Gonadotropin treatment for infertility

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The body produces two types of gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). After they are produced by the pituitary gland, gonadotropins trigger production of other sex hormones. Gonadotropins therefore play a part in egg and sperm production, as well as female and male physical traits such as voice, muscle, hair, and breast development.

Human menopausal gonadotropin (hMG) and recombinant human follicle-stimulating hormone (rFSH) are gonadotropin fertility drugs.

• hMG contains natural FSH and LH, purified from urine from postmenopausal women. (After menopause, women produce high levels of gonadotropins, which are excreted in their urine.)
• rFSH is genetically synthesized in the laboratory.

Human chorionic gonadotropin (hCG) is similar to LH. It contains equal amounts of LH and FSH. These hormones play a central role in egg production.

In women. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are necessary for egg production (ovulation). Early in the menstrual cycle, a woman with low hormone levels who is not ovulating can have daily human menopausal gonadotropin (hMG) or recombinant human FSH (rFSH) injections for an average of 12 days. If this helps develop mature follicles, the ovary is ready to ovulate. One dose of human chorionic gonadotropin (hCG) is then used to stimulate ovulation.

In men with low testosterone and FSH. LH stimulates the production of testosterone, and FSH promotes the formation of sperm. If a semen analysis, LH testing, and FSH testing suggest that abnormal hormone levels are preventing sperm production, these gonadotropins may be prescribed together to promote sperm formation. The man gets an hCG injection 3 times weekly until blood testosterone level is within the normal range (this may take 4 to 6 months). Treatment continues with injections of hCG 2 times a week and hMG or FSH 3 times a week until the sperm count rises to normal levels.

Gonadotropins are given by injection to help the body make the hormones needed for egg or sperm production.

In women. Gonadotropins may be used:¹

• To stimulate ovulation related to low natural gonadotropin or estrogen levels. (This is most commonly seen in women with excessive exercise or eating disorders.)
• When clomiphene alone or clomiphene combined with another medicine has been ineffective for correcting irregular or no ovulation caused by polycystic ovary syndrome (PCOS).
• For developing multiple egg follicles on the ovaries. Multiple eggs are harvested and used in assisted reproductive techniques such as in vitro fertilization or gamete intrafallopian transfer.
• In combination with intrauterine insemination for couples with unexplained infertility when clomiphene has not worked.

In men. Gonadotropin therapy can treat low sperm counts caused by low levels of natural gonadotropins.

The combination human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or recombinant human follicle-stimulating hormone (rFSH)/hCG treatment can consistently stimulate ovulation. It results in pregnancy in 60% of women failing to ovulate. But of those pregnancies, up to 35% end in miscarriage.²

Side effects are more common and more serious with gonadotropin treatment than with clomiphene (Clomid).

• Up to 35% of women who become pregnant after hMG/hCG or rFSH/hCG therapy have a miscarriage.² This is higher than the risk of miscarriage in the general population.
• In 5% to 10% of treatment cycles, women develop detectable ovarian enlargement. Multiple follicles (cysts with eggs) make the ovaries larger and more tender.²
• There is a risk of ovarian hyperstimulation syndrome (OHSS), which (in rare cases) can be life-threatening. But when a woman is closely monitored for side effects, she has less than a 1% risk of developing severe OHSS.²
• Ovarian stimulation increases the likelihood of multiple pregnancy (twins, triplets, or more). Multiple pregnancy is considered high-risk for both a mother and her fetuses.
• Other side effects include headache and abdominal pain.
• Men may experience temporary breast enlargement.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

During gonadotropin treatment, frequent monitoring of egg follicle development is necessary.² This is done with ultrasound and blood tests. Without careful monitoring, the ovaries may become hyperstimulated. Ovarian hyperstimulation syndrome can be a very serious condition. It usually goes away by itself in 2 to 4 weeks, but a woman may need bed rest or hospitalization and intravenous fluid therapy, or may need a procedure to remove fluid from the abdomen.

Gonadotropins should only be used by doctors who are specially trained in infertility and who are familiar with the management of possible complications.

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Citations

1. Burney RO, et al. (2007). Infertility. In JS Berek, ed., Berek & Novak's Gynecology, 14th ed., pp. 1185–1275. Philadelphia: Lippincott Williams and Wilkins.

2. Lobo RA (2007). Infertility: Etiology, diagnostic evaluation, management, prognosis. In VL Katz et al., eds., Comprehensive Gynecology, 5th ed., pp. 1001–1037. Philadelphia: Mosby.