Ovarian hyperstimulation syndrome

OHSS occurs when the ovaries are hyperstimulated and enlarged due to fertility treatments, resulting in the shift of plasma from the intravascular space to third spaces, predominantly the peritoneal cavity.

In most cases, symptoms are mild and self-limiting (typically lasting 10-14 days), with supportive treatment usually sufficient. However, in a small number of cases, it can be severe and life-threatening.

The syndrome is more prolonged and severe in women who are pregnant.

OHSS is more frequently seen in:

• Younger patients (<35 years)
• Patients weighing <60 kg
• Patients with polycystic ovarian syndrome

Clinically, OHSS is characterized by:

1. Ovarian enlargement
2. Increased vascular permeability

Epidemiology

The incidence of OHSS is approximately 5% following ovulation induction with exogenous gonadotrophins. The WHO estimates severe OHSS in 0.2% to 1% of stimulation cycles.

Pathophysiology

Although not fully understood, OHSS is characterized by increased capillary permeability leading to fluid loss into third spaces. Gonadotrophin administration is the pivotal trigger, resulting in:

• Excessive production of vascular endothelial growth factor (VEGF)
• Release of vasoactive substances leading to increased vascular permeability

Risk Factors

• Polycystic ovarian syndrome
• Previous OHSS
• High or rapidly rising estradiol levels
• Pregnancy (increases risk, severity, and duration due to hCG)
• Younger age (<35 years)
• Low body weight (<60 kg)

Complications

1. Hypotension: Due to fluid loss into third spaces (peritoneal, pleural, pericardial)
2. Dehydration/Electrolyte Imbalance: Due to vomiting
3. Renal Impairment/Failure
4. Respiratory Distress (ARDS)
5. Ovarian Torsion
6. Sepsis
7. Thromboembolic Disease: Arterial or venous events due to hemoconcentration and hypercoagulation

Classification of Severity

Mild

• Mild abdominal pain
• No clinical ascites
• Ovaries <8 cm

Moderate

• Moderate abdominal pain
• Ultrasound-detected ascites
• Nausea, vomiting
• Ovaries 8-12 cm
• Hematocrit >41%, WCC >15,000
• Estradiol 10,000-20,000 pmol/L

Severe

• Moderate-severe pain
• Clinical ascites, pleural effusion
• Intractable nausea, vomiting
• Ovaries >12 cm
• Hematocrit >55%, WCC >25,000
• Elevated LFTs
• Estradiol 20,000-30,000 pmol/L
• Oliguria

Critical

• Severe pain, ascites, vomiting
• Ovaries >12 cm
• Organ dysfunction: renal failure, pleural/pericardial effusion, thromboembolism, cardiovascular collapse, ARDS

Clinical Features

OHSS is characterized by:

• Ovarian enlargement
• Increased vascular permeability

Diagnosis is based on:

• History of ovarian stimulation
• Typical clinical features
• Transvaginal ultrasound (enlarged ovaries)

History:

• Common: Abdominal pain, distension
• Less common: Dyspnea
• Severe: Cardiovascular collapse, thromboembolic events

Examination:

• Vital signs (check for sepsis, circulatory compromise)
• Abdominal tenderness (rule out ectopic, torsion, sepsis)
• Signs of third space complications (ascites, effusions)
• PV exam with caution

Investigations

Guided by severity:

Bloods:

• FBE (Hematocrit, WCC)
• CRP
• U&Es, glucose
• Beta-HCG
• Coagulation profile (consider thrombophilia screen)
• LFTs
• Estradiol

Ultrasound:

• Ovarian size, ascites, differential diagnosis (e.g. ectopic, torsion)

Imaging:

• CXR (if respiratory symptoms/effusion suspected)
• ECG (if pericardial effusion suspected)
• Echocardiography (to detect tamponade)

Management

Most cases are mild and self-limiting. Management depends on severity:

General Measures:

• Resuscitate as needed
• Analgesia (paracetamol for mild pain)
• Avoid diuretics (due to intravascular contraction)
• Heparin/enoxaparin for prophylaxis (moderate-severe cases, after ruling out bleeding)

Severe Cases:

• ICU and obstetric coordination
• Fluid management:
  • Normal saline to maintain urine output ≥30 mL/hr
  • Normalize hematocrit
  • CVC and urinary catheter for monitoring

Respiratory support:

• CPAP for ARDS

Paracentesis:

• For tense ascites impairing breathing/venous return
• May consider ultrasound-guided culdocentesis

Cardiovascular collapse:

• May require inotropes

Disposition

Severe/critical cases require ICU referral

All suspected OHSS cases must be referred to the O&G Unit

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References

FOAMed

• Nickson C. Ovarian Hyperstimulation Syndrome. CCC

Publications

• Nastri CO, Ferriani RA, Rocha IA, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology and prevention. J Assist Reprod Genet. 2010 Feb;27(2-3):121-8.