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.