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The Journal of Emergency Medicine, Vol. 33, No. 1, pp. 65–70, 2007Copyright © 2007 Elsevier Inc.

Printed in the USA. All rights reserved0736-4679/07 $–see front matter

Case Presentations of the HarvardEmergency Medicine Residency

ABDOMINAL PAIN AND ASCITES

Ruth Lamm, MD,* Eric S. Nadel, MD,*†‡ and David F. M. Brown, MD*‡

*Division of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, †Department of Emergency Medicine,Brigham and Women’s Hospital, Boston, Massachusetts, and ‡Department of Emergency Medicine, Massachusetts General Hospital,

Boston, MassachusettsReprint Address: Eric S. Nadel, MD, Department of Emergency Medicine, Brigham and Women’s Hospital, 75 Francis Street,

Boston, MA 02115

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r. Ruth Lamm: Today’s case is that of a 29-year-oldoman who presented to the Emergency Department

ED) complaining of diffuse abdominal pain and disten-ion, worsening over the past 9 days. The patient deniedonstipation, diarrhea, blood in her stool, or fever. Thereas no dysuria or frequency. She denied abdominal

rauma, recent travel, sick contacts, or vaginal symp-oms. After 2 days, the pain intensified and becameonstant, and she presented to another hospital, wherehe was admitted for intravenous (i.v.) hydration andbservation. She was discharged 3 days later. The patientescribed multiple episodes of emesis and complained ofild shortness of breath. She denied chest pain, calf pain,

r leg swelling. Of note, the patient had recently under-one her first cycle of in vitro fertilization with subse-uent oocyte retrieval and embryo implantation approx-mately 2–3 weeks before presentation.

Dr. Eric Nadel: Are there any questions about thenitial history?

Dr. Stephen Thomas: At this point, the differential isuite broad. The abdominal pain could be related toregnancy, in vitro fertilization, or unrelated to either. Itould be important to know if she was pregnant and if

here was any more information regarding her past med-cal history to narrow this differential.

Dr. Lamm: The patient’s last menstrual period hadeen just over 1 month earlier. The past medical historyas significant as she was receiving fertility treatments

nd had undergone ovulation induction with leuprolide,ollicle stimulation hormone (FSH), and human chori-nic gonadotropin (hCG) a few weeks before presenta-ion. As mentioned earlier, she had had oocyte retrieval9 days before presentation and embryo implantation 15

ays before presentation. She also had a remote history a

65

f gonorrhea. The past surgical history was significantor two prior ectopic pregnancies treated laparoscopi-ally with one requiring a right salpingectomy. Medica-ions included progesterone and a pre-natal vitamin. Theatient had an 8-pack-year tobacco history, but had quitmoking 3 months before presentation. She denied alco-ol, recreational drug or supplement use. The familyistory was non-contributory.

Upon arrival to the ED, the patient’s vital signs were:emperature 37.1°C, heart rate 130 beats/min, blood pres-ure 123/87 mm Hg, respiratory rate 20 breaths/min, andxygen saturation 100% on room air. The patient ap-eared uncomfortable, but was in no acute distress. Theead was normocephalic and atraumatic. Pupils werequal, round, and responsive to light, and extraocularuscles were intact. The conjunctiva was pink and mu-

us membranes were slightly dry. The neck was supple.valuation of the heart revealed a normal S1 and S2 witho murmurs, rubs, or gallops. The lungs were clear touscultation. There were normoactive bowel sounds. Thebdomen was markedly distended and tense, with vol-ntary guarding and diffuse tenderness to palpation.here was no rebound tenderness. Shifting dullness wasresent. Examination of the back revealed no bony ab-ormalities and no costovertebral angle tenderness. Ex-remities revealed no clubbing, cyanosis, or edema. Thekin was warm and well perfused with 2� distal pulseshroughout. She was alert and oriented and the neurolog-cal examination was non-focal.

Dr. Nadel: At this point, are there any questionsegarding the initial presentation or thoughts as to thenitial management of this patient?

Dr. Thomas: Although it is important to think about

ll causes of abdominal pain and distension in the eval-

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ation of a possibly pregnant patient, if the hCG wereositive, the foremost concern should be a ruptured ec-opic pregnancy in this setting. Once an ectopic is ex-luded, other causes can be more carefully explored.

Dr. Alison Lozner: Given the nature of the com-laints and timing of her ovulation induction, retrievalnd implantation, one possible etiology would be ovarianyperstimulation syndrome (OHSS), a known complica-ion of these processes caused by the desired ovariannlargement and hyperfunctionality. Of course, given thebstetrical history, complications such as ectopic or het-rotopic pregnancy are also possible. Alternatively, sheould have had a ruptured ovarian cyst, or less likely,iven the temporal nature of her pain, torsion of thevary. A gastrointestinal etiology such as liver disease,ancreatitis, or peptic ulcer disease must also be consid-red. In addition to a urine and serum quantitative hCG,aboratory data should be obtained, including electro-ytes, creatinine, and liver function tests (LFTs).

Dr. Lamm: As discussed, the hCG level was ofaramount importance. In addition, CBC, chemistries,nd LFTs were ordered. A chest radiograph (CXR) wasrdered to assess her shortness of breath. A pelvic ultra-ound was considered, pending the results of the hCG.

Laboratory data revealed: white blood cell count 13.8/mm3, hemoglobin 13.9 gm/dL, hematocrit 40.0% (base-

ine 36–38%), and platelets 644 K/mm3. Chemistries re-ealed sodium 135 mmol/L, potassium 4.4 mmol/L, chlo-ide 99 mmol/L, carbon dioxide 22 mmol/L, and a BUNnd creatinine 17 mg/dL and 2.1 mg/dL, respectively. Theaseline creatinine had been 1.0 mg/dL. Amylase, lipase,nd coagulation studies were normal. The serum hCGas 980 IU/L. The CXR was normal and did not show

ny worrisome effusions or edema (Figure 1). A pelvicltrasound was obtained and revealed bilateral enlargedvaries (8 cm � 7 cm on right, 7 cm � 7 cm on left) bothith many complex cysts, a large amount of free fluid inoth adnexa, as well as free fluid in both upper quadrantsFigure 2). There was no comment on whether there wasn intrauterine pregnancy at that point. Whereas all otherata pointed to the diagnosis of OHSS, the ultrasoundonfirmed it.

Dr. Nadel: Could you describe ovarian hyperstimu-ation syndrome?

Dr. Lamm: Ovarian hyperstimulation syndrome issually an iatrogenic complication of ovulation inductionherapy (1). It is characterized by potentially massivevarian enlargement, multiple ovarian cysts, and fluidhifts resulting in extravascular fluid accumulation,ntravascular volume depletion, and the sequelae ofhock (2). This patient is at particular risk to developHSS due to her treatment regimen containing FSH.lthough OHSS can be seen with induction with clomi-

hene citrate or GnRH (gonadotropin-releasing hor- i

one), it is more common when FSH or LH (lutenizingormone) is used.

In addition, other risk factors include: age less than 35ears, secondary to the higher number of follicles stillresent in the ovary; low body weight; high serum es-radiol levels before induction; the presence of a greaterumber of natural follicles on ultrasound before induc-ion; a history consistent with polycystic ovarian syn-rome, also secondary to the increased number of naturalollicles; history of allergies; completed pregnancy; andistory of OHSS with prior pregnancy (3).

Dr. Thomas Burke: Can you explain why these sameormones do not cause OHSS with natural ovulation?

Dr. Lamm: In spontaneous ovulation, follicle re-ruitment is limited by normal feedback mechanisms.he hypothalamus secretes GnRH in a pulsatile fash-

on. This stimulates the anterior pituitary to secreteSH and LH. FSH at physiologic doses causes recruit-ent of a dominant follicle. As the follicle matures, it

roduces more and more estrogen, which has bothirect and indirect feedback inhibition on FSH, andevels decline. However, ovulation induction uses muchigher doses of gonadotropins to bypass this feedbackystem (4). Ovulation induction is used for women whore having trouble achieving fertilization, implantation,nd pregnancy. The goal is to create a large number ofollicles to increase the chance of pregnancy. Ovariannlargement, follicle and cyst formation is, in part, theoal of treatment (5). There is also a spontaneous form ofHSS that can occur without a history of ovulation

igure 1. Initial AP chest X-ray showing no significantbnormalities.

nduction. In these cases, mutations in the FSH receptor

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Ascites 67

ause it to be “promiscuous,” and activated by stimula-ion from hCG as well. This also leads to excessive

igure 2. (A, B) Sagittal ultrasound views of the left and rightvaries, respectively, showing multiple large ovarian folliclesnd significant free fluid. (C) Ultrasound view of the rightpper quadrant showing extent of abdominal free fluid.

ollicular development (2). o

With sustained development of this large cohort ofollicles, they produce excessive amounts of normalytokines and second messengers including vascularndothelial growth factor, renin, histamine, and pros-aglandins. These cytokines cause an exaggeratederifollicular neovascularization and increased perme-bility of these new vessels. As a result, there isscape of perifollicular fluid, containing high concen-rations of these messengers, into the peritoneal cavitynd subsequently into the general vascular bed. Func-ional impairment of all blood vessels occurs, leadingo massive fluid shift from the intravascular compart-ent to the third space (4). This results in hypovolemic

hock physiology. The results are what would be ex-ected from any other cause: hypovolemia, edema, as-ites, hydrothorax, hydropericardium, renal failure, acuteespiratory distress syndrome (ARDS), myocardialtress, hemoconcentration, thrombosis, impaired immu-ity, and multisystem organ failure.

The clinical presentation depends on the severity ofisease and timing of presentation. OHSS is divided intohree clinical stages and five grades, although the mani-estations and complications of the disease are a contin-um. All of the symptoms and manifestations result fromuid shifts and resulting circulatory dysfunction (1).ymptoms usually start a few days after oocyte retrievalnd should regress in 10–14 days, or slightly longer ifregnancy is achieved (6). However, when complica-ions occur, the disease course is much longer and re-ression may not occur. Symptoms of mild disease in-lude transient lower abdominal discomfort, distinctlyot described as pain, as well as bloating, mild nausea, orbdominal distension. On ultrasound, ovaries will mea-ure up to 5 cm � 5 cm for mild disease (1). Manyatients will experience mild symptoms. Moderate dis-ase occurs in approximately 3.4% of patients undergo-ng treatment cycles and is usually diagnosed when theiscomfort progresses to pain. A sudden weight gain ofreater than 3 kg is also indicative of progression tooderate disease (6). Patients experience nausea and

omiting. There is only minimal hemodynamic instabil-ty limited to orthostatic hypotension, mild tachypnea, andlightly decreased urine output. Ovaries may enlarge up to2 � 12 cm on ultrasound. Severe OHSS is even lessommon, with an incidence of 0.8–1% of patients receivingreatment. Tense ascites is usually present (7). Laboratoryvaluation will reveal leukocytosis, hemoconcentration �5%, thrombocytosis, renal failure, hyponatremia, and hy-erkalemia. The patient may have thromboembolic compli-ations or pulmonary manifestations including lobar pneu-onia secondary to immunocompromised state due to loss

f circulating immunoglobulins, pulmonary embolism,ydrothorax, atelectasis due to abdominal compression,

r ARDS. Some practitioners classify a grade 6, or

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life threatening” OHSS as leukocytosis � 25,000,ematocrit � 55%, creatinine � 1.6 mg/dL, and reduc-ion of creatinine clearance to � 60 mL/min, oliguria,ense ascites with or without hydrothorax, thromboem-olic phenomenon, or ARDS (1).

Dr. David Brown: Summarizing this patient, she hadnduction with FSH, and had a pre-pregnancy low bodyeight. She had subjective dyspnea, without any evi-ence of respiratory compromise, and had tense ascites.aboratory evaluation showed leukocytosis, relativeemoconcentration, thrombocytosis, and acute renal in-ufficiency. In addition, by the hCG, she had achievedregnancy. Her ultrasound showed enlarged ovaries witharge amounts of free fluid. This would put her in theategory of moderate disease, although she had somelements of severe disease. How does this classificationhange management?

Dr. Lamm: Management is based on the severity ofhe disease. Key to the management of mild disease isducation on possible symptoms or signs of diseaserogression. Oral analgesics or anti-emetics can be usedf necessary. Fluid intake should be limited to � 1 literer day, with sports drinks preferred to limit free waterntake (7). Patients should avoid strenuous physical ac-ivity or intercourse to reduce the risk of ovarian torsion,ut should maintain light activity to decrease the risk ofhrombosis. The patient should receive close follow-upncluding daily weights to assess for worsening ascites oraboratory evidence of worsening disease. For patientsho have not had embryos implanted, cryopreservationf embryos can be considered if there are concerns aboutisease progression (6).

Once the disease progresses, management of the com-lications is paramount. Indications for admission in-lude severe abdominal pain or peritoneal signs, intrac-able nausea or vomiting (especially if the onset is within8 h of hCG administration, as this is prognostic oforse outcome), tense ascites, severe oliguria or anuria,ypotension, lightheadedness or syncope, electrolyte ab-ormalities, hemoconcentration, or abnormal LFTs (5).npatient monitoring should include regular vital signsith continuous O2 saturation monitoring, strict input/utput calculations necessitating urinary catheter inser-ion, daily weights, daily abdominal circumference, dailyaboratory evaluation including complete blood countnd chemistries, CXR if pleural or pericardial effusion isuspected or if the patient has respiratory distress, andegular ultrasounds to assess for increasing ascites or touide paracentesis. Baseline coagulation studies shoulde done in case anti-coagulation is needed. Regular phys-cal examination is important, although bimanual exam-nation should not be done due to risk of cyst rupture.

The main goal of treatment is fluid management. Main-

aining appropriate volume status will treat or prevent all of t

he other possible complications including hemoconcentra-ion, thrombosis, electrolyte abnormalities, and organ dys-unction. Volume status is carefully managed via controlleduid intake and removal. Secondary goals of treatment

nclude management of complications if they occur, such asnticoagulation, control of respiratory status, antibiotics, orurgery. Finally, there are some theoretical interventionsased on proposed pathophysiologic mechanisms that maye helpful in the future.

Dr. Daniel Egan: This seems like a very difficultssue. On one hand, one must maintain intravascularolume status, but on the other, increasing ascites mayorsen renal function. How is this balanced? What is theest way to volume resuscitate these patients?

Dr. Lamm: Correction of volume status should alwaysave priority over accumulation of ascites, as ascites canlways be removed if needed. Central venous access shoulde established in any patient who is hemodynamically un-table, if central venous pressure (CVP) monitoring is nec-ssary, or to allow for faster i.v. hydration. The goal shoulde a urine output of at least 20–30 cc/h. Some authorsecommend administering crystalloid boluses until thisrine output is achieved, and continue i.v. fluid at mainte-ance rate after that point (5). During this time the hemat-crit should be checked every 4 h to ensure the hemocon-entration is reversing. Therapy should continue until theatient develops spontaneous urine output or auto-diuresis.his will often correspond to clinical return of appetite andymptom resolution. At this point, keep PO fluids � 1 L peray to prevent hemodilution and intravascular overload ashe patient will have a strong return of fluid to the intravas-ular space (6).

Choice of volume expander is less clear-cut. If usingrystalloid, consider the tendency toward hyponatremian OHSS when picking fluid (8). The evidence forlasma expanders in OHSS is less clear. A recent Co-hrane review of five randomized, controlled, clinicalrials showed a definite benefit of albumin infusion givent the time of oocyte retrieval to prevent the occurrencef severe OHSS (9). However, there is no such evidenceither for or against the use of albumin during acuteisease. The indications for colloid therapy include fail-re of crystalloid therapy, hemoconcentration (hemat-crit � 45%), severe hypoalbuminemia � 3.0 g/dL,nd tense ascites (1). Albumin should be given inoses of 50 –100 mg of 25% albumin, repeated in 4- to2-h intervals as necessary (7). It should be infusedlowly as rapid reversal of hemoconcentration mayead to build up fluid in new third spaces, causingroblems such as pulmonary edema before renal fil-ration is able to improve (6).

Dr. Pina Patel: The oncotic action of albumin lasts less

han 36 h, as eventually even albumin may translocate into

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Ascites 69

he extravascular space. Does this limit its use in OHSS?re there any benefits of other plasma expanders?Dr. Lamm: This is certainly an issue of contention.

upporters point out that the increased permeability inHSS can be short-lived. Therefore, albumin may beeeded only temporarily, and if it leads to increasedxtravascular oncotic pressure after the acute phase, theatient will be able to compensate at this point (5). Theres still not enough evidence on the use of albumin in thecute phase, but it may be worth using in patients meet-ng the criteria mentioned before.

Regarding alternative plasma expanders, there was amall study of 6% hydroxyethyl starch that showed thatatients treated with this had increased urine output, feweraracenteses, and shorter hospital stays than patients whoad received albumin (10). There is also a small study onextran vs. albumin. Dextran was found to have a betterffect than albumin, but the only statistically significantariable was the duration it took to lower hematocrit to �0% (11). In addition, dextran is thought to have a higherssociation with ARDS. Finally, there have been smallnquiries into mannitol or fresh frozen plasma, but neitheras been shown to be superior to albumin (6). The netesult, again, is that there may be a place for these agents inhe treatment of OHSS, but we do not yet have sufficientvidence.

Although the primary goal is to attempt normal intra-ascular volume status, the role of ascites in the devel-pment of the complications of this disease is important.irst, the increased abdominal pressure is transmitted to

he renal artery, causing poor renal perfusion. Secondly,ltration is decreased, resulting in worsening renal fail-re. Finally, pressure on abdominal venous structuresmpedes outflow, which compromises venous return tohe heart, leading to decreased cardiac output and hypo-ension. Hypotension can also contribute to the compli-ations of the disease. As a result, paracentesis can bentegral in management. The indications for paracentesisnclude severe pain, pulmonary compromise manifestedy persistent tachycardia, low oxygen saturation, or hy-rothorax, and renal compromise not responding to fluid6). The size of the ovaries may make a transabdominalpproach difficult. Ultrasound guidance should be usedor either transabdominal or transvaginal approaches.

ost authors caution against the removal of too muchuid as compensatory fluid shifts will occur. Serial para-entesis or insertion of a pigtail catheter may be helpful.here may also be a role for peritovenous shunting,lthough more data are needed (1).

Dr. Nadel: Can you discuss recognition and manage-ent of the complications of OHSS?Dr. Lamm: Recognition and management of specific

omplications is secondary to fluid management, but still

mportant. Thrombotic complications occur more fre- p

uently secondary to hemoconcentration and hyperco-gulability in the setting of high estrogen levels. Inddition, some of the cytokines implicated in OHSS haveeen found to increase pro-coagulopathic factors, such asWF, platelets, fibrinogen, and factor V. The mean timeo thrombotic complication is 25.5 days after oocyteetrieval. Although more common with more severe dis-ase, 8.2% of all patients with OHSS who also havehrombotic disease will have mild OHSS (12). Interest-ngly, thromboses are often seen in locations that areot usually common, such as the upper torso, neck,nd intracranial vessels. All patients should wear anti-mbolism compression stockings compression stock-ngs, which will also help with their circulatory status,nd receive prophylactic dose anticoagulation. Pa-ients should be encouraged to ambulate unless pain orther complications limit activity to bed rest. At thisoint, pneumoboots should be used. Most importantly,here should be suspicion for thromboembolic diseasen these patients.

Pulmonary complications are also common. Almost allatients complain of subjective trouble breathing. This isikely due to abnormal lung mechanics secondary to ab-ominal pressures and girth, but can also result from hy-rothorax, as well as pneumonia, ARDS, or pulmonarymbolism (13). Thoracentesis can be helpful, but paracen-esis may stop the flow of fluid into the chest. As a result, ithould be reserved for patients who do not improve witharacentesis or for those who have severe, bilateral pleuralffusions. ARDSnet ventilation should be used if needed1). For most other complications, including infection, car-iac stress, and shock, management should proceed astandard for any other critically ill patient.

Dr. Tracy Farkas: Other than supportive treatment,uid management, and treatment of complications, are

here specific therapies aimed at disease mechanism?Dr. Lamm: Suggested therapies aimed at disease

athogenesis include prostaglandin inhibitors, steroids, andngiotensin-converting enzyme inhibitors/angiotensin re-eptor inhibitors. Given the release of prostaglandins fromollicles, it makes sense that inhibition of prostaglandinsould slow or stop disease progression. A study with in-omethacin on rabbits in 1976 seemed to support thisheory (14). However, since then, evidence is limited.he finding that the follicles secrete prorenin and reninuggests the importance of the ovarian-renin-angiotensinystem. Angiotensin-converting enzyme inhibitors haveeen used in rabbit models, but due to the teratogenecityf these medications, they have not been studied inumans. There has been shown to be no role for steroids15). Surgical treatments should be used only in the casef ovarian torsion, cyst rupture, or cyst hemorrhage.inally, if no treatments are effective, termination of

regnancy should cause cessation of disease.

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Dr. Burke: What is the outcome of pregnancy inhese patients, and what was the course in this patient?

Dr. Lamm: There has only been one study looking athis issue. This study showed that OHSS patients hadimilar outcomes compared with matched controls with-ut OHSS. However, this study was performed by as-essing several factors at birth, such as weight, APGARcore, etc. (16). As a result, the patients who did notomplete their pregnancies would not have been in-luded, which may have drastically changed the results.

Our patient was admitted to the hospital for fluidesuscitation and paracentesis. On hospital day 4, thereatinine had improved to 1.8 mg/dL and the patientas discharged. Over the course of the next 2 weeks,

he had two more paracenteses performed as an out-atient. Approximately 9 weeks after initial presenta-ion she was found to have a shortened cervix and aerclage was placed. Unfortunately, 2 weeks after thatoint she had spontaneous rupture of membranes andecame febrile. Dilatation and evacuation was performedor severely pre-term/premature rupture of membranes inhe setting of possible chorioamnionitis.

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