Perforated duodenal ulcer associated with ovarian hyperstimulation syndrome: Case Report

Meike L. Uhler1,4, G.R.Scott Budinger2, Sheryl G.A. Gabram3 and Michael J. Zinaman1

1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology and Departments of 2 Internal Medicine and 3 Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois, USA


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Ovarian hyperstimulation syndrome (OHSS) remains the most serious medical complication of controlled ovarian stimulation. An unusual case of perforated duodenal ulcer following critical OHSS is presented. A 29 year old nulligravid woman with polycystic ovarian syndrome underwent her first attempt at in-vitro fertilization. She was admitted to the hospital with critical OHSS and subsequently found to have a perforated posterior duodenal ulcer. She underwent exploratory laparotomy, antrectomy and gastrojejunostomy. Pathological analysis of her gastric antrum confirmed chronic gastritis and Helicobacter pylori. She required prolonged assisted ventilation, vasopressor support, multiple i.v. antibiotics, blood product replacement and nutritional support. The patient was hospitalized for a total of 47 days and then transferred to a rehabilitation facility for an additional 30 days before being discharged to home. In this critically ill patient with OHSS, severe stress associated with invasive monitoring and multiple medical therapies in the intensive care unit as well as H. pylori infection appear to be the most probable causative factors of her perforated viscus. Prompt recognition of potential complications and proper medical intervention are essential in the management of patients with OHSS. Avoidance strategies are still needed.

Key words: assisted reproduction/critical care/duodenal ulcer/ovarian stimulation


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Despite advances in monitoring techniques, ovarian hyperstimulation syndrome (OHSS) continues to be the most serious complication of controlled ovarian stimulation (Rouzi, 2000Go). Available data suggest an incidence of 0.2–1.0% with severe OHSS with controlled ovarian stimulation (Abramov et al., 1999Go) and 0.5–2.0% with IVF (Brinsden et al., 1996Go). Severe OHSS is a life-threatening condition characterized by massive ascites, increased blood viscosity and renal or hepatic dysfunction (Beerendonk et al., 1998Go). Critical OHSS is further defined by renal failure, thrombo-embolic phenomena and adult respiratory distress syndrome (Navot et al., 1992Go). Other rare sequelae of OHSS have also been reported and include myocardial infarction (Ludwig et al., 1999Go), cerebral infarction (Cluroe and Synek, 1995Go), internal jugular vein thrombosis (Fournet et al., 1991Go) and recurrent cholelithiasis (Midgley et al., 1999Go). We report a case of perforated posterior duodenal ulcer during admission to the intensive care unit for management of critical OHSS.


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 29 year old nulligravid woman with infertility secondary to polycystic ovarian syndrome underwent her first cycle of IVF at her doctor's office. She had no prior history of peptic ulcer disease or gastritis. She was given oral contraceptives beginning with day 5 of the menstrual cycle followed by a standard long protocol using mid-luteal down-regulation induced by leuprolide acetate (LA) 1 mg/day administered subcutaneously starting on day 21 of oral contraception for 10 days. At this point, serum oestradiol concentration was <20 pg/ml, and the daily LA dose was continued at 1 mg/day. Follicle stimulating hormone (FSH) 225 IU/day was administered subcutaneously for 5 days after which the dose was steadily decreased because of the follicle number, size and oestradiol concentrations. A total of 20.5 ampules of FSH was given. After 10 days of FSH administration, more than 10 follicles measuring at least 18 mm in mean diameter were noted on ultrasound, and the serum oestradiol concentration was 4245 pg/ml on the day prior to administration of HCG (human chorionic gonadotrophin). At 36 h after administration of HCG 5000 IU, transvaginal ultrasound guided follicular aspiration yielded 19 oocytes. No fresh embryos were transferred, and all 11 cleaved embryos were cryopreserved.

Two days later the patient complained of abdominal distension, shortness of breath and mid-to-upper abdominal pain. She presented to her physician's office for assessment for possible OHSS. Physical examination revealed stable vital signs, clear lung fields and a distended abdomen. Transvaginal ultrasound demonstrated bilateral ovarian enlargement, each approximately 10x10 cm, with a small amount of free peritoneal fluid. Laboratory evaluation showed WBC = 26 000 IU/l,haemoglobin = 15.2 g/dl, haematocrit = 45.6%, platelet = 487 000 IU/l, sodium = 131 mEq/l, protime = 12.9 s. The patient was admitted to a nearby hospital for observation and i.v. hydration.

On hospital day 2, the patient was noted to have increasing difficulty breathing with a marked increase in abdominal distension and decrease in urinary output. She underwent transvaginal ultrasound guided aspiration of 5400 ml of peritoneal fluid. She was subsequently transferred to the intensive care unit where she required ventilatory support and i.v. dopamine. Because of the deterioration in her status, arrangements were made for transfer of this patient to a tertiary care centre, and she was air evacuated to our hospital the same evening.

Upon admission to our intensive care unit and over the ensuing several days, the patient continued to show decline in her respiratory and renal status. On hospital day 8, she developed a fever with further elevation of her WBC and her physical exam showed a markedly distended abdomen. She underwent paracentesis, yielding yellow cloudy fluid, with pH = 7.00, WBC = 6000 IU/l, 95% polymorphonuclear cells, LDH = 1176 IU/l, amylase = 1889 IU/l. It was unclear whether this reflected abdominal sepsis or an inflammatory ascitic fluid related to her OHSS, thus a repeat paracentesis was performed 12 h later that showed an increase in LDH to 1791 IU/l. An emergent computed tomography scan of her abdomen and pelvis raised the possibility of extravasated contrast, thus a ruptured viscus was suspected. On hospital day 10, the patient underwent exploratory laparotomy at which time posterior perforation of the duodenum was found and her ovaries were noted to be massively enlarged extending to her umbilicus. Given the location of the perforation, a Graham patch could not be performed and she required antrectomy, gastrojejunostomy and lateral tube duodenostomy for control of her disease. The final pathology report confirmed chronic gastritis and H. pylori in the resected antrum.

Postoperatively, the patient remained critically ill for several weeks with sepsis, adult respiratory distress syndrome, pneumonia and renal insufficiency. She was placed on multiple i.v. antibiotics and received total parenteral nutrition. She was transfused a total of 4 units of packed red blood cells. On hospital day 22, she required tracheostomy tube placement. She was weaned to a tracheostomy collar of humidified air and her nutritional support was via a feeding tube. Because of her prolonged hospitalization and extreme muscle atrophy, she was a candidate for transfer to a nearby rehabilitation centre which occurred on hospital day 47.

The patient had removal of her tracheostomy tube during her 2 week stay at a rehabilitation facility. She was subsequently transferred to another rehabilitation centre for an additional 2 weeks for intensive physical and occupational therapy. She was finally discharged to her home 86 days after her IVF cycle.


    Discussion
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
To our knowledge, this is the first reported case of perforated duodenal ulcer with critical OHSS. A multicentre study reviewing the incidence and aetiologies of febrile morbidity in severe and critical OHSS in 209 patients revealed no patients with peritonitis (Abramov et al., 1998Go). This patient had no prior history of peptic ulcer disease or gastritis and was considered to be in excellent health. The severity of her OHSS required a prolonged stay in the intensive care unit necessitating ventilatory, vasopressor and nutritional support. The profound stress associated with the combination of critical OHSS and subsequent required complex care as well as the diagnosis of H. pylori on pathological examination were likely the causative factors of her perforated duodenal ulcer. Prostaglandins, cytokines and other growth factors may also have played a contributory role in this disease process (Beerendonk et al., 1998Go). The diagnosis of a ruptured viscus was not initially clear in this patient since an inflammatory ascitic fluid is often seen in patients with OHSS (Brinsden et al., 1996Go). The patient's condition further declined on hospital day 8 with an elevated temperature and markedly distended abdomen. A paracentesis was performed and repeated 12 h later, and the severe elevation in LDH, low pH and predominance of polymorphonuclear cells in the peritoneal fluid raised the suspicion of abdominal sepsis. Computed tomography of the abdomen and pelvis was helpful in the establishing the diagnosis and justifying the high risk laparotomy. The patient was ultimately successfully treated with proper surgical and medical intervention. Prophylactic administration of antacids and selective histamine receptor blockers should be considered in patients requiring prolonged hospitalization.

This case illustrates once again that OHSS can be a serious and life-threatening complication of controlled ovarian stimulation. In particular, this patient developed critical OHSS despite the avoidance of pregnancy and lack of further luteal exposure to HCG. Close vigilance on the potential of OHSS as well as on the variable appearance of its possible sequelae is imperative in providing care to otherwise young and healthy women. The natural course of OHSS is eventually to improve over time, and a marked worsening in status should prompt an aggressive search for secondary complications. Preventative strategies (Fluker et al., 2000Go) are still needed more effectively to avoid or attenuate the course of clinically significant OHSS.


    Notes
 
4 To whom correspondence should be addressed at: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. Back


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Submitted on July 3, 2000; accepted on October 9, 2000.