbers by age 40. A fetal
ovary contains about 6-7 million oocytes by the 20th week of gestation. From
mid-gestation onward there is a relentless and irreversible loss of oocytes by a process
known as atresia. At birth, girls have lost about 80% of their initial reserve of oocytes,
only one to two million are present in the ovaries at this time. The number of oocytes
decreases even further to about 300, 000 by the onset of puberty. Of these oocytes, only
400-500 will ovulate in the course of a reproductive life span, less than 1% of the total
number of initial oocytes. When the women are about 50 years old, the number of oocytes is
exhausted and they enter the menopause.
In the fetal ovary, soon after they are formed, the oocytes are surrounded by a layer
of supporting cells and enter a resting state where they remain until they resume growth.
There are intra- and extra-ovarian factors that regulate oocyte growth. Little is known
about those development intra-ovarian factors but once an oocyte leaves the resting stage
to enter the growing phase it has two options: ovulation or death by atresia. The oocytes
are constantly leaving the resting stage and continue their development. Even during
pregnancy the oocytes are leaving the ovarian pool, and because they do not have the
correct hormonal environment they stop growing and are lost. The oocyte development can be
sustained after the onset of puberty with help of the reproductive hormones FSH and LH
during normal menstrual periods. These two hormones would be the main extra-ovarian
factors regulating oocyte development.
The oocyte in the resting state is surrounded by a number of cells that will support
its development once it leaves the resting state. Those surrounding cells will develop in
number and will form the follicle and become active under the influence of the
reproductive hormones FSH and LH. The follicle is what you see in the ovaries at the time
of ultrasound scanning. When the follicles grow they initially produce estrogen or
Estradiol, which helps the uterine endometrium to develop. After the LH surge or hCG
injection they switch functions to produce progesterone, which will prepare the
endometrium for implantation. If no implantation occurs the lack of progesterone support
will result in menstrual bleeding. And the cycle starts again.
During the menstrual period several oocytes/follicles leave the resting stage and upon
the influence of FSH and LH start to form the follicle. As they continue their development
they become more dependent on FSH and LH. If a leading follicle does not find the proper
balance of these hormones, it stops its development and another follicle takes its place.
The follicle that is destined to ovulate is the one that found the proper balance of
hormones all along its development. Why is only one follicle ovulated in most of the
occasions? There is an intense level of competition among follicles and the leading or
dominant follicle releases a substance known as Inhibin, that inhibits the development of
the other follicles. If the leading follicle stops developing then the level of inhibin
secreted by that follicle decreases and another follicle takes over the lead and it starts
to secrete its own inhibin to delay the development of the rest of follicles in the
growing pool.
There are several important facts that we need to highlight from the previous
discussion. Women are born with a limited number of oocytes. The oocytes leave the resting
state everyday prior to puberty, during the menstrual cycles and even during pregnancy.
Most of them will be lost by atresia for the lack of the proper stimulus to continue their
development. It is not until puberty that women obtain the capability of ovulation as
evidenced by the menstrual cycle. The follicle that is destined to ovulate is the one that
found the proper balance of hormones (FSH and LH) during all its phase of development.
This mechanism of oocyte losses is responsible for the womens diminished
reproductive potential once they are 35 years or older. It should be clear to you now why
only one follicle is ovulated during a normal menstrual period.