Carotid thrombosis after in vitro fertilization: a relatively new thrombotic complication in women
Article first published online: 19 MAR 2008
© 2008 The Authors. Journal Compilation © 2008 Blackwell Publishing Ltd
British Journal of Haematology
Volume 141, Issue 6, pages 897–899, June 2008
How to Cite
Martí, E., Santamaría, A., Mateo, J., Tolosa, A., Querol, L., Viscasillas, P. and Fontcuberta, J. (2008), Carotid thrombosis after in vitro fertilization: a relatively new thrombotic complication in women. British Journal of Haematology, 141: 897–899. doi: 10.1111/j.1365-2141.2008.07120.x
- Issue published online: 22 APR 2008
- Article first published online: 19 MAR 2008
- in vitro fertilization;
- ovarian hyperstimulation syndrome
The increase in assisted reproductive techniques (ART), such as in vitro fertilization (IVF), has given rise to new pathologies and their sequela. Ovarian hyperstimulation syndrome (OHSS) represents a rare complication that results from IVF and is estimated to occur in 2–6% of treatment cycles (Vlahos & Gregoriou, 2006). It is related to increased hypercoagulability and thromboembolic complications. The majority of thromboses are in venous sites, but there are also cases of arterial thrombosis (Aboulghar et al, 1998). However, arterial thromboses are rare, especially carotid thromboses (Di Micco et al, 2003). The role of genetic and other acquired factors in the development of this relatively new thrombotic complication associated with IVF is not known.
We report the case of a carotid thrombosis with amaurosis as the initial clinical manifestation in a woman who suffered from moderate-severe OHSS after IVF. This 34-year-old woman was admitted to our hospital because of acute loss of vision in her left eye. She had a five-year history of primary infertility and had undergone a standard cycle of ovarian stimulation with gonadotrophin-releasing hormone agonist and human menopausal gonadotrophin and ovulation induction with human chorionic gonadotrophin (β-HCG). Eighteen oocytes were recovered and three embryos were transferred to the uterus. Seventy-two hours after the transfer, the patient complained of loss of vision in her left eye. Clinical examination revealed elevated blood pressure (150/110 mmHg) and a distended abdomen. Ophthalmic examination showed very low visual acuity in her left eye. Fundoscopy disclosed a left eye with diffuse retinal pallor with narrow capillaries and macular oedema, compatible with left retinal central artery occlusion. Enlarged ovaries with multiple images of follicles and a minimal amount of ascitic fluid were detected with transabdominal ultrasound (Fig 1). The haematocrit was 47·9%, Hb was 165 g/l and clotting tests were normal. d-dimer was 5519 μg/l. Carotid artery ultrasonography revealed occlusion of the left internal artery from the junction. An angio-magnetic resonance imaging showed a small ischemic lesion in left epithalamus and confirmed that she had an internal carotid occlusion (Fig 2). Echocardiography showed only a slightly enlarged left atrium with normal ventricle and functional valves. With the diagnosis of carotid thrombosis associated with moderate-severe OHSS, we started perfusion with saline solution and serum albumin and treatment with enoxaparin at a dose of 1 mg/kg/12 h. Twenty-four hours after admission, the patient had partially recovered vision in her left eye and the OHSS symptoms improved. A complete thrombophilia study was performed including factor VIII coagulant activity (FVIII:C); functional antithrombin; amidolytic Protein C; total, free and functional Protein S; F5 (factor V) Leiden; F2 (prothrombin) G20210A mutation; SERPINC1 (antithrombin) Ala384Ser mutation (antithrombin Cambridge II); F12 46 C/T polymorphism; homocysteine levels, and anticardiolipin and antiphosphatidylserine antibodies. All these tests were normal, except FVIII:C levels in plasma that were 368% (normal range: 45–175%). After 2 weeks of treatment with enoxaparin and two determinations of β-HCG < 2U/l, the patient began treatment with acenocumarol. After 6 months of anticoagulant treatment, the patient still presented a decreased visual acuity without other symptoms and ultrasonography revealed a persistence of internal carotid occlusion. At that time FVIII:C levels were normal (187%) and acenocumarol was replaced by aspirin at a dose of 300 mg/d.
Thrombosis can be a significant problem when using ART, which involves superovulation and ovulation induction. The aetiology of OHSS-associated thromboembolic disorders is unclear. Significant research will be required to elucidate the potential coagulation changes that might occur with treatment cycles extending into early pregnancy. Currently, it is clear that ovarian stimulation creates a state of hypercoagulability. This activation appears to be exaggerated and prolonged with OHSS. Some studies have found changes on blood coagulation and fibrinolytic activity during ovarian stimulation for IVF (Aune et al, 1991). Whether these changes by themselves explain the occurrence of thromboembolic complications is unknown. Another question is the importance of screening for thrombophilia. Because there have been only a few prospective studies in this area (Grandone et al, 2004), the prevalence of thrombosis and thrombophilia in women undergoing IVF with or without OHSS is not known. Dulitzky et al (2002) found an increased prevalence of thrombophilia parameters in women who developed OHSS after ovulation induction, and three of these patients experienced thromboembolic events during the acute phase of OHSS or during the pregnancy that followed the OHSS episode. In view of these findings, it would seem prudent for physicians to routinely screen for thrombophilia in women undergoing ART. In contrast, other authors propose that thrombophilia screening in IVF in the general population is not cost-effective (Fàbregues et al, 2004).
It is important to recognize that thrombosis, as a complication of ovarian stimulation or OHSS, is an increasing problem. As the use of ART increases, the occurrence of related thromboembolic complications must also be investigated to determine their causes. Clearly, further research is needed to identify women at risk and to develop adequate therapeutic and prophylactic measures.
We are indebted to Prof. W. H. Stone for his help in the revision and discussion of the manuscript. This work was supported in part by Red Cardiovascular RECAVA (RD 06/0014/0016) from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo) and by Departament d’Innovació, Universitats i Empresa from Generalitat de Catalunya (2005 SGR 0168).
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