For many years, Clomid has been used as a first line method of ovulation induction in couples with unexplained infertility. There are many advantages to Clomid like its ease of use and low cost. However, Clomid can also have some side effects. One negative side effect that some women experience is the thinning of the endometrium, or the blood lining of the uterus, that is seen with repeated Clomid use. We think of the endometrium as the soil for the seed. If the soil is too thin, the seed will not implant and grow, making it even harder to achieve pregnancy.

Recently a new medication has been used for ovulation induction. This new medication is called Letrozole or Femara. Letrozole works differently than Clomid but has the same effect of stimulating the ovary to release eggs.

If Letrozole and Clomid can both be used for ovulation induction, is one better than the other?

A recent study1 evaluated this question using gold standard (the highest quality) research methods. Couples with a diagnosis of unexplained infertility were enrolled and then randomly chosen to use letrozole, clomid, or gonadotropins (FSH injections)  for up to four cycles. When comparing the three methods, gonadotropin use was associated with the highest live birth (per treatment plan) at 32.2%, Clomid at 23.3%, and Letrozole was associated with a live birth of 18.7%. However, gonadotropins had a much higher rate of twin and triplet pregnancies. Importantly, the difference in live birth between Clomid and Letrozole was not significant.

The short answer is that there was not a significant difference in success between Clomid and Letrozole. Also, repeated Letrozole use has not demonstrated the thinning of the lining that is seen with Clomid.

This evidence is reassuring that both Clomid and Letrozole can be used. It is incredibly important to have a treatment plan that is individualized to your situation. For some women, Clomid may be better than Letrozole, or vice versa. I would love to hear your experience with these medications or if you have any questions about which one may be better for you.

Wishing you success on this journey!