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Letrozole or Clomid - Which Drug is Best for PCOS Patients?

Letrozole vs. Clomid

Polycystic ovary syndrome (PCOS) affects 6 – 8% of women and is a common cause of infertility. Women with PCOS often have absent or irregular menses. They therefore either do not ovulate or ovulate infrequently.

Getting pregnant with PCOS can be possible with the right diagnosis and treatment. For the past many decades, clomiphene citrate (Clomid, Serophene) has been the drug of choice for making PCOS patients ovulate. The ovulation rates with clomiphene citrate are good, however, the pregnancy rates are quite low.

For the past 10 years or so, Letrozole (Femara) has been available in the U.S. as a drug used for treating hormonally responsive breast cancer after surgery. Letrozole is a selective estrogen receptor modulator (SERM) like clomiphene citrate and can also be used to induce ovulation. Letrozole does indeed work, however, there was an early publication suggesting it was associated with birth defects.

This led to the drug manufacturer sending a letter to physicians asserting that it was approved only for breast cancer patients (basically discouraging its use for ovulation induction). Subsequent studies have shown Letrozole to be effective and the incidence of birth defects was no different than with clomiphene citrate. Many physicians, however, refrained from using Letrozole “off-label” for ovulation induction because of this controversy.

New Study Evidence Supporting Letrozole

Recently, a research study was published in the New England Journal of Medicine, comparing the live birth rates of patients with PCOS who used Letrozole instead of Clomid to help achieve pregnancy. They concluded that women who received Letrozole had significantly more live births than those who received Clomid – 27.5 % vs. 19.1% or 31 more births in the Letrozole group.

This study followed 750 women who were diagnosed with PCOS and were randomly assigned to take either Letrozole or Clomid. The patients and their partners agreed to have regular intercourse during the study. In addition to the increased live birth rate, the patients who received Letrozole also had a higher ovulation rate (61.7% vs. 48.3%) than those who received Clomid. This is a key finding as well, because women with PCOS often do not ovulate on their own.

It is also important to note that the drugs did not show any significant differences in terms of birth defects, pregnancy loss or twin pregnancies. This is further reassurance that Letrozole is a safe alternative in the treatment of infertility.

Since Clomid has normally been used as the primary medication prescribed to induce ovulation in the past 40 years, this study may prompt physicians to consider Letrozole as an alternative first-line treatment for patients who struggle with infertility due to PCOS.

To see a fertility specialist who will answer your questions about PCOS and IVF, make an appointment at one of InVia’s four Chicago area fertility clinics.


Infertility treatment IVF Ovulation Induction PCOS

Janet Chiaramonte

Janet Chiaramonte

Janet Chiaramonte joined the staff of Invia Fertility as a registered nurse in 2005. Years ago (too many to count), she received her Bachelor's Degree in Psychology, and then worked for a decade at Children's Memorial Hospital in an administrative position. She always wanted to be part of the patient care side of medicine though, so she went back to school and received an Associate's Degree in Nursing.


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