Femara (Letrozole) and TTC

Should I use it?

Ovulation problems are among the most common causes of infertility and they are responsible for up to 50% of all cases of infertility.

Inducing ovulation often helps many couples overcome infertility because when ovulation is achieved many women with ovulation problems can become pregnant and have a healthy pregnancy.

For a long time clomiphene citrate (CC or Clomid) has been the first choice of drug to induce ovulation. Many studies show that up to 80% of women ovulate on clomiphene citrate, and up to 50% of those who ovulate are able to become pregnant, usually within 3 months.

Yet despite many medical advances the success of getting women pregnant with clomiphene citrate has not changed dramatically. Not all women will ovulate with clomiphene citrate and even if they do, there are often side effects. Clomiphene citrate can, for example have a negative influence on the development of the endometrium, the lining of the uterus, thus preventing the fertilized egg from implanting. Clomiphene citrate can also negatively affect cervical mucus and have other severe side effects limiting it’s use.

Recently doctors have evaluated other medications such as Letrozole (Femara) for ovulation induction in women who do not ovulate on their own. Letrozole is in a class of drugs known as “aromatase inhibitors” (AI). Aromatase inhibitors  have been used for many years to treat women with advanced breast cancer. Aromatase inhibitors are drugs which decrease estradiol production by the ovary. Estrogen is a hormone naturally produced by the body, but it can also stimulate and maintain the growth of certain types of cancer. Letrozole is often given to treat cancer in postmenopausal women with advanced breast cancer because it slows or stops the growth of cancer cells by decreasing the amount of estrogen produced.

There are several reports which show a very promising effect on ovulation of letrozole alone or in combination with other medications such as gonadotropins. Most studies show similar success rates, though letrozole seems to have less adverse side effects.
Because letrozole has a very short half-life it is quickly cleared from the body and for this reason, it is less likely to adversely affect the endometrium and cervical mucus.
It seems that contrary to clomiphene citrate the use of Letrozole does not seem to be associated with as many adverse endometrial or other adverse effects. Letrozole may also decrease the risk of twins and multiple pregnancies. But at the present time there are no sufficient studies (randomized prospective studies) which can show with enough confidence that Letrozole is definitely superior to clomiphene citrate.

Several questions need to be answered before letrozole is introduced into the routine use of the infertility specialist. The best protocol and the optimal dose of letrozole (2.5 mg, 5.0, and 7.5 mg have been used) needs to be established. In addition, the patient group that could benefit the most has to be identified as well. As with any new course of treatment, it will be important to study long-term effects on the patient, the pregnancy and the conceived children.

Letrozole has not yet been approved by the FDA to be used for induction of ovulation, and at this point it would be premature to completely replace clomiphene citrate with letrozole. There is no proof that it’s safer than clomiphene citrate. But under a research protocol and supervision of an experienced infertility specialist it would be acceptable to try using letrozole in some patients and if Clomid has not previously been successful.