A 35-year-old female (G0P0) presented to the emergency department with two days of worsening, severe abdominal pain. Three days prior, she underwent transvaginal oocyte retrieval (TVOR) for cryopreservation. She received half of the normal hCG dose two days prior to the TVOR.

Figure 1: Coronal CT scan of the abdomen and pelvis demonstrating bilateral cystic ovaries up to 16 cm and ascites. (Click to enlarge.)

She reported nausea, vomiting, decreased bowel movements, and scant vaginal bleeding, but no fevers. Initially, she was tachycardic, with otherwise unremarkable vital signs. She appeared pale and diaphoretic. Abdominal examination was notable for distension with diffuse tenderness to percussion and palpation. Labs were notable for mild leukocytosis but no anemia. A point-of-care ultrasound (POCUS) revealed dilated bowel loops with free fluid in the right upper quadrant, left upper quadrant, and suprapubic region. A computed tomography (CT) scan of the abdomen and pelvis with IV contrast was obtained after the case was discussed with OBGYN and surgery in order to investigate for causes of peritonitis. (Figure 1)

The second patient was also a G0P0 35-year-old female who had undergone TVOR for cryopreservation that morning and presented to the emergency department with severe abdominal pain, nausea, and vomiting. Her last leuprolide dose was 3 days prior, and no hCG trigger shot had been administered due to her elevated estradiol levels putting her at higher risk of ovarian hyperstimulation syndrome. She was hypotensive but otherwise had unremarkable vital signs. She appeared pale and diaphoretic. Abdominal examination was notable for a soft, but distended abdomen, and suprapubic tenderness to palpation without pain with percussion and no rebound tenderness. Labs were notable for leukocytosis with mild anemia. POCUS revealed free fluid in all three views of the abdomen with enlarged ovarian follicles (Figure 2.) A CT scan of the abdomen/pelvis with IV contrast was obtained after discussion with OBGYN to rule out other etiology of peritonitis including bowel perforation or active bleed due to the recent egg retrieval.

Figure 2: Transabdominal ultrasound of the first patient demonstrating enlarged ovarian follicles. (Click to enlarge.)

Both patients received fentanyl, acetaminophen, ondansetron, and a crystalloid fluid bolus in the emergency department with normalization of vital signs and improvement in symptoms. 

Diagnosis and Management

CT scans and ultrasounds of both patients revealed ascites and bilateral enlarged ovaries containing numerous follicles (Figure 1 and 2).  The first patient also had small bilateral pleural effusions.  

The first patient was admitted to the hospital for management of severe ovarian hyperstimulation syndrome (OHSS). She required management with albumin for intravascular volume repletion and anticoagulation with heparin. Later in the hospitalization, she required a therapeutic paracentesis with 2.5 L of fluid drained and was discharged 5 days after admission to close follow-up with OBGYN.

The second patient was admitted to the hospital with moderate OHSS. Ultimately, she only required supportive care and heparin for anticoagulation. She was discharged 2 days later.

OHSS is attributed to overstimulation of the ovaries from an assisted reproductive therapy (ART) cycle.  Risk factors for OHSS include age younger than 30 years old, large number of follicles or eggs retrieved, history of polycystic ovary syndrome or OHSS, low BMI, and embryo transfer that results in pregnancy right after IVF.¹ The incidence of severe OHSS is between 0.1% to 2.0%, however mild cases may be as common as 20% to 33%.^1,2

In an ART cycle, and during the ovarian stimulation stage, gonadotropins are administered to stimulate multiple follicles to develop simultaneously.  Final oocyte maturation is sometimes assisted with the administration of human gonadotropin hormone (hCG) 1-3 days before retrieval. 

OHSS is caused by increased capillary permeability, mainly from vascular endothelial growth factor (VEGF) secreted from granulosa cells causing a shift of fluid from intravascular spaces to extravascular spaces. hCG (given in IVF) triggers this increased secretion of VEGF. hCG can also activate the renin-angiotensin-aldosterone pathway in the ovaries to exacerbate the fluid accumulation.³ This leads to intravascular hypovolemia with extravascular fluid accumulations such as ascites and pleural effusions. Peritonitis may result from the release of inflammatory compounds or irritation from hemoperitoneum caused by cyst rupture.

Table 1: Classification of OHSS severity. (Click to enlarge.)

Mild OHSS generally causes mild abdominal pain and distension, while severe OHSS is caused by large ovarian cysts leading to hyponatremia, hypoproteinemia, hyperkalemia, hydrothorax, renal injury, and hypovolemic shock.⁴ (Table 1)

Diagnosis includes clinical features such as abdominal pain, bloating, and decreased urine output after ovarian stimulation followed by hCG administration. Examination will often show shifting dullness on abdominal examination due to ascites, with intraperitoneal fluid and significantly enlarged ovaries visualized on transvaginal ultrasound.⁵ 

OHSS is generally treated with symptomatic management. Treatment with albumin and fluids can increase intravascular oncotic pressure to increase intravascular fluid volume.⁴ Paracentesis and thoracentesis may be performed for relief of severe pain and shortness of breath, as well as if a patient becomes hemodynamically unstable or oliguric.⁶ Patients do require anticoagulation with low molecular weight heparin. Although there is currently no single cause of hyper-coagulability in OHSS, studies have shown there is an increased risk of thrombosis likely from hemoconcentration and alterations in the hemostatic pathways.⁷

OHSS may start early, within days after hCG injection, or late (> 10 days post hCG) from placental hCG secretion. Mild to moderate OHSS has a favorable prognosis and severe OHSS carries a favorable prognosis with early identification and management.⁴ The median recovery from OHSS is 11 days, but may take several weeks depending on the severity, with hypoalbuminemia and PCOS often leading to a longer recovery time.⁸

Dr. Romero is faculty and an emergency physician at MedStar Washington Hospital Center in Washington, D.C.

Dr. Koo is faculty and an emergency physician at MedStar Washington Hospital Center in Washington, D.C., and St. Mary’s Hospital in Leonardtown, Maryland.

Dr. Borhart is faculty and an emergency physician at MedStar Washington Hospital Center in Washington, D.C.

References

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9. Golan A, Weissman A. Symposium: Update on prediction and management of OHSS. A modern classification of OHSS. Reprod Biomed Online. 2009;19(1):28-32. doi:10.1016/s1472-6483(10)60042-9