Standard treatment for unexplained infertility better than new options

The proposed alternatives to the standard drug in some cases resulted in fewer live births but many more multiple births.

By Stephen Feller

BETHESDA, Md., Sept. 24 (UPI) -- Researchers found that the common standard treatment for couples with unexplained infertility, a drug called clomiphene, results in more live births than a potential alternative, letrozole.

Couples with unexplained infertility are generally healthy -- the woman ovulates normally and has no obvious abnormalities in the reproductive tract, and the man produces an adequate number of motile sperm -- but have trouble conceiving. Drugs used to help these couples conceive often stimulate a woman's ovaries to release an egg and doctors insert the man's sperm directly into the uterus.


"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," said Dr. Ruben Alvero, director of the Division of Reproductive Endocrinology and Infertility at Women and Infants Hospital of Rhode Island, in a press release. "Unfortunately, ovarian stimulation can be complicated by ovarian hyperstimulation syndrome, which results in multiple gestations with increased risk of preterm birth."


Researchers began considering the breast cancer drug letrozole based on doctors using it off-label because of anecdotal evidence that helped women conceive with less risk of multiple births. A previous study also showed it helped women with polycystic ovary syndrome ovulate, conceive, and have successful pregnancies with live births more often than clomiphene.

"In a typical monthly cycle, there is usually one follicle and one egg that develop to the point of ovulation," said Dr. Michael Diamond, a reproductive endocrinologist and Chairman of the Department of Obstetrics and Gynecology at Georgia Regents University, in a press release. "What happens with the fertility drugs, you are overriding the mechanisms which usually only lead to development of one dominant follicle and release of one egg."

The researchers, part of the National Institute of Child Health and Human Development's Cooperative Reproductive Medicine Network, worked with 900 women between the ages of 18 and 40 at 12 facilities. The women were broken into three groups for test treatment: 300 women were given clomiphene, 299 were given letrozole, and the remaining 301 were treated with gonadotropins, substances produced by the pituitary gland that cause the ovary to release an egg.


Conception occurred in 46.8 percent of patients given gonadotropin , in 35.7 percent of those receiving clomiphene, and in 28.4 percent of those who got letrozole. The drugs followed a similar pattern for live births, with 32.2 percent of women on gonadotropin, 23.3 percent of those treated with clomiphene, and 18.4 percent delivering a live child.

Researchers also considered which drug resulted in the fewest multiple pregnancies: Clomiphene had the fewest, at 1.3 percent, followed by 2.7 percent of women given letrozole and 13.4 percent of those given gonadotropins. All of the multiple pregnancies in groups of women taking clomiphene or letrozole were twins, while 24 of the gonadotropin pregnancies were twins and the other 10 involved triplets.

The higher number of multiple pregnancies resulting from gonadotropins was not entirely surprising to researchers, as the number of doctors prescribing the treatment has dropped in recent years because of its propensity to cause them, Dr. Esther Eisenberg, of the NICHD, said in a press release. asdf

"The conclusion for couples with unexplained infertility is that clomiphene probably still remains the first-line therapy," Diamond said.

The study is published in the New England Journal of Medicine.


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