Neurol Sci (2008) 29:463–466
DOI 10.1007/s10072-008-1018-y

C A S E R E P O RT

Acute ischaemic stroke in pregnancy: a severe complication
of ovarian hyperstimulation syndrome
Andrea Bartkova · Daniel Sanak · Jiri Dostal · Roman Herzig · Pavel Otruba · Ivanka Vlachova ·
Petr Hlustik · David Horak · Petr Kanovsky

Received: 21 February 2008 / Accepted in revised form: 29 August 2008 / Published online: 15 October 2008
© Springer-Verlag 2008

Abstract Ovarian hyperstimulation syndrome (OHSS) is
the most serious complication of sterility treatment. It is
characterised by ovarian enlargement, ascites, electrolyte
disturbance, hypovolaemia and haemoconcentration. A
case of ischaemic stroke due to right middle cerebral
artery (MCA) occlusion in a young female with OHSS
after pharmacological treatment of sterility is reported.
Left central hemiparesis occurred suddenly within a few
days after the embryo transfer. Magnetic resonance imaging diffusion-weighted images showed infarction in the
right basal ganglia and magnetic resonance angiography
(MRA) revealed the occlusion of the M1 segment of the
right MCA. The haemodilution and the anticoagulation
therapy were effective. Twenty-four hours after the stroke
onset, MRA showed MCA recanalisation. The neurological deficit resolved completely within 3 months. The
patient delivered 2 healthy infants at term. This case
emphasises that the recent advent of ovulation induction

A. Bartkova (쾷) · D. Sanak · R. Herzig · P. Otruba · I. Vlachova ·
P. Hlustik · P. Kanovsky
Stroke Centre, Department of Neurology
Faculty of Medicine and Dentistry
Palacký University and University Hospital Olomouc
I. P. Pavlova 6
CZ-775 20 Olomouc, Czech Republic
e-mail: abartkova@seznam.cz
J. Dostal
Department of Obstetrics and Gynecology
Faculty of Medicine and Dentistry
Palacký University and University Hospital Olomouc
Olomouc, Czech Republic
D.Horak
Department of Radiology
Faculty of Medicine and Dentistry
Palacký University and University Hospital Olomouc
Olomouc, Czech Republic

and reproductive techniques is a newly recognised cause
of cerebral stroke in otherwise healthy females.
Keywords · Ovarian hyperstimulation syndrome ·
Pregnancy · Ischaemic stroke

Introduction
Ovarian hyperstimulation syndrome (OHSS) is a serious
iatrogenic complication of infertility treatment. OHSS
can be considered as the loss of control over the intended
therapeutic ovarian hyperstimulation [1] and an increase
in its incidence after the development of a new method of
in vitro fertilisation [2]. Characteristic pathophysiological
phenomena of OHSS include overproduction of ovarian
hormones and vasoactive peptides increasing the capillary
permeability, leading to the massive accumulation of
extravascular exudates with intravascular volume depletion and to haemoconcentration. The resulting clinical
manifestation may vary. OHSS is characterised by ovarian enlargement, abdominal distension, ascites, pleural
effusion and electrolyte disturbance. In its severe form,
OHSS can lead to multiple organ failure with adult respiratory distress syndrome, renal and liver insufficiency,
and to thromboembolic events. These thromboembolic
events represent the most serious complications of OHSS.
Their exact incidence in severe OHSS is unknown and,
according to the literature, ranges from 0.2% to 10%
[1–3]. Most (75%) of the thrombotic events are of venous
origin and the remaining 25% are of arterial origin [4]. It
seems that thrombotic events in OHSS are related to the
thrombophilic reaction caused by oestrogens, low plasma
circulation volume and haemoconcentration.
Stroke represents a rare but life-threatening complication of severe OHSS. A case of acute ischaemic stroke
(IS) caused by OHSS is reported.

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Neurol Sci (2008) 29:463–466

Case report
A 31-year-old female, without the presence of thromboembolic risk factors, had a 6-year history of primary infertility
and 2 unsuccessful cycles of ovulation induction. The third
course of controlled ovarian hyperstimulation (COH) (long
protocol E2 4 400) during in vitro fertilisation (IVF) was
used in this patient. Two embryos were transferred 4 days
after the aspiration of 19 oocytes. In that time, the oestradiol
level was 1440 pg/ml and 10,000 IU of human chorionic
gonadotropin (hCG) was administered. Seven days after the
embryo transfer, the patient developed nausea, vomiting and
abdominal distension with ovarian enlargement. The ultrasound revealed the presence of ascites and polycystic ovaries.
She was admitted to the hospital because of suspected OHSS.
The pregnancy test was positive (hCG level was 46 IU). Nine
days after the embryo transfer, she suddenly developed a
severe central left-sided hemiparesis, with the central lesion
of the left facial nerve, deviation of the head to the right with
left-side conjugate gaze palsy and drowsiness (National
Institute of Health Stroke Scale (NIHSS) of 11 points).
Magnetic resonance imaging diffusion-weighted images
(MRI-DWI) showed acute infarction (volume 23.2 ml) of the
right basal ganglia (Fig. 1) and magnetic resonance angiography (MRA) showed the occlusion of the main stem of the
right middle cerebral artery (MCA/M1) (Fig. 2). The patient
was transferred to the Stroke Unit. Laboratory tests, including tests for thrombophilia used in young stroke patients
were performed. Leukocytosis (total leukocyte count
29,200/mm3) and the evidence of haemoconcentration
(haematocrit 45%, fibrinogen level 5.6 g/l) were found. The
use of intravenous thrombolysis (IVT) was considered, but
the patient refused this treatment because of a probable pregnancy. She was treated with subcutaneous administration of

Fig. 2 MRA. Occlusion of the right middle cerebral artery in the M1
segment

Fig. 3 MRI-DWI – performed 24 h after stroke onset. Slight progression of infarct volume with haemorrhagic transformation of the
infarction

Fig. 1 MRI-DWI. Acute cerebral infarction of the right basal ganglia

nandroparine 0.6 ml twice daily and haemodilution with
crystalloid fluid infusions with target haematocrit of 35%.
The MCA/M1 recanalised (as detected with MRA performed
24 h after the stroke onset (Fig. 3)) and the neurological status improved (NIHSS decreased to 6 points). MRI Turbo
Spin Echo (TSE) T2 and DWI sequences demonstrated the
haemorrhagic transformation of infarction with slight infarct
growth (volume 32.5 ml) (Fig. 4). The nandoparine dose was
reduced to 0.3 ml twice daily. Due to the successful gravidity, the OHSS symptoms, such as dyspnoea, arterial hypotension (100/60 mmHg), tachycardia (120 beats/min), hypoalbuminaemia (26 g/l), ascites and fluidothorax worsened.

Neurol Sci (2008) 29:463–4667

Fig. 4 MRA – performed 24 h after stroke onset. Successful recanalisation of the right middle cerebral artery

Repeated transabdominal aspiration of the ascitic fluid and
intravenous administration of albumin 100 ml daily for a
period of 7 days was used. The OHSS symptoms resolved
slowly over 14 days.
The neurological state of the patient normalised gradually; after 3 months she manifested no residual neurological deficit. She delivered healthy twins at term by
caesarean section. During the pregnancy and puerperium
she was maintained on acetylsalicylic acid 100 mg daily.

Discussion
The incidence of IS during pregnancy is 0.003/1000 (RR
0.7); two days before and one day after delivery the risk
of stroke incidence increases (RR 2.5) [5]. The risk has
also increased with the higher frequency of in vitro fertilisation during recent years [2].
OHSS is an iatrogenic complication of ovarian stimulation usually occurring during the luteal phase or during the
early phase of pregnancy [6]. The most common form of
OHSS occurs within a few days after follicular rupture or
puncture, when follicular growth has been medically
induced [1]. The prevalence of the severe form of OHSS is
low, with a reported value ranging from 0.5% to 5% of stimulated ovarian cycles resulting in severe OHSS [1] with an
estimated mortality rate of 1/50,000–450,000 patients [7].
It is difficult to estimate the incidence of the thromboembolic events, because no systematic registration of OHSS
cases and their complications exists. Delvigne and Rozenberg
reported a 0.2% incidence of thrombotic events and 10% incidence of a severe OHSS in a series of 2924 IVF cycles [1].
Stroke represents a rare but often fatal thromboembolic complication of OHSS.
The following factors were recognised as presenting an
increased risk for the severe form of OHSS with thromboem-

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bolism: rapid rise of oestradiol levels (with serum concentration >2500 pg/ml), increased number of developing follicles
and the number of oocytes retrieved during IVF (>14), previous history of OHSS, age under 35 years, use of gonadotropin
releasing agonist (GRA) protocol, higher or repeated dose of
exogenous hCG and polycystic ovary. Our patient was 31
years old and underwent a long-term GRA protocol; she presented with a serum oestradiol level of 1440 pg/ml and a high
number of oocytes [8] were retrieved. Routine screening of
the mentioned risk factors should be performed. Screening
for thrombophilia (personal and family history of thrombosis)
should be recommended to rule out thrombophilia before the
ovulation induction. It is important to prevent thromboembolism in OHSS [1]. In our case, heterozygosity of MTHFR
without a homocysteine plasma level increase was found.
However, it is difficult to establish its relationship to IS,
because of a very mild thrombotic potential, although a similar case was reported by Di Micco et al. [9].
The diagnostic approach in suspected stroke in a pregnant female does not significantly differ from that in a
non-pregnant one. The radiation dose during a routine
head examination with computed tomography (CT) is as
low as 1 mrad and seems to be safe for the foetus [10].
Thus, brain CT can be performed during the whole period
of pregnancy in indicated cases, as long as the uterus is
protected during the examination [10].
Nevertheless, the use of MRI scanning during pregnancy remains controversial. MRI use is mostly not recommended within the first 12 weeks of pregnancy due to
the higher frequency of congenital anomalies [11, 12].
The safe use of MRI is reported in the third trimester and
the potential benefit of MRI should be considered in individual cases in the first and second trimesters. Although
the MRI was performed 9 days after the embryo transfer,
no foetal injury occurred in the presented case.
In our opinion, consistent with the literary data, the use
of haemodilution and rehydration therapy seems rational,
because haemoconcentration is one of the factors leading to
thrombotic events [1, 13]. The use of infusion of crystalloids represents the method of the choice in these cases.
Intravenous administration of albumin is recommended in
cases of severe OHSS (as a plasma expander) and in cases
of severe hypoalbuminaemia or tense ascites [1, 13].
Abdominal paracentesis is a common procedure used in
severe OHSS. Paracentesis may be needed for symptomatic
relief of tense ascites, but it may also be indicated in cases
of oliguria, increasing creatinine or decreasing creatinine
clearance, and haemoconcentration refractory to medical
therapy [1, 13]. In our case, paracentesis was performed
due to haemodynamic instability.
IVT should be considered as the first treatment method in
a case of IS caused by the cerebral artery occlusion.
However, it is not recommended in pregnancy and lactation
according to recent guidelines [14]. The major concern
regarding the use of thrombolytics during pregnancy is their

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effect on the placenta, possibly resulting in premature labour,
placental abruption or foetal demise. Most pregnant females
were treated with intra-arterial thrombolysis [15–17].
Reported complication rates were similar when compared to
thrombolytic treatment of non-pregnant females. Child outcomes appeared not to be affected. Considering the best level
of medical evidence, alteplase should not be withheld in the
pregnant patient with acute IS, and limited risks and benefits
must be carefully weighted [14, 18]. Also our patient refused
IVT because of its potential risk of abortion and she was
anticoagulated with nandroparine. Antithrombotic primary
prevention is not used in all COH cycles, as the incidence of
OHSS is low. In COH with signs of severe OHSS, anticoagulant therapy is indicated if there is clinical evidence of a
thromboembolic complication or laboratory evidence of
hypercoagulability [8, 19]. The Authors presume that early
administration of heparin at the time of first OHSS symptoms could prevent serious thromboembolic events.
In the presented case, a complex treatment (rehydration, haemodilution, anticoagulation, close gynaecological monitoring) was effective, with a good clinical outcome for the patient and no harm to the infants.

Conclusion
The reported case emphasises that the development of
ovulation induction and reproductive techniques is a
newly recognised cause of cerebral stroke in otherwise
healthy women. Females with mild forms of OHSS without neurological symptoms should be closely monitored
and a sudden onset of neurological deficit in such
patients with OHSS symptoms must be considered as an
acute IS and a severe OHSS complication.

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