1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital and 2 Department of Radiology, Queen Mary Hospital, Pokfulam Road, Hong Kong, China
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Abstract |
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Key words: IVF/severe OHSS/vascular thrombosis
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Introduction |
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Case report |
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The patient had her first cycle of IVF-embryo transfer in February 1997. Gonadotrophin-releasing hormone agonist (Buserelin; Hoechst Marion Roussel, Germany) 150 µg four times per day was started on day 21 of the pre-treatment cycle for pituitary down-regulation. Transvaginal ultrasound-guided oocyte retrieval was performed after 9 days of human menopausal gonadotrophin (HMG) (Pergonal; Serono, Geneva, Switzerland). Twenty-two ampoules (75 IU per ampoules) of HMG were used. The oestradiol concentration was 17504 pmol/l on the day of human chorionic gonadotrophin (HCG; Profasi; Serono). Nineteen oocytes were obtained, of which 15 fertilized. Three fresh embryos were replaced. Six embryos were of good quality and were frozen. The patient failed to get pregnant and returned for frozen embryo transfer in June 1997. Three embryos were replaced and she conceived. Unfortunately, she aborted at 12 weeks of gestation. She came back for another cycle of frozen embryo transfer in February 1998. Three frozen-thawed embryos were replaced but she failed to get pregnant.
The patient had her second IVF-embryo cycle in January 1999. The pituitary down-regulation and ovarian stimulation were the same as for the first cycle. Twenty-two ampoules (75 IU per ampoule) were used. Transvaginal ultrasound guided oocyte retrieval was performed after 9 days of HMG. The oestradiol concentration was 20808 pmol/l on the day of HCG. Twenty oocytes were obtained of which 19 fertilized. Two embryos were replaced and nine embryos were frozen. She was given progesterone suppository (Utrogestan; Laboratories Besins Iscovesco, Paris, France) 200 mg three times per day for luteal support. She complained of progressive abdominal distension 13 days after embryo transfer and was admitted to hospital. Ascites was demonstrated on clinical examination. Haemoglobin was 14.5 g/dl and the haematocrit was 0.422. The serum electrolytes were normal and the albumin was 30 g/l. Clotting profile was normal. Urinary output was 1.5 l/day. She was treated conservatively with i.v. fluid 2 l/day.
The patient developed generalized seizure on the next day. She also complained of mild difficulty in writing and other fine motor function of her right hand before the seizure episode. Clinically there was no post-ictal neurological deficit. Serum concentrations of electrolytes were normal. MRI of the brain showed an abnormal area, about 3x2 cm, over the left high frontal lobe just anterior to the left precentral gyrus. The lesion was predominantly bright on both T1-weighted and T2 weighted images with evidence of mild vasogenic oedema in the surrounding white matter (Figure 1a). The features were in keeping with a small subacute haematoma. The nature of this lesion was unknown but the provisional diagnosis was a cavernous angioma with haemorrhage. The neurosurgeon was consulted. Since there was no evidence of continuous bleeding and the lesion exhibited no significant mass effect, it was decided to observe the patient and to repeat the MRI of the brain in 4 weeks time to monitor the progress of the lesion. She was given carbamazepine 200 mg twice daily to prevent further seizure. Carbamazepine was used since there was a possibility that she could be pregnant.
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One week later, the patient complained of left hip pain for 1 week. The left calf was mildly oedematous. There was no dilated superficial vein. Doppler study of the lower limb showed a hypo-echoeic thrombus in the left common femoral vein extending into the left external iliac vein. There was no flow signal from these vessels, indicative of acute complete thrombosis. Computerized tomography of the abdomen revealed extensive venous thrombosis up to infrarenal portion of the inferior vena cava (IVC) (Figure 2). Partial thrombosis of the right common iliac vein was also detected (Figure 3
). The diagnosis of deep vein thrombosis of lower limbs with extension to the lower IVC was made. In view of the recent history of intracranial bleeding, further assessment of the intracerebral haemorrhage was performed before starting heparin. A repeat MRI of the brain (Figure 4
) showed decreased flow void and increased T1 signals in a cortical vein which corresponded to the previously noted subacute haematoma at the left high frontal lobe. The finding suggested cortical vein thrombosis with resultant venous infarct and haemorrhagic change. Intracranial angiogram, which showed normal findings, was also performed to rule out any arteriovenous malformation and aneurysm that might contraindicate the use of anticoagulant.
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Discussion |
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Most of the reported cases of intracerebral thrombosis presented as ischaemic lesions. Both venous and arterial thrombosis have been reported (Stewart et al., 1997). The exact pathogenesis of thrombo-embolism in OHSS is not completely understood. Hypercoagulation state and haemoconcentration have been suggested as the predisposing factors. It is thought that the hypercoagulation status might be due to activation of the plasma kinin system in OHSS (Kodama et al., 1995). A disruption in the coagulation and thrombolysis may explain the hypercoagulable status in OHSS (Aune et al., 1991
). In the same investigation, a significant increase in fibrinogen was found and a reduction in antithrombin III concentration in OHSS. Haemoconcentration was proposed as a cause for thrombosis. However, deep cerebrovascular thrombosis has been reported in a patient with moderate ovarian hyperstimulation in whom the haematocrit was not raised (Aboulghar et al., 1998
). This raised the concern that some women are genetically predisposed to thrombosis. Screening for genetically determined risk factors like antithrombin III deficiency, Leiden factor V, Protein C and S deficiency has been advocated. This practice, however, may not be cost-effective.
Anticoagulation therapy is the usual recommended treatment in thrombo-embolism complicating OHSS. In this patient, the initial diagnosis of intracranial thrombosis was not made because MRI showed a haemorrhagic lesion instead of an ischaemic lesion, as commonly reported in the literature. The initial diagnosis was some co-existing lesion in the brain that caused secondary intracranial bleeding. The patient was initially managed conservatively, as there was no neurological deficit. The use of anticoagulation therapy is contraindicated even if the diagnosis of cortical vein thrombosis is known at first presentation because of the risk of inducing further bleeding. She developed deep vein thrombosis of the lower limbs subsequently. Anticoagulation therapy was indicated to prevent pulmonary embolism. The history of recent intracranial haemorrhage made the use of anticoagulant relatively contraindicated. MRI was repeated and the diagnosis of cortical vein thrombosis was revealed. The haemorrhagic change that is not uncommon in venous infarct masked the underlying pathology. Thus, a single pathogenesis of veno-occlusive disease explained both the intracranial lesion and the deep vein thrombosis. Anticoagulation was started after balancing the risk of further intracranial bleeding and pulmonary embolism. This was a joint decision between the haematologist and the neurosurgeon.
This case illustrates that thrombo-embolism in OHSS is a systemic and generalized phenomenon. The hypercoagulable state can last for several weeks after the onset of OHSS especially if the patient is pregnant. Anticoagulation therapy is the treatment of choice. In cases when anticoagulant is contraindicated, adequate hydration is required. The possibility of deep vein thrombosis should also be monitored. Graduated compression stockings can be used to prevent thrombosis in the lower limbs.
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Notes |
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References |
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Submitted on January 20, 2000; accepted on May 18, 2000.