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PLoS One. 2018 Oct 22;13(10):e0203446. doi: 10.1371/journal.pone.0203446. eCollection 2018.

Pancreatic autoimmunity: An unknown etiology on patients with assisted reproductive techniques (ART)-recurrent reproductive failure.

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Department of Immunology and Department of Reproductive Endocrinology and Infertility, Valentian Infertility Institute (IVI), IVI RMA, Madrid, Madrid, Spain.
Department of Endocrinology and Diabetes, Gregorio MaraƱon University Hospital, Madrid.
Valencian Infertility Institute (IVI), IVI RMA, Madrid, Spain.
Valencian Infertility Institute (IVI), IVI RMA, Zaragoza, Spain.
Valencian Infertility Institute (IVI), IVI RMA, Valencia, Spain.
Rey Juan Carlos University, Madrid, Spain.


Pancreatic Autoimmunity is defined as the presence of autoantibodies and more frequent need for insulin treatment. Affected women presenting recurrent implantation failure (RIF) or recurrent miscarriage (RM) are often misdiagnosed. The objective of thestudy was to describe clinical and metabolic profiles suggestive of Pancreatic Autoimmunity and therapeutic strategy in patients with RIF/RM. We analyzed retrospectively 735 patients, and have identified a subset (N = 20) with similar metabolic characteristics. At the same time, we included a control group (n = 39), with similar demographic characteristics and negative for pancreatic, thyroid or celiac disease autoimmunity. The patients identified with autoimmune metabolic problem (N = 20) had relatives with diabetes mellitus. At 120 minutes after Oral Glucose Tolerance Test (OGTT) low level of insulin secretion (<2 IU/ml) was found in 70% of patients. Glutamic acid decarboxylase 65 (GAD 65) antibodies, with or without other autoantibodies, were positive in80% of patients and anti-IA2 alone were positive I the rest. Since pregestational period, insulin administration was recommended for 10 patients, metformin for 4 patients and exclusively diet control in 5 of them. Significantly increased live bith rates (LBR) per cycle were observed after metabolic control (52%) compared with live birth rate (LBR) after cycles without control (7.5%) (p<0.0001). We noticed 2 cases of pre-eclampsia and 6 low-birth weights. Insulin administration was needed during the pregnancy in 68% of patients and after childbirth in 31.57% of them. In our control group, all of patients (n = 39) underwent ART (53.8% SET and 46.1% DET) with a 50% (SET) and 61.9% (DET) live birth rate (LBR) per cycle. Patients with RIF/RM, normal BMI, low insulin levels after OGTT could benefit from additional metabolic immune testing. A correct diagnosis and treatment could have a positive impact on their reproductive results and live birth rate.

Conflict of interest statement

The authors have declared that no competing interests exist.

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