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Clomiphene outperforms new treatment for unexplained fertility

28 September 2015
Appeared in BioNews 821

A study shows that treatment of unexplained infertility with the standard treatment clomiphene results in more live births, and a lower risk of multiple births, than a potential new drug letrozole.

The research, called the Assessment of Multiple Intrauterine Gestations for Ovarian Stimulation (AMIGOS) trial, compared three drugs that stimulate the ovaries to produce an egg – clomiphene, gonadotropin and letrozole.

Women in the trial – aged 18 to 40 years – received either injectable gonadotropin, or clomiphene or letrozole administered orally. Ovarian stimulation was followed by intrauterine insemination in 900 couples with unexplained infertility for up to four cycles.

The study authors report in the NEJM that the rate of clinical pregnancies, as assessed by the presence of fetal heartbeat, was significantly higher in the gonadotropin and clomiphene groups (35.5 and 28.3 percent, respectively) than in the letrozole treatment group (22.4 percent). Live birth rates were also significantly higher at 32.2 and 23.3 percent with gonadotropin and clomiphene, respectively, compared to 18.7 percent in the letrozole group.

The rate of multiple pregnancies was also lower in the clomiphene group at 9.4 percent compared to 13.4 percent with letrozole therapy. And multiple pregnancy rates were highest in the gonadotropin group (31.8 percent). All the live-birth multiple pregnancies in the clomiphene and letrozole group were twins compared to treatment with gonadotropin, which resulted in 25 twins and 6 triplets.

Ovarian stimulation using gonadotropin or clomiphene with intrauterine insemination is a standard treatment approach for unexplained infertility, the authors explain.

However, ovarian stimulation is frequently complicated by ovarian hyperstimulation syndrome and by multiple gestations, which leads to an increased risk of preterm birth and neonatal morbidity. It had been hoped that letrozole might overcome these issues by maintaining the live birth rate and lowering the multiple gestation rate.

The authors note that previous research showed that letrozole successfully stimulates ovulation in women with polycystic ovarian syndrome with no increased risk of multiple pregnancies.

However, co-author Dr Esther Eisenberg, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development said they conclude that in unexplained infertility 'Letrozole treatment offered no advantages over clomiphene treatment.'

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility
NEJM |  24 September 2015
Multiple-Birth Rates Lower With Letrozole Than Gonadotropin
Medscape |  24 September 2015
Standard treatment better than potential alternative for unexplained infertility
National Institutes of Health (press release) |  23 September 2015
Study tests success rates of common fertility drugs
CBS News |  24 September 2015
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