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Background: Ovarian hyper stimulation syndrome (OHSS) and its consequences, especially thromboembolic events, are of the most dangerous complications of assisted reproductive technologies (ART). It is unclear whether a thrombophilic predisposition or changes in blood components during clinical presentation of OHSS increase thrombotic risks. Testing for certain thrombophilias in selected high risk patients may help risk assessment and decision-making about prophylactic measures. Methods: In this study carried out in April 2010 to March 2011, 108 in vitro fertilization candidates with ≥20 follicles following ovarian stimulation were recruited. Protein S, protein C, antithrombin, lupus anticoagulant and anticardiolipin antibodies were measured. Blood tests were compared between severe and non-severe OHSS groups and their changes were traced after onset of clinical OHSS in 43 patients presenting with severe symptoms by repeating the tests at hospital admission. Results: Mean protein S activity was lower in severe OHSS group (101.7±16.3 vs. 118.4±17.0; P<0.001). After clinical presentation of severe OHSS, this level decreased to 91.6±20.1 (P<0.001). Antithrombin levels decreased 2.09% after the onset of symptoms in the group with severe OHSS, but this difference was not statistically significant (P=0.051). Protein C, lupus anticoagulant and anticardiolipin antibodies were not correlated to severe OHSS development. Conclusion: Patients with relatively lower protein S activity were at higher risk for the development of severe OHSS, and its dangerous consequences. During clinical OHSS presentation, protein S decreased even more, and patients were more vulnerable to hypercoagulability states. These points should be kept in mind in risk assessment and adoption of prophylactic strategies. [ABSTRACT FROM AUTHOR]