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Information and Consent to the Use of
Gonadotropins for Ovulation Induction
DESCRIPTION
Ovulation induction refers to the process of stimulating the ovaries to produce eggs. Gonadotropins are a
class of drugs that are used in this process. These drugs are made up of two hormones, FSH (follicle
stimulating hormone) and LH (luteinizing hormone). FSH and LH are the two hormones that are
responsible for stimulating the development of eggs in the ovary. There are a variety of gonadotropins on
the market. Most women will be prescribed one or a combination of the following: Follistim® Gonal-F®,
Bravelle® and/or Menopur®.
Menopur® is a mixture of follicle stimulating hormone (FSH) and luteinizing hormone (LH) while
Follistim®, Bravelle and Gonal-f® are pure preparations of FSH. All of these medications must be
administered by injection into the fat tissue under the skin (SC injection). They may either be packaged in
vials containing powder that must be reconstituted with a diluent or come already pre-mixed in cartridges.
Your physician will decide which formulation will work better for you.
Most women require 7-10 days of these medications to stimulate the ovaries. While taking these
medications, you will need to be monitored with ultrasounds and lab work to assess your ovaries’ response
to these medications.
MODE OF ACTION
Gonadotropins act directly on the ovaries to stimulate the development of eggs. Eggs are contained within
fluid-filled sacs in the ovary called follicles. These follicles can be visualized by ultrasound. As an egg
matures in response to gonadotropins, the fluid within the follicle increases and the follicle grows in size.
The follicle can then be measured by ultrasound to determine the maturity of the egg. In addition, each
maturing egg produces a hormone called estradiol (a type of estrogen). This hormone can be measured
through a blood test. Although gonadotropins stimulate growth and maturation of follicles, they usually do
not trigger ovulation (the release of the eggs). Therefore another medication called human chorionic
gonadotropin (hCG) must be administered when the eggs are mature to mimic the hormonal surge that
causes ovulation.
INDICATIONS
Gonadotropin therapy is indicated in the following situations:
1. Women who fail to ovulate or conceive after optimal doses of clomiphene citrate.
2. Couples with infertility and normal tubal anatomy who have failed simpler forms of therapy. In this
situation it is often combined with intrauterine inseminations.
MONITORING AND ADMINISTRATION
In most cases, gonadotropins are started on the third day of a woman’s menstrual cycle. You will be asked
to call our office the first day you begin your period so that we can give you instructions regarding
your medication dosage and first ultrasound appointment. If you start your period on the weekend,
don’t panic. Call our office early on Monday morning. Monitoring your response to gonadotropin
therapy is essential in order to adjust dosage and to minimize the possibility of adverse reactions. A
combination of both ultrasonography and estradiol measurements will be used to monitor your ovaries
response to the medications.
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Ultrasound and estradiol monitoring will generally begin after you have been on gonadotropins for 3-5
days. You will then need to come in every two-three days until your eggs are mature. All appointments
will be in the morning so that decisions about the next dose of therapy can be made in the afternoon. The
timing of the hCG injection is based on both the size of the eggs and the estradiol level.
GONADOTROPIN ADMINISTRATION
All gonadotropins are given by injection. Your gonadotropin injection should be given at about the same
time each day in the early evening. If you are on twice daily injections, your injections should be given
roughly 11-12 hours apart. This ensures accurate measurement of both your follicles and estradiol level.
You will need to keep up with how much drug you have and reorder when you get low. We don’t
stock any drug in our office.
hCG DOSAGE AND ADMINISTRATION
Because most patients do not ovulate with gonadotropin treatment alone, ovulation is triggered with an
injection of 10,000 Units of hCG when the eggs are mature. HCG acts like the LH surge. This LH surge or
hCG injection triggers the process of ovulation within 36 hours after the injection. Other names for hCG
include Ovidrel® and Novarel®. Novarel and generic hCG come in powder form and must be
reconstituted with diluent. Ovidrel is a synthetic hCG and comes premixed in a syringe. All of the hCG
products are given by subcutaneous injection.
Once you have a dominant follicle between 16-18mm and your estradiol level is below 2000 pg/ml,
ovulation can be triggered with hCG. You will be given specific instructions as to the date and time of this
injection. If your treatment also includes intrauterine insemination (IUI), your IUI procedure will be
scheduled between 24-36 hours after your hCG injection.
PROGESTERONE SUPPORT
All patients being treated with gonadotropins are given a progesterone supplement. This is a hormone that
aids in implantation of the embryo and support of the developing pregnancy. It is generally in the form of a
pill to be taken nightly beginning the day after ovulation. Occasionally progesterone cream given vaginally
is used. DO NOT BEGIN THIS UNTIL AFTER OVULATION or your cycle might be cancelled.
ADVERSE REACTIONS/SIDE EFFECTS
Side effects associated with gonadotropin therapy include local irritation at the site of the injection and
excessive ovarian stimulation (see below). Applying warm, moist heat to irritated areas can provide relief
to local irritation. Other reported side effects, such as dizziness, nausea, headaches, irritability and hot
flashes, have been reported and may be associated with increased estrogen levels.
Improper injection techniques may result in injury or damage to the nerves. Therefore, it is important to
review injection technique with your nurse and follow the injection instructions provided.
There has been some concern that the use of ovulation induction agents may increase a person's risk of
developing ovarian cancer. Recent studies have addressed this question and have not shown an increase in
ovarian cancer rates in women who have used gonadotropins. Women with a history of infertility,
independent of their use of gonadotropins or other ovulation induction agents, do have a higher incidence
of ovarian cancer. Pregnancy and past use of oral contraceptives appears to have a protective effect.
Ovarian Hyperstimulation
Hyperstimulation of the ovaries is a potential risk when taking ovulation induction agents.
Hyperstimulation occurs when the ovaries become enlarged. In mild to moderate cases of
hyperstimulation, a person may experience abdominal distension and/or abdominal pain. Approximately
20% of patients will experience mild hyperstimulation. Symptoms usually resolve with the onset of
menses, but in the case of pregnancy may continue for several weeks.
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In severe hyperstimulation, ovarian enlargement is accompanied by accumulation of fluid in the abdomen,
nausea, vomiting, weight gain and a decrease in urine output. Women who experience severe
hyperstimulation require hospitalization.
Mild to moderate uncomplicated ovarian hyperstimulation, which may be accompanied by abdominal
distension and/or abdominal pain, occurs in approximately 20% of patients treated with gonadotropins and
hCG. It generally regresses without treatment within two to three weeks. However, if a pregnancy occurs, it
may persist several weeks into the pregnancy. Patients experiencing mild to moderate ovarian enlargement
usually report pelvic fullness and some abdominal pain and discomfort, usually about four to ten days after
administration of hCG. The degree of hyperstimulation is related to both the estradiol level and the number
of eggs. Moderate or severe cases may need hospitalization (greater than 10 pounds weight gain).
If there is a concern about hyperstimulation, you will be asked to report the following:
- weight gain of 5 lbs. or greater
- severe pelvic pain
- decrease in urine output
You will also be asked to refrain from the following:
- intercourse
- strenuous activity
- letting anyone perform a pelvic exam
- running/jumping type exercise
If your estradiol goes above 2000 and you develop many eggs, your cycle will be canceled due to the fear
of severe hyperstimulation. If this happens, hCG will not be given and you may be placed on birth control
pills.
Multiple Gestation
The incidence of multiple gestation is approximately 30% and roughly 5% of all gonadotropin pregnancies
result in triplets or greater. Multiple pregnancies can be complicated by premature delivery, hypertension
and diabetes. If there is a significant concern of multiple births, then hCG and intercourse and/or IUI can be
withheld. In some cases the risk of multiple pregnancy (triplets or higher) is so great that the physician will
cancel the cycle. This more commonly happens in the first cycle.
Miscarriage and Congenital Anomalies
The incidence of miscarriage (15-25%) or congenital anomalies (2-5%) is felt to be no greater with
gonadotropins than that found with spontaneous conceptions. However, taking 400 mcg (micrograms) of
folic acid everyday has shown to decrease the incidence of neural tube defects in infants.
PREGNANCY RATE
Gonadotropins have been used for years to help women become pregnant. The success of these
medications largely depends upon the diagnosis of the patient using the medication. Women who do not
ovulate on their own or have irregular periods and no other medical problem can expect a 25% chance
pregnancy per cycle. Couples with unexplained infertility or endometriosis can expect a 10-20% chance of
conception per cycle. If conception does not occur after three to four cycles of gonadotropins, we will
encourage you to meet with your physician to discuss further options. In addition, age also impacts your
pregnancy rate on these medications.
COST
The expense of treatment includes:
- Gonadotropins ($45-72 per vial - 15 to 25 vials /cycle)
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- Ultrasounds ($135 per exam - 3 to 5 per cycle)
- Estradiols (3 to 5 per cycle)
Insurance may or may not pay for the gonadotropin therapy.
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Before proceeding with gonadotropin therapy it is important that you fully
understand the use, mixing, and proper administration of these medications. It is
also important that you follow your physician’s and nurse’s instructions. All
appointments will be in the morning. It is important that you arrive at your
scheduled appointment time; this helps us stay on schedule and meet your needs
effectively. If you have back to back cycles, you will need a baseline ultrasound
before starting injections, to rule out ovarian cysts.
SIGNATURE STATEMENT
I consent to the use of gonadotropin therapy in order to increase my chances of becoming pregnant. I
understand that the use of these medications does not guarantee a pregnancy.
I understand that while taking these medications I will need to be monitored closely with the use of
ultrasounds and blood tests as determined by the physician. My inability to make these appointments may
necessitate the need for my cycle to be cancelled. I also understand that the physician may need to cancel
my cycle if it is felt that I may be a risk for hyperstimulation or multiple pregnancy.
I have been fully advised as to the use, administration, monitoring, and adverse effects and benefits of
gonadotropins in the treatment of infertility. I have had an opportunity to have all our questions answered
by our physician.
I understand that my insurance may not cover the medications, ultrasounds, and lab work related to the use
of gonadotropins.
An executed copy of this form has been provided to me for my records.
Patient Signature
Date
Witness
Date