The mechanism of thromboembolism in the course of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an uncommon complication of controlled ovarian hyperstimulation. Although principal risk factors for OHSS have been determined, unfortunately, to date we are unable to precisely predict the appearance of OHSS. Still more infrequent are thromboembolic complications of OHSS. The background for the increased blood clotting in such cases includes, but is not limited to, increased permeability of blood vessels in response to excessive vasoactive substances of ovarian origin, vasoconstrictive effects of some other agents of ovarian origin, hemoconcentration and hypovolemia with resultant arterial hypotension, gonadotropin administration, supraphysiological concentrations of 17β-estradiol following ovulation induction, and inherited thrombophilias. Arterial events are predominantly cerebrovascular accidents, usually occurring concurrently with the onset of OHSS. Venous thromboses occur several weeks later and are mostly reported in unusual yet specific sites such as large veins of the upper extremities and neck. There is some evidence that arterial events may be rather embolic by their nature. Thus, the mechanisms standing behind arterial and venous events are likely to be different. Laboratory studies on hypercoagulability in OHSS indicate a broad array of possible changes, from the disturbed balance between tissue factor and tissue factor pathway inhibitor to elevated levels of D-dimer, thrombin-antithrombin complexes, prothrombin fragment 1 + 2, plasmin-antiplasmin complexes, and von Willebrand factor antigen. Increased levels of factors I, V, and VIII, thrombocytes, and decreased levels of tissue plasminogen activator and plasminogen activator inhibitor type I have also been reported. The quite unique localization of venous thrombi requires further careful attention for understanding. Although thromboembolic events are not frequently encountered in the course of OHSS, they are strikingly serious in a proportion of affected patients, and we agree with the recommendation by Grygoruk et al. from the current issue of the Journal that anticoagulant therapy should be prophylactically administered in all OHSS patients. As we discuss it, a precautionary good practice point could be the combined administration of low-dose aspirin and low-dose heparin in all controlled ovarian hyperstimulation patients.