Fertility Drugs Letrozole

Letrozole in Ovulation Induction

Letrozole (Femara®) belongs to the class of drugs known as aromatase inhibitors. Aromatase inhibitors (AI) are currently only FDA approved for decreasing the risk of recurrence of breast cancer.  The drug manufacturer does not support the use of Femara® for infertility treatment.  However, research has shown that these agents may be beneficial in some cases of infertility. 

Letrozole can be particularly helpful for assistance in inducing ovulation in PCOS patients. Aromatase inhibitor medications work by blocking the enzyme conversion of androgenic hormones to estrogenic hormones, thereby lowering levels of estrogen in the body.  This therapy minimizes the number of eggs released during ovulation induction. This is especially important in women with polycystic ovarian syndrome (PCOS) who tend to release multiple eggs with ovulation induction.

Letrozole does not seem to have some of the adverse side-effects such as decreased cervical mucus, thinning of the endometrial lining or emotional irritability that are common with the use of Clomid. The incidence of twins is 2-3% with the use of Femara compared to 10% with the use of Clomid. The addition of FSH injections to either of these medications can increase the risk of multiples.

Aromatase inhibitors, like letrozole, may be harmful to a developing baby and they should therefore not be taken during pregnancy.  To rule out pregnancy, our infertility specialists recommend a pregnancy test each cycle before beginning Femara.  Preliminary data (abstract presented at the American Fertility Society Meeting in Montreal in October 2005) suggested the incidence of birth defects in babies born after the use of Femara was approximately 4.7% (based on approximately 150 babies born). 

Although this is higher than the control group in this small study, this rate of birth defects is not significantly different from the anticipated rate of 3-4% in the general population. A more recent study suggests that the incidence of birth defects may be as low as 2.4% (based on more than 500 babies born), which is certainly not different from the normal population.  The rate of malformations in the Clomid group was 4.8%.  Further research is warranted in order to confirm that all agents like Letrozole are safe. 

Letrozole has not been used for fertility therapy for a long time, and there may be more risks, which are not currently known.  The usual dose of Femara® is 2.5mg on cycle days 3-7. Side effects can include hot flashes, nausea, and vomiting.