What are the risk factors, classification, management, and prevention strategies for ovarian hyperstimulation syndrome (OHSS)?

Ovarian Hyperstimulation Syndrome (OHSS)

Risk Factors

Women with polycystic ovary syndrome, high antral follicle count, elevated estradiol levels, age <35 years, history of previous OHSS, pregnancy, and underlying thrombophilia face substantially increased risk of developing OHSS. 1, 2, 3

• Underlying thrombophilia specifically amplifies the likelihood of severe OHSS and warrants special consideration, particularly in patients with antiphospholipid antibodies 1, 4
• Pregnancy following ovarian stimulation prolongs and worsens OHSS, making it a critical risk factor 1, 4

Classification and Clinical Presentation

Severity grading should include serial abdominal girth measurements, assessment for tense ascites, respiratory examination for pleural effusion, hematocrit/hemoglobin for hemoconcentration, renal function tests (creatinine, BUN), and coagulation studies to gauge thrombotic risk. 1

Key Clinical Features:

• Oliguria reflects acute kidney injury from intravascular volume depletion 1
• Shortness of breath indicates pleural effusion from third-spacing of fluid 1
• OHSS complicates up to 30% of assisted reproductive technology cycles 2
• Severe OHSS carries a VTE risk of up to 4.1% (95% CI 1.1-13.7%) 5, 1

Thrombotic Complications (Critical Priority)

The most life-threatening aspect of OHSS is thromboembolism, with 90% of arterial and 78% of venous thrombotic events occurring in the presence of OHSS. 4

Unique Thrombotic Pattern:

• Upper-body venous thrombosis (neck and arm veins) accounts for ~80% of venous cases, not the typical lower extremity DVT pattern 5, 4
• Venous events occur later (median 42 days post-embryo transfer) versus arterial events (median 11 days) 5, 1
• Thrombotic events can arise 2 days to 11 weeks after OHSS resolution, indicating prolonged risk 6, 5, 1

Management

Thromboprophylaxis (Highest Priority)

For moderate-to-severe OHSS, initiate low-molecular-weight heparin (enoxaparin 40 mg subcutaneously once daily) immediately upon diagnosis and continue for at least 3 months after symptom resolution, or throughout pregnancy and postpartum if pregnancy occurs. 6, 1, 4

• LMWH prophylaxis prevents approximately 26 VTEs per 1,000 treated women (NNT = 39) 5, 1
• LMWH does not increase clinically significant bleeding risk 5, 1
• For patients with established antiphospholipid syndrome on therapeutic anticoagulation, switch to therapeutic-dose LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours) 1, 4
• In patients with known thrombophilia or antiphospholipid syndrome, start thromboprophylaxis at the beginning of ovarian stimulation 4

Pain Management

NSAIDs (naproxen 550 mg or ibuprofen 600-800 mg) are first-line analgesia for mild-to-moderate OHSS. 1, 4

• Avoid aspirin before oocyte retrieval due to increased bleeding risk 1, 4

Volume Management

• Expand intravascular volume and maintain adequate urine output for moderate to severe cases 3, 7
• Paracentesis may be required for tense ascites or abdominal compartment syndrome 2, 3

Cycle Management

Freeze all embryos (elective cryopreservation) when OHSS is present, as pregnancy prolongs and worsens the syndrome. 1, 4

Prevention Strategies

For high-risk patients, use a GnRH-antagonist stimulation protocol combined with a GnRH-agonist trigger for final oocyte maturation, which markedly reduces severe OHSS incidence. 5, 1

Additional Prevention Measures:

• Withhold hCG when >2 dominant follicles >15 mm or >5 follicles >10 mm are present at time of trigger 6
• Use gonadotropin regimens of 75 IU or lower, as higher doses increase multiple pregnancy rates without improving pregnancy rates 6
• Consider clomiphene citrate or tamoxifen as alternatives to gonadotropins for lower multiple pregnancy rates, though at lower live birth rates 6
• Aspiration of excess follicles at time of hCG injection may reduce multiple pregnancy risk as an alternative to cycle cancellation 6

Common Pitfalls

Assuming IVF-related VTE follows the classic lower-extremity DVT pattern leads to missed diagnoses; the predominant pattern is upper-body venous thrombosis (neck/arm). 5, 4

• Discontinuing LMWH prophylaxis too early results in thrombotic events occurring up to 11 weeks after OHSS resolution 5
• Applying routine prophylaxis to all IVF patients (baseline VTE risk 0.2%, NNT = 781) provides little benefit; target only those with actual OHSS or additional risk factors 5, 1, 4
• Upper-extremity or neck swelling should prompt immediate evaluation for venous thrombosis 5
• Consultation with the primary obstetrics/gynecology team improves patient outcomes 2