Ovulation Problems and Infertility: Treatment of ovulation
problems with Clomid and other fertility drugs
Advanced Fertility Center of Chicago
Gurnee & Crystal Lake, Illinois
Our IVF Success Rates
Our IVF with Donor Eggs Success Rates
What is induction of
ovulation?
Ovulation induction
involves the use of medication to stimulate development of one or more mature follicles
(where eggs develop) in the ovaries of women who have anovulation
and infertility. These women do not regularly
develop mature follicles without help from ovulation enhancing drugs.
Some of the women with
anovulation have a condition known as PCOS or polycystic ovarian syndrome.
These women often have irregular menstrual cycles, increased body
hair, and infertility.
Ovulation induction is
somewhat different from controlled ovarian hyperstimulation
which involves use of some of the same medications to stimulate development of multiple
mature follicles and eggs in order to increase pregnancy rates with various infertility
treatments.
Who should be treated with induction of ovulation?
Women, such
as those with PCOS, who do not
ovulate on their own regularly, and want to get pregnant.
Ultrasound
picture of a polycystic ovary from a woman with PCOS - polycystic ovarian disease
These women do not develop mature follicles or ovulate without medication
treatment
About 12 immature follicles (black circles) are seen here
Ultrasound
photo of a polycystic ovary after Clomid treatment
Some mature size follicles are now present, as well as some small ones
How is induction of
ovulation performed?
There are four basic
types of medication that are used to induce ovulation. Treatment with these
drugs has the potential to result in pregnancy if the woman has good quality eggs remaining in
her ovaries, and if other causes of infertility are not present.
For women with ovarian
failure or extremely very poor quality eggs there is
not currently
any drug available to allow a reasonable chance of conception with any type of
ovarian stimulation. Egg donation is the only
realistic option for getting pregnant with premature ovarian failure.
The four major types
of drug therapy for ovulation problems include Clomid (Serophene, clomiphene
citrate), injectable
gonadotropins, GnRH pump, and bromocriptine. These ovulation drug therapies are all discussed below.
Pregnancy
success rates for
induction of ovulation:
Success rates for
induction of ovulation vary considerably and depend on the age of the woman, the type of
medication used, whether there are other infertility factors present in the couple, etc..
Clomid or
Serophene (brand names), or clomiphene citrate (generic name), for
induction of ovulation
Clomid is
an oral tablet that is usually taken either days 3-7 or 5-9 of the woman's menstrual
cycle. Many women with anovulation do not have regular menstrual cycles on their own and
therefore the menses would be induced by having the woman take a medication. Either medroxyprogesterone acetate (Provera) or birth control pills can be used to induce menses.
She would then take
the Clomid drug beginning shortly after the induced menstrual period begins. Clomid is
usually given at an initial dose of 1 tablet (50 mg) a day for 5 days and if this is not
successful in causing ovulation the dose is increased in the next cycle to 2 tablets per
day for 5 days.
If two tablets a day
are not successful in causing ovulation we would either try 3 tablets per day or move on
to injectable gonadotropins, or to IVF. Women who do not respond to two tablets per day have some
chance for ovulating and conceiving with 3 or more tablets a day. However, the
pregnancy success rate at 150mg or higher of Clomid are quite low. If the Clomid stimulates good follicle development
then the couple is instructed to have timed intercourse or to come to the office for
intrauterine insemination at the time of ovulation.
The timing of ovulation
can be detected in several ways, including urine LH predictor kits that can be used at
home, blood work that is drawn in the physician's office and / or ultrasound performed in the
physician's office to determine when a mature follicle is present and ready for
release.
Giving the woman an
injection of HCG (human chorionic gonadotropin) can control the time of ovulation.
Ovulation will then occur approximately 36-42 hours later and allows proper timing of either
timed intercourse or intrauterine insemination, IUI.
Clomid is
an inexpensive form of ovulation induction that often does not require much if any
monitoring with blood or ultrasound. However many women do not respond to Clomid and
for these women other, more expensive, medications will be needed.
Ovulation and
pregnancy rates using Clomid for induction of ovulation
On a per cycle basis,
and pregnancy rates with Clomid are about 10-15% per ovulatory cycle for the
first 3 cycles. After 3 cycles without a pregnancy, pregnancy rates are lower for
subsequent cycles. After 6-9 failed cycles, the chances are substantially lower that
pregnancy will occur with further Clomid therapy.
Although about 50-80%
of anovulatory women will be able to have ovulation induced with this medication,
pregnancy rates are approximately half of the ovulation rates. For example, if 80% of
women in a large population of anovulatory women can be made to ovulate with
Clomid only about 40% of the women will actually achieve pregnancy. Therefore, many women
will ovulate and not become pregnant while using this medication.
There are probably
several issues that contribute to this phenomenon. Possibilities include a decrease in the
quality of the eggs when Clomid is used, the negative impact of the Clomid on the quantity and quality of cervical mucus, and a negative impact on the
quantity and/or quality of the endometrial lining (lining of the inside of the uterine
cavity).
Metformin
treatment for women with PCOS, polycystic ovarian syndrome, that fail with Clomid
Metformin
(brand name Glucophage) is an oral
medication that has been used in the last few years by some infertility physicians to
assist in inducing ovulation in some women with anovulation and polycystic ovaries. For
more information on this new form of therapy, follow the link above.
Fertility drugs after Clomid
Injectable
gonadotropins for induction of ovulation
Injectable
fertility medications, called gonadotropins, contain follicle stimulating hormone (FSH) which causes development of
one or
multiple follicles when injected into women that do not ovulate.
These medications are
given by intramuscular injections or subcutaneous
injections on a daily basis. The injections are started early in the menstrual cycle
and are continued for approximately 8-14 days until one or more mature follicles are seen
with ultrasound examination of the ovaries. At that point an injection of HCG is given
which induces ovulation to occur approximately 36 hours later.
Over 90% of
anovulatory women can have ovulation induced with this type of therapy. Pregnancy rates
per month are better than those with use of Clomid and for relatively young
women with no other contributing causes to the infertility pregnancy rates per month of
approximately 15% can be expected when this form of treatment is combined with intrauterine insemination. Pregnancy rates with injectable
gonadotropins combined with intercourse are somewhat lower.
This type of therapy
is usually tried for 6-12 months and if it does not result in a pregnancy in vitro fertilization should be considered.
The cost of using this
medication is substantial. In the United States injectable gonadotropins cost
approximately $35-70 per ampule and the required dose will range from one half ampule per
day to 6 or more ampules per day for about 8-14 days.
Ultrasound and blood
monitoring of the stimulation cycle is essential when using injectable gonadotropins as
there are substantial risks associated with overstimulation if the ovaries should over
respond to the medication.
This monitoring is
usually done 2-3 days a week during the time the woman is taking the injectable
medications. This adds substantially to the cost of the cycle. Some health insurance plans
will pay for the entire cost of ovulation induction including insemination if that is
desired. Other health insurance plans will pay for some or none of the costs associated
with this treatment.
Complications
associated with use of these medications include the possibility of overstimulation, which
is reported to occur in approximately 1% of cycles. Hyperstimulation involves enlarged
ovaries, abdominal pain, fluid build-up within the abdomen, and may require
hospitalization in extreme cases to control pain or manage the syndrome. Careful
monitoring and use of the injectable gonadotropins can almost always avoid severe
overstimulation.
Multiple pregnancy is
also a possibility when these medications are used. In general approximately 75% are
single, 20% are twins, 5% are triplets and 1% are quadruplets or higher.
In very rare cases, 9
or more fetuses have implanted and shown heartbeat activity on ultrasound studies. Rarely
can a pregnancy of more than 5 fetuses result in viable live birth unless a fetal
reduction procedure (selective abortion) is performed at about 9-11 weeks of gestation.
The risk of multiple
pregnancy increases with the number of mature follicles that are seen on ultrasound
examination of the ovaries. However, it is usually not possible to stimulate the patient
so that only one mature follicle develops and multiple follicle development is the rule.
When many mature
follicles develop the couple and the physician can have a discussion about the risks of
multiple pregnancy and there is always the option of canceling the cycle by not giving the
injection that causes ovulation. This essentially eliminates the risk of any pregnancy
(single or multiple) occurring in that cycle.
More multiple pregnancy
risks with ovarian stimulating drugs
IVF with blastocyst
transfer can reduce the multiple birth risks
Bromocriptine for
induction of ovulation
Anovulation caused by
an elevated level of the hormone prolactin can be treated with a medication called
bromocriptine. This is an uncommon type of anovulation disorder. Women with this condition
often have no menstrual periods - amenorrhea.
Bromocriptine is an
oral medication that is given once or twice daily. It is not expensive.
When women have a mild
to moderate elevation in their prolactin, bromocriptine is very effective in reducing the
level back down to the normal range in most cases. This usually allows normal ovulation to
occur every month. Women with high levels
of prolactin are less likely to respond well to bromocriptine therapy.
All women with
unexplained elevations of prolactin over about 50-100 (normal < 20) need to have
specialized imaging studies (CT or MRI) of the area of the pituitary gland at the
base of the brain. This is to make sure that there is not a significant tumor causing the
disturbance.
The most common tumor
that causes a high prolactin is a benign (non-cancerous) tumor called a prolactinoma.
These tumors if very small can be managed with bromocriptine to keep the prolactin in the
normal range and yearly CT or MRI scans to look for significant tumor growth. Larger
tumors often will require surgery.
Cost for
induction of ovulation:
The costs associated
with induction of ovulation depend on the type and dose of medication required and the
number of ultrasound and blood tests (if any) required to adequately monitor the cycle.
Sometimes artificial insemination will also be recommended which increases the chances for
a pregnancy, as well as the cost of the cycle.
A Clomid cycle
usually costs between $100 and about $1200, depending on what is done.
A cycle using
injectable gonadotropins usually costs between $1500 and about $5000, depending on what is done
and how much of the fertility medication the woman needs to stimulate ovulation.
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