Thursday, February 8, 2007

New study results shed light on infertility
By Jonathan McCall and Cathi Bodine (Communications)

DCRI faculty and staff contribute to groundbreaking study

A study published in this week’s New England Journal of Medicine may affect the way doctors treat infertility associated with polycystic ovary syndrome (PCOS), a common cause of infertility in women. A diabetes drug called metformin XR has recently been the focus of interest among infertility researchers and clinicians. But recent clinical trial results suggest that metformin XR is less effective in successfully treating PCOS-related infertility than the standard treatment, a drug called clomiphene.

Evan Myers, MD

Funding for this clinical trial, the Pregnancy in Polycystic Ovary Syndrome (PPCOS) study, was provided by the National Institutes of Health (NIH) and National Institute of Child Health and Human Development (NICHD) Reproductive Services Branch through the Reproductive Medicine Network (RMN), a cooperative network of research centers, with DCRI acting as the coordinating center. Dr. Evan Myers, director of DCRI obstetrics and gynecology research, was the DCRI’s principal investigator for this study.

PCOS is a common cause of female infertility, affecting up to 8% of all women. Although the exact causes of PCOS are not fully understood, women with PCOS typically have higher than normal levels of male hormones, which reduce the frequency of ovulation, thus making it harder for women to achieve pregnancy. PCOS can cause other problems, including the growth of ovarian cysts, irregular menstrual cycles, excess body or facial hair, and acne.

Women with PCOS are also more likely to be overweight and to suffer from a prediabetic condition called insulin resistance, in which the body needs more insulin than usual to process blood sugar (glucose). Previous research has shown that when women with PCOS and insulin resistance were treated with the diabetes drug metformin, their rates of ovulation improved.

These early results led doctors to try using metformin in combination with the standard therapy, a drug called clomiphene, which stimulates the body to release hormones that induce ovulation. Researchers thought that by combining the two therapies, they could increase the rate of fertility in women with PCOS.

To test this theory, researchers from the Reproductive Medicine Network randomly assigned 626 infertile women with PCOS who were attempting to get pregnant to receive one of three different treatments: clomiphene plus a placebo, metformin plus a placebo, or metformin plus clomiphene. The study participants continued these treatments for 6 months or until they became pregnant, whichever came first.

While women receiving the metformin plus clomiphene therapy ovulated more frequently than women who took only clomiphene, this did not actually translate into a higher rate of live births. The rate of live births was not significantly different between the two groups (26% for metformin plus clomiphene versus 22.5% for clomiphene alone). Meanwhile, the group of women receiving metformin alone had a live birth rate of only 7.2%. This study, the largest to date comparing the effectiveness of metformin and clomiphene in treating PCOS-related infertility, seems to suggest that increasing the frequency of ovulation does not increase the number of babies, and that the standard treatment, clomiphene, is the most effective.

The DCRI played a significant role in this trial, providing data management and analysis services and acting as the coordinating center for the Reproductive Medicine Network. Dr. Richard Legro, Pennsylvania State University, Hershey was the lead study investigator. In addition to Myers, the DCRI/Duke contributors include Huiman X. Barnhart, PhD and Phyllis C. Leppert, MD, PhD.. Other DCRI trial team members included Lindsay Lambe, Rebecca DeWire, Kristi Gatlin, H. Yang, Cathi Bodine, and Deb Mark.