|
Induction of ovulation
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 medication.
Some women with anovulation have a condition known as polycystic ovarian syndrome. These
women usually 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 who do not ovulate regularly on their own and want to become pregnant.
Ultrasound image of an ovary from a woman with polycystic ovarian disease
These women do not develop mature follicles or ovulate without medication
About 12 immature follicles (black circles) are seen here
Ultrasound image of an ovary from the same woman after clomiphene treatment
Multiple mature follicles are now present
How is induction of ovulation performed?
There are four basic types of medication that are used to induce ovulation. Treatment
with these medications 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 currently
no medication available to allow a reasonable chance of conception with any type of
ovarian stimulation. Egg donation is their best option for getting pregnant.
The four major types of drug therapy for ovulation problems include clomiphene citrate,
injectable gonadotropins, GnRH pump, and bromocriptine. These are all discussed below.
Pregnancy 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..
Clomiphene citrate for induction of ovulation
Clomiphene citrate 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 clomiphene beginning shortly after the induced menstrual period
begins. Clomiphene 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. 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, at these doses pregnancy rates are low. If the clomiphene citrate
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 time 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 or
ultrasound performed in the physician's office to determine when a mature follicle is
present.
Giving the woman an injection of HCG (human chorionic gonadotropin) can control the time
of ovulation. Ovulation will then occur approximately 36 hours later and allows proper
timing of either timed intercourse or intrauterine insemination.
Clomiphene citrate 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 clomiphene and for these women other more expensive medications will be
required.
Ovulation and pregnancy rates using clomiphene for induction of ovulation
On a per cycle basis, and pregnancy rates with clomiphene 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 clomiphene 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 clomiphene citrate 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 clomiphene citrate is used, the
negative impact of the clomiphene citrate 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 therapy for clomiphene resistant women with polycystic ovarian syndrome
Metformin 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.
Injectable gonadotropins for induction of ovulation
Injectable gonadotropins contain follicle stimulating hormone (FSH) which causes
development of multiple follicles when injected into anovulatory women.
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 clomiphene citrate 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 85% are single, 15% are twins, 3% 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.
GnRH Pump for induction of ovulation
A GnRH pump can induce ovulation in some anovulatory women. This pump must be worn at
all times. It releases a very small bolus of medication in to the woman's body every
60-90 minutes.
The pump is a small devise that is worn on the body. Many women find this inconvenient,
as they must also wear it while sleeping and it also involves placement of needles into
her skin.
This form of treatment is relatively more effective for patients with hypothalamic
amenorrhea, which is a relatively rare condition in which the woman has no menstrual
periods and is lacking the proper production of a hormone that is released from the
brain that is involved in follicle development.
The GnRH pump has also been used for women other types of anovulation. However it is
less effective for these other cases.
The advantages of the GnRH pump include a much lower risk of multiple pregnancy and that
little or no monitoring of the patient is required. Little monitoring is required
because this therapy is supposed to induce a situation very similar to that of natural
menstrual cycles with development of a mature follicle and natural ovulation without any
additional injections.
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 very
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:
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.
|
