Ovulation induction is the stimulation of the ovaries to produce multiple follicles,
each containing an egg. In the month prior to ovulation induction, oral contraceptives are
given as a gentle means of preventing ovarian cysts, which are fluid sacs in the ovary.
Such cysts, which were common prior to use of oral contraceptives, delayed the start of
the cycle and interfered with normal ovarian function. Cysts are rare when oral
contraceptives are used. A few days before finishing the oral contraceptives, Lupron
or Synarel is started. These are medications that turn off your normal menstrual
cycles and prevent premature ovulation. Lupron and Synarel are very similar, but Lupron is
taken by subcutaneous injection, and Synarel by nasal spray.
Lupron and Synarel may cause mild side effects -- hot flushes, mild headaches, and
vaginal spotting a week to 10 days after beginning the medication; these symptoms are
normal, and are signs that the medication is working. Please be certain that you are not
pregnant prior to starting Lupron/Synarel, since these drugs can interfere with the normal
hormones that support early pregnancy. (Note that Lupron/Synarel is discontinued well
before you become pregnant).
The nurse coordinator assigns a date for a vaginal ultrasound and blood test around
the time the period starts. Using vaginal ultrasound, the ovaries are examined for
ovarian cysts. Cysts often disappear on their own, but a cyst may be aspirated (removing
the fluid) to help it collapse faster. The blood test measures estrogen, a hormone
produced by the ovary. Most women are ready to start stimulation immediately, but if the
estrogen level is elevated or a cyst is present on the ovaries, you may need another 5 to
14 days of Lupron/Synarel treatment before proceeding.
Occasionally, the male will be asked to give a backup sperm sample early in the
cycle. This will be frozen and stored, to be available as an emergency backup. Let us
know if obtaining a sperm sample on the day of egg retrieval might be difficult.
In a typical stimulation protocol, daily or twice daily injections of human
gonadotropins, Humegon, Pergonal, Repronex, Gonal-F, or Follistim are started after the
menstrual period. These medications are concentrated forms of the natural hormones
which stimulate ovulation in a normal menstrual cycle. These medications are very similar,
but Humegon and Pergonal and Repronex contain two hormones, luteinizing hormone (LH), and
follicle stimulating hormone (FSH), while Gonal-F and Follistim contain pure FSH. Although
these are different medications, there are only small differences in the way the body
responds to them, so we will refer to all of them as gonadotropins in this web site.
The day gonadotropins begin is stimulation day 1, or "stim day 1"
regardless of when it occurs after the period. The Lupron dose may be reduced when
stimulation starts.
The follicles are egg-containing areas inside the ovary. There are hundreds of
thousands of follicles in each ovary, but during any one stimulation cycle only a few will
accumulate fluid and grow large enough to appear on an ultrasound exam. Only the large
follicles hold mature eggs. The eggs are about a tenth of a millimeter in diameter, just
under a size that is visible to the naked eye, so the actual egg cannot be seen on
ultrasound. The follicle is about two hundred times bigger than the egg, and can be seen
clearly when it is large enough. Each follicle usually contains one egg surrounded by
granulosa cells. Granulosa cells surround the egg, produce the follicular fluid,
produce estrogen, and support the egg in its development. In the normal menstrual
cycle, only one follicle matures, reaching about an inch in diameter. Occasionally a
follicle may not contain an egg, and even more rarely there may be two or more eggs per
follicle.
Gonadotropins cause several follicles to enlarge at once. The number can vary
from one or two to 30 in some women. The dose of gonadotropin is based on a prediction of
how the ovaries will respond, and usually varies from one to eight ampules per day. Women
who are very sensitive to the medication need only a small amount of gonadotropins, while
those who are resistant require more.
The main risk of gonadotropins is ovarian hyperstimulation syndrome. Ovarian
hyperstimulation occurs in a small percentage of patients when too many follicles develop
in the ovary. The ovary then grows to a large size and leaks fluids, resulting in nausea
and bloating, dehydration, and, if severe, fluid collection around the abdominal organs,
or ascites. In very severe cases, fluid collects around other organs, such as the lungs
and heart, and blood clots and strokes can occur. If the ovary enlarges too much, rupture
of the ovary and abdominal bleeding can occur. In rare cases, hospitalization and removal
of abdominal fluid may be required to regulate fluid balance. In years past,
fatalities have been reported, but are extremely rare.
Fortunately, serious cases of ovarian hyperstimulation are quite rare, and your
doctor can predict and prevent hyperstimulation by monitoring the ovaries with ultrasound
and blood estrogen levels. Removal of the granulosa cells during egg retrieval reduces the
risk of hyperstimulation, so the risk with in vitro fertilization is lower than with
gonadotropin use for simple ovulation induction. If the risk is very high, a cycle may be
canceled. Although this is a rare event, it provides complete safety, in that
hyperstimulation almost never occurs after a canceled cycle. If a cycle proceeds to egg
retrieval, embryos may be frozen and saved for a later cycle, after the risk of
hyperstimulation has subsided.
When ultrasound examination and estrogen levels suggest that the follicles are large
enough and the eggs are mature, you will stop Lupron/Synarel and gonadotropins and take
one dose of human chorionic gonadotropin (hCG). hCG prepares the eggs for ovulation
and fertilization. Egg retrieval is performed at about 36 hours after hCG, since ovulation
normally begins about 40 hours after the hCG injection. The timing of hCG is critical,
so it must be taken at the exact time you are instructed to give it.
The usual dose of hCG is 5000 IU, a half vial, although this may vary. The pharmacist
gives you a box with a vial of powder and a vial of sterile water. You can dissolve the
hCG in just one cc of fluid; don't use the full 10 cc of fluid to dissolve the powder. You
might receive hCG in a piggyback vial that contains fluid and powder in separate chambers
of the same vial. This package is difficult to use, so make sure your pharmacist has not
dispensed this form, but instead has given you the two vial package, with powder and fluid
in separate containers.