Letrozole Use for Treating Infertility

Letrozole (Femara), when used for fertility, can stimulate ovulation in people with PCOS. Learn more about its use and the side effects.

Letrozole is often used as a fertility drug, especially for people with polycystic ovary syndrome (PCOS) and unexplained infertility. Also known by the brand name Femara, letrozole is an oral medication used to stimulate ovulation.

It is often prescribed over clomiphene (Clomid) because it has fewer side effects and a lower risk of multiple pregnancies. Clomid was once the first choice for treating infertility associated with PCOS, but studies show that letrozole may offer significantly higher rates of pregnancy.

Femara (Letrozole) for fertility

Parents / Cindy Chung

How To Use Letrozole for Fertility

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

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 of Letrozole

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 letrozole 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 health care provider immediately.

While it is rare, people taking letrozole 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.

Letrozole Use for Infertility

Letrozole is used in several types of fertility treatments, including:

  • 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

Letrozole vs. Clomiphene

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

  • According to a 2014 study, 27.5% of people 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.
  • In that study, the ovulation rate was higher with Femara (61.7%) compared to Clomid (48.3%). There was also a higher birth rate among people who have obesity and PCOS who used Femara. Not to mention, there were fewer multiple pregnancies in people 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%).
  • A 2015 study concluded there was no significant difference in the overall rate of birth defect among children born to parents who conceived naturally or those who used letrozole or clomiphene.
  • A 2018 report stated that letrozole should be the first 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."
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Sources
Parents 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.
  1. Letrozole for Female Infertility. Frontiers in Endocrinology. 2021.

  2. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. The New England Journal of Medicine. 2015.

  3. Ovarian hyperstimulation syndrome: a clinical retrospective study on 565 inpatients. Gynecological Endocrinology. 2020.

  4. Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome. The New England Journal of Medicine. 2014.

  5. Congenital Malformations among Babies Born Following Letrozole or Clomiphene for Infertility Treatment. PLOS ONE. 2014.

  6. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertility and Sterility. 2018.

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