Clomid Better Than Letrozole for Unexplained Infertility! By manara99 on January 26, 2015



A study supported by the National Institute of Health (NIH) included 900 couples with unexplained infertility, each of whom was treated for up to four months with one of three different treatments.  Three hundred couples were treated with gonadotropins (follicle stimulating hormone and luteinizing), 301 couples were treated with Clomid, and 299 couples were treated with letrozole, followed by IUI.




Pregnancy occurred in 46.8% of patients treated with gonadotropin injections, 35.7% of patients conceived with Clomid, and 28.4% of patients conceived with letrozole treatment.  Live birth rates were 32.2%, 23.3%, and 18.7% respectively.


As would be expected, the multiple birth rate was highest among patients treated with gonadotropin injections (10.3%).  Interestingly the multiple birth rate with letrozole was higher than Clomid (2.7% vs. 1.3%).  Among the multiple births with gonadotropins, there were 10 triplet pregnancies, whereas all of the multiple births with Clomid and letrozole were twins.




Very few studies have compared treatment outcomes of Clomid versus letrozole.  This study included a large group of couples (900) with unexplained infertility.  It addresses the important question, “What is the best non-IVF treatment for unexplained infertility?” It provides clinicians with guidance for first line treatment in the context of unexplained infertility.  While gonadotropin treatment offered the highest pregnancy and live birth rate, it also resulted in the highest multiple birth rate of any treatment (10.3%), including 10 triplet pregnancies.  Clomid in conjunction with intra-uterine insemination resulted in better live birth rates compared with letrozole (35.7% vs. 28.4%).  Clomid in conjunction with IUI resulted in acceptable pregnancy and multiple birth rates and should be the first treatment offered to couples with unexplained infertility. 



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Dr. Louis R. Manara

Center for Reproductive Medicine and Fertility

Dr. Louis R. Manara and the Center for Reproductive Medicine and Fertility team are dedicated to helping families achieve parenthood through safe, versatile, and personalized treatment options. We are affiliated with several noteworthy organizations including:

  • American Society for Reproductive Medicine
  • Society for Assisted Reproductive Technology
  • American Osteopathic Association®

​If you are struggling with infertility, a professional diagnosis is the best way to explore your treatment options. Schedule your initial consultation today by contacting us online or calling us at (856) 767-0009.

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