Trial examines three commonly used medications to treat unexplained infertility

A new study will help physicians evaluate simple fertility treatments for couples who have unexplained infertility, defined as being unable to get pregnant after trying for a year without success for no apparent reason.

Until a study published today September 24, 2015 in The New England Journal of Medicine, physicians had no published research to guide them in describing the relative pros and cons of specific kinds of treatments for these patients. A study co-authored by University of Florida Health obstetrician Gregory Christman, M.D., outlines three different infertility treatments and the rate at which they help patients become pregnant.

“The literature for treatment for unexplained infertility is vague, and it’s been hard to counsel patients based on this literature,” said Christman, the J. Wayne Reitz professor and director of the division of reproductive endocrinology and infertility in the College of Medicine department of obstetrics and gynecology. Christman conducted the study while a researcher at the University of Michigan. Christman said patients who have unexplained infertility may often be advised to undergo in-vitro fertilization, or IVF, a type of fertility treatment in which embryos are placed into a woman’s uterus. Compared with other fertility treatments, IVF is much more expensive.

“If you have been advised that these simple fertility treatments simply don’t work for unexplained infertility, and that you should probably go straight to IVF, that statement does not appear to be true,” Christman said. “Finally, women will now have a way of comparing treatments, and can see that when undergoing less complex treatments short of IVF, there is a lot of hope for a successful pregnancy.”

Researchers followed 900 women at seven different sites across the country during the trial led by Michael Diamond, M.D., chair of the department of obstetrics and gynecology and associate dean for research at Georgia Regents University’s Medical College of Georgia. The trial is the most comprehensive study addressing infertility care ever done, according to Christman.

Women were randomly assigned to three different types of treatment: letrozole, a drug traditionally used to prevent the recurrence of breast cancer in women, which was found recently to be the most effective fertility drug for women with polycystic ovarian disease; clomid, a commonly used oral fertility drug that triggers the body to produce more estrogen, which in turn triggers ovulation; and gonadotropins, which are injected medications that stimulate the ovaries directly. The women were treated for four or fewer cycles, or about four months.

The study found that 35.5 percent of the women given gonadotropins became pregnant, whereas the pregnancy rates for clomid and letrozole were 28.3 percent and 22.4 percent, respectively. Of these women, 31.1 percent who took gonadotropins gave birth, whereas 23.3 percent of the women who took clomid and 18.7 percent of the women who took letrozole gave birth.

The researchers also were able to determine the rate of multiple pregnancies with each treatment. When women were treated with gonadotropins, their rate of multiple pregnancies was 31.8 percent. With clomid, the rate was 9.4 percent and with letrozole, it was 13.4 percent.

Physicians don’t typically recommend a woman carrying more than one fetus at a time because of the risks both to the mother and the babies, Diamond said.

“I don’t think there had been a study of this magnitude conducted previously that looked at these methods of treatment,” Diamond said. “Clinical care providers will want to consider the other agents that we had used previously, weighing the benefits and risks of each as well as the risk of multiple gestations in counseling patients as to which medications to prescribe.”

The study further clarified the use of clomid versus letrozole from the results of a prior 2014 trial. In this trial, clomid was shown to be more effective in a patient population of women with unexplained infertility.

The trial was conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network, a consortium of 12 clinical locations throughout the United States. Grants U10 HD 39005, U10 HD38992, U10HD27049, U10 HD38998, U10 HD0055942, HD0055944, U10 HD0055936, U10 HD055925 and U10 U540HD29834 from the NIH/Eunice Kennedy Shriver NICHD supported the study. The American Recovery and Reinvestment Act provided the funding.