Gonadotropin-Releasing Hormone Analogues for Infertility

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Gonadotropin-Releasing Hormone Analogues for Infertility


Gonadotropin-releasing hormone (GnRH) agonists and antagonists belong to a group of hormone drugs called GnRH analogues.

Gonadotropin-releasing hormone agonists

Generic NameBrand Name
leuprolideLupron, Eligard

Gonadotropin-releasing hormone antagonists

Generic NameBrand Name

Some GnRH analogues are taken as nasal sprays and some are injected under the skin.

How It Works

Daily GnRH agonist injections overstimulate the pituitary gland, triggering production of more luteinizing hormone (LH) and follicle-stimulating hormone (FSH) than normal, which makes the pituitary gland temporarily shut down. The "disabled" pituitary gland then stops producing LH and FSH, which in turn stops ovulation.

GnRH antagonist injection is a recent addition to infertility treatment. While agonists act over several days to stop ovulation, antagonists act almost immediately by blocking the effect of GnRH on the pituitary gland. Because an antagonist stops the pituitary from making LH within an hour or two, it doesn't have to be used for as many days as an agonist does.

Why It Is Used

GnRH analogue treatment is used to "shut down" the pituitary hormones that control the ovaries.

To treat infertility concerns, a GnRH analogue (agonist or antagonist) is used:

  • To closely time and control ovulation before an assisted reproductive technology (ART) procedure by shutting down the pituitary gland. This is called "pituitary down-regulation." At the same time or afterward, an ovulation-stimulating medicine is used to trigger ovulation, with the goal of harvesting good-quality eggs on a predictable schedule. Increasing numbers of doctors are now using a GnRH antagonist (instead of a GnRH agonist) at the same time that ovulation medicine is used, quickly suppressing the luteinizing hormone that can cause early ovulation.
  • To closely time ovulation before some insemination procedures, when unpredictable ovulation would make it hard to know when to introduce sperm into a woman's reproductive tract.

How Well It Works

GnRH analogues (agonists and antagonists) predictably stop ovulation and menstruation. Agonists take more days of treatment than antagonists do to shut down the ovaries.

Controlling ovulation timing before an infertility procedure. Shutting down the pituitary with GnRH analogue treatment, paired with a hormone to stimulate egg production, lowers the chance that an ART procedure will be cancelled because of early ovulation. For controlling egg production before an infertility treatment, a longer course of GnRH agonist treatment has been shown to produce higher pregnancy and live birth rates, when compared with a short course of doses.1

Side Effects

When paired with ovulation-stimulating treatment, GnRH analogues don't cause low-estrogen symptoms. But when GnRH analogues are taken alone, they produce a temporary condition similar to menopause, with many of the same effects.

Side effects that go away when a GnRH agonist is stopped include:

At first, GnRH antagonist treatment can cause headache, nausea, or swelling, redness, or itching at the injection site.

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

What To Think About

Before insemination, GnRH analogue treatment paired with an ovulation-stimulating treatment increases the risk of conceiving a multiple pregnancy, which is dangerous for a mother and her fetuses. In the case of an assisted reproductive technology such as in vitro fertilization, this risk is controlled by limiting the number of fertilized eggs that are transferred to the uterus.

Drawbacks of GnRH analogue treatment are menopausal symptoms and cost of the medicine.

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


By Healthwise Staff
Primary Medical Reviewer Sarah Marshall, MD - Family Medicine
Specialist Medical Reviewer Femi Olatunbosun, MB, FRCSC - Obstetrics and Gynecology
Last Revised April 27, 2010

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