Fertility Drugs- Letrozole (Femara)

Letrozole is an oral medication which has been FDA approved and marketed in order to lower blood levels of estrogen in certain medical conditions such as breast cancer. It acts by preventing formation of estrogen. There is a growing body of medical research showing that Letrozole when taken briefly early in the menstrual cycle, increases the production of the hormone FSH and can promote ovulation in patients who are not ovulating. Letrozole is not FDA approved for treatment of infertility and ovulation. Like many drugs, after FDA approval for a different reason, physicians have conducted clinical research studies showing usefulness of the drug for a different form of therapy. It is now a commonly used medication internationally for infertility.

At this point, the medical literature contains somewhat conflicting information about the effectiveness of letrozole in the treatment of ovulation failure. Most studies suggest that it is similar in effectiveness to Clomid (FDA approved for many years for treatment of ovulation). Because the mechanism by which letrozole acts is somewhat different than Clomid it may reduce the incidence of several undesirable clomiphene citrate side effects: reduced endometrial thickness, reduced cervical mucus, emotional mood swings. The side effects of brief use (5 days) of letrozole tend to be minimal: headache, nausea, hot flashes, bone pain and reduced energy level (longer therapy related to other applications has other side effects).

Similar to clomiphene citrate, letrozole may result in development of more than one egg and therefore there is a somewhat higher risk of multiple pregnancy. The precise risk with this drug has not been defined. It is probably similar to clomiphene citrate with twins at approximately 8% and higher order multiple pregnancy (triplets) less than 1%.

There is no conclusive human data regarding use of letrozole for ovulation treatment and risk of fetal anomalies. There is animal data to suggest increased risk of fetal anomalies and pregnancy loss if the drug is taken during early pregnancy. Treatment for ovulation is administered days 3-7 of the menstrual cycle and the drug is metabolized rapidly (two days)-therefore, by the time ovulation occurs and pregnancy may be established the drug should be gone from the system.

Therefore, there does not appear to be any reason for concern about birth defects from Letrozole. Nevertheless, the manufacturer has warned against using this drug for the purpose of ovulation/fertility treatment-clearly to avoid liability issues. We believe this medication is safe for your use but we consider it a “second-line” agent because there is less research with letrozole compared to clomiphene or FSH.

Cost: letrozole 2.5 mg, five tablets costs approximately $75 (the cost of clomiphene citrate for 5 tablets at Wal-Mart is $9).

Therapy Regimen

  • Cycle day 1 is the first day of full menstrual flow.
  • In some cycles we may do a “mid cycle” ultrasound to evaluate your response ($170)-usually performed on cycle day 13 or 14. At the time of the ultrasound we will instruct you on when to time intercourse or schedule IUI.
  • If you are not doing a mid cycle ultrasound and combining treatment with an intrauterine insemination (IUI) then follow IUI instruction sheet. If timing intercourse, either have intercourse every other day cycle days 10-20, or use a urinary ovulation prediction kit to time intercourse on the day of and the day after a positive result.
  • In some cycles a blood test will be performed on day 21 or 22 or 23 to measure progesterone level ($56). We will let you know-usually the first cycle of use.
  • If you were not examined by the doctor at your visit on cycle day, 21, 22 or 23 then schedule an “ovary check” at the end of each cycle (when menstrual period is due; $85).
  • Do a home pregnancy test at the end of each Letrozole treatment cycle (during period) to avoid possible early pregnancy exposure.