Ovarian Hyperstimulation Syndrome (OHSS)

Summary

 Ovarian hyperstimulation syndrome is a preventable, iatrogenic complication of assisted reproduction. While most cases are mild and self-limiting, severe OHSS can cause multiorgan dysfunction and significant morbidity. Vigilant risk assessment, careful monitoring during ovarian stimulation, and evidence-based preventive measures are central to reducing its incidence and improving patient safety.

Definition

Ovarian hyperstimulation syndrome (OHSS) is a rare but potentially life-threatening iatrogenic complication of ovarian stimulation, most commonly following ovulation induction with exogenous human chorionic gonadotropin (hCG). It is characterized by exaggerated ovarian enlargement, cyst formation, and increased vascular permeability, leading to third spacing of fluid and potentially severe systemic complications. The incidence ranges from 1–3% of women undergoing ovulation induction or assisted reproductive technologies.

Pathophysiology

The hallmark of OHSS is the overproduction of vascular endothelial growth factor (VEGF) by luteinized granulosa cells after hCG administration. VEGF induces capillary hyperpermeability, resulting in fluid extravasation into the peritoneal, pleural, and other third-space compartments. This causes hemoconcentration, hypovolemia, and organ hypoperfusion. Additional contributors include activation of the renin–angiotensin system and high circulating levels of estrogen and cytokines. Clinically, ovarian enlargement with multiple cysts and ascites is typical, with severity correlating to serum renin activity and estradiol levels.

Risk Factors

• Young age and low body mass index

• Polycystic ovarian syndrome (PCOS)

• High serum anti-Müllerian hormone (AMH)

• Elevated antral follicle count

• Excessive ovarian response during stimulation (high estradiol levels, numerous large follicles)

• Use of high-dose gonadotropins or hCG as the trigger for ovulation

Clinical Features

OHSS may present early (within 7 days of hCG administration) or late (≥10 days post-hCG, often after conception). Clinical manifestations range from mild to critical severity:

• Mild: Abdominal bloating, mild pain, ovarian enlargement

• Moderate: Nausea, vomiting, ultrasound evidence of ascites

• Severe: Marked ascites, oliguria, hemoconcentration (hematocrit >45%), hypoalbuminemia, electrolyte disturbances

• Critical: Tense ascites, anuria, massive pleural effusions, thromboembolic events, acute respiratory distress syndrome (ARDS), and multiorgan failure
  

Diagnostics

• Laboratory tests: Complete blood count (hemoconcentration, leukocytosis), electrolytes, renal and liver function tests

• Imaging: Transvaginal ultrasound to assess ovarian size and detect ascites

• Monitoring parameters: Daily weight, urine output, and hematocrit levels to guide fluid status

Complications

• Venous and arterial thromboembolism

• Renal failure

• Acute respiratory distress syndrome

• Pericardial effusion

• Sepsis

• Electrolyte imbalance and arrhythmias

• Rarely, death

Management

• Mild to Moderate OHSS (outpatient):

  • Limit physical activity

  • Adequate oral hydration (1–2 L/day)

  • Daily monitoring of weight and urine output

  • Analgesia with acetaminophen

  • Therapeutic paracentesis if symptomatic ascites

• Severe OHSS (inpatient):

• Multidisciplinary care with strict monitoring

• Intravenous fluids and colloids (e.g., albumin) to restore intravascular volume

• Prophylactic anticoagulation (low-molecular-weight heparin) to prevent thromboembolism

• Paracentesis or thoracentesis for symptomatic relief

• Intensive care admission if critical, with support for respiratory or renal failure

Prevention

• Individualized ovarian stimulation protocols with reduced gonadotropin dosing

• Use of GnRH antagonist protocols rather than agonists

• Triggering ovulation with a GnRH agonist or low-dose hCG instead of full-dose hCG

• Careful monitoring with serial estradiol measurements and follicular ultrasound during stimulation

• Withholding the hCG trigger (“cycle cancellation”) in extreme cases