What is the recommended dose of Cabgolin (cabergoline) for the prevention or treatment of Ovarian Hyperstimulation Syndrome (OHSS)?

Cabergoline Dosing for OHSS Prevention

For prevention of ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing assisted reproductive technology, administer cabergoline 0.5 mg orally once daily for 8 days, starting on the day of hCG injection.

Recommended Dosing Protocol

The standard evidence-based regimen is cabergoline 0.5 mg orally once daily for 8 consecutive days, initiated on the day of human chorionic gonadotropin (hCG) administration 1, 2, 3. This dosing has been validated in multiple randomized controlled trials and represents the most commonly studied and effective protocol 1, 2.

Timing Considerations

• Optimal initiation: Start cabergoline on the day of hCG injection, or preferably a few hours earlier when the leading follicle reaches 15 mm diameter 1, 3
• Early administration (when leading follicle reaches 15 mm) may be a safer and more effective approach compared to waiting until after oocyte retrieval 3
• Starting treatment earlier allows for VEGF receptor blockade before the cascade of vascular permeability begins 3

Patient Selection Criteria

High-risk patients appropriate for cabergoline prophylaxis include those with 1, 3:

• More than 20 follicles >12 mm in diameter
• Estradiol (E2) levels >3,000-3,500 pg/ml when the leading follicle is >15 mm
• History of previous OHSS, even without current evident signs

Efficacy Data

The evidence demonstrates significant reduction in OHSS incidence 2:

• Overall OHSS reduction: Cabergoline reduces moderate or severe OHSS with an odds ratio of 0.40 (95% CI 0.20-0.77), requiring treatment of only 7 patients to prevent one case 2
• Moderate OHSS: Statistically significant reduction (OR 0.38,95% CI 0.19-0.78) 2
• Severe OHSS: No statistically significant difference, though studies were underpowered for this endpoint (OR 0.77,95% CI 0.24-2.45) 2
• In one case series of 126 high-risk patients, severe OHSS occurred in only 0.9% and moderate OHSS in 9.5% using early cabergoline administration 3

Mechanism of Action

Cabergoline works by blocking the increase in vascular permeability through dephosphorylation of VEGF receptors, which are the primary mediators of OHSS pathophysiology 3. This dopamine agonist effect specifically targets the VEGF-driven increase in capillary permeability that characterizes OHSS 1.

Impact on Pregnancy Outcomes

Importantly, cabergoline does not negatively affect reproductive outcomes 2, 4:

• Clinical pregnancy rates remain unchanged (OR 0.94,95% CI 0.56-1.59) 2
• Miscarriage rates are not increased (OR 0.31,95% CI 0.03-3.07) 2
• Implantation rates are comparable to control groups 4

Alternative Dosing Considerations

While 0.5 mg daily for 8 days is the standard regimen, some studies have explored variations 1:

• Duration: Treatment durations have ranged from 4-21 days in various trials, though 8 days is most commonly validated 1
• Dose: Some protocols use 0.25 mg daily, but 0.5 mg daily has stronger evidence 1
• Route: Oral administration is standard, though rectal bromocriptine (2.5 mg daily for 16 days) is an alternative dopamine agonist option 1

Important Clinical Caveats

• Timing is critical: Starting cabergoline after oocyte retrieval may be less effective than starting on or before the day of hCG injection 1, 3
• Late-onset OHSS: The evidence for preventing late-onset OHSS (occurring after pregnancy establishment) is less robust than for early-onset OHSS 1
• Monitoring: No specific cardiac monitoring is required for this short 8-day course, unlike the chronic high-dose therapy used for prolactinomas where doses >2 mg/week require echocardiographic surveillance 5
• Safety profile: The short duration and relatively low cumulative dose (4 mg total over 8 days) used for OHSS prevention carries minimal risk compared to chronic prolactinoma therapy 2

Comparison with Other Interventions

When compared to albumin infusion, cabergoline showed statistically significant reduction in overall OHSS incidence (53.7% vs 46.3%, p=0.04), though no significant difference in severe OHSS rates 6. Compared to coasting, cabergoline demonstrated similar efficacy with 0% OHSS versus 3.6% with coasting (not statistically significant) 4.