[ Basics about Infertility ] [ Intrauterine Insemination ] [ Polycystic Ovarian Syndrome [PCOS] ] [ Ovarian Drilling for PCOS ] [ Ovulation Induction ]
Ovulation induction medications, often referred to as fertility drugs, are used
to stimulate the follicles in your ovaries resulting in the production of
multiple eggs in one cycle. The medications also control the time that you
release the eggs, or ovulate, so sexual intercourse, intrauterine inseminations,
and in vitro fertilization procedures can be scheduled at the most likely time
to achieve pregnancy.
There are risks associated with the use of ovulation induction medications
including an increase in the chance for high order multiple births and the
development of ovarian cysts. A rare side effect that can occur is ovarian
hyperstimulation syndrome (OHSS); symptoms include severe pain in the pelvis,
abdomen and chest, nausea, vomiting, bloating, weight gain and difficulty
The medications most commonly used in fertility treatment are clomiphene
citrate, gonadotropins, Metformin and Parlodel.
Clomiphene Citrate (Siphene) - This medication comes in a tablet form and is
used for women who have infrequent periods or long menstrual cycles. Common side
effects include headaches, blurred vision and hot flashes.
Gonadotropins - This is an injectable medication that is used to induce the
release of the egg once the follicles are developed and the eggs are mature.
Side effects may include abdominal distention/discomfort, bloating sensation,
mood swings, fatigue or restlessness. In most cases, the side effects are
relieved by follicular aspiration.
Glucophage (Metformin) - Metformin is given to patients as an insulin lowering
medication. Most commonly used in PCOS patients, the medication has been shown
to reverse the endocrine abnormalities seen with polycystic ovary syndrome
within two or three months. The use of Metformin can result in decreased hair
loss, diminished facial and body hair growth, normalization of elevated blood
pressure, regulation of menses, weight loss and normal fertility.
Bromocryptine - Bromocryptine is a medication used to lower prolactin levels. It
will also reduce pituitary tumor size, should one be present. An oral medication
taken with meals, Bromocryptine has few side effects and is relatively
There are different levels of ovulation induction commonly used to treat
infertility related to ovulation disorders, male factor or unknown causes. One
method of treatment involves clomiphene citrate taken in pill form for 5 days at
the beginning of a cycle. For women whose only infertility problem is
anovulation, up to 80% of patients will ovulate using this medication and 50% of
those will conceive . Clomiphene may be combined with intrauterine insemination
to boost the success of the medication by placing the sperm and egg in closer
proximity to each other.
The more aggressive level of ovulation induction is called superovulation. This
treatment uses gonadotropins or sometimes a combination of clomiphene and
gonadotropins to stimulate the production of multiple eggs. Patients undergoing
superovulation must be closely monitored by blood tests and ultrasounds.
Monitoring ensures that the patient does not hyperstimulate and also helps the
physician administer the correct dosage of medication so that only a few
follicles develop. This is a critical step to keeping the multiple pregnancy
rates low. At the end of the superovulation treatment process, a low dose HCG
(human chorionic gonadotropin) may be prescribed to stimulate ovulation.
Ovulation will occur between 24-36 hours after HCG. The patient is instructed to
either have intercourse during this time or to come in for an intrauterine
insemination. Depending on the cause of infertility, the success rate per
superovulation treatment cycle is approximately 10-20% based on the woman's age.
Clomiphene & Letrozole
Both clomiphene citrate and letrozole are
medications used to treat infertile women who have an ovulation problem. These
medications work by helping your pituitary gland (located at the base of the
brain) improve the stimulation of developing follicles (eggs) in the ovaries.
Neither clomiphene citrate nor letrozole may help a woman become more fertile if
she is already ovulating normally. For that reason, these medications are most
often prescribed to those patients who have been found to have an abnormality
with their cycle.
Clomiphene is often referred to as the "fertility pill". Letrozole is very
similar to clomiphene in the way it works. However, letrozole is quickly cleared
from the body. It only works for the cycle in which it is taken and is less
likely to adversely affect the uterine lining and cervical mucous. With
clomiphene, one may experience effects 6-8 weeks after stopping the medication.
Both medications are prescribed for five days each cycle, usually beginning on
day three and continuing through day seven. The usual initial dose for
clomiphene is 50 mg, one tablet daily. The number of tablets can be increased to
as many as four daily, if a lesser dosage does not result in ovulation. Rarely
are more than two tablets required. Clomiphene should be repeated each cycle
until pregnancy occurs, or your doctor discontinues it. The usual dosage of
letrozole is 2.5 mg., one tablet each day.
Of all women treated with clomiphene, or letrozole, 60% to 80% will ovulate
normally. However, only half of those patients who ovulate will become pregnant.
It is not known why only half of the women who apparently ovulate with
clomiphene or letrozole therapy become pregnant. It is suspected that factors
other than inadequate ovulation may be contributing to the fertility problem.
Therefore, if you are not pregnant after three or four cycles, additional
testing such as hysterosalpingogram or laparoscopy may be necessary. If you have
polycystic ovary syndrome, a trial of metformin (Glucophage) therapy may be
Some 10% to 20% of women taking clomiphene or letrozole will experience side
effects. By far, most of these are minor and temporary in nature. They include
such things as hot flashes, blurred vision, nausea, bloating sensation, and
headache. Serious side effects are rarely seen with either medication. There are
two side effects associated with clomiphene or letrozole therapy that warrant
specific discussion. The first is the possibility of multiple pregnancy. The
frequency of twins occurring in women who conceive while taking clomiphene or
letrozole has been reported to be as high as 10%. Triplets may occur as
frequently as 1 in 400 births, and quadruplets in 1 in 800 births. Neither
clomiphene nor letrozole is the "fertility drug" you may have heard in the news
bulletins often associated with large numbers of infants, such as quintuplets.
Newer studies suggest that long-term use of either clomiphene or letrozole for
more than 12 cycles may place you at an increased risk of developing ovarian
cancer. Secondly, clomiphene and letrozole have also been associated with the
occasional development of ovarian cysts. These cysts are not true growths of the
ovary and within a few weeks will resolve without treatment. However, on an
extremely rare occasion, these cysts have been known to cause internal bleeding
or twist, requiring surgery and removal of the involved ovary. However, I must
again emphasize that such a complication is extremely rare.
Clomiphene or letrozole stimulated cycles are not unlike normal cycles in that
there is only a 20-25% chance of conception occurring each cycle during the
first three to four treatment cycles, even if the medication is working
properly. (Results may be lower with unexplained infertility.) This means that
at least four to six cycles of treatment are necessary before one has given
either medication an adequate trial. Recent studies indicate that if a pregnancy
occurs as a result of the clomiphene/letrozole treatment, there is no clinically
significant increased risk of miscarriage or congenital birth defects when
compared to other infertile couples who conceived without clomiphene/letrozole
treatment. However, women with polycystic ovary syndrome may be at higher risk
for miscarriage during a pregnancy conceived using either of these medications.
More than half the clomiphene/letrozole pregnancies
occur during the first three cycles and more than 3/4 occur at the 50mg. (or 2.5
mg letrozole) dose. Rarely will pregnancy occur when more than 100mg/day (two
tablets) are necessary. If you have not conceived after three cycles,
intrauterine insemination will be recommended to improve your chances of
conceiving. If you have not conceived after four to six cycles, either combined
clomiphene (or letrozole)/hmg/insemination or Gonal-F/Follistim injections and
intrauterine insemination will be recommended.
How is a treatment cycle with
Clomiphene/Letrozole carried out?
Beginning on cycle day 3, start clomiphene citrate 50
mg (or letrozole 2.5 mg), one by mouth each day through cycle day 7.
On day 9 or 10, lab work may be carried out (LH
and FSH). If the LH level is two to three times higher than the FSH
level, clomiphene citrate/letrozole is less likely to work for you.
On day 12, you will begin daily/alternate day
ultrasounds - called follicular monitoring. This helps show the exact
size and growth of both the follicles [eggs] as well as the thickness of
the endometrium [lining of the inside of the uterus]
When the follicle is "ripe" you may be given an
injection for it to rupture
Around the time of rupture you will be asked to have
timed sexual intercourse OR to come in for an IUI
If you miss your period you will be asked to come in
for a pregnancy test and if the pregnancy test is positive, you
will be asked to carry out some blood tests (a specific kind of
pregnancy test, a quantitative hCG). You will then be asked to return in
two days to have this specific pregnancy test repeated. This test is
repeated so that we can measure the amount of hCG (human chorionic
gonadotropin, which is produced after pregnancy occurs), looking for at
least a 60% increase in the level. This helps us to know whether this is
a pregnancy that is progressing appropriately.
If it appears the pregnancy is progressing
appropriately, you would then be scheduled for your first pregnancy
ultrasound approximately 2 weeks later.