| Anovulation ( not ovulating)
is one of the common reasons of infertility. Normally,
one of the ovaries releases a single mature egg every
month, and this is called ovulation. Egg maturation
and ovulation is stimulated by two hormones secreted
by the pituitary - follicle stimulating hormone (FSH)
and luteinizing hormone (LH) . These two hormones must
be produced in appropriate amounts throughout the monthly
cycle for normal ovulation to occur. Every month, at
the start of the menstrual cycle, in response to the
FSH produced by the pituitary gland, about 30-40 primordial
follicles start to grow. Of these, only one matures
to form a large fluid-filled structure, called a Graafian
follicle which contains a mature egg, while the others
die ( a process called atresia). The mature egg is released
from the follicle when the follicle ruptures in response
to a surge of LH produced by the pituitary.After ovulation
has occured, the follicle from which the egg has been
released forms a cystic structure called the corpus
luteum. This is responsible for progesterone production
in the second half of the cycle.
Most women who have regular periods have ovulatory
cycles. Women who fail to ovulate or who have abnormal
ovulation usually have a disturbance of their menstrual
pattern. This may take the form of complete lack of
periods (amenorrhoea), irregular or delayed periods
(oligomenorrhoea) or occasionally a shortened cycle
due to a defect in the second part (luteal phase) of
the cycle.
Abnormal ovulation
Abnormalities of ovulation ( anovulation) may appear
in several ways. Menstrual cycles shorter than 21 days
or longer than 35 days are often associated with anovulation.
In addition, patients may skip menstrual periods for
time intervals of three months or more and this is called
oligomenorrhea (infrequent periods) . If the periods
stop entirely, this is called amenorrhea.
Many hormonal systems work together to produce regular
menstrual periods, and the blood levels of the hormones
that make up these systems need to be tested in order
to determine the reason for the ovulatory disorders.
The hormone blood tests, which are usually done on
the third day of your cycle, test for the levels of
the following key reproductive hormones :
The FSH level: The FSH level gives
a good idea of the number of eggs remaining in the ovaries.
A high FSH level suggests that the ovary has either
failed or has started to fail. If the FSH level is very
high (in the menopausal range) then the diagnosis is
ovarian failure. If the level is borderline, then some
doctors will do a clomiphene stimulated FSH level, which
allows for an earlier diagnosis of failing ovaries.
On the other hand, a low FSH level suggests hypogonadotropic
hypogonadism. This seemingly verbose term simply means
that the ovary in these patients is not working properly
because of inadequate production of FSH by the pituitary
gland. However, in most anovulatory patients, the FSH
level will be in the normal range, and this can be reassuring.
The LH level: This is the other gonadotropin
hormone produced by the pituitary; and provides much
the same information the FSH level does. Another useful
test is the LH:FSH ratio which is normally 1:1.
If, however, the LH level is much higher than the FSH
level,this suggests a diagnosis of polycystic ovarian
disease.
Thyroxine and TSH: These tests for
thyroid function. The thyroxine level is high in patients
with overactive thyroid glands (hyperthyroidism). In
patients with decreased thyroid function (hypothyroidism),
the TSH level is increased.
Prolactin: Prolactin is a hormone
produced by the pituitary gland that induces lactation
or milk formation.. High prolactin levels (hyperprolactinemia)
can interfere with ovulation . A milky discharge from
the breast nipple , not related to pregnancy or nursing
, is called galactorrhea, and this is a telltale symptom
of high prolactin levels and needs to be investigated.
If the prolactin level is elevated, the doctor will
need to recheck it to confirm it is persistently high.
There are many reasons for an elevated prolactin level,
including certain drugs as well as stress. In some women,
the reason for a high prolactin level can be a small
tumour in the pituitary gland. This is called a prolactinoma
or microadenoma, and the doctor may advise you have
an X-ray of the skull ( or even a CT scan or MRI scan)
to rule out this possibility. However, most infertile
women with hyperprolactinemia can be easily treated
with a medicine called bromocryptine, which is a dopamine
agonist medication . Another medication which can be
used to treat hyperprolactinemia is oral cabergoline,
which is usually taken twice a week. Only if the pituitary
tumour is very large ( microadenoma) is surgical removal
needed, and this is very uncommon.
Ovarian failure
Ovarian failure is a disease in which the ovaries fail
to produce eggs. This disease is uncommon, occurring
in only about 10% of women whose periods do not occur
at all, a condition called amenorrhea (absence of periods).
Ovarian failure may be genetic (for example, in girls
with Turner's syndrome, a chromosomal disorder) or may
be acquired (for example, following radiation or chemotherapy
for cancers; surgery to remove the ovaries for treating
ovarian cancer or severe endometriosis; autoimmune ovarian
failure; or for unexplained reasons.) Ovarian failure
is diagnosed by finding a high FSH level. In such patients
it is usually not possible to stimulate ovulation and
they have any eggs, and they suffer a premature menopause.
The only effective medical treatment for these patients
is the use of egg donation for IVF or GIFT. However,
in a very small proportion of these patients, ovulation
can resume spontaneously.
Induction of ovulation
What forms of treatments are available for inducing
ovulation?
The most commonly prescribed medicines for induction
of ovulation include the following: clomiphene citrate,
human menopausal gonadotrophin (HMG) and follicle stimulating
hormone (FSH), HCG (human chorionic gonadotropin), bromocriptine,
GnRH (gonadotropin releasing hormone) and GnRH analogue.
For women with hypogonadotropic hypogonadism (low FSH
and LH levels), the treatment of first choice is HMG.
This is effective replacement therapy; and excellent
pregnancy rates can be achieved in these women.
For women affected by hyperprolactinemia, the drug
of first choice is bromocriptine.
For most other women, the drug of first choice is clomiphene
- the "workhorse" of ovulation induction.
If this does not work, then HMG is resorted to.
Poor responders to HMG can be treated with GnRH analogues
in conjunction with the HMG; or by adding a hormone
called the human growth hormone.(HGH).
HCG (human chorionic gonadotropin) is given to trigger
off the release of the egg.
In patients with high androgen levels (high blood levels
of male hormones), dexamethasone can be used as an adjunct,
since this suppresses androgen production.
Often ovulation induction requires an investment of
time, money, energy and emotion before a satisfactory
response is achieved. After all, every woman is different
and there can be no standard "formulae". Careful
monitoring of the response to ovulation induction is
the key to therapy - and this usually involves daily
ultrasound scans and/or blood tests. It is often a tedious
process - which may involve "trial and error"
to tailor the therapy to the individual patient's ovulatory
response. With the treatments available today, however,
correcting ovulatory dysfunction is one of the most
rewarding and successful of infertility treatments.
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