Standard clomiphene treatment better than proposed alternative for unexplained fertility

It is estimated that approximately 10 percent of women of child-bearing age may be unable to get pregnant or to carry a pregnancy to term. While recent years have seen a tremendous growth in fertility treatments and options, many assisted reproductive technologies like in vitro fertilization (IVF) and embryo transfer are very expensive and not often covered by insurance.

Many women, especially those with unexplained infertility, are commonly treated with ovarian stimulation medications - letrozole, gonadotropins or clomiphene citrate. Not only is this course of treatment quite successful, it is also significantly less costly. The challenge has been to determine which medication is best at achieving and maintaining pregnancy while reducing multiple gestations.

Research entitled "Letrozole, Gonadotropins, or Clomiphene Citrate for Unexplained Infertility" has been published in the New England Journal of Medicine (NEJM). The research was co-led by Ruben Alvero, MD, FACOG, FACS, director of the Division of Reproductive Endocrinology and Infertility (REI) in the Department of Obstetrics and Gynecology at Women & Infants Hospital of Rhode Island and The Warren Alpert Medical School of Brown University and was funded by a grant from the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The research was conducted when Dr. Alvero was at the University of Colorado School of Medicine.

"Ovarian stimulation medication promotes pregnancy by increasing the number of eggs that a woman ovulates and by enhancing implantation through hormonal effects in the endometrium. Unfortunately, ovarian stimulation can be complicated by ovarian hyperstimulation syndrome, which results in multiple gestations with increased risk of preterm birth," explained Dr. Alvero. "We designed this trial to assess whether ovarian stimulation with letrozole, as compared with clomiphene or gonadotropins would result in lower rate of multiple gestations without lowering the likelihood of pregnancy. What we found is that clomiphene citrate should be used as the first line agent for patients with unexplained fertility," said Dr. Alvero.

Dr. Alvero's team performed a multicenter randomized trial of couples with unexplained infertility - those who have not been diagnosed with a particular problem that is causing their infertility. Women age 18 to 40 who were ovulating and had at least one Fallopian tube were randomized to up to four cycles with ovarian stimulation with gonadotropins, clomid or letrozole. The primary outcome being observed was the frequency of multiple gestations among women with clinical pregnancies.

The research team concluded that standard treatment with clomiphene is better than the proposed alternative for unexplained fertility. They wrote, "In women with unexplained infertility, ovarian stimulation with letrozole resulted in significantly lower frequency of multiple gestations, but also a lower frequency of live births, as compared with gonadotropins, but not as compared with clomiphene."


Care New England


  1. Jennie Vargas Jennie Vargas Philippines says:

    I'd rather know the reason why I can't get prego than an unexplained fertility. With that, you don't even know where to start. Thankfully, I only need to know when my fertile days are in order to get pregnant for baby#2. I'm using a free conceive easy book and I hope this helps.

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