Stroke in ovarian hyperstimulation syndrome in early pregnancy treated with intra-arterial rt-PA

Case report.

The patient is a nonsmoking 28-year-old nulligravida with 7 years of primary infertility and four unsuccessful cycles of ovulation induction. In vitro fertilization was undertaken for male factor infertility using an oral contraceptive–gonadotropin-releasing hormone agonist–recombinant follicular stimulating hormone (rec-FSH) long protocol starting with 200 IU rec-FSH daily. Despite close observation she over-responded to the gonadotropins, and her estradiol peaked at 11,500 pmol/L. She was coasted (no medication given) for 3 days prior to her human chorionic gonadotropin (HCG) injection (to mature her oocytes) on day 14 when her estradiol was 10,460 pmol/L. Sixteen mature eggs were retrieved from her ovaries and injected with her husband’s sperm. Two excellent quality day 3 embryos were transferred back into the patient, and eight of good quality were cryopreserved for future use. Four days after embryo transfer she had abdominal bloating and enlarged ovaries on examination, with normal complete blood count (CBC), electrolyte, and albumin determinations. She was assessed as needed in the fertility clinic and presented at 7 days after embryo transfer with dehydration, dyspnea, and nausea. She was immediately admitted to the hospital with severe OHSS and a large right pleural effusion. She was treated with IV fluids, albumin, and prophylactic subcutaneous heparin. Her initial CBC, after a 1-liter bolus of IV saline showed a white blood cell count (WBC) of 21.5 109/L (normal 3 to 10), hemoglobin 165 g/L (normal 115 to 155), hematocrit 0.50 L/L (normal 0.35 to 0.45), and platelet count 423 109/L (normal 125 to 400). Seven hours after admission and IV rehydration, she developed sudden left hemiplegia, dysarthria, left facial paralysis, and drowsiness (National Institute of Health Stroke Scale score of 11). Her blood pressure was 100 to 115/50 to 65 mm Hg throughout. An emergency CT scan confirmed subtle ischemic changes in the right middle cerebral artery (MCA) distribution including the perisylvian, frontal, and parietal opercular regions as well as the posterior aspect of the right basal ganglia (figure 1A). Angiography at 4 hours after stroke onset revealed complete occlusion of the right M1 segment of the MCA (figure 2A). Selective intermittent injection of a total of 15.5 mg of intra-arterial rt-PA via microcatheter over 68 minutes resulted in recanalization of the main trunk and anterior branch of the MCA (figure 2B), with marked concomitant improvement in neurologic status (NIHSS score 3). A postlysis CT showed a small 1.5- × 2.0-cm hematoma in the right basal ganglia (figure 1B). Three hours later she suffered worsening hemiparesis and hemisensory loss, with a repeat CT showing enlargement of the hematoma to 3.0 cm. General treatment included IV fluids and bilateral pigtail catheter drainage of her pleural effusions. Her hyperstimulation resolved slowly over 3 weeks, as she was pregnant with a singleton. There was no evidence of thrombophilia on extensive testing, and there were no structural cardiac anomalies. Her neurologic status improved gradually, and by 3 months she had only a mild incomplete left inferior quadrantanopia, normal strength, slight subjective sensory alteration in the left leg, and mild circumduction when ambulating. She was maintained on low-dose dalteparin for stroke prophylaxis until the last 2 months of her pregnancy. She delivered a healthy male infant at term by spontaneous vaginal delivery.

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Figure 1. (A) Axial noncontrast CT obtained before thrombolysis showed effacement of sulci in the right hemisphere in the perisylvian area and extending toward the convexity to involve the frontal and parietal opercular regions. The insular ribbon was preserved, but subtle hypodensity was seen in the right basal ganglia on other cuts. (B) Repeat CT obtained shortly after completion of intra-arterial thrombolysis with 15.5 mg of rt-PA showed a 1.5- × 2.0-cm hematoma in the posterior aspect of the right basal ganglia. The patient had virtually no neurologic deficits at this point.

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Figure 2. (A) Prelysis arteriogram (anteroposterior view) showed complete occlusion of the M1 segment of the right middle cerebral artery (arrow). (B) Repeat injection after selective administration of 15.5 mg of rt-PA demonstrates recanalization of the anterior branch of the MCA (arrowheads), but the posterior branch remained occluded. Because of marked neurologic improvement, the procedure was terminated at this point and the patient sent for repeat CT (figure 1B).

Discussion.

Close monitoring of follicular development and serum estradiol levels is mandatory in patients at high risk for the development of severe OHSS. In patients at extremely high risk, some clinics delay HCG administration, which can prevent OHSS and its attendant complications. We found 14 published case reports (1960 to present) of stroke in patients suffering from OHSS: six patients recovered with minimal or no sequelae, six were left with hemiparesis, and two died.3-6⇓⇓⇓ The MCA was occluded in six cases. While six cases were treated with IV heparin, there are no reports where intra-arterial thrombolysis was administered. Because most of these cases reported large arterial branch occlusions, which are associated with a relatively poor outcome,7 and given that anticoagulation alone offers little benefit in the acute phase,8 a more aggressive approach in these patients may be indicated.

Overall a net benefit of IV and intra-arterial thrombolysis has been demonstrated in acute ischemic stroke.9 Given the time elapsed after symptom onset and fairly widespread subtle ischemic changes on the initial CT, we elected to proceed with intra-arterial lysis in our case. The initial dramatic recovery paralleled partial reopening of the M1 occlusion. Approximately 10% of patients so treated will deteriorate due to intracerebral hemorrhage, but despite these complications, a significantly improved clinical outcome was observed. Our patient may have been at higher risk of hemorrhage because of early CT changes and a relatively proximal MCA occlusion that involved fragile lenticulostriates. Although there is significant debate in the field of acute stroke intervention, there nevertheless appears to be general agreement that intra-arterial thrombolysis is a reasonable treatment option for selected patients.10 Our case suggests that in addition to standard treatment of severe OHSS (IV fluids, electrolyte and serum protein monitoring, thoraco-paracentesis, and prophylactic heparin), treatment of acute ischemic stroke can be done relatively safely and effectively with intra-arterial thrombolysis using rt-PA. The rapid onset of severe dehydration and prothrombotic tendency highlight the need for close monitoring and rapid intervention in women with symptomatic OHSS.