Protein missing in endometriosis cases.

A woman diagnosed with endometriosis experiences the frustration of enduring an inexplicable disease. And a woman suffering infertility because of endometriosis experiences the double frustration of being told that pregnancy "cures" the disease -- if only she could get pregnant.

It's the ultimate catch-22 situation, says Bruce A. Lessey of the University of North Carolina at Chapel Hill.

But if Lessey and his research team prove correct about the role of a protein known informally as beta-3 -- the beta-3 subunit of the vitronectin receptor integrin -- they may have taken one step closer to understanding the puzzling nature of endometriosis and its association with infertility.

Though the disease was named in the 1920s, the causes of endometriosis remain poorly understood. Recent research, however, has indicated a link between this disorder and exposure to dioxin (SN: 11/27/93, p.356).

Endometriosis occurs in 2 to 5 percent of all women. In the disorder, the endometrium, or uterine lining, grows where it shouldn't -- on the ovaries, fallopian tubes, bladder, urethra, intestines; more rarely, on the kidneys, lungs, and thorax; and rarest of all, on the brain. The chief symptoms are pain, heavy bleeding, and infertility. About 40 percent of infertile women suffer from endometriosis.

In the August JOURNAL of CLINICAL ENDOCRINOLOGY and METABOLISM, Lessey and his coworkers report potentially excellent news for the future of endometriosis sufferers. They find that beta-3 analysis has a "positive predictive value as a nonsurgical diagnostic test for minimal and mild endometriosis." Currently, the only accurate diagnosis of the disease requires a laparoscopy, a procedure involving a "belly-button cut" and insertion of a lighted instrument into the navel.

Lessey and his team analyzed endometrial biopsies of 241 women with regular menstrual cycles. They compared 105 women diagnosed with endometriosis to 116 infertile women with no known endometriosis and 20 fertile women.

In normal, healthy women, Lessey says, beta-3 appears on the endometrial epithelium "like clockwork" on the 19th to the 20th day of the menstrual cycle, corresponding to the body's preparation for implantation and pregnancy.

The researchers collected biopsies from 89 of the infertile controls prior to laparoscopic examination. Of these, 22 displayed an absence of beta-3 on day 19 and day 20. Laparoscopy confirmed minimal endometriosis in 19 of the 22 women, making the beta-3 marker accurate in 86 percent of the cases.

However, the team notes, "Not all patients subsequently found to have endometriosis were missing the beta-3 subunit."

Scientists have no clear understanding of how the egg implants in the uterine wall or beta-3's function in that process, though Lessey believes the protein is indeed involved in implantation. However, he cautions that the process isn't simple: Infertility doesn't result solely from an absence of beta-3. "Implantation might be a cascade of molecular events."

Even so, Lessey and his colleagues hope that using beta-3 deficiency as a marker will soon lead to the development of "a cheap and easy test" to diagnose endometriosis. This will reduce the need for laparoscopy, which requires a general anesthetic. A biopsy can be performed in a doctor's office in a few minutes at a fraction of the cost of surgery.

Christos Coutifaris of the University of Pennsylvania Medical Center in Philadelphia calls the findings encouraging, but he remains cautious about making clinical generalizations based upon them. "The patient population he [Lessey] studied is extremely skewed toward endometriosis," he says.

Coutifaris also expresses concern that the 86 percent success rate of beta-3 noted in the study resulted from such a small number of women. "This study, in terms of becoming a valid clinical tool, needs higher numbers," he says. "Take all patients coming into an infertility clinic and get 200 controls and 200 cases."

"However, this study gives us good reason to design a multicenter study," Coutifaris adds. "The data are limited, but they're very exciting." Adds Luigi Mastroianni Jr., also from the University of Pennsylvania, "This opens the window for a glimmer of understanding of how endometriosis affects fertility. I'm sure it will be pursued."