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Single Serum Activin A Testing to Predict Ectopic Pregnancy

Obstetrics and Gynecology, Department of Paediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100 Siena, Italy

Address all correspondence and requests for reprints to: Felice Petraglia, Chair of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico "Le Scotte," viale Bracci, 53100 Siena, Italy. E-mail: petraglia{at}unisi.it.

Context: Ectopic pregnancy (EP) is an important cause of maternal deaths in early pregnancy because most fatal cases result from delayed diagnosis and inappropriate investigation.

Objective: We evaluated whether the measurement of activin A may be useful in the diagnosis of EP in women with unknown pregnancy location.

Design: The study was designed as an open observational study.

Setting: The study was set in a tertiary referral center for obstetric care.

Patients: Patients were women with unknown pregnancy location (n = 536) who had complaints of bleeding, pain, or cramping.

Interventions: Interventions included clinical examination; transvaginal ultrasound scan; human chorionic gonadotropin (hCG), progesterone, and activin A measurements; laparoscopy; uterine curettage; and histological examination.

Main Outcome Measures: Main outcome measures were pregnancy outcomes and evaluation of sensitivity, specificity, and predictive values of hCG, progesterone, and activin A as diagnostic tests for the detection of EP.

Results: Pregnancy outcomes included 155 (28.9%) viable intrauterine pregnancies (IUP), 305 (56.9%) first-trimester spontaneous abortion (SAB), and 76 (14.2%) EP. SAB had the lowest (P < 0.0001) hCG and progesterone concentrations, significantly lower than EP (P < 0.001) and IUP (P < 0.001). In EP, levels were significantly (P < 0.001) lower than in IUP. On the contrary, activin A levels were lowest (P < 0.0001) in EP, significantly lower than in SAB (P < 0.001) and IUP (P < 0.001). IUP had significantly (P < 0.001) lower activin A levels than SAB. When evaluated by the receiver operating curve analysis, activin A at the cutoff of 0.37 ng/ml combined a sensitivity and a specificity of 100 and 99.6%, respectively, for prediction of EP. When activin A concentrations were below the cutoff, the positive predictive value for EP was 97.43%, and 0% for concentrations higher than 0.37 ng/ml.

Conclusions: Activin A measurement may identify patients at risk of EP with a high sensibility and specificity.

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