The pituitary gland which sits at the base of the brain secretes chemical messengers (or hormones) which control the function of other glands, such as the thyroid, adrenal and ovary. Two chemical signals emitted by the pituitary that control the ovaries are follicle stimulating hormone (FSH) and luteinizing hormone (LH). LH and FSH are called gonadotropins.

FSH causes one or more of the eggs resting in the ovary to activate. As eggs mature, fluid collects around them forming what is called a follicle. The cells of the follicle wall produce estrogen. Luteinizing hormone (LH) triggers the follicle to release its ripe egg and produce the hormone progesterone.

Gonadotropins are ideal substances to stimulate the ovaries of women who either have no pituitary gland or lack their own gonadotropins. Also, gonadotropins may be more effective than fertility pills for stimulating the ovaries of individuals whose own FSH and LH are not properly coordinated. Finally and most commonly, gonadotropins are used to purposely hyperstimulate the ovaries of infertile women who ovulate normally. Controlled hyperstimulation is a part of several advanced reproductive technologies, including gamete interfallopian transfer (GIFT) and in vitro fertilization (IVF).

Monitoring

In a natural ovulation cycle, follicles and surrounding cells emit chemical signals which feedback to the pituitary so that only one egg proceeds to ovulation each month. Because they override this innate feedback system, gonadotropins require careful monitoring in order to prevent unwanted hyperstimulation of the ovary.

Hyperstimulation has two undesirable consequences. First, too many eggs release, giving rise to multiple gestation (twins, triplets, quadruplets, etc.). Second, hyperstimulated ovaries become enlarged and cystic. These hyperstimulated ovaries may twist or produce chemical signals that cause fluid to leak out of blood vessels into body cavities, endangering a woman’s health.

We employ ultrasound and blood testing to monitor our patients who take gonadotropins. Ultrasound predicts the number of eggs that will be released. (Remember, not every released egg will be fertilized.) Blood tests help determine the extent of overstimulation and time ovulation properly. If monitoring suggests too much risk of multiple birth or hyperstimulation, the treatment cycle may be cancelled.

Taking the Medication

Since FSH and LH are not absorbed intact into the body from the stomach, the medication is given by injection. Gonadotropins are dispensed as a powder which is dissolved in a sterile water vehicle just before it is injected. The procedure for reconstituting the medication is not difficult to learn. Often a spouse, relative or friend will be recruited to administer the medication.

A typical gonadotropins cycle begins 2 to 7 days after a menstrual flow. Injections are usually given daily until the follicles are ripe. The number of injections required will vary from woman to woman and from cycle to cycle. The usual range is between 5 to 12 shots. Once the process has begun, frequent trips to the doctor’s office for blood tests, exams and ultrasounds will be scheduled.

When the monitoring studies show that the follicles are ripe, ovulation is triggered with another gonadotropin product called human chorionic gonadotropin (hCG) . hCG functions similarly to luteinizing hormone (LH). It initiates the three aspects of ovulation – release of the egg, production of progesterone and maturation of the egg. The eggs are released from their follicles about 40 hours after the hCG injection.

After ovulation hormone levels essential to implantation are supported by either booster shots of hCG or progesterone in pill, suppository or injection form. Pregnancy cannot be detected until two weeks after ovulation.

Preparations

Currently, there are five brands of injectable gonadotropins available for ovulation induction. One of these products – Repronex – is a combination of FSH and LH hormones that is obtained from the urine of postmenopausal women. Although Repronex has recently been approved for subcutaneous injection, we prefer the intramuscular route. Menopur is a purified version of Repronex which patients may inject subcutaneously (with a small needle just beneath the skin).

Bravelle is a highly purified FSH preparation also derived from postmenopausal urine. Because the LH activity and impurities have been removed, Bravelle can be given through a shorter needle under the skin (subcutaneously).

Gonal-F and Follistim are preparations of FSH hormone that are produced in animal cells by bio-recombinant technology (as opposed to obtained from the urine of postmenopausal women). . These preparations can be given subcutaneously.

The most obvious differences between preparations are the route of administration (intramuscular versus subcutaneous) and the cost. Recombinant FSH is more convenient and slightly stronger than gonadotropins from menopausal urine but not enough to outweigh its higher cost. Thus, we usually prescribe Repronex to our patients who do not have a prescription plan that covers injectibles.

An exhaustive list of the side effects and complications of gonadotropins is provided in the product package inserts.

Side Effects Common side effects include:

• pain at the injection site
• fatigue weight gain/water retention
• mood change
• pain at the time of ovulation pain in the week(s) following ovulation (from ovaries enlarged by cysts)

Less common but more serious complications include:

• multiple gestation (30% twins, 6% triplets; multiple gestation increases the risk of pregnancy complications)
• pregnancy and miscarriage (slightly increased over normal rates)
• rupture, bleeding or twisting of ovarian cysts
• severe hyperstimulation

We are concerned that the use of fertility drugs may increase the chance that women will develop ovarian cancer later in life. Current information suggests that some women who are infertile are carry an increased risk of future ovarian cancer which is not further increased by the use of fertility drugs. These concerns underscore the need to use fertility drugs with care and caution.