Evaluating the safety of letrozole for fertility treatments

This review looked at the safety of using letrozole (Femara) to promote ovulation. It found that letrozole does not increase birth defects or miscarriage. It also found that letrozole led to higher birth rates than clomiphene citrate (Clomid).

Infertility is a growing issue. Not ovulating regularly, or releasing an egg, is a common cause of infertility. For ovulation to occur, follicles containing the eggs must first grow and mature. Lack of ovulation can be treated with ovarian stimulation (OS) medications. OS is also used for couples with unexplained infertility.

The most OS common medication is clomiphene, which blocks glands in the brain from responding to estrogen. This causes the body to increase hormones which stimulate ovulation. However, clomiphene can cause side effects such as ovarian hyperstimulation syndrome (OHSS). OHSS causes the ovaries to swell and be painful.

Letrozole is increasingly used instead of clomiphene. Letrozole works by preventing the ovaries from creating estrogen. Letrozole may have higher pregnancy rates than clomiphene. It also has lower rates of OHSS and of twin births, which are more dangerous. However, a few small studies have suggested letrozole may increase heart defects in the babies. After this, more research was called for on the safety of letrozole.

This review included 46 studies of letrozole for ovulation. 18 studies assigned women to take either letrozole or a comparison such as clomiphene or placebo. 21 studies followed the outcomes of women who were taking letrozole or a different medication.

A similar number of babies had birth defects among women taking letrozole and clomiphene (a 1% increase in risk with letrozole). The risk was also similar between letrozole and natural conception (2% increase for letrozole). There was no difference in major heart defects between letrozole and clomiphene (1% lower risk for letrozole).

When patients were randomly assigned to a treatment, letrozole led to a similar rate of miscarriage as clomiphene (1% lower risk). Among women prescribed medication by their doctors, those taking letrozole had significantly fewer miscarriages (9% lower risk). 

Letrozole significantly increased the chance of having a baby compared to clomiphene (4% higher chance).

This review found that letrozole can be safely used for fertility treatments and does not increase miscarriage or birth defects.

Letrozole is used in the first week of the menstrual cycle and leaves the body within ten days. It is no longer in the woman’s body when the baby’s organs are forming.