Ovarian Hyperstimulation Syndrome

Aka: Ovarian Hyperstimulation Syndrome, Ovarian Hyperstimulation

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II. Pathophysiology

  1. Hyperstimulation occurs with gonadotropin stimulation for Assisted Reproductive Technology (ART)
    1. Ovulation induction
    2. Invitro Fertilization (IVF) Cycles
  2. Hyperstimulation triggers proinflammatory and vasoactive Cytokines overproduction
    1. Increases inflammation
    2. Increases ovarian capillary permeability and neoangiogenesis
    3. Increases edema and third spacing (and intravascular Hypovolemia)

III. Epidemiology

  1. May complicate up to 30% of Assisted Reproductive Technology (ART) cycles

IV. Risk Factors

  1. Younger patients (age <35 years)
  2. Lower body weight
  3. Polycystic ovarian syndrome
  4. High dose exogenous gonadotropins
  5. Increased Serum Estradiol (E2) levels (rapidly increasing or high absolute level)
  6. More than 24 oocytes retrieved
  7. Past history of Ovarian Hyperstimulation Syndrome (OHSS)
  8. Pregnancy

V. Types

  1. Early
    1. Follows Ovulation trigger by HCG by 3 to 7 days
    2. Excessive ovarian response to exogenous HCG
  2. Late
    1. Follows Ovulation trigger by HCG by 12 to 17 days
    2. Implanting pregnancy releases excessive endogenous HCG

VI. Findings

  1. Genitourinary
    1. Uterine and ovarian enlargement
  2. Gastrointestinal
    1. Abdominal discomfort
    2. Abdominal Distention (increased abdominal circumference)
      1. Due to Ascites (among the first diagnostic findings)
    3. Nausea or Vomiting
    4. Diarrhea
  3. Systemic
    1. Rapid weight gain
    2. Tachypnea or respiratory distress
    3. Oliguria
    4. Anuria

VII. Grading: Golan Classification for Ovarian Hyperstimulation Syndrome (OHSS)

  1. Mild Ovarian Hyperstimulation (20-33% of OHSS cases)
    1. Ovarian Size <6 cm
    2. Grade 1: Abdominal Distention
    3. Grade 2: Abdominal Distention, Nausea, Vomiting and Diarrhea
  2. Moderate Ovarian Hyperstimulation (3-6% of OHSS cases)
    1. Ovarian Size 6-12 cm
    2. Hematocrit >41% and White Blood Cell Count >15,000/uL
    3. Grade 3: Ascites on Ultrasound and weight gain, in addition to Grade 2 symptoms
  3. Severe Ovarian Hyperstimulation (2% of OHSS cases)
    1. Ovarian Size >12 cm
    2. Clinical Ascites and Pleural Effusions (hydrothorax)
    3. Intractable Nausea and Vomiting
    4. Hematocrit >55% and White Blood Cell Count >25,000/uL
    5. Creatinine Clearance <50 ml/min and Serum Potassium >5 mEq/L
    6. Elevated liver transaminases (AST, ALT)
    7. Grade 4: Ascites and Hydrothorax, in addition to Grade 2 Symptoms
  4. Critical Ovarian Hyperstimulation (0.1 of OHSS cases)
    1. Grade 5: Ascites and Hydrothorax with Hypovolemia, hemoconcentration, Coagulation Disorder, Oliguria, shock

VIII. Labs

  1. Complete Blood Count
    1. Hemoconcentration (increased Hematocrit >45%)
    2. Leukocytosis (White Blood Cell Count >15,000)
  2. Comprehensive Metabolic Panel
    1. Hyponatremia (Serum Sodium <135)
    2. Hyperkalemia (Serum Potassium >5.0)
    3. Iincreased ALT and AST liver enzymes
    4. Increased Serum Creatinine (>1.2 mg/dl)

IX. Imaging

  1. Pelvic Ultrasound
    1. Measure ovarian size (<6 cm, 6-12 cm or >6 cm)
    2. Evaluate for Ascites (significant free abdominal fluid)
      1. Ascites and hemoperitoneum (e.g. ruptured Ovarian Cyst) may be indistinguishable on Ultrasound
      2. Consider CT Abdomen and Pelvis to characterize large intraabdominal fluid collection
  2. Lung Ultrasound or Chest XRay
    1. Indicated in Dyspnea, for evaluation of Pleural Effusions or hydrothorax
  3. CT Abdomen and Pelvis
    1. Consider in severe cases (Hounsfield Units may distinguish intraabdominal blood from Ascites)

X. Management

  1. Urgent Consultation with patient's reproductive specialist
  2. Supportive care
    1. Correct Electrolyte abnormalities
    2. Manage fluid status
  3. Hospital monitoring indications
    1. Severe Ovarian Hyperstimulation Syndrome (OHSS)
    2. Hemodynamic Instability
    3. Intractable Pain
    4. Intractable Nausea or Vomiting and unable to maintain hydration
    5. Respiratory distress
    6. Severe laboratory abnormalities
  4. Outpatient management is often indicated in Mild to moderate Ovarian Hyperstimulation Syndrome (OHSS)
    1. Requires close interval follow-up
    2. Serial labs (interval and lab type per reproductive specialist guidance)
    3. Monitor intake and output, daily weight and abdominal circumference

XI. Complications

  1. Acute Renal Failure
  2. Acute Respiratory Distress Syndrome (ARDS)
  3. Ruptured Ovarian Cyst with Hemorrhage
  4. Thromboembolism (OHSS is a Hypercoagulable state)
  5. Abdominal Compartment Syndrome
  6. Infection or Sepsis

XII. References

  1. Gallo, Suyama and Snook (2020) Crit Dec Emerg Med 34(10): 3-7
  2. Long and Werner (2023) EM:Rap 23(6): 6-8
  3. Zivi (2010) Semin Reprod Med 28(6): 441-7 [PubMed]

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