Letrozole (Femara) for Getting Pregnant: Side Effects, Success Rates

Who Should Consider Letrozole and What to Expect During Treatment

Woman taking a pill with water
If Clomid doesn't work, your doctor may suggest letrozole. Tom Merton / Getty Images

Letrozole, also sold under the brand name Femara, is an oral medication used off-label as a fertility treatment. Letrozole may help women get pregnant who couldn’t conceive on Clomid. In some cases, letrozole may be used as a first-line treatment. In other words, it may be used without trying Clomid first.

Letrozole is most commonly known as a breast cancer drug. Though letrozole only has FDA approval for use as a cancer drug, it has been used off-label for years in the treatment of infertility.

Why might your doctor prescribe letrozole? Why is a cancer drug being used for fertility treatment? And is it safe?

Why Might Your Doctor Prescribe Letrozole?

Letrozole is most commonly used in these cases:

  • In women with PCOS: Letrozole has been shown to possibly be more effective than Clomid for stimulating ovulation in those with polycystic ovarian syndrome.
  • In cases of Clomid resistance: Clomid resistance is when Clomid does not stimulate ovulation over at least three treatment cycles, even after raising the dose. Letrozole may be more effective for these women.
  • For fertility preservation, pre-cancer treatment: If a woman has estrogenic cancer, like breast cancer, using fertility drugs to stimulate ovulation and retrieve eggs for preservation can be problematic. Drugs that boost estrogen levels may lead to faster tumor growth. Letrozole can help stimulate ovulation without increasing estrogen and worsening cancer.

    Sometimes, letrozole is used along with Clomid.

    Letrozole may not be an appropriate medication for women with primary ovarian insufficiency (also known as premature ovarian failure) or women facing age-related infertility. 

    It may also not an appropriate medication in couples with male factor infertility or in women with blocked fallopian tubes.

    Side note: letrozole may also be used in the treatment of endometriosis, but in this case, it is not typically being used to stimulate ovulation. Instead, it is taken continuously for months to reduce pelvic pain. In this article, I will not be addressing this use of letrozole.

    What Can You Expect During Letrozole Fertility Treatment?

    As always, follow the instructions your doctor has provided, and always ask questions if you’re unsure about treatment.

    With that said, here’s what you might expect during treatment with letrozole.

    Your doctor will likely ask that you call when you get your next period. She may order a pregnancy test just to be absolutely sure you’re not currently pregnant. If you’re not sure if you’ve got your period or not – for example, if you’re experiencing light spotting or something else that feels unusual – let your doctor know.

    Once you get the all clear, your doctor will either ask you to take the letrozole pills for five days. You may take the pills on day 3, 4, 5, 6 and 7 of your cycle, or on days 5, 6, 7, 8, and 9. There’s some debate between doctors whether days 3 to 7 or days 5 through 9 are best, but success rates seem to be the same either way.

    Letrozole tablets are typically 2.5 mg.

     Your doctor may tell you to take one to three pills per day.

    If you’re taking Clomid along with letrozole, you will be taking those pills on the same days. As always, speak to your doctor if you’re not sure.

    Your doctor may schedule an ultrasound and/or blood work on day 12 through 15 of your cycle, to determine whether ovulation stimulation as been successful.

    You should have sex on the same days as you would when taking Clomid.

    It’s also possible to combine letrozole with IUI treatment.

    What Is the Pregnancy Success Rate for Letrozole?

    According to a study published in the New England Journal of Medicine, women with PCOS taking letrozole had a live birth rate of 27.5%.

    In this study, women who took Clomid had a slightly lower live birth rate of 19.1%.

    Other studies have found lower live birth success rates. The range between studies is approximately between 15 and 30%.

    Your personal odds will depend on a number of factors, including your age and other fertility factors.

    Live birth rates are not the same as the pregnancy rates, which would include miscarriages, and ovulation rates, which would include cycles in which women didn’t conceive.

    A study published in Fertility and Sterility found that ovulation rates for letrozole and Clomid were similar, with women ovulating 67.5% of the time in letrozole cycles versus 70.9% of the time in cycles with Clomid.

    A meta-analysis of several studies on letrozole and Clomid found a slight increase in pregnancy and live birth rates in women with PCOS related anovulation.

    What Are the Side Effects of Letrozole?

    Letrozole’s side effects are the result of lower levels of circulating estrogen in the body. This is the cause for most of the side effects.

    Side effects of letrozole may include:

    • Fatigue
    • Dizziness
    • Headache
    • Bloating
    • Hot flashes and night sweats
    • Blurred vision
    • Upset stomach
    • Difficulty sleeping
    • Spotting or unusual menstrual bleeding
    • Breast pain

    The most common side effects of letrozole in women taking it for fertility purposes are fatigue and dizziness.

    If your symptoms are especially bothersome, contact your doctor. The same goes for any unusual symptoms.

    If you experience blurred vision, severe headache, or any symptoms that are severe, contact your doctor immediately.

    There is a slight risk of developing ovarian hyperstimulation syndrome (OHSS) when taking letrozole, but this appears to be very rare.

    What is Your Risk of Twins When Taking Letrozole?

    Letrozole, as with any fertility drug, can increase your risk of twins. The odds of having twins when taking letrozole is slightly lower than when taking Clomid.

    Between 2 and 4% of pregnancies conceived with letrozole are twin pregnancies. 

    Isn’t Letrozole a Cancer Drug?

    Yes, letrozole was initially developed as a cancer medication for estrogenic cancers, specifically breast cancer. However, it was discovered that it also stimulates ovulation.

    Letrozole is not a chemotherapy drug. It does not attack cells or cell growth. Letrozole works by decreasing estrogen levels in the blood stream.

    In cancers that feed on estrogen, this can slow cancer growth.

    For fertility purposes, the lower levels of estrogen in the blood stream stimulate an increased production of FSH, the hormone that stimulates egg development. This is how letrozole works as a fertility drug.

    Is Letrozole Safe?

    Letrozole has not received FDA approval for use in women trying to conceive. Using it as a fertility drug is considered to be off-label use.

    However, off-label use of a medication doesn’t necessarily mean it’s unsafe. Receiving FDA approval for specific uses of medications is partially a political issue, and once a medication has received approval in some way, it’s unusual for a drug to attempt to receive approval for additional uses.

    There has been some concern over a study finding a slight increase in birth defects in women who take letrozole when compared to Clomid. Some fertility specialists will not prescribe letrozole for this reason.

    However, the study that found the higher rate of birth defects in letrozole babies was never published and has been criticized as being poorly designed.

    Other studies have found that letrozole may have a lower rate of birth defects than is seen with Clomid, or at least a similar rate.

    To add to the confusion, the half-life of letrozole is known to be shorter than with Clomid. While with Clomid the medication is still circulating in the body when conception takes place, this isn’t true for letrozole.

    Research on this important issue is ongoing.  

    It's important to know that letrozole is known to cause birth defects if taken during pregnancy. This risk why the drug's manufacture recommends the drug only for postmenopausal women. Remember that for women taking this for cancer treatment, it's taken over many months. The risk of accidental pregnancy when taking the medication is of concern. 

    Because letrozole is associated with a risk of birth defects during pregnancy, it’s important you take a pregnancy test before you start treatment. This is especially important if your cycles are irregular.

    As always, you should discuss your concerns with your doctor.

    More on fertility drugs and treatment:



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