SAN ANTONIO – The results of a prospective study showed that, in patients without a surgical endometriosis diagnosis, a serum test of microRNA (miRNA) levels yielded a very high predictive value when endometriosis was later surgically confirmed.
“This is the first prospective study performed within a diverse population that identifies miRNAs can reliably be used to differentiate between endometriosis and other gynecologic pathologies,” Sarah Moustafa, MD, said at the annual meeting of the American Society for Reproductive Medicine.
Dr. Moustafa and her collaborators found that the area under the receiver operating characteristic curve (AUC) for the combination of miRNAs 125, 451, and 3613 was 0.917. The AUC of another combination was even higher: the miRNAs let-7b, 150, 342, and 451 yielded an AUC of 0.977 for endometriosis. These figures support that the miRNA combinations give “an excellent diagnostic potential for endometriosis,” Dr. Moustafa said.
The study enrolled 86 women of reproductive age who were scheduled to have a laparotomy or laparoscopy for benign gynecologic reasons. Pregnant patients and those with malignancy were excluded. Patients had blood drawn before their surgeries to have blinded miRNA analysis via quantitative reverse transcriptase polymerase chain reaction.
Dr. Moustafa and her colleagues looked at the diagnostic value of individual miRNAs and also examined combinations of promising miRNAs by seeing which levels were elevated or depressed in patients who were later found to have surgically diagnosed endometriosis. The study built on previous retrospective work that had identified some candidate miRNAs.
In this prospective study, women with endometriosis had significantly lower serum levels of miRNAs 3613 and let-7b and significantly higher serum levels of miRNAs 150, 125b, 451, and 342. The investigators also analyzed the data to see if there were miRNA level differences between women who were on hormones and those who were not, and also to see if cycle timing affected results; neither of these factors affected miRNA levels, Dr. Moustafa reported.
When the enrolled patients had surgery, 36 were found to have endometriosis and 50 had a variety of other diagnoses, with uterine fibroids (48%) and no abnormal pathology (28%) predominating.
“A noninvasive diagnostic test does not currently exist” but is sorely needed, Dr. Moustafa said.
There’s a long gap from the onset of endometriosis symptoms to diagnosis, with one study showing that symptoms can be present for an average of 6.7-11 years before surgical diagnosis occurs. In one survey of more than 7,000 women, nearly half (46%) saw more than five physicians before they got the correct diagnosis, said Dr. Moustafa, a resident in the obstetrics, gynecology, and reproductive sciences department at Yale University, New Haven, Conn.
In a discussion following the presentation, attendee Steve Young, MD, PhD, professor of reproductive endocrinology and fertility at the University of North Carolina, Chapel Hill, said it would be useful to have a biomarker that could be a surrogate for disease burden. “You could look at miRNAs after surgery. Do you see changes back toward normal?” Dr. Young said.
Dr. Moustafa responded that the research team is in the process of collecting postoperative data to see whether levels change when the disease burden is diminished by surgery.
Next steps, she said, include looking for miRNAs in saliva to explore whether an even less invasive test might be possible. Also, there are suggestions that miRNA 125 might be a marker for more severe disease, so the team is investigating this association as well.
Whether the combination miRNA screen is ready for prime time is still an open question, she said. “Any time a new screening test is developed we have to have caution.” Current thinking, she said, points toward the utility of miRNA screening for patients with unexplained fertility, for example.
“At this point, the pendulum is so far on the side of underdiagnosis that we think patients would benefit from a screening test,” Dr. Moustafa added.
The study was supported by OvaScience. Dr. Moustafa reported having no relevant financial disclosures.
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