CASE REPORT: Fatal mesenteric artery thrombus following oocyte retrieval
Dr B. Celebioglu, Department of Anesthesiology and Reanimation, Faculty of Medicine, Hacettepe University, 06100, Sihhiye, Ankara, Turkey.
The patient was a 38 year old woman (ASA I, 157 cm height, 61 kg weight) with a 14-year history of secondary infertility due to endometriosis who had undergone in vitro fertilisation and embryo transfer after ovarian stimulation with gonadotrophins.
Between 1989 and 2003, she had two-third trimester and six first and second trimester miscarriages. Her clotting profile studies, including protein-C activation, the resistance of active protein-C and LIA test free protein-S, were all normal. All her autoimmune tests were negative. Her homocysteine level was 10.89 μmol L−1 and normal. Her anti-toxoplasma IgG–IgM, anti-CMV IgM and HSV-IgM were negative but anti-CMV IgG and HSV-1 IgG were positive. Thyroid function tests were normal. Her fasting blood glucose level was 96 mg dL−1 and after 75 g oral glucose tolerance test, type II DM was detected and she was put on a diabetic diet.
Diagnostic laparoscopy and hysteroscopy were performed. The right fallopian tube was obstructed. There were no pelvic adhesions. Endometritis and adenomyosis were found in an endometrial biopsy. Semen analysis of the husband was normal. After these tests were performed, she was treated with in vitro fertilisation and embryo transfer.
The patient had her first cycle of in vitro fertilisation–embryo transfer in October 2003 when 50 IU × 27 = 1350 units of human menopausal gonadotrophin (HMG) (Pergonal; Serono, Geneva, Switzerland) were administered. After 12 days of stimulation, the patient developed 17 follicles with a diameter of 12–17 mm. Follicle aspiration was carried out 36 hours after administration of 10,000 IU of human chorionic gonadotrophin (hCG) while the oestradiol concentration was 2337 PG mL−1 and seven oocytes were obtained. She had not had any procedures under anaesthesia or embryo transfer prior to this time.
After the oocyte pick-up procedure the patient was discharged from hospital, but a few hours later she came to the emergency service with acute abdominal pain and in poor general condition. Her heart rate was 130 minute−1, blood pressure 110/70 mmHg, fever 36°C and respiration rate 24 minute−1. On physical examination she had abdominal tenderness and rebound. Bowel sounds were hypoactive, there was costovertebral angle tenderness. On rectal examination, the cervix was rigid, and no blood or melena was detected. Flat and upright abdominal X-rays showed air–fluid levels. Ultrasonography showed massive fluid in the left paracolic area and minimal fluid was seen behind the bladder. At culdocentesis no fluid was aspirated.
Laboratory findings are shown in Table 1. She was treated conservatively with intravenous infusion of 8 Litre/day crystalloids. A few hours later she developed restlessness, tachycardia (heart rate = 180 minute−1), hypotension (80/60 mmHg), hypercapnia (respiratory rate = 44 minute−1), leucocytosis, and her temperature was 38°C. In view of these findings indicative of sepsis, the infectious disease consultant recommended intravenous sulbactam–ampicillin 4 × 1.5 g and ciprofloxasin 2 × 400 mg. The patient was transferred to the intensive care unit (ICU), ECG, heart rate, invasive blood pressure, respiratory rate, temperature and central venous pressure and urine output were all continuously monitored. Twelve hours later, she had cardiac arrest and cardiopulmonary resuscitation was started. Defibrillation was ineffective and no heart rhythm returned. Intracardiac 1.2 lmg adrenaline was given after which, cardiac rhythm was noted. Cardiopulmonary resuscitation was performed for 17 minutes.
Table 1. Laboratory findings in service, ICU and operation room.
|Hb (g dL−1)||9.2||8.6||9.8||9.6||12 to 18|
|WBC (xlO3μL−1)||25||17||5||5.4||3.6 to 10.00|
|Platelet (xlO3μL−1)||346||248||127||114||150 to 450.00|
|Glucose (mg dL−1)||162||147||101||104||70 to 110|
|ALT (U L−1)||67||91||195||211||5 to 40|
|AST (U L−1)||52||62||359||367||8 to 33|
|BUN (mg dL−1)||14.1||18.4||31.7||30.4||4.6 to 23|
|Creatinine (mg dL−1)||1.2||1.6||2.9||2.9||0.6 to 1.2|
|Total protein (g dL−1)||8.1||7.7||3.9||3.9||6.0 to 8.7|
|Albumin (g dL−1)||4.6||4.4||2.0||1.9||3.2 to 4.8|
|INR (seconds)|| ||1.61|| || ||0.75 to 1.5|
|aPTT (seconds)|| ||47.5|| || ||25 to 40|
|pH||7.50||7.44||7.159||7.254||7.35 to 7.45|
|Pco2 (mmHg)||19.1||24.1||311||22.8||32 to 45|
|Po2 (mmHg)||81.5||88.5||118.7||105.3||80 to 97|
|BE (mEq L−1)||−5.3||−8.9||−16.6||−152||−2 to 3|
|HCO3 (mEq L−1)||14.9||14.6||10.8||9.9||22 to 26|
After resuscitation, her blood pressure was 39/25 mmHg and dopamine infusion (10 μg kg−1 minute−1) was started. The blood pressure increased to 63/56 mmHg. On neurological examination, she was unconscious and there was no response to verbal or noxious stimulation. Bilateral plantar reflexes were weak. Pupil diameter was 4 mm/2 mm and pupillary light reflex was sluggish. She was intubated and put on mechanical ventilation.
On electrocardiography, sinus tachycardia, ST segment depression in all derivatives and incomplete right bundle branch block were noted.
After paracentesis and aspiration of free fluid the decision for explorative laparotomy was made. Her haemodynamic status worsened and the dosage of dopamine was increased to 20 μg kg−1 minute−1.
When the patient arrived at the operating room, her first measured parameters were: blood pressure 63/52 mmHg; Spo2 100%; heart rate 155 minute−1; CVP 17 mmHg and total urine in the catheter. Then, 144 mg NaHCO3 and digoxin 30 mL were given intravenously. Dopamine infusion was decreased to 15 μg kg−1 minute−1. Mannitol 20% 150 cc, colloids 500 cc and crystalloid 500 cc were infused. Two units of fresh frozen plasma and 1 unit of packed erythrocytes were infused during the operation. The systolic blood pressure raised from 63 to 110 mmHg, heart rate decreased from 152 to 130 min−1, central venous pressure was between 17 and 19 mmHg, saturation 100% and urine output was 1.5 mL kg−1 minute−1. During exploration, a superior mesenteric artery thrombus was detected and all the intestinal parts in the territory of the artery were necrotic. At the beginning of the operation, 80 mg heparin was given and control ACT was found to be 318 seconds. From the jejunum to the transverse colon, 70 cm of the bowel was removed and jejunotransversostomy was performed. Total blood loss was 150 mL. The patient was transferred to the intensive care unit and intubated. She died on the post-operative fourth day in ICU.
Causes of acute abdomen after oocyte retrieval are not restricted to direct complications of the procedure. Differential diagnosis can be difficult because clinical manifestations are not specific for a given disease. An essentially, identical clinical picture can result from a wide variety of acute processes within or near the peritoneal cavity. Known complications of ultrasound guided oocyte retrieval include ruptured tubo-ovarian abscess, ovarian torsion, urethral obstruction, bradycardia and bradypnea due to local or intravenous anaesthetics, pelvic inflammatory disease and abscess formation, broad ligament haematoma and symptoms due to compression and bleeding. Other posibilities are appendicitis due to needle puncture, dermoid cyst rupture and subsequent peritonitis, ruptured endometriotic cyst, intra-abdominal bleeding and most commonly vaginal bleeding, which is usually self-limited. Hospital admission due to per operative complications is needed approximately in 1.5% of patients.1 Primary factors predisposing to peri-operative morbidity and mortality are a history of previous pelvic inflammatory disease and/or adnexial adhesions. Dicker et al.2 reported 14 cases out of 3656 patients undergoing the procedure presenting with a clinical picture of acute abdomen. Nine were diagnosed as cases of tubo-ovarian abscess.2
Acute mesenteric vascular occlusion associated with oocyte retrieval is an unusual complication, which might not initially be considered. Acute occlusion of the superior mesenteric artery may be the result of an embolus or an in situ thrombus. Thrombotic occlusion of the vessel occurs as a result of pre-existing atherosclerotic plaque progression and accounts for 20–50% of the cases.3 At presentation, 64% of patients demonstrate peritonitis, and 30% hypotension that is due to systemic inflammatory response syndrome/sepsis. Overall, 82% of patients have bowel necrosis.4 Acute mesenteric ischaemia has a mortality rate of 59–95%.5 In approach to a patient with acute abdomen after oocyte retrieval, investigation should include transvaginal sonography, abdominal sonography and/or abdominal computed tomography. The ultrasound in our patient showed intraperitoneal fluid in the left paracolic gutter and rectouterine pouch, which was interpreted as a needle perforation of viscus when the patient's history and clinical findings were taken into account. Evidence-based management of iatrogenic bowel perforation either during laparoscopy or oocyte retrieval is not possible. A conservative approach was taken so that the patient was observed first. The management trend in recent literature is less invasive, non-operative therapy, given advancements in ICU care and antibiotics.6 If laboratory and clinical findings do not reveal the diagnosis, exploration of the abdomen remains the gold standard. Patients with unstable vital signs should undergo urgent laparotomy exploration.
Acute thrombogenic events are routinely reported as a complication during the course of in vitro fertilisation procedures.7,8 There are reports of thromboses of the internal jugular vein, superior vena cava and major cortical veins in patients undergoing this treatment. The thrombosis of mesenteric artery associated with in vitro fertilisation has never been reported in literature previously. Also, it is interesting to see mesenteric artery thrombosis in a young patient due to its common occurrence in the elderly. It is important that gynaecologists be aware of the possibility of embolic complications of oocyte retrieval and that they communicate this risk to the patient.
Risk factors for arterial thrombosis include smoking, hypertension, hyperlipidaemia, diabetes mellitus, cholesterol embolism, hereditary and acquired thrombophilias, homocysteine, CRP, fibrinogen levels, and in the case of in vitro fertilisation, patients' ovarian hyperstimulation syndrome. High dose gonadotrophin administration for ovulation induction creates hypercoagulable environment secondary to hyperoestrogenaemia and haemoconcentration after ovarian hyperstimulation. Insulin resistance state in our patient also is a risk factor for arterial thrombosis.
Underlying factors causing infertility of in vitro fertilisation patients might predispose to coagulation. Both hereditary (factor V Leiden mutation, protein C deficiency, protein S deficiency, anti-thrombin III deficiency, prothrombin gene mutation [Prothrombin G20210A], methylene-tetrahydrofolate reductase muation, PAI-1 gene mutation, platelet glycoprotein gene IIIa A1/A2 mutation) and acquired thrombophilias (antiphospholipid antibody syndrome) are associated with recurrent early pregnancy loss, stillbirth, third trimester fetal loss, severe intrauterine growth restriction, placental abruption, and pre-eclampsia. In vitro fertilisation patients with a history of recurrent pregnancy loss and family history of thrombogenic events should be screened for thrombophilias as with our patient. The synergistic effect of pregnancy and hyperoestrogenism increases the risk of these patients. All laboratory values for thrombophilia screening were normal in our patient.
Risk factors must be considered individually before each in vitro fertilisation attempt. Stimulation of the ovaries by means of the gonadotrophins might predispose the patient to increased procoagulant activity and endothelial dysfunction. In vitro fertilisation protocol due to supraphysiologic increase in oestrogen level is associated with an overall increase in clot formation. At the time of oocyte retrieval, significant alteration in coagulation variables was reported (faster clot formation, increased coagulation strength).7 This increase might be an incipient factor in the triggering of mesenteric thrombosis. Ovarian hyperstimulation syndrome is an iatrogenic complication, which can sometimes be fatal. A higher incidence of ovarian hyperstimulation syndrome has been reported in patients with hyperinsulinism (our patient also had insulin resistance but we did not see any features of severe ovarian hyperstimulation syndrome) and polycystic ovarian syndrome; incidence was quoted as 0.6–14%. Activation of plasma kinin system, rise in platelets, increase in fibrinogen, reduction in anti-thrombin levels and haemoconcentration might cause hypercoagulation in ovarian hyperstimulation syndrome patients.9,10 However, Delvigne et al.11 reported indifference of coagulation tests between the ovarian hyperstimulation syndrome group and the control group with the exception of fibrinogen, which was slightly higher in ovarian hyperstimulation syndrome patients. Katayama et al.12 investigated microvascular permeability and leucocyte–endothelial cell interactions in the rat mesenteric microcirculation associated with induction of ovulation. Administration of hMG and hCG significantly increased vascular protein leakage within a few hours, and also reduced rolling of leucocytes in venules and increased the number of leucocytes adherent to endothelium at 16 hours following hCG injection. By ovulation induction vascular permeability is increased not only on the surface of the ovary but also in the mesentery.
Both endothelial dysfunction and accelerated clotting during oocyte pick-up might have induced thrombosis of the superior mesenteric artery in our patient.