• Definition
    • Ovarian Hyperstimulation Syndrome (OHSS) occurs with hyperstimulation of the ovaries secondary to fertility therapy during assisted reproductive technology cycles (ART) or an inherited mutation in the FSH receptor — ultimately leading to complications due to capillary leakage and the third spacing of fluid
  • Epidemiology
    • 263,577 cycles of assisted reproductive therapy completed in 2016, with number of cycles increasing year over year (Timmons, PMID 31097257)
    • Incidence (% of all stimulation cycles)
      • Overall: up to 30% (ibid.)
      • Moderate OHSS (see below for criteria): 0-6.0% (Delvigne, PMID 12498425)
      • Severe OHSS (see below for criteria): 2-1.0% (Binder, PMID 17987884)
    • Morbidity and Mortality
      • Although OHSS can be associated with significant morbidity and mortality from thromboembolic events, acute respiratory distress syndrome, decreased end organ perfusion, and abdominal compartment syndrome, there is limited data available regarding their estimated incidences
    • Risk Factors
      • Prior OHSS
      • PCOS (OR 6.8, 95% CI 4.9-9.6) (Tummon, PMID 15954867)
      • Increased number of oocytes retrieved in an IVF cycle (Asch, PMID 1770133)
    • Pathophysiology (Timmons, PMID 31097257)
      • Ovulatory triggers — like hCG, clomiphene (selective estrogen receptor modulator), and GnRH agonists — either directly or indirectly stimulate the release of vasoactive factors including VEGF and pro-inflammatory cytokines from the ovary, ultimately leading to increased capillary permeability and leakage of fluid
      • Subsequent symptoms are a result of the systemic leakage of fluid into extravascular spaces

Presentation and Diagnosis

  •  History
    • Early OHSS:
      • Occurs 4-7 days after most recent ovulatory dose of exogenous hCG (or other FSH receptor agonist)
      • Presentation is usually mild to moderate in severity
    • Late OHSS:
      • Occurs at least 9 days after most recent ovulatory dose of exogenous hCG (or other FSH receptor agonist) with conception
      • Presentation is usually more severe due to rising levels of hCG in pregnancy
    • Symptoms, Exam, and Labs
      • Mild:
        • Abdominal pain and distention
        • Occasionally nausea, vomiting, and diarrhea
        • No laboratory abnormalities
      • Moderate: (includes all of the above and one of the following)
        • Ultrasonographic evidence of intra-abdominal free fluid
        • More severe gastrointestinal symptoms
        • Sudden increase in weight (>3kg)
        • Laboratory abnormalities
          • Hct > 41%
          • WBC > 15,000
          • Hypoproteinemia
        • Severe: (includes all of the above and one of the following)
          • Evidence of ascites on physical exam
          • Severe abdominal pain
          • Intractable nausea and vomiting
          • Hypovolemia
          • Pleural effusion
          • Weight gain of 15-20kg
          • Reduced renal perfusion (oliguria and anuria)
          • Reduced liver perfusion (depleted anti-clotting factors)
          • Laboratory abnormalities
            • Hct > 55%
            • WBC > 25,000
            • Hyponatremia and hyperkalemia
          • Critical: (includes all of the above and one of the following)
            • Severe multi-organ hypoperfusion
            • Anuria with acute renal failure
            • Cardiac arrhythmia
            • Respiratory insufficiency with possible hydrothorax
            • Pericardial effusion
            • DIC
          • Other Considerations: (Common Concurrent Diagnoses)
            • Torsion
              • Secondary to increased ovarian volume during fertility therapy
            • Thromboembolic Events
              • Secondary to hemoconcentration, increased circulation of clotting factors, and elevated serum estrogen
              • Can occur in arterial (25%) or venous (75%) systems (Stewart, PMID 9402276)

Management and Disposition

  • Early obstetrics and gynecology team consultation and collaborative decision making
  • ED treatment is based on severity of presentation and managing individual complications of OHSS
    • Mild and Moderate:
      • Symptomatic treatment
      • Counsel on monitoring fluid intake with a suggested maximum of 2L of water daily and avoiding nephrotoxic agents (e.g. NSAIDs)
      • Consider prompt initiation of anticoagulation in conjunction with obstetrics team
      • Outpatient follow up in 2-3 days
    • Severe and Critical:
      • Maintain hemodynamic stability with focus on mobilizing fluid from the third space back intravascularly
        • Can consider albumin in conjunction with isotonic crystalloid for fluid resuscitation
        • Consider vasopressor therapy if indicated
      • Correction of underlying electrolyte abnormalities
      • Pulmonary support
      • Consider paracentesis with oliguria, dyspnea, and abdominal distention
      • Prompt recognition and management of thromboembolic events and torsion
      • Manage abdominal compartment syndrome if present
      • Inpatient admission to appropriate unit

Take Home Points

  • Suspect OHSS in any woman undergoing ART; some female patients may not be forthcoming and volunteer information that they are taking ovulatory triggers such as Clomiphene. Be sure to ask if relevant
  • Involve obstetrics and gynecology early
  • Diagnosis involves history of fertility therapy, ultrasonography, CBC, BMP, LFTs, bHCG, and appropriate additional imaging depending on symptoms
  • Treatment is focused on treating the individual complications of increased intraabdominal pressure and third spacing of fluid


Timmons D, Montrief T, Koyfman A, Long B. Ovarian hyperstimulation syndrome: A review for emergency clinicians. The American journal of emergency medicine. 2019. PMID: 31097257

Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Human reproduction update. 2002;8(6):559-577. PMID: 12498425

Binder H, Dittrich R, Einhaus F, et al. Update on ovarian hyperstimulation syndrome: Part 1–Incidence and pathogenesis. International journal of fertility and women’s medicine. 2007;52(1):11-26. PMID: 17987884

Tummon I, Gavrilova‐Jordan L, Allemand MC, Session D. Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review. Acta obstetricia et gynecologica Scandinavica. 2005;84(7):611-616. PMID: 15954867

Asch RH, Li H-P, Balmaceda JP, Weckstein LN, Stone SC. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Human Reproduction. 1991;6(10):1395-1399. PMID: 1770133

Stewart J, Hamilton P, Murdoch A. Thromboembolic disease associated with ovarian stimulation and assisted conception techniques. Human reproduction (Oxford, England). 1997;12(10):2167-2173. PMID: 9402276