The group also developed a simple blood test for that identifies the variation in the scavenger receptor class B type 1 gene (SCARB1) but emphasizes that no approved therapy as yet exists to address the problem in infertile women.

Follow up studies of female mice linked a deficiency in these receptors for HDL - the so called "good" or "healthy" cholesterol - and infertility. Researchers report finding the same link in studies of women with a history of infertility. With further investigation, the John Hopkins team believes their study will offer clues into a genetic cause, and could lead to infertility treatment for women based on results already shown to work in mice.

"Infertility is fairly common and a lot of the reasons for it are still unknown," says endocrinologist Annabelle Rodriguez, M.D., an associate professor of medicine at the Johns Hopkins University School of Medicine and the leader of the study published online in the journal Human Reproduction.

"Right now, the benefit of this research is in knowing that there might be a genetic reason for why some women have difficulty getting pregnant. In the future, we hope this knowledge can be translated into a cure for this type of infertility."

For three years, Rodriguez and her colleagues analyzed ovarian cells and fluid collected from 274 women unable to become pregnant and who were undergoing in-vitro fertilization (IVF). Some 207 went on to have their eggs collected, fertilized in a test tube and implanted in their wombs.

The scientists then measured whether there was evidence of a gestational sac or a fetal heartbeat 42 days after embryo transfer. Of the nine women in the group found to have a mutated SCARB1gene, none were pregnant.

Rodriguez says she believes the genetic variation could be present in 8 to 13 percent of the population.

Researchers also showed that all nine women with the mutated gene had low levels of progesterone, a hormone critical to sustaining pregnancy in its earliest stages, despite having received progesterone as part of the IVF process.

Rodriguez is director of the Johns Hopkins Diabetes and Cholesterol Metabolism Center, and based her research on mice genetically engineered without the receptor for good cholesterol. Without the receptor, the mice had abnormally high levels of HDL and were at increased risk for heart disease, as well as being infertile.

However, researchers at the Massachusetts Institute of Technology studying the genetically engineered mice have found a treatment for their infertility. A cholesterol medication developed decades ago called probucol, which lowered levels of cholesterol circulating in the blood and restored the rodents' fertility.

Probucol is no longer approved for use in the United States, partly because of concerns that it unsafely lowered HDL, the very "side effect" deemed good for mice with missing HDL receptors. In Japan Probucol is still available for use under some conditions.

"I'm an optimist that this drug or one like it could also restore fertility in women," Rodriguez says. "Everything else that was found in mice so far has borne out in humans."

Rodriguez hopes to conduct a clinical trial to see if probucol can help infertile women with the gene variation. She is also planning to collect data on HDL levels in infertile women with the genetic variation to see if that would prove to be an early clue to a genetic cause of their infertility.

This study was supported by a Burroughs Wellcome Clinical Scientist Award in Translational Research. Other researchers involved in the study, all of Johns Hopkins, are Melissa Yates, M.D., Antonia Kolmakova, Ph.D., and Yulian Zhao, M.D., Ph.D. Original article: http://www.eurekalert.org/pub_releases/2011-05/jhmi-gvl051611.php