Researchers Identify A Possible Cause of Infertility In Some Women With Endometriosis

Last Updated: Nov. 1, 2003

NIH funded researchers report that some women who have infertility as a result of endometriosis lack molecules in the uterus that allow the embryo to attach to the uterine wall. The researchers suspect that because the embryo cannot attach to the uterine wall, a pregnancy cannot become established, and infertility results. Endometriosis is a major cause of infertility, occurring in from 35% to 50% of women who have difficulty becoming pregnant.

The finding appears in the July 2003 issue of Endocrinology. The researchers also reported that a number of genes present in the uteri of endometriosis patients appear to be functioning inappropriately. Many of the genes identified in this study had not been shown previously to contribute to endometriosis and the infertility that commonly accompanies the disorder.

Endometriosis is a major cause of infertility, occurring in from 35% to 50% of women who have difficulty becoming pregnant.

The research builds upon an earlier NICHD funded study, which reported that the molecule L-selectin, needs to be present on the uterine wall before an embryo can attach itself to the uterus and a pregnancy can begin.

In the current study, researchers found that at the time the uterus is most receptive to the embryo, women with infertility because of endometriosis have very low levels of an enzyme that is involved in synthesizing the ligand for L-selectin. The ligand is a rubber-band like molecule that tethers L-selectin to the wall of the uterus. Because the women lack the enzyme that makes the L-selectin ligand, the embryo may not be able to attach to the uterine wall, and a pregnancy could not begin.

Endometriosis is a disorder in which endometrial tissue – tissue that normally lines the inside of the uterus– begins growing in other areas within a woman’s abdomen – on the fallopian tubes, on the outside of the uterus, the ovaries, or intestines. This disorder affects 10% to15% of women of reproductive age and often causes pelvic pain.

To conduct the study, researchers at Stanford University, the University of California in San Francisco, Vanderbilt University, and the University of North Carolina in Chapel Hill, collected samples of endometrium from 15 non-pregnant volunteers, eight with endometriosis and seven without. They did this during the “window of implantation,” the days of a woman's menstrual cycle (day 20-24 of a 28-day cycle) when the uterus is receptive to an embryo.

The scientists in this study used a new technology called microarray analysis, which makes it possible to screen a large number of genes at one time. This allows researchers to identify genes much more quickly than do traditional methods that look for only one gene at a time. The researchers measured gene expression – the turning on or off of a particular gene, like a light switch turns a light on or off.

They analyzed over 12,000 genes. They found 91 genes that had more than a two-fold increase in gene expression in women with endometriosis, compared to those without the disease, and 115 genes that had more than a two-fold decrease in expression in women with endometriosis compared to those without. These genes are likely to play a role in the development of endometriosis in the pelvis and its associated infertility.

The researchers’ data support the theory that having certain genes present in the incorrect amount contributes to the development of endometriosis.

In addition, the researchers found three groups of genes that appear to play a role in endometriosis. One group of genes increased in expression during the window of implantation in women without endometriosis, but significantly decreased at this time in women with the disease. The gene for the enzyme needed to synthesize the ligand for L-selectin appeared in this group. The second group of genes normally decreased, but instead increased in women with endometriosis. The third group of genes consisted of only one gene, which normally decreased during the window of implantation, but in women with endometriosis, it decreased even further.

The researchers’ data support the theory that having certain genes present in the incorrect amount contributes to the development of endometriosis. It may also create an inhospitable environment for an embryo to attach to the uterus. The findings also add weight to the hypothesis that the endometrium of women with endometriosis is abnormal.

The study’s findings might lead to a new way to screen women for the disease. Currently, diagnosis requires a laparoscopy (a procedure in which a small incision is made in the abdomen) or laparotomy (a larger incision is made), usually with a general anesthetic. This new research may one day enable scientists to develop a less invasive test, based on the detection of abnormal gene activity.

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