Sometimes infertility cannot be explained. Everything appears normal with both the male and female partners. The most common treatment is medications to stimulate the woman’s ovaries to release an egg (ovarian stimulation). Then a physician inserts sperm directly into the uterus (intrauterine insemination).
To stimulate the ovaries, doctors use either clomiphene or injectable gonadotropins. However, gonadotropins are linked to increased adverse effects and multiple pregnancies, which can raise the risk of pregnancy and birth complications. Results of a 2014 study suggested that another drug, letrozole, could be more effective than clomiphene for achieving live births in certain women with polycystic ovary syndrome, a leading cause of infertility. Other studies indicated that it might work for ovarian stimulation in couples with unexplained infertility as well.
To find out, a nationwide research network, funded largely by the National Institutes of Health, enrolled 900 couples with unexplained infertility. The women, 18 to 40 years old, were randomly assigned to treatment with letrozole, clomiphene or gonadotropins.
The findings, published in the New England Journal of Medicine, show that ovarian stimulation therapy with clomiphene is at least as effective as letrozole, with a slightly lower frequency of multiple births (though the difference was not statistically significant). “The conclusion for couples with unexplained infertility is that clomiphene still remains the first-line therapy,” says first author Michael P. Diamond, M.D., of Georgia Regents University.