Side Effects and Risks of Fertility Drugs

From Headaches to Twins, Hot Flashes to Mood Swings

Tripets, three boys sitting on the floor, twins and triplets are a possible risk/side effect of fertility drugs
Fertility drugs increase your odds of conceiving triplets, and multiple pregnancies come with higher risks for the mother and baby. Thinkstock / Stockbyte / Getty Images

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.)

That said, 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.

Short disclaimer: 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 section below entitled How to Reduce Fertility Drug Side Effects and Risks.

Side Effects of Commonly Used Fertility Drugs

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.

Important note! Not all possible side effects and risks are listed. If you are experiencing severe side effects, unusual symptoms, or are concerned for any reason, contact to your doctor.

Possible side effects of Clomid include:

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

Read more about Clomid side effects here.

Possible side effects of letrozole include:

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

Read more about letrozole for fertility treatment here.

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

Read more about gonadotropin side effects and risks here.

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

Read more about GnRH agonist side effects.

Possible side effects of GnRH antagonists include:

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

Read more about GnRH antagonist side effects.

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%. Your chance of having triplets or more is less than 1%.

As many as 30% 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 lose 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 theoretically 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.

More on fertility treatment:


Complications and Problems Associated With Multiple Births: Fact Sheet. American Society of Reproductive Medicine. Accessed August 20, 2008.

Ovarian hyperstimulation syndrome. Medical Encyclopedia, MedlinePlus. Accessed August 20, 2008.

Medications for Inducing Ovulation: A Guide for Patients. American Society of Reproductive Medicine. Accessed August 20, 2008.

Risks of In Vitro Fertilization: Fact Sheet. American Society of Reproductive Medicine. Accessed August 20, 2008.

Side effects of injectable fertility drugs (gonadotropins.) Fact Sheet. American Society of Reproductive Medicine. Accessed April 10, 2016.