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Clomiphene better than letrozole to treat women with unexplained infertility

Large randomized trial data show that, although a safe treatment, the live-birth rate was lower with letrozole than with clomiphene or gonadotropin treatment



When the cause of infertility is unexplained, what is the best first-choice treatment option? Could letrozole, an oral nonsteroidal aromatase inhibitor, result in fewer multiple gestations than current standard therapy—gonadotropins or selective estrogen receptor modulators (clomiphene citrate)—without worsening the live birth rate?

Researchers from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) trial investigated this question and presented data at the recent annual meeting of the American Society of Reproductive Medicine. The research was supported by the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Study details

This prospective, randomized, multicenter clinical trial involved 900 women aged 18 to 40 with at least one patent fallopian tube and regular menses. Patients underwent ovarian stimulation for up to four cycles with an injectable gonadotropin (Gn; n = 300), clomiphene citrate (n = 301), or letrozole (n = 299), followed by intrauterine insemination (IUI).

Birth rate. Conception occurred in 46.8%, 35.7%, and 28.4% of women receiving Gn, clomiphene, and letrozole, respectively, with a live birth occurring in 32.2%, 23.3%, and 18.7% of respective cases. Pregnancy rates with letrozole were significantly less than with Gn (P<.001) and less than with clomiphene (P<.015).

Multiple gestations. The rate of multiple gestations was highest among women treated with Gn (10.3%). But the multiple gestation rate for letrozole was higher than that for clomiphene (2.7% vs 1.3%, respectively). All multiples treated with letrozole and clomiphene were twins; in the Gn group, there were 24 twin and 10 triplet gestations.

No significant difference was found in the rates of infants with congenital anomalies or other fetal or neonatal complications.1

Clomiphene plus IUI remains first-line therapy for unexplained infertility

Although ovarian stimulation with letrozole was safe overall, the number of live births was reduced when treatment with letrozole was compared with clomiphene or Gn, and the multiple pregnancy rate for letrozole fell between clomiphene and Gn.

“CC [clomiphene citrate] /IUI remains first-line therapy for women with unexplained infertility,” concludes Michael P. Diamond, Chair and Professor of the Department of Obstetrics and Gynecology at Georgia Regents University in Augusta, Georgia.

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