154: The role of circulating alpha-1 antitrypsin in recurrent pregnancy loss

Abstract

in recurrent pregnancy loss Tamar Madar, Eli C Lewis, Galit Shahaf, Guy Twina, Joel Baron, Shimrit Yaniv Salem, Moshe Mazor, Arnon Wiznitzer, Gershon Holcberg, Eyal Sheiner Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Meitar, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Clinical Biochemistry, Faculty of Health Sciences, Beer-Sheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Beer-Sheva, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, IL, Israel, Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, Israel OBJECTIVE: Alpha-1 antitrypsin (AAT) inhibits a wide variety of proteases and possesses anti-inflammatory, immune modifying and tissue-protective properties. AAT levels rise 4 to 6-fold during acute phase responses, as well as during pregnancy. Low AAT levels and activity were previously linked with several pregnancy complications. Various causes have been attributed to recurrent miscarriages, including immunologic and inflammatory factors. Therefore, the purpose of the present prospective study was to examine whether low plasma concentration and activity of AAT might correlate with recurrent pregnancy loss. STUDY DESIGN: We conducted a prospective case control study that included patients with recurrent pregnancy loss (two or more consecutive miscarriages; n 18), patients with sporadic pregnancy loss (n 16) and individuals undergoing elective termination of normal pregnancy per social considerations (n 13). Blood samples were drawn before performing dilatation and curettage and immediately transferred in cold to the analysis lab. AAT activity and concentration were determined in maternal serum samples by standard ELISA and enzymatic assays. Analyses were performed in duplicates and repeated twice for each sample in separate sessions. RESULTS: Patients with recurrent pregnancy loss as well as patients with sporadic miscarriages depicted AAT levels that were significantly lower than the control group of normal pregnancies; the levels in recurrent miscarriage was 2.39 0.33 -fold lower than the control group (1.344 0.09222 vs. 3.224 0.4498 mg/ml; p 0.001), and sporadic miscarriage was 2.05 0.28 -fold lower than the control group (1.569 0.1415 vs. 3.224 0.4498 mg/ml; p 0.001, figure). Although a consistent trend could be observed regarding circulating AAT anti-proteolytic activity between the groups, statistical significance was not attained. CONCLUSION: Alpha-1 antitrypsin concentrations are significantly lower in patients with sporadic and recurrent miscarriages compared to normal pregnancies. Accordingly, AAT may play an important role in the pathogenesis of spontaneous pregnancy loss.