Overview of GnRH Antagonists Used in IVF Treatments

Woman lying in bed with abdmonial cramps and headache, possible side effects of Ganirelix
The most common side effects of GnRH antagonists like Ganirelix are abdominal tenderness and headache. AnaBGD / iStock Photo

GnRH antagonists are injectable medications that are used during IVF treatment. They prevent premature ovulation, so your doctor will be able to retrieve the eggs from the ovaries before they are released and “lost.”

Don’t confuse GnRH agonists (like Lupron) with GnRH antagonists. GnRH agonists cause a surge in reproductive hormones and then, after several days, shut down those hormones. When used during IVF treatment, they need to be started at least a couple of weeks before the IVF treatment cycle begins.

GnRH antagonists do not create this initial surge in hormones. They are started after the IVF cycle has begun and may be taken once or daily for a few days.

Since GnRH antagonists are taken for a shorter period of time, they cause fewer side effects. Those that do occur usually last for a shorter period of time.

Not all possible side effects and risks are included in the list below. If you are taking a GnRH antagonist and have severe side effects, unusual symptoms, or are concerned for any reason, contact your doctor.

What Medications Are GnRH Antagonists?

There are two basic GnRH antagonists on the market: ganirelix acetate and cetrorelix acetate. Brand names for ganirelix acetate include Antagon, Ganirelix, and Orgalutran. Cetrotide is the brand name for cetrorelix acetate.

These medications are taken via injection. Treatment may involve one injection, daily injections over several days, or single injections are taken a few days apart. It all depends on your particular IVF treatment plan.

GnRH antagonists are slightly more expensive than GnRH agonists, but the additional cost may not make a big impact since antagonists are taken for a shorter period of time. Also, some women believe the fewer side effects are worth the additional costs.

While some fertility doctors prefer GnRH agonists because they have been around longer, research has not found a difference in pregnancy success rates between agonists and antagonists. Talk to your doctor if you would like to consider a GnRH antagonists instead of GnRH agonist.

Side Effects of GnRH Antagonists

Cetrorelix acetate and ganirelix acetate both work by shutting down the pituitary gland’s ability to produce and release FSH and LH.

The shutdown induces a state of temporary menopause, which can have side effects. Which side effects you experience usually depends on how long you are taking the medication.

Common side effects of cetrorelix acetate (Cetrotide) include:

  • A rash that looks like hives at the site of the injection, which lasts up to two hours but not long-term (this is not an allergic reaction, but a normal side effect)
  • Abdominal pain and tenderness (4.4% when taken daily, 2.1% when taken as a single dose)
  • Headache (1.3% with the daily dose, 0% when taken as a single dose)
  • Nausea (1.3% with the daily dose, 1.1% with the single dose)

Common side effects of ganirelix acetate (Antagon, Ganirelix, Orgalutran) include:

  • Abdominal tenderness by the ovaries (4.8%)
  • Headache (3%)
  • Vaginal bleeding (1.8%)
  • Injection site pain or bruising (1.1%)
  • Nausea (1.1%)
  • Stomach ache (1%)

Risks of GnRH Antagonists

As with any medication or treatment, there are risks of taking GnRH antagonists. Discuss the pros and cons with your doctor, as they can help you weigh the risks and benefits.

  • Fetal death. During clinical studies, 3.7% of pregnancies conceived while taking ganirelix acetate ended in fetal death, or stillbirth. Whether this is connected to GnRH antagonists specifically, or to the other IVF drugs, IVF itself, or to infertility, is unknown.
  • Birth defects. Studies have found a slightly higher risk of birth defects in a pregnancy conceived while taking ganirelix acetate. Whether this is connected to this particular medication, other IVF drugs, the IVF procedures themselves, or to infertility is unknown.
  • Ovarian hyperstimulation syndrome (OHSS). Occurred in 2.4% of women being treated with ganirelix acetate. The OHSS is not really caused by the GnRH antagonists, but by the gonadotropins are taken at the same time. Studies have found that the risk of developing OHSS is slightly lower with GnRN antagonists when compared to treatment with GnRH agonists.
  • Severe OHSS. Occurs in less than 1% of patients. Contact your doctor immediately if you experience vomiting, severe abdominal or pelvic pain, sudden weight gain, or severe bloating. 
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