Infertility: the link with high cholesterol

BUFFALO, N.Y. – A study of 500 couples trying to conceive a baby has revealed that higher levels of cholesterol reduce their chances of conceiving a healthy embryo.

University at Buffalo biochemist Richard W. Browne, PhD, is a co-author on this research, one of a series of publications involved in the National Institutes of Health-funded Longitudinal Investigation of Fertility and the Environment (LIFE) study.

“This study reinforces the potential for cholesterol to be an important determinant in fertility and pregnancy,” says Browne, an associate professor in the Department of Biotechnical and Clinical Laboratory Sciences in the UB School of Medicine and Biomedical Sciences.

Lead author on the paper is Enrique Schisterman, PhD, chief of the Epidemiology Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); co-authors are Sunni L. Mumford, Zhen Chen and Germaine L. Buck-Louis, all from NICHD, and Dana Boyd Barr of Emory University.

The current study, published online in the Journal of Endocrinology and Metabolism, revealed that, on average, couples who did not achieve pregnancy within a year of trying, had the highest cholesterol levels. Difficulty achieving pregnancy also was associated with couples in which the woman had high cholesterol levels but the man did not.

The NICHD release is here.

The study measured ‘free’ and total cholesterol levels in the blood. Free cholesterol – which is not measured in routine blood tests – is a component of total cholesterol, which is routinely measured on standard blood tests.

“While high levels of total cholesterol were significant predictors of infertility, the study revealed that the free cholesterol component was an even more powerful indicator of infertility,” says Browne.

Browne’s interest in women’s health and fertility began with his work on the NIH-funded BIOcycle study, with colleagues in the UB School of Public Health and Health Professions, led by Schisterman and NICHD. In that project, scientists examined lipids, lipoproteins and oxidative stress and its effect on women throughout the menstrual cycle.

Those studies demonstrated unique fluctuations in lipid and lipoprotein metabolism in women, particularly as it relates to the menstrual cycle.

Browne then teamed up with Victor Y. Fujimoto of the University of California at San Francisco and Michael Bloom of the University at Albany to do pilot studies of women undergoing in vitro fertilization (IVF).

“We then decided to look at the cholesterol within a woman’s ovarian follicle,” says Browne.

They discovered that HDL cholesterol was particularly important in the follicular fluid, the fluid compartment that surrounds and bathes the developing oocyte (egg) within the ovary.

“We found that the higher the levels of good cholesterol, or HDL, the more likely it was that IVF would result in a healthy embryo,” says Browne. By contrast, he said, lower levels of HDL increased the chances of embryo fragmentation, which is detrimental to embryo health and a major problem during IVF.

These pilot studies were the impetus for a more comprehensive study of follicular fluid components and IVF outcomes. Last month, Browne and his co-authors, led by Bloom, reported on HDL particles in follicular fluid.

The study involved the collection of follicular fluid from two ovarian follicles in each of 171 women undergoing IVF. Levels of various HDL-particle components in the follicles were measured in Browne’s laboratory at UB.

The researchers found that the variability in these components within each woman was often greater than the variability between different women. This suggests that each ovarian follicle appears to be an independent micro-environment for the developing egg.

The extent of that variability seemed to correlate with demographic factors, such as age, body mass and cigarette smoking of the woman, meaning there is the potential to modify these influences through lifestyle changes.

“With IVF resulting in healthy babies 30 to 40 percent of the time at best,” says Browne, “we are highly motivated to better understand how follicular fluid parameters may help to predict IVF success or failure.”

Bloom was lead author on that paper, published in Fertility and Sterility, with co-authors Fujimoto and UAlbany doctoral candidate Keewan Kim in addition to Browne. The research was supported by the National Institute on Aging of the NIH.