Ovarian hyperstimulation syndrome complicated by peritonitis due to perforated appendicitis: Case Report

Akihisa Fujimoto, Yutaka Osuga,, Tetsu Yano, Maki Kusumi, Takako Kurosawa, Tomoyuki Fujii and Yuji Taketani

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan


    Abstract
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 Abstract
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 Case report
 Discussion
 References
 
We describe a case of ovarian hyperstimulation syndrome (OHSS) complicated by peritonitis due to perforated appendicitis. A 29-year-old woman presented with abdominal distension after ovarian stimulation with HMG followed by ovulation induction with HCG. Massive ascites with swollen ovaries was observed on ultrasound, and she was admitted on the diagnosis of OHSS. Daily infusion of serum albumin and low dose dopamine failed to increase her urine output and her abdominal symptoms became increasingly deteriorated after her urine pregnancy test turned out to be positive. Paracentesis performed for alleviation of her abdominal distension revealed infected, foul-smelling fluid. An emergency laparotomy was performed, and the definite diagnosis was made as panperitonitis due to perforated appendicitis with right tubal pregnancy. Appendectomy, right tubectomy and vigorous irrigation with drainage were performed. The case implies that OHSS might not only mask typical manifestations of appendicitis, but could also compromise concurrent intraperitoneal infection.

Key words: appendicitis/ectopic pregnancy/ovarian hyperstimulation syndrome/peritonitis


    Introduction
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Ovarian hyperstimulation syndrome (OHSS) is a relatively common complication associated with ovarian stimulation. The life-threatening sequelae of the syndrome include thrombosis, renal and respiratory failure, all of which are essentially caused by massive extravasation of protein rich fluid and secondary intravascular volume depletion. Here, we present a case of OHSS complicated by panperitonitis due to perforated appendicitis. Underlying conditions with OHSS might mask typical manifestations of appendicitis, thus increasing the time taken to reach a definite diagnosis.


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 Case report
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A 29-year-old nulligravid woman had been under infertility treatment for a few years in a local hospital. Standard primary screening tests for infertility revealed that her serum chlamydia antibody test was positive, and right proximal tubal stenosis was suspected by hysterosalpingography. Otherwise no apparent abnormalities were found. Because of clomiphene citrate being unsuccessful, she underwent ovarian stimulation with a total dose of 1050 IU HMG for 9 days. Subsequently, HCG of 5000 IU was injected on the day when eight growing follicles >15 mm in diameter were detected on transvaginal ultrasound. On the following day, she attempted natural intercourse. Eleven days after HCG injection, she was admitted to the hospital with the complaints of abdominal distension and epigastralgia. She gained 5 kg in weight after HCG injection. Massive ascites associated with bilateral swollen ovaries (both 8 cm in diameter) was observed on ultrasound. No remarkable pain or tenderness was detected in the lower abdomen by pelvic and abdominal examinations. Laboratory data showed elevated leukocyte count (15 600/mm3) with slight haemoconcentration [haematocrit = 38.6]. These findings were compatible with severe OHSS (Grade 5) according to the classification of Golan et al. (Golan et al., 1989Go). In the evening of the day of admission, her temperature rose to 39°C. Two days later, her urine pregnancy test turned out to be positive. Paracentesis was performed to alleviate abdominal distension, 1 l of serous clear ascites being drained. Her oliguria was unresponsive to daily infusion of serum albumin and low dose dopamine, such that daily urine output finally decreased to 280 ml on day 16 of HCG injection. Under the diagnosis of severe OHSS, she underwent emergency transfer to our hospital.

On admission, she had severe abdominal distension, which made it difficult to localize pain or tenderness. Her temperature was 38.8°C associated with tachycardia (138/min) and decreased O2 saturation (96.5%). Her blood pressure was kept normal. A chest X-ray demonstrated mild right hydrothorax. Although total leukocyte count (7700/mm3) was in the normal range, differential count revealed a marked left shift (48% band neutrophils and 4% segmented neutrophils). Blood chemistry showed hypoproteinaemia (4.7 g/dl), hypoalbuminaemia (2.4 g/dl) and elevated C-reactive proteins (18.6 mg/dl).

Paracentesis for alleviation of abdominal distension revealed turbid, foul-smelling fluid, in which numerous bacteriae were detected under microscope. Emergency laparotomy was performed with the diagnosis of infectious panperitonitis of unknown origin. At laparotomy, a total of 4500 ml foul-smelling ascites and massive pus all over the abdomen were found. The abdominal cavity was thoroughly examined and perforation of a swollen appendix at the proximal portion was found. In addition, we found an enlarged isthmus of the right tube, in which villous tissues were detected. With the diagnosis of perforated appendicitis and right tubal pregnancy, appendectomy and right tubectomy were performed. After vigorous irrigation, five drains were placed in the abdominal cavity. The diagnosis of both appendicitis and tubal pregnancy was histologically confirmed. Bacteriae in the ascites were identified to be Group F streptococci, E.coli and bacteroides.

After operation, the patient's urine HCG titre decreased promptly. Although she had intra-abdominal abscesses in the Morisson pouch and cul-de-sac post-operatively, they were conservatively treated with antibiotics. Having had a complete recovery, she was discharged on post-operative day 37.


    Discussion
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Peritonitis associated with perforated appendicitis complicated by OHSS, as presented here is, to the best of our knowledge, the first case in the literature. Although it is open to question at this time whether these two pathologies are causally related or not, either condition seems to influence the clinical course of the other. Whatever the case, the presence of OHSS makes it difficult for us to establish the diagnosis of co-existing pathologies such as intraperitoneal inflammatory diseases.

Generally, the pain associated with appendicitis initiates in the lower epigastrium or umbilical area. Epigastralgia in the present case might be related to appendicitis. However, epigastralgia is not an uncommon symptom in patients with severe OHSS with massive ascites. Furthermore, a right lower quadrant pain, a typical symptom of appendicitis, was not manifested in this case. Febrile morbidity is often observed in patients with severe OHSS without infection (Abramov et al., 1998Go). An elevated white blood cell count is also found both in patients with severe OHSS (Fabregues et al., 1998Go) and in those with appendicitis.

The possibility is raised that OHSS might affect the course of concurrent appendicitis. An increased rate of infectious disease was reported in patients with OHSS, possibly due to immunodeficiency as a consequence of hypoglobulinaemia, a frequent occurrence in patients with severe OHSS (Abramov et al., 1998Go). Severe stress associated with symptoms of OHSS, a hospital stay, multiple monitoring and therapies might also impair immunoprotective status (Agarwal and Marshall, 2001;GoCohen et al., 2001Go). In a recent report of perforated duodenal ulcer with OHSS, severe stress was suggested to be a causative factor (Uhler et al., 2001Go). Following this logic, it may be that appendicitis with OHSS could be more aggressive and likely to rupture than without OHSS. Once bacteria are seeded into the peritoneal cavity associated with OHSS, they may grow rapidly to form abdominal abscesses, because ascitic fluid of OHSS serves as excellent culture medium for bacteria with its rich source of nutrients including albumin (Laroche and Harding, 1998Go). It seems that OHSS, if complicated by intraperitoneal inflammatory disease, may worsen its potentially life-threatening conditions.

As a very rare complication of IVF–embryo transfer, a case of acute appendicitis was reported (Roest et al., 1996Go). In this case, an appendix punctuated with the needle for oocyte retrieval was the suspected cause of appendicitis. Transvaginal procedures are also suggested to be potential inducers of pelvic inflammatory diseases. In this regard, our case is unique because transvaginal procedures were not performed.

In the present case, a right tubal pregnancy co-existed. Although a few cases of tubal pregnancy complicated by appendicitis have been reported (Pelosi et al., 1979Go; Barnett et al., 1999Go), causal relationship between these two conditions remains unknown. The present case was noted with positive serum antibodies for Chlamydia trachomatis and stenosis of the right tube on HSG, these being possible risk factors for tubal pregnancies. As the right tube is anatomically close to the appendix, it is tempting to speculate that local inflammatory reactions associated with appendicitis might affect tubal functions, resulting in the development of tubal pregnancy.

The lesson from this case is that severe OHSS, apart from itself being life-threatening, could further compromise the conditions when intraperitoneal pathologies concurrently take place. Careful observations of its clinical courses and prompt optimum procedures including a surgical approach, when appropriate, are mandated.


    Notes
 
1 To whom correspondence should be addressed. E-mail: yutakaos-tky{at}umin.ac.jp Back


    References
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 Abstract
 Introduction
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 Discussion
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Uhler, M.L., Budinger, G.R., Gabram, S.G. and Zinaman, M.J. (2001) Perforated duodenal ulcer associated with ovarian hyperstimulation syndrome: case report. Hum. Reprod, 16, 174–176.[Abstract/Free Full Text]

Submitted on September 17, 2001; accepted on December 11, 2001.