OHSS prevention: how modern protocols avoid severe hyperstimulation

What Causes Ovarian Hyperstimulation Syndrome?

During controlled ovarian stimulation, multiple follicles produce massive quantities of estradiol. When a conventional human Chorionic Gonadotropin (hCG) trigger is administered to induce final egg maturation, it binds avidly to LH receptors, triggering prolonged secretion of Vascular Endothelial Growth Factor (VEGF).

Excess VEGF increases capillary permeability throughout the body:

• Intravascular fluid leaks into the third space (abdominal cavity, causing ascites, and around lungs, causing pleural effusion).
• Hemoconcentration (thickened blood) elevates the risk of venous thromboembolism.
• Electrolyte imbalances and renal hypoperfusion can develop.

Who is at High Risk for OHSS?

• Women with Polycystic Ovary Syndrome (PCOS).
• High Anti-Müllerian Hormone (AMH > 3.5 to 4.0 ng/mL).
• High Antral Follicle Count (AFC > 20 to 25 total follicles).
• Retrieval of >18 to 20 mature oocytes in a single cycle.

The Modern Zero-Severe-OHSS Protocol

In accredited centres adhering to ESHRE guidelines, severe OHSS is considered a preventable event through four synchronized interventions:

• GnRH Antagonist Protocol: Replaces old agonist "long" protocols, allowing rapid suppression of endogenous LH without ovarian desensitization.
• GnRH Agonist Trigger (Decapeptyl / Lupride): Instead of hCG (which has a long half-life of 6–8 days), an agonist trigger releases an endogenous LH surge with a short physiological half-life of only 24 to 36 hours, completely preventing the sustained VEGF surge.
• Mandatory "Freeze-All" Strategy: No fresh embryo transfer is performed. Endogenous pregnancy is the primary trigger of "late OHSS" (due to rising embryonic hCG). Vitrifying all embryos completely eliminates late OHSS.
• Dopamine Agonist Therapy (Cabergoline): Oral cabergoline blocks VEGF receptor-2 phosphorylation, preventing vascular leakage.