Femara (Letrozole) for Treating Infertility in PCOS

Fertility drug may offer key advantages over Clomid

woman taking a pill
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Femara (letrozole) is an oral medication used to stimulate ovulation in women with polycystic ovary syndrome (PCOS) and unexplained infertility. While Femara was approved by the U.S. Food and Drug Administration for use as a breast cancer drug, it has been used off-label by fertility doctors since 2001 because it has fewer side effects the Clomid (clomiphene) as well as a lower risk of multiple pregnancies.

Clomid is the current first-line choice for treating infertility in women with PCOS. Recent research, however, has suggested that Femara may offer significantly higher rates of pregnancy within this population of women

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

How to Use Femara

Femara is offered in 2.5-milligram yellow, film-coated tablet. 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. While there remains debate on which option is truly best, current research seems to suggest that success rates are more-or-less the same.

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.

    Femara can also be used with intrauterine insemination (IUI) treatment. Clomid is sometimes prescribed alongside Femara and 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 a woman to have symptoms. Those most commonly seen with Femara use include:

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

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

    While rare, women taking Femara may develop a condition known as ovarian hyperstimulation syndrome (OHSS) which can manifest with symptoms ranging from bloating and diarrhea to extreme shortness of breath and chest pains.

    Effectiveness of Femara

    There is increasing evidence that Femara may be a more suitable for women with PCOS suffering from ovulation problem.

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

    • The ovulation rate was higher with Femara (61.7 percent) compared to Clomid (48.3 percent).
    • 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 percent) compared to those who used Clomid (7.4 percent).

    The risk of pregnancy loss, meanwhile, was more-or-less the same for both drugs (Femara 31.8 percent versus Clomid 28.2 percent).

    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.

    Sources:

    Franik, S.; Kremer, J;, Nelen, W.; and Farquhar, C. “Aromatase inhibitors for subfertile women with polycystic ovary syndrome.” Cochrane Database Syst Rev. 2014; 2:DOI 10.1002/14651858.CD010287.

    Kar S. “Current evidence supporting letrozole for ovulation induction.” J Hum Reprod Sci. 2013; 6(2):93-8.

    Legro, R.; Brzyski, R.; Diamond, M. et al. “Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.” N Engl J Med. 2014; 371(2):119-29.

    Sharma, S; Ghosh, S.; Singh, S. et al. "Congenital Malformations among Babies Born Following Letrozole or Clomiphene for Infertility Treatment." PLoS ONE. 2015; 9(10):e108219. 

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