Abstract
Severe ovarian hyperstimulation syndrome (OHSS) affects 2–4% of in vitro fertilization (IVF) patients, which may rarely result in an ischemic stroke secondary to a hypercoagulable state. We describe a case of a 38-year-old IVF patient who developed early-onset OHSS with a viable pregnancy who presented at 18 days post embryo transfer with an ischemic stroke resulting from a thrombus in the right middle cerebral artery. As the use of recombinant tissue plasminogen activator was relatively contraindicated owing to a recent intra-abdominal drain placement, a radiologically guided thrombectomy was performed. This resulted in neurological improvement in the mother and the birth of a normal term infant, without significant ionizing effects to the developing embryo.
Introduction
Severe ovarian hyperstimulation syndrome (OHSS) affects 2–4% of patients undergoing in vitro fertilization (IVF) treatment, which may rarely result in a thrombotic stroke. While the standard treatment is through acute thrombolysis with a thrombolytic agent [6], this may be complicated where thrombolysis is contraindicated, and where pregnancy has occurred. Here, we present a case of IVF pregnancy complicated by an ischemic stroke where a timely radiologically guided thrombectomy, with the radiation dose to the pelvis being below the threshold for adverse embryonic outcomes, resulted in neurological improvement in the mother and the term birth of a normal newborn.
Case report
The patient is a 38-year-old Chinese primigravida, with bilateral tubal disease secondary to endometriosis. She underwent an IVF cycle with leuprorelin acetate downregulation, follitropin-α stimulation, followed by human chorionic gonadotropin (hCG) trigger before oocyte retrieval. After fertilization through intracytoplasmic sperm injection, four good-quality embryos were generated. Following double-embryo transfer and hCG luteal phase support, she developed early-onset severe OHSS with significant ascites and hemoconcentration (hematocrit, 46%) 4 days later. She was admitted for intravenous fluid therapy, institution of dopamine agonists, and abdominal drainage of ascites with a Cope loop drain. Additionally, antiembolism stockings and low-molecular-weight heparin prophylaxis with 20 mg of enoxaparin twice a day were initiated. She was discharged, with a normal hematocrit, on thromboembolic stockings and a Cope loop in situ 7 days later.
Eighteen days after the embryo transfer, she presented with an acute onset of left-sided paralysis consistent with a right-sided ischemic stroke. Magnetic resonance imaging (MRI) and angiography indicated a complete right middle cerebral artery thrombotic occlusion (Figure 1). As thrombolysis with urokinase was felt to be relatively contraindicated in view of her pregnancy and recent placement of a Cope loop drain, a thrombectomy revascularization of large vessel occlusion (TREVO) procedure under fluoroscopic imaging was eventually performed within 7 h of the onset of symptoms, with neurological improvements (Figure 1). A total of 1116 mGy was used in the intervention, with an upper limit of 111 mGy of radiation delivered to the pelvi-abdominal region, below the 200-mGy threshold for inducing structural malformations and miscarriages at 20 days post fertilization [3].
Screening for thrombophilia was negative, as was all screens for paradoxical venous thromboembolism and cardiac and carotid pathologies, and she was commenced on low-molecular-weight heparin for the remainder of her pregnancy. The patient improved neurologically through the rest of her pregnancy, with normal fetal growth parameters and structural scans for fetal anomalies. She eventually delivered a healthy normally grown baby boy at 39 weeks’ gestation by elective cesarean delivery. At the time of delivery, she had full recovery of the use of her left lower limb, and had grade 3/5 power in her left upper limb.
Discussion
The occurrence of an ischemic stroke associated with OHSS is extremely rare, with just a few case reports published [1]. In this patient, timely thrombectomy after ischemic stroke resulted in clinical improvements. Exposure of the pelvis to radiation during advancement of the catheter from the femoral artery has led to concerns about the possible deleterious effects of radiation on the embryo.
The use of recombinant tissue plasminogen activator (rtPA) is another option for the treatment of acute strokes, especially when used within 3 h of presentation, as suggested by the American Stroke Association [2, 6], with its use in pregnancy for thromboembolic events being described [8]. However, in a case series of the use of rtPA for the treatment of stroke in pregnancy, it was noted that two out of six patients in the first trimester of pregnancy had spontaneous miscarriage, two pregnancies were terminated for other reasons, and two patients had live births [5]. Owing to the small numbers accrued to date, the teratogenicity and extent of possible fetal side effects cannot be reliably established. In our case, it was felt that the recent placement of an intra-abdominal drain was a relative contraindication to the use of rtPA. Thus, the patient was offered a TREVO procedure.
As the TREVO procedure necessitates delivering ionizing radiation to the pelvis during access of the femoral vessels, concerns have been raised. Exposure to ionizing radiation has been linked to an increased risk of miscarriages, fetal malformations, growth restriction, and a risk of various malignancies in the future child; however, the exposures must exceed the exposures that occur in the majority of diagnostic radiological studies [4]. In this case, the exposure was below the threshold for malformations, growth retardation, mental retardation, and miscarriage. The background risks that apply to all pregnant women are 3% for birth defects and 15% for miscarriage. Environmental factors account for up to 10% of congenital malformations that are seen in the first year of life. However, ionizing radiation exposures to the embryo that are <0.20 Gy (<200 mGy) are below the threshold for producing congenital malformations, growth retardation, mental retardation, and pregnancy loss [3, 4]. The majority of congenital anomalies (65–75%) are considered to be due to unknown causes, while genetic abnormalities account for 15–25% of birth defects [3].
During the preimplantation and presomite phase of development, the deleterious results of radiation conform with the “all-or-none phenomenon” [3]. The patient may miscarry from high radiation exposures. If the pregnancy is sustained, it is unlikely that there is an increase in the risk of fetal malformations at this stage. During early organogenesis, from the 18th to the 40th day post conception, the threshold level for major malformations is >0.2 Gy. The critical period for mental retardation and microcephaly is from the 8th to the 15th week of gestation, where exposure to 1 Gy can lead to a reduction of 30 points on the IQ scale [7]. During early organogenesis, the developing central nervous system (CNS) is resilient because CNS cortical primordial cells that were killed are readily replaced [4, 7]. Mental retardation is not a risk from exposures below 0.20 Gy. In this case, the patient had no further antenatal complications and the newborn was noted to be healthy at the 6-week postnatal review.
To our knowledge, this is the first report of an image-guided thrombectomy procedure performed in early pregnancy with a positive outcome. Concerns of radiation exposure can be allayed through minimal radiation exposure to the pelvis and directed counseling regarding radiation risks.
References
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The authors stated that there are no conflicts of interest regarding the publication of this article.
©2012 by Walter de Gruyter Berlin Boston