Side Effects and Risks of Fertility Drugs

From Headaches to Twins, Hot Flashes to Mood Swings

Fertility drug side effects and risks depend on which medication you’re taking. Oral fertility drugs (like Clomid or letrozole) have milder side effects than injectable fertility drugs (like gonadotropins or GnRH agonists and antagonists.)

The most common fertility drug side effects are bloating, headache, breast tenderness, upset stomach, hot flashes, and mood swings. The most common fertility drug risks are conceiving a multiple pregnancy (like twins or triplets or more) and developing ovarian hyperstimulation syndrome (OHSS). These aren’t the only potential side effects and risks, just the most common ones.

Fertility drugs can create miracles and are generally effective. Still, it's important to know what can go wrong and how to possibly lower your chances of complications.

Side Effects

Side effects are unwanted and unintentional symptoms that result from a medication.

Whether or not you’ll experience side effects will depend on…

  • the medication you take
  • the dosage of the medication (higher doses usually mean increased risk)
  • your particular body

Take, for example, the fertility drug Clomid. Some women take Clomid and feel fine. Others experience headaches or mood swings. It’s difficult to predict how you will react until you take a medication. Below are brief lists of common fertility drugs side effects.

If you are experiencing severe side effects, unusual symptoms, or are concerned for any reason, contact your doctor.

Anxiety Over Possible Side Effects

Reading about possible side effects can increase anxiety and may even increase the risk you’ll experience certain side effects. This is known as the nocebo effect. (It’s like the placebo effect, just negative.) Of course, you should always discuss with your doctor the risks of any medication before you take it.

However, if you tend towards anxiety, you might want to skip the detailed side effect/risk information and focus on the sections below on how to reduce and cope with the side effects.

Clomid Side Effects and Risks

Clomid works by tricking the body into thinking there isn't enough circulating estrogen. To do this, it blocks the receptors in the body that react to the estrogen hormone. Most side effects of Clomid are caused by these perceived low estrogen levels.

Possible side effects of Clomid include:

  • Hot flashes
  • Bloating and abdominal discomfort
  • Weight gain
  • Headaches
  • Mood swings
  • Nausea
  • Dizziness
  • Breast tenderness
  • Abnormal menstrual bleeding / spotting
  • Vaginal dryness

A rare but serious risk of Clomid is blurred vision. Occurring in less than 1.5 percent of women during the clinical trials, you may experience blurred vision, see flashing lights, or see floaters. If this happens to you, tell your doctor right away.

Like most fertility drugs, Clomid can also lead to a twin pregnancy. About 7 in 100 Clomid-conceived pregnancies will result in twins.

Letrozole Side Effects and Risks

Letrozole is used off-label as a fertility drug. (Letrozole, also known as Femara, is actually intended for use in the treatment of breast cancer.) Letrozole works in a similar way as Clomid (blocking estrogen receptors). Studies have found that women with PCOS and women who are Clomid resistant (don't ovulate on Clomid) may have more success with letrozole.

Possible side effects of letrozole include:

  • Fatigue
  • Dizziness
  • Headache
  • Bloating / abdominal discomfort
  • Hot flashes
  • Blurred vision
  • Trouble sleeping
  • Abnormal menstrual bleeding / spotting
  • Breast pain

There is a risk of vision disturbances and an increased risk of conceiving twins on letrozole, just as with Clomid.

Gonadotropins Side Effects and Risks

Gonadotropin fertility drugs are injectable hormones. They include drugs like Gonal-F (FSH), Follistim, and Ovidrel (hCG). Injectables may be used alone, or in combination with other drugs during an IVF cycle.

Possible side effects of gonadotropins include:

  • Headaches
  • Nausea / upset stomach
  • Upper respiratory tract infection
  • Bloating / abdominal tenderness
  • Mood swings
  • Acne
  • Weight gain
  • Abnormal menstrual bleeding / spotting
  • Injection site soreness and redness
  • Dizziness

When compared to Clomid and letrozole, the risk of twins is significantly higher with gonadotropins: up to 30 percent may result in multiples. If you're having IVF, choosing a single embryo transfer can reduce this risk.

Lupron and Other GnRH Agonist Side Effects and Risks

GnRH agonists like Lupron are most commonly used during IVF treatment. They shut down the body's natural reproductive system so that your doctor can control ovarian stimulation and maturation. Low estrogen levels are responsible for many of the side effects of GnRH agonists.

Possible side effects of GnRH agonists (like Lupron) include:

  • Hot flashes
  • Headache
  • Mood swings / depression / anxiety
  • Vaginal dryness
  • Acne
  • General body aches / joint pain
  • Nausea
  • Fluid retention
  • Upset stomach
  • Weight gain
  • Decreased sex drive
  • Dizziness
  • Injection site soreness

GnRH Antagonist Side Effects and Risks

Like GnRh agonists, GnRH antagonists are used to shutdown the body's reproductive system during IVF treatment. They have significantly fewer side effects than GnRH agonists.

Possible side effects of GnRH antagonists include:

  • Abdominal tenderness
  • Headache
  • Nausea / upset stomach
  • Abnormal menstrual bleeding / spotting
  • Injection site soreness

Rare But Potentially Serious Risks of Fertility Drugs

In rare cases, fertility drugs can cause severe side effects. Your doctor should discuss these with you. Always tell your doctor if you’re experiencing worrisome symptoms, even if you’re not sure if they’re related to the medication. It’s better to call your doctor if you’re concerned and have him tell you everything is fine, than ignore a serious side effect that could lead to medical harm or danger.

Vision Changes: A very small percentage of women will experience vision disturbances when taking Clomid or letrozole. If this happens to you, you have see flashes of light, a sudden increase in “floaters”, or blurred vision.

The blurred vision may come along with a severe headache. Tell your doctor right away if this happens to you. The vision problems should go away once you stop taking the medication. In very rare cases, long-term damage may occur.

Ectopic pregnancy: women taking gonadotropins have a slightly increased risk of ectopic pregnancy. Ectopic pregnancy can be life-threatening if ignored! If you experience severe pelvic pain, contact your doctor immediately.

Ovarian hyperstimulation syndrome (OHSS): fertility drugs intentionally stimulate the ovaries to produce more eggs than they usually would.

With OHSS, the ovaries become dangerously overstimulated. This is more common during IVF treatment, but can also occur with Clomid and gonadotropin treatment. Most cases of OHSS are mild, but severe OHSS can occur. In rare cases, OHSS can lead to blood clots and kidney failure.

Severe OHSS can threaten your fertility and even your life. Catching the symptoms quickly and receiving early treatment is key.

Ovarian torsion: ovarian torsion is a possible complication of OHSS. Less than 2% of women taking gonadotropins will experience ovarian torsion. Fertility drugs cause the ovaries to enlarge. Sometimes, the ovary can twist on itself, cutting off blood supply. Surgery to untwist the ovary or even remove the ovary may be required.

Ovarian torsion may put your life and fertility at risk. If you experience severe pelvic pain, go to the nearest emergency room immediately.

Allergic reaction: allergic reaction to fertility drugs is rare. However, as with any medication (or food), a reaction is possible.

Twins, Triplets, and High-Order Pregnancies

If you're plugged into the media in any way, you already know about the risk of multiples when using fertility drugs. Your risk of conceiving multiples will depend on what fertility treatment you are having and which medication you’re taking. For example, the risk of having twins when taking gonadotropins is three times as high as it is with Clomid.

Some people mistakenly think that multiples are only a risk with IVF treatment. This isn't true. Your risk of multiples is much higher with IUI (insemination) treatment than with IVF.

Generally, with Clomid, your chance of having twins is 10 percent. Your chance of having triplets or more is less than 1 percent.

As many as 30 percent of pregnancies from gonadotropin fertility drugs are multiples. Two-thirds of those pregnancies are twin pregnancy, and a third are triplets or higher-order pregnancies.

Sometimes, a couple will hope that they do get pregnant with twins or triplets, or even ask their doctors to help. This isn't the best choice, for you or your baby.

How to Reduce Fertility Drug Side Effects and Risks

It’s impossible to completely avoid all side effects. However, there are some things you or your doctor can do to reduce your risks.

Some side effects may be avoided or lessened by taking the medication at night or with food. Always talk to your doctor about the best time and way to take your medications.

Your doctor should also use the lowest effective dose. This is why it’s almost always better to start at a lower dose, and then increase the dosage if it doesn’t work, rather than start high.

Let your doctor know if your side effects are bad, even if they are mood-related side effects (which many people keep from their doctors.) There may be an alternative drug.

To reduce your risk of conceiving twins or multiples, close monitoring of your cycle is important. With gonadotropins or Clomid, ultrasound can be used to determine how many potential follicles are developing. Every follicle is a potential baby, if you conceive.

Your doctor may cancel your cycle if she thinks your risk of multiples is high. You may be asked to avoid sexual intercourse. Listen to your doctor. Remember that a multiple pregnancy puts you and your future babies health (and even life) at risk.

With IVF treatment, your risk of multiples can be reduced with single embryo transfer (SET). This isn’t appropriate for every couple, though. Talk to your doctor about your options.

Beware of fertility clinics that are overly aggressive in their treatment of infertility. On the one hand, it may feel good to have a doctor promising you success and starting with the “best” or strongest treatments first. On the other hand, jumping up the ladder too quickly might lead to a premature fall.

Of course, even with careful monitoring and a responsible doctor, you still may develop OHSS or get pregnant with twins or more. In that case, the best thing to do is to follow your doctor's treatment advice and take care of yourself.

Good prenatal care can lower the risks that come with multiple pregnancies. With early detection and treatment, OHSS is rarely severe and usually can be dealt with at home.

Coping with Fertility Drugs Side Effects

What can you do to relieve or reduce the discomfort of side effects? You should always talk to your doctor about this first. Let them know what you're experiencing. That said, here's some general advice.

Tylenol (or acetaminophen) is best for headaches or cramps. Talk to your doctor first, of course, but typically acetaminophen is the pain reliever of choice during fertility treatment. You should not take ibuprofen (Advil, Motrin) or naproxen (Aleve, Midol) because there is some concern these drugs can interfere with ovulation and embryo implantation. 

Dress in layers if you're experiencing hot flashes. You may also want to avoid drinking hot drinks, which might trigger a hot flash. If you dress in layers, and you're suddenly "burning up," being able to strip (a bit) might help.

Take out your yoga pants. Or your sweatpants, or a long flowing summer dress—whatever will fit comfortably around your waist when you're bloated.

Reach out for support and be forgiving of yourself. Infertility and fertility treatment alone are likely to have you feeling vulnerable and emotional. Add in some mood swings—thanks to the side effects of some hormones—and you'll likely be crying after a touching tire replacement commercial. Let your support circle know what you're going through and how they can help. You don't have to try to do this alone.

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Article Sources

  • Complications and Problems Associated With Multiple Births: Fact Sheet. American Society of Reproductive Medicine.
  • Medications for Inducing Ovulation: A Guide for Patients. American Society of Reproductive Medicine.
  • Ovarian hyperstimulation syndrome. Medical Encyclopedia, MedlinePlus.
  • Risks of In Vitro Fertilization: Fact Sheet. American Society of Reproductive Medicine.
  • Side effects of injectable fertility drugs (gonadotropins.)Fact Sheet. American Society of Reproductive Medicine.