The Most Effective Rx for Unexplained Infertility

Clomiphene may be more effective than letrozole in unexplained infertility patients


When it comes to unexplained infertility, the type of treatment you receive could make a difference in your outcome.

A new study from the National Institutes of Health (NIH) found that clomiphene (brand name Clomid) — the standard treatment for women with unexplained infertility — may result in more live births than a proposed alternative treatment called letrozole (Femara).

"Letrozole treatment offered no advantages over clomiphene treatment," said lead study author Esther Eisenberg, MD, of the NIH, in a press release. "Women in the letrozole treatment group had fewer live births, but four times as many multiple pregnancies as women in the clomiphene group."

Couples with unexplained infertility are generally healthy — the woman's ovulation and reproductive tract are normal, and the man produces an adequate number of mobile sperm.

Drugs used to help these couples conceive typically stimulate the woman's ovaries to release an egg. Doctors then insert the man's sperm directly into the woman's uterus.

Letrozole is typically used to treat breast and ovarian cancer in postmenopausal women.

Past research found that letrozole may help women conceive with a lower risk of multiple births than other options. Letrozole has also been found to be more effective for promoting fertility in women with polycystic ovary syndrome than clomiphene.

Another treatment option for unexplained infertility is gonadotropin, a hormone that can trigger an egg's release.

According to these researchers, treatment with gonadotropin has declined in recent years due to a potentially increased risk of multiple pregnancies. Multiple pregnancy increases the chance that babies will need to be delivered via cesarean section and that they will be born prematurely.

For this study, Dr. Eisenberg and team randomly assigned 900 women to one of three treatment groups. All of the women were between ages 18 and 40.

The women were given either letrozole, clomiphene or gonadotropin for four monthly menstrual cycles, or until they became pregnant or discontinued treatment.

About 47 percent of women on gonadotropin, 36 percent of women on clomiphene and 29 percent of women on letrozole became pregnant during this time.

Live births occurred in about 33 percent of the women on gonadotropin, about 23 percent of the women on clomiphene and about 19 percent of the women on letrozole.

The clomiphene group had the fewest multiple pregnancies, at 1.3 percent. The letrozole group followed at 2.7 percent and the gonadotropin group at 13.4 percent.

Because gonadotropin resulted in the most multiple pregnancies, Dr. Eisenberg and team concluded that clomiphene was the most effective treatment for women with unexplained infertility.

This study was published Sept. 23 in the New England Journal of Medicine.

The National Institutes of Health funded this research. No conflicts of interest were disclosed.