High-tech analysis of genetic data may yield new test for endometriosis

NIH-funded study may offer alternative to surgical diagnosis

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Using sophisticated computer-based technology to analyze genetic data obtained from uterine tissue, researchers have identified patterns of genetic activity that can be used to diagnose endometriosis, an often-painful condition that occurs when tissue that normally lines the inside of the uterus grows outside the uterus. The prototype diagnostic method, developed with funding from the National Institutes of Health, can not only distinguish endometriosis from other disorders of the uterus, but can also identify the severity of the disease.

The finding is the first step toward the eventual development of a test to diagnose endometriosis that wouldn’t require surgery. Currently, a surgical procedure known as laparoscopy is the only definitive way to diagnose and stage endometriosis that occurs on the pelvic lining and organs.

A study by NIH researchers estimated that as many as 11 percent of women have endometriosis.

In their study, the researchers used a computer-based technology known as machine learning to analyze the gene activity of samples of tissue taken from the endometrium — the inner lining of the uterus. Machine learning allows computers to learn from an activity without being explicitly programmed. Biomedical researchers rely on the technology to analyze the interactions that take when information on large numbers of genes is translated into proteins, a process called gene expression. The method enabled the researchers to develop a highly accurate grouping system to distinguish samples that came from women with endometriosis from samples that came from women with other conditions affecting the uterus and pelvis, and samples that came from normal controls.

“Laparoscopy involves general anesthesia and making an incision in the abdomen,” said Louis DePaolo, Ph.D., chief of the Fertility/Infertility Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and a coauthor of the study. “These findings indicate that it may be possible to avoid the surgical procedure and diagnose endometriosis from a tissue sample obtained in the office setting without anesthesia.”

The study, appearing in the journal Endocrinology, was conducted by researchers at the University of California, San Francisco (UCSF) through the NIH Specialized Cooperative Centers Program in Reproduction and Infertility Research, funded by the NICHD. Additional support came from the University of California Office of the President.

In most cases, endometriosis results from retrograde menstruation, in which endometrial tissue flows backward, through the fallopian tubes and into the pelvic cavity, rather than out through the cervix, explained Linda Giudice, M.D., Ph.D., an obstetrician, gynecologist, and reproductive endocrinologist at UCSF and the lead author of the study. In women with endometriosis when the endometrial tissue enters the abdominal cavity it attaches to organs in the abdominal and pelvic cavities, such as the ovaries, the outside of the uterus, the intestines, or other organs or tissues. This tissue continues to follow the monthly menstrual cycle, and the resulting bleeding can cause inflammation, scarring, and pain. In the long term, endometriosis may lead to infertility.

The researchers used samples from the NIH/UCSF Human Endometrial Tissue and DNA Bank

, established by Dr. Giudice. The samples in the bank came from women who were undergoing procedures involving the uterus or pelvis.

Dr. Giudice and her colleagues used DNA microarray technology to identify which genes were expressed (involved in making protein) in each woman’s endometrial tissue. They analyzed 148 samples: 77 from women with endometriosis, 37 from women without endometriosis but with other uterine/pelvic problems, and 34 from women without any uterine conditions (the control group).

Not only could the researchers distinguish between samples from endometriosis patients and those who did not have endometriosis, they could also tell the difference between samples from endometriosis patients and those from patients with other uterine disorders. Moreover, they could tell the difference between lesser and more advanced stages of endometriosis, and identify endometriosis at different points in the menstrual cycle.

“We’re looking ahead to potentially being able to do a test for endometriosis in the office, as opposed to general anesthesia in the operating room,” Dr. Giudice said. Such a procedure would likely involve inserting a tiny, thin plastic catheter through the cervix into the uterus to remove a sample of endometrial cells – a procedure that takes about 5-10 minutes, Dr. Giudice explained.

The NIH NICHD Reproductive Medicine Network has begun a multisite clinical trial that will test the method in a larger number of volunteers, Dr. De Paolo said.

In the endometrium of women with endometriosis, the researchers found distinct patterns of gene expression involving inflammation and in activating the immune system. The also observed specific patterns of gene expression involved in building new blood vessels. Women with uterine fibroids and other pelvic disorders also showed signs of immune activation, although the gene expression in these conditions differed from that in women with endometriosis.

For investigators seeking to further refine the method into a diagnostic test, the study, along with the genomic data the researchers identified, is available online at http://press.endocrine.org/doi/abs/10.1210/en.2014-1490?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website athttp://www.nichd.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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