Research update: Letrozole vs Clomid – Which oral fertility medication for PCOS patients?

By: Danielle E. Lane, M.D.

A recent study published by the National Institutes of Health compared the use of clomiphene citrate (Clomid) and letrozole (Femara).

Who: women aged 18-40 with polycystic ovary syndrome.

Treatment: Women were randomly selected to receive either 2.5 mg of Letrozole or 50 mg of Clomiphene for up to 5 cycles. Because the study was designed to look at achieving ovulation in patients who were possibly NOT ovulating, intrauterine insemination was not required.


  1. Women who took Letrozole had higher livebirth rates (27.5% over 5 cycles) than women who took clomiphene (19.1% over 5 cycles).
  2. There were no significant differences seen in birth defects or miscarriage.
  3. Women who took clomiphene suffered from a higher rate of hot flashes, while more patients who took letrozole experienced fatigue and dizziness.

Notes: This study looked only at the ability of these medications to cause ovulation. It should not be applied to women who are using these medications to increase the number of eggs available each month as this was not studied.

Reference: Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome, Legro et al, N Engl J Med 2014; 371:119-129.


Danielle E Lane, MD, Reproductive Endocrinology and Infertility specialist. Dr. Lane attended McGill University before completing her medical training at the University of Pittsburgh school of medicine, her residency at Yale-New Haven Hospital and her fellowship at the University of California, San Francisco. She opened the Center for Reproductive Health at Kaiser Permanente in Napa-Sola-no in 2005. In 2009 she founded Lane Fertility Institute. The Institute has grown to a four physician, multi location practice with a state of the art embryology laboratory. She is committed to providing education for women about preservation of their fertility and developing lower cost models to improve access to care.