Ovarian hyperstimulation syndrome

The ovarian hyperstimulation syndrome (OHSS) is a complication that most often occurs as a complication of ovarian-stimulation treatments (ovarian unduction therapy) for in vitro fertilisation but may also rarely occur as a spontaneous event in pregnancy (see spontaneous ovarian hyperstimulation later in the article).

The syndrome consists of ovarian enlargement with extra-vascular accumulation of exudates leading to varying degrees of 

• weight gain
• increase in abdominal circumference
• ascites
• pleural effusions
• intravascular volume depletion with haemoconcentration  
• oliguria 

Epidemiology

The syndrome is relatively common, occurring in approximately 5% of patients undergoing in-vitro fertilisation (IVF) ¹².

Clinical presentation

The clinical picture may vary from abdominal distension and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration in a third space. Pain, abdominal distention, nausea, and vomiting are frequently seen as symptoms.

Pathology

It is characterised by massive cystic ovarian enlargement and fluid shift from the intravascular compartment into the peritoneal, pleural or pericardial cavities. The vascular fluid leakage is thought to result from an increased capillary permeability of mesothelial surfaces under the action of one or several vasoactive ovarian factor(s) produced by multiple corpora lutea. This can lead to third spacing of fluid.

Risk factors

• baseline ovarian volume ⁸
• background polycystic ovaries ⁹
• low body weight ⁸
• long ovulation induction cycle duration ⁸

Markers

• serum oestradiol(E₂) levels are elevated

Sub types

Spontaneous ovarian hyper-stimulation

This sub type occurs in the absence of any external stimulation. This form can occur in pregnancy. 

There are also very rare sporadic forms which carry a genetic components. These have an association with early pubertal development and primary hypothyroidism. Ovarian stimulation in the hypothyroid child may result in oestrogen production, breast development, endometrial proliferation, and vaginal bleeding. It is likely that raised TSH concentrations bind and stimulate the FSH receptor, although a similar overlap phenomenon might occur at the level of the pituitary, with enhanced TRH production stimulating the GnRH receptor with subsequent ovarian enlargement. The cystic ovarian enlargement resolves with thyroid hormone replacement. A hyperstimulation phenomenon in patients with an abnormal FSH receptor has been described. 

Classification

Based upon the clinical manifestation and imaging findings, OHSS can be classified into

• mild OHSS : characterised by bilateral multicystic ovarian enlargement;
• moderate OHSS : if there is associated ascites and abdominal distension
• severe OHSS : characterised by hypovolemia, haemoconcentration, thrombosis, oliguria, pleural and pericardial effusion

Radiographic features

Imaging findings can be similar on ultrasound, CT and MR imaging. 

Ultrasound

Typically shows bilateral symmetric enlargement of ovaries (ofte > 12 cm in size) with multiple cysts of varying sizes, giving the classic wheel-spoke appearance. Associated ascites and pleural + / - pericardial effusion (which is due to capillary leak) may also be present.

Complications

• hypo-volaemic shock with resultant
  • thromboembolic disease
  • stroke
• ovarian torsion ⁶

Familiarity with ovarian hyperstimulation syndrome and the appropriate clinical setting should help avoid the incorrect diagnosis of an ovarian cystic neoplasm.

Treatment and prognosis

The syndrome is usually self limiting on most cases and management is mainly supportive. Severe cases may require hospital administration and a close monitoring of the haematocrit, liver function, renal function, serum electrolytes and oxygen saturation.

Differential diagnosis

For ultrasound appearances for mild cases consider

• polycystic ovaries 
  • cysts are typically small
  • no ascites or pleural effusions
• theca lutein cysts associated with gestational trophoblastic disease : some also considered a part of OHSS