In Vitro Fertilization-Induced Alterations in Coagulation and Fibrinolysis as Measured by Thromboelastography

Abstract

Supraphysiologic increases in estrogen produced by in vitro fertilization (IVF) promote the expression of hemostatic markers. Although quantitative studies of individual markers have been performed during IVF, their results are conflicting and do not reveal the qualitative effect of each marker on the overall coagulation and fibrinolytic processes. Thrombelastograph (TEG) coagulation analysis, by contrast, provides a global measure of coagulation and fibrinolysis and can indicate the relative contributions of clotting factors, fibrinogen, and platelets to each process. We studied the serum estrogen concentrations and TEG variables in 24 women at the beginning and conclusion of an IVF stimulation cycle. Serum estradiol (E(2)) concentrations (mean +/- SD) increased from 26.9 +/- 8.6 to 2098 +/- 913 pg/mL (P < 0.005) at baseline and oocyte retrieval, respectively. The measured TEG indices demonstrated alterations in coagulation rather than fibrinolysis. Although significant changes were noted in both the clot formation time and the coagulation index (P < 0.005), all TEG values remained within the normal range. In addition, an increased role of fibrinogen in promoting clot strength was observed. These findings may assist in the treatment of IVF patients who ultimately develop thromboembolic complications as a result of ovarian hyperstimulation. IMPLICATIONS. The dramatic changes in estrogen produced by in vitro fertilization therapies result in hemostatic marker alterations. Thrombelastograph coagulation analysis, which provides a global assessment of these changes, demonstrated significant alterations in two coagulation indices (clot formation time, coagulation index), although all variables remained within normal limits. The relative importance of fibrinogen versus platelets in determining clot strength was observed. No significant alterations in fibrinolysis were detected.

The ‘ART’ of thrombosis: a review of arterial and venous thrombosis in assisted reproductive technology

“…All these changes suggest the possible development of a 'prothrombotic' state. In contrast to these findings, however, in-vitro platelet function was not reportedly altered with ovarian stimulation [99], and overall 'clotting time' of whole blood was not significantly shortened in these patients [103]. Clot lysis time was reported to be increased in one study [94], but a global measure for fibrinolysis was not significantly different in another study [99].…”

“…From longitudinal studies [92][93][94][95][96][97][98][99][100][101][102][103][104] performed on women undergoing controlled ovarian stimulation, coagulation factors such as Von Willebrand factor (vWF), factors VIII and V, fibrinogen are increased; there is increased activated protein C resistance, reduced antithrombin, proteins C and S activity as well. In addition to these changes, many markers of fibrinolysis such as tissue plasminogen activator (tPA) and plasminogen activator inhibitor type I (PAI-1) decline [92][93][94]96,97,100,101].…”

Haemostatic monitoring during postpartum haemorrhage and implications for management

“…110 Abciximab has been added to celite-activated TEG ® assays to distinguish between platelet and fibrin(ogen) components of clotting in pregnant patients, 111 to demonstrate elevated fibrin-based clot formation after in vitro fertilization, 112 and to dissect the effects of contaminating blood with amniotic fluid in vitro . 113 However, no evidence was identified for the use of platelet-inhibited TEG ® assays during PPH.…”

Anesthesia for Assisted Reproductive Technologies

“…4,5 In extremis, these alterations produce a phenomenon termed OHSS, which may result in follicular rupture and hemorrhage, pleural effusion, ascites, hemoconcentration, oliguria, and thromboembolic events. 6 Although oocyte retrieval is still performed to salvage the cycle and, more importantly, to minimize the effects of OHSS, the resulting embryos are often cryopreserved rather than transferred as the medications needed to support early embryo growth may worsen the syndrome.…”