Femara (Letrozole) for Fertility

Letrozole can stimulate ovulation in people with PCOS

Side Effects of Femara

Verywell / Cindy Chung 

Femara (letrozole) is an oral medication used to stimulate ovulation in people with polycystic ovary syndrome (PCOS) and unexplained infertility. While letrozole was approved by the U.S. Food and Drug Administration for use as a breast cancer drug, it has been used off-label for fertility for more than two decades because it has fewer side effects than Clomid (clomiphene) and a lower risk of multiple pregnancies.

Clomid was once the first-line choice for treating infertility associated with PCOS. But studies show that letrozole may offer significantly higher rates of pregnancy in people with PCOS.

Other research suggests that in some cases, a combination of Clomid and letrozole is effective, at least for inducing ovulation. But the study was small and did not evaluate live birth rates.

Femara is also commonly used in cases of Clomid resistance. This occurs when Clomid is unable to stimulate ovulation over at least three treatment cycles and despite increasing dosages.

How to Use Letrozole for Fertility

Femara (letrozole) is offered in 2.5-milligram yellow, film-coated tablets. Based on when your period begins, your doctor will advise you when to start treatment. Treatment will be taken over five consecutive days.

Some fertility experts recommend taking the pills on days 3, 4, 5, 6, and 7 of your cycle. Others endorse days 5, 6, 7, 8, and 9. There remains debate on which option is truly best, although research published in 2020 suggests that earlier may be better.

Based on when treatment began, you can anticipate when you would need to start having sex:

  • If you started treatment on day 3, you likely ovulate sometime between day 14 and day 17 of your cycle. To conceive, you would want to begin having sex before you ovulate. In this scenario, you would begin having sex every day (or every other day) starting on day 11 and ending on day 18.
  • If you started treatment on day 5, you would most likely ovulate between days 16 and 19. In this case, would start having sex between days 13 and 21.

To better pinpoint the time of ovulation, you can use an ovulation predictor kit. You would start testing once you've completed treatment and test daily until you receive a positive result (indicating that you are nearing ovulation). This is the signal to begin having sex.

Letrozole can also be used for intrauterine insemination (IUI) treatment. Clomid is sometimes prescribed alongside letrozole and they are taken together on the same days.

Side Effects

Letrozole works by reducing estrogen levels in order to stimulate ovulation. Low estrogen levels of any sort can cause symptoms. Those most commonly seen with Femara include.

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

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

While it is rare, people taking Femara may develop a condition known as ovarian hyperstimulation syndrome (OHSS). It causes symptoms ranging from bloating and diarrhea to extreme shortness of breath and chest pains.


There is increasing evidence that Femara may be more suitable for people with PCOS suffering from ovulation problems.

According to a 2014 study published in the New England Journal of Medicine, 27.5% of women with PCOS who took Femara had a successful birth compared to 19.5% who took Clomid. The same study demonstrated advantages in several other areas.

For example, the ovulation rate was higher with Femara (61.7%) compared to Clomid (48.3%). There was a higher birth rate among obese women with PCOS who used Femara. There were fewer multiple pregnancies in women who used Femara (3.2%) compared to those who used Clomid (7.4%).

The risk of pregnancy loss, meanwhile, was about the same for both drugs (approximately 30%).

Similarly, a 2015 study published in PLoS One concluded that there was no significant difference in the overall rate of birth defect among children born to mothers who conceived naturally or those who used Femara or Clomid.

A 2018 report stated that letrozole should be the first-line treatment for ovulation induction in people with PCOS who can't conceive because of ovulation problems (and no other infertility factors) "to improve ovulation, pregnancy and live birth rates."

Lastly, a review of studies published in 2021 reported on the effectiveness and safety of letrozole in several kinds of fertility treatments:

  • For inducing ovulation, followed by timed intercourse or IUI
  • On its own for unexplained infertility
  • Along with gonadotropins during ovarian stimulation
  • To prepare for a frozen embryo transfer
  • To treat infertility associated with endometriosis
  • To preserve fertility in people undergoing cancer treatment

While success rates vary, letrozole seems to be promising for many of these treatments, and it appears to be safe as well as less expensive than some other treatments.

11 Sources
Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Rachel Gurevich, RN
Rachel Gurevich is a fertility advocate, author, and recipient of The Hope Award for Achievement, from Resolve: The National Infertility Association. She is a professional member of the Association of Health Care Journalists and has been writing about women’s health since 2001. Rachel uses her own experiences with infertility to write compassionate, practical, and supportive articles.