General principles in the evaluation of infertile
couple are almost universal, including midluteal
phase progesterone assay, semen analysis and a
test for tubal patency such as hysterosalphingography.
Before starting the treatment, especially
in the form of assisted reproduction technology
(ART), existing pregnancy must be ruled out (
We are presenting a cerebral venous thrombosis case associated with lack of proper medical evaluation required for confirmation of suppression and exclusion of current pregnancy before starting ART cycle.
In this case-report study, a 37-year old woman presented to our emergency room with abdominal pain. Her pulse rate was 72 beats per minute, and blood pressure was 80/50 mmHg. We revealed abdominal tenderness, muscular defence and rebound tenderness on her pelvic examination. In initial, complete blood count analysis hemoglobin level was 7.9 g/dL, hematocrit level was 31% and platelet count was 177×103/μl. Initial human chorionic gonadotropin (hCG) value was 17616 IU/L. With ultrasound examination, we determined 4×2 cm cystic structure at right adnexial region, which is compatible with corpus luteum and bilaterally enlarged ovaries. Additionally, endometrium was heterogenous, but it was not compatible with a normal intrauterine pregnancy with a hCG value as 17616 IU/L.
According to knowledge from patient’s history, 38 days ago, on the second day of her menstrul cycle, she had admitted to another infertility clinic with secondary infertility (unexplained). Before starting ART therapy, only basal transvaginal- ultrasonography (TV-USG) had been performed, while basal hormone profile, the thickness of endometrium and antral follicle count had not been measured. We also learned from patient that on her first vist of the center, on the second day of her menstrul cycle, controlled ovarian stimulation had been started with 375 IU doses of gonadotrophin. Treatment had been continued with constant doses. On the sixth day of the stimulation, GnRH antagonist-Cetrorelix 0.25 mg/day had been started. On the twelfth day of the stimulation, 250 mcg hCG had been administered. Transvaginal oocyte retrieval had been performed on the fourteenth day of the stimulation, and one oocyte had been yielded. Sixteen hours after intracytoplasmic sperm injection (ICSI), since oocyte had not been fertilized, embryo transfer did not happen.
After the first evaluation in emergency room, we took the patient to the operation room with indication of surgical exploration of abdomen for suspicion of ectopic pregnancy. In the exploration, we observed a material which was consistent with ectopic pregnancy within hemorrhagic ruptured region of the right tuba uterina. Partial salpingectomy was applied because of actively bleeding ectopic pregnancy. We made sequential measurement of hCG, so on first and fifth postoperative days, hCG values were 4563 IU/L and 1200 IU/L, respectively. Patient was discharged from hospital without any complaints with suggestions for hCG follow-up. Pathologic result of the material was 'immature chorion villus and desidual tissue', being consistent with ectopic pregnancy.
Two days after hospital discharge, she presented to emergency room again with syncope and generalized tonic-clonic seizure. On neurological examination, she showed apathy and no lateralization. Generalized edema and suspicious cerebral venous thrombosis were determined on the cranial computerized tomography. She was admitted to the neurology department. On complete blood counts, white blood cells were in normal range, while hemoglobin (9.9 g/dl) and hematocrit (29.8%) were slightly decreased. Platelet counts were normal (273×103/μl). Serum concentrations of electrolyte were also in normal range.
Following hospitalization, she had generalized tonic-clonic seizures with half hour intervals. Rapidly enoxaparine sodium 0.6 ml twice daily, midazolam infusion, and phenytoin sodium 100 mg twice daily were administered. She was also conservatively treated with balanced electrolyte solution. The result of screening test for antithrombin III, Leiden V factor, protein C and S deficiency, antinuclear antibodies (ANA), Anti-DNA, lupus anticoagulant and ENA panels were negative. After recovery, venous phase magnetic resonance (MR) angiography was performed. MR angiography demonstrated irregular filling on the superior sagittal sinus. The patient was assessed as cerebral venous thrombosis with these findings. Her neurologic status was stabilized after a few days. Six days after hospitalisation, she was discharged with normal neurological examination under phenytoin 200 mg daily and enoxaparine sodium 0.6 ml daily. For two consecutive months after discharge from the hospital, we monitored the patient with routine neurological and gynecological examinations.
Essential adaptation of mother’s hemostatic system to pregnancy is generally protective for peripartum
unwanted bleeding, but also contributes to
increased risk of thromboembolic complications.
Venous thromboembolism is a rare disorder occurring
in approximately 1/1000 to 1/2000 pregnancies,
which can lead to serious mortality and morbidity
in pregnant women (
One of the most devastating result of thromboembolism
during pregnancy is cerebrovascular
event due to thrombosis of dural sinuses, cerebral
veins or arteries. The overall risk of pregnancy-
related stroke was generally 34 in 100,000
It is evident that the increas in level of estradiol
accompanying ART treatment is one of the most
important factors for complications as OHSS or
thromboembolism. In addition, increase in the levels
of both coagulation factors (such as Von Willebrand
factor (vWF), factors VIII and V, and fibrinogen)
and protein C-S activity, while decrease in
antithrombin-III (AT-III) during controlled ovarian
hyperstimulation are responsible for complications.
Venous thromboembolism (75%) is commonly
found more than arterial thromboembolism
(25%) in following ovarian stimulation for ART,
and also it is shown in up to 95% of cases associated
with OHSS (
With the advancement of new perspectives
in ART, evaluation of the infertile couple also
changed. Today, a widely accepted approach to infertility
does not include the diagnosis of an exact
etiology. The scope and sequence of the modern infertility
evaluation have shifted focus, from making
a speciﬁc diagnosis to using the most efﬁcient and
cost-effective tests. It is now obvious that investigation
of infertile couple should be concluded rapidly
and inexpensively with least invasive tests (
Our case had two major risk factors, including:
i. delayed diagnosis of existing ectopic pregnancy
due to absence of vaginal bleeding from high estradiol
level resulted in tubal rupture and ii. cerebral
venous thrombosis. Inherited or acquired
thrombophilia was not detected in our case. Although
syndrome of ovarian hyperstimulation
was reported in 90% of all cases involving arterial
thrombosis and in 78% of women with venous
thrombosis, it was not a mandatory predisposing
factor in our patient because she did not show any
sign of OHSS (
Therefore, this is a unique case with a history of COH treatment with insufficient control masked the existing ectopic pregnancy, and was also complicated with cerebral thrombosis. ART became a rather frequently administered treatment option for infertile couple in recent years, but clinicians must always bear in mind complications of ART. Therefore, for prevention of any complications, the major steps in evaluation of infertile couple should be taken in order to prove the suppression or to rule out the possibility of pregnancy before starting COH cycle.