Lupron Side Effects and Risks When Used for IVF

syringe and GnRH agonist vial with Lupron on glass dish, used during IVF treatment
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Lupron, a GnRH agonist, is one of the best known and most hated of IVF treatment injectable fertility drugs. This is primarily because of the unpleasant side effects: mood swings, headaches, and hot flashes.

GnRH agonists like Lupron are primarily used for the treatment of endometriosis and fibroids. Less commonly, a GnRH agonist can be used to stimulate ovulation instead of the usual hCG trigger shot during an IUI cycle.

Using Lupron for fertility treatments like IVF is considered "off-label." That said, Lupron has been a part of fertility treatments for many years.

In the long-term, Lupron side effects can be serious. Long-term lupron treatment occurs with endometriosis or fibroid treatment. When used for fertility treatment, Lupron is a short-term use drug.

What Medications Are GnRH Agonists?

Leuprolide acetate, sold under the brand name Lupron Depot, is taken via injections, usually starting in the cycle before IVF treatment begins. When used for IVF, Lupron may be given as one injection or daily injections.

Lupron is only one brand of GnRH agonists. Nafarelin acetate, sold under the brand name Synarel, and buserelin, sold under the brand name Suprecur, are GnRH agonists taken via a daily nasal spray. They are also usually started the month before IVF is scheduled.

Goserelin, sold under the brand name Zoladex, is a GnRH agonist delivered via a small, biodegradable implant, injected just under the skin. One implant lasts one month.

Side Effects of Lupron

Lupron essentially put the body into a reversible, temporary menopausal state. Most of the side effects are similar to what women experience during menopause.

The good news is that once gonadotropin treatments are started, many of the side effects will be alleviated. However, you will then be dealing with gonadotropin side effects and risks.

While the percentages may differ between different forms of the GnRH agonists, the general list of possible side effects is similar.

Lupron is the most frequently used GnRH agonist during fertility treatment, but the side effects you experience will depend on why and for how long you’re taking the GnRH agonists.

The side effect percentages listed below refer to research done specifically on Lupron when taken for several weeks.

Common side effects of Lupron include:

  • Hot flashes (70 to 80%)
  • Headaches (25 to 32%)
  • Mood swings and depression (10 to 22%)
  • Vaginal dryness and irritation (11 to 28%)
  • Acne (10%)
  • General body aches (8 to 19%)
  • Nausea (8 to 13%)
  • Joint pain (7 to 8%)
  • Edema (5 to 7%)
  • Nervousness (4 to 6%)
  • General upset stomach (3 to 7%)
  • Weight gain (3 to 13%)
  • Decreased libido (2 to 11%)
  • Dizziness (2 to 11%)
  • Tingling (“pins and needles”) in the arms and legs (1 to 7%)
  • Breast tenderness (2 to 6%)

Not all possible side effects and risks are listed here. If you are experiencing severe side effects, unusual symptoms, or are concerned about Lupron for reason, contact your doctor.

If you take a GnRH agonist long-term (such as for treating endometriosis or fibroids) you might stop getting your period. However, this is not considered a side effect because shutting down the hormones that cause menstruation is an intended effect of the drug.

When GnRH agonists are taken via injection, soreness and redness at the injection site may occur. When taken as a nasal spray, irritation of the sinuses may occur.

What Are GnRH Agonists? How Are They Used During IVF?

A kind of fertility drug, GnRH agonists are artificial hormones that mimic the body’s natural hormone gonadotropin-releasing hormone (GnRH).

A GnRH agonist first leads to a rapid increase in the production of the hormones FSH and LH. However, after this brief increase, the pituitary gland stops producing the hormones, preventing ovulation.

That initial boost in FSH and LH is why GnRH agonists can sometimes be used to trigger ovulation. It is also why, when being used to treat endometriosis, symptoms can worsen at first.

In IVF treatment, drugs like Lupron are used along with gonadotropins. The agonists prevent natural ovulation. Instead, a fertility doctor will artificially stimulate ovulation with other fertility drugs in a controlled manner known as superovulation.

The drug also prevents the natural LH surge. A natural LH surge could lead to the eggs ovulating before they can be retrieved from the ovaries.

If the eggs are ovulated before they are retrieved, they get “lost” inside the pelvic cavity. When this occurs, they cannot be used for IVF treatment.

How Are GnRH Agonists Used to Treat Endometriosis and Fibroids?

When used to treat endometriosis, GnRH agonists are taken continually over a period of three to six months. How frequently you’ll receive injections and/or the nasal spray depends on the drug being used.

The goal in endometriosis treatment is to stop the production of estrogen, which feeds the endometrial deposits. By “starving” these deposits, pain is reduced.

During the first two to three weeks of treatment, your symptoms may worsen. This occurs because of the initial boost in FSH and LH. After about four to eight weeks, your endometriosis symptoms should improve.

When used to treat fibroids, the goal is usually to reduce the size of the fibroid before surgery. By “starving” the fibroid of estrogen, the mass shrinks. Treatment may take place for three or four months before scheduled surgery.

These drugs cause a temporary menopausal state. You can’t get pregnant while taking GnRH agonists for endometriosis or fibroids.

These drugs are not a fertility treatment for endometriosis or fibroids. They can help improve some symptoms of these conditions, but won’t improve your fertility. If you want to get pregnant, you will need to discontinue treatment.

Depending on the medication you’re taking, it may take anywhere from four to six weeks (with nasal spray agonists) or six to ten weeks (with injections) for your fertility to return.

You should not rely on GnRH agonists to absolutely prevent ovulation. When taken continuously, if you do get pregnant, GnRH agonists can harm a developing fetus.

Your doctor might advise you to use a barrier method of birth control (like condoms or a diaphragm) to prevent pregnancy while you are taking these medications.

Risks of GnRH Agonists

The Food and Drug Administration (FDA) has not formally approved Lupron and other GnRH agonists to be used as fertility treatments. The drug's use during IVF is considered “off-label.” Therefore, it’s not really known what all the risks are when used for fertility treatment.

Here is a brief overview of the known risks of using Lupron to treat endometriosis, fibroids, or prostate cancer. The risks during IVF treatment may be similar.

Depression

If you have a history of depression, GnRH agonists may lead to severe depression.

Don’t keep this from your doctor; tell them if you experience worsening depression or are concerned about mood-related side effects.

Decreased Bone Density

In women who used Lupron over a period of three months, bone density decreased 2.7 percent. Six months post-treatment, bone density seemed to improve, but the long-term after-effects are not really known.

It is also not known at what point the decreased bone density becomes irreversible. For this reason, treatment for more than three to six months is not recommended.

Lupron is not recommended for women who are at risk of having decreased bone density. If you have a family history of osteoporosis, mention this to your doctor.

Pituitary Apoplexy

This is when a pituitary tumor (usually not yet diagnosed) bleeds. This is extremely rare, usually occurring within the first two weeks of treatment, and sometimes within the first hours.

If you experience sudden severe headache, vomiting, visual changes, paralysis of the muscles within or around your eyes, an altered mental status, or signs of a heart attack, get medical attention immediately.

Increased Health Risks

Some people taking GnRH agonists were found to be at a slightly increased risk for developing diabetes, heart attack, and stroke

However, these risks were primarily found in men taking GnRH agonists to treat prostate cancer. It is not known if these risks extend to people taking the drugs as IVF treatment.

Alternatives to GnRH Agonists

It’s important to know that GnRH agonists are not the only option for IVF. An alternative includes GnRH antagonists, like Antagon (ganirelix acetate) and Cetrotide (cetrorelix).

Unlike GnRH agonists, GnRH antagonists are FDA approved for use during IVF treatment. You also take them for a shorter period of time. This may reduce the amount or length of time you experience side effects.

GnRH antagonists may be safer, according to some studies. When used during fertility treatment, women had a lower risk of developing ovarian hyperstimulation syndrome when compared to GnRH agonists.

The possible downsides are that GnRH antagonists are more expensive and not all fertility specialists are accustomed to using them.

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