Chapter 13b
Ovulation -- Normal and Abnormal
from the book How to Have a Baby:
Overcoming Infertility
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
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The role of ultrasound
The egg develops within a follicle in the ovary. This follicle is a
thin-walled structure containing fluid with the egg attached to the wall.
Usually, only one follicle develops per month. This follicular growth can be
measured with a painless procedure called ultrasound, usually done with a
vaginal probe, which projects an image of the ovary onto a screen. The follicle
appears as a circular fluid-filled bubble on the screen, and can be seen when it
is about 7 to 8 mm in size. It grows at about 1 to 2 mm per day, and is ready
for ovulation when it measures 18 to 25 millimeters in diameter. Following
ovulation, the follicle usually disappears from the scan picture completely and
this is the best evidence of ovulation. Often, at the same time, fluid can also
be detected in the abdomen behind the uterus - this is the follicular fluid
which is released when the follicle ruptures. Defects detectable by ultrasound
are follicles that do not grow at all, or do not grow to a big enough size, or
occasionally follicles that do not rupture at the appropriate time (luteinised
unruptured follicle). Since ultrasound allows assessment of follicular
development, it is especially useful for patients having timed intercourse or
having ovulation regulated with fertility drugs. It is usually done on a daily
basis, from about the 11th day of the cycle.
Follicle tracking on ultrasound usually takes about 5 minutes to perform. No
preparation is needed; except that the bladder must be emptied before the scan.
Ask to see the picture of the follicle on the monitor - and you should be able
to see the growth of the follicle and its rupture for yourself on the screen.
Older ultrasound machines used abdominal probes . These require that the
patient have a full bladder, so that the sound waves can reach the ovary. Not
only are they much more uncomfortable for the patient (who has to sit waiting
till the bladder is almost bursting ) but the quality of the pictures is also
much poorer as compared to the vaginal scan.
Commercially available ovulation prediction kits (OPK)
Ovulation prediction test kits (OPK) are available abroad (or in India at a
few chemists) over the counter . These kits detect LH which is produced in large
quantities shortly before ovulation and can be found in the urine . Once the LH
surge has occurred, ovulation usually takes place within 12 to 44 hours. Urine
testing is started about two days prior to the expected day of ovulation and
continues until the test becomes positive. The urine should be collected at the
same time every day - and testing the first morning urine sample is a good idea.
If your menstrual cycles are irregular, testing should be timed according to
the earliest and latest possible dates of ovulation. For example, if your cycle
ranges between 27 and 34 days, you could possibly ovulate between days 13 and
20. Therefore, testing should begin on day 11 and continue until ovulation is
indicated or through day 20. There is an 80 percent chance of detecting
ovulation with five days of testing and a 95 percent chance with ten days of
testing. Occasionally, ovulation may not occur in a particular cycle. If the
ovulation prediction test has been timed and performed accurately and has not
turned positive, you should discontinue testing and begin again with your next
menstrual cycle. Persistent failure of the test to turn positive may indicate a
problem with regard to ovulation.
Once a test has registered positive, indicating that ovulation is about to
take place, it is no longer necessary to continue testing. Remaining tests in a
kit may be saved and used in the following menstrual cycle if pregnancy does not
occur.
Ovulation prediction kits offer the advantage that they allow you to predict
when ovulation will occur - thus maximising the chances that intercourse will be
timed at your most fertile period. They can also be done in the privacy of your
own home. However, they are expensive; and some of the kits have very tedious
and involved testing procedures, so that errors are not uncommon.
A newer device, The ClearPlan EasyTM Fertility Monitor, is a palm-sized,
electronic system, that provides information about fertility status by
interpreting the levels of two hormones, estrogen and luteinizing hormone, in
the urine. You need to test your urine for the presence of these, using dip
sticks, and the information is then input into the system, which uses it to
calculate your fertile days.
Salivary ferning
Another way of monitoring ovulation uses a pocket microscope, to check for
the phenomenon of "saliva ferning." You need to let your saliva dry on
a glass slide, and then examine it under the devise, to check for ferning. Prior
to ovulation, the saliva shows the presence of crystallisation or ferning when
it dries, and this suggests that ovulation will occur soon. Though these devices
are now commercially available, their reliability is still unclear.
Blood tests
The growing follicle secretes the hormone estradiol in increasing amounts and
its blood level rises rapidly several days prior to ovulation. If ovulation is
being induced through fertility drugs, estradiol blood tests may be done on a
daily basis in order to determine if the developing follicles are growing
properly. Normally, the estradiol blood levels should increase rapidly (as a
rule of thumb, they double every 24 hours).
Since the luteinizing hormone (LH) blood level rises rapidly just before
ovulation (this is called the LH surge), frequent blood samples for measuring
the LH level can also be taken a few days prior to the anticipated time of
ovulation in an attempt to predict when the follicle is mature and ready for
ovulation.
Abnormal ovulation
Abnormalities of ovulation 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, include:
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.
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
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