How should venous thromboembolism risk be assessed and prevented in IVF patients, particularly those with severe ovarian hyperstimulation syndrome or additional thrombosis risk factors?

IVF Treatment and Thrombosis Risk

Risk Assessment

Women undergoing IVF have a low baseline thrombosis risk (0.1-0.3% of cycles), but this increases dramatically to 4.1% in severe ovarian hyperstimulation syndrome (OHSS), making risk stratification essential. 1

Baseline IVF Risk Without OHSS

• Overall VTE incidence in standard IVF cycles is 0.1-0.3% 1
• Risk increases 4-fold for singleton pregnancies and 6-fold for twin pregnancies achieved through IVF 1
• First trimester carries 5- to 10-fold higher risk compared to later pregnancy 2
• 98% of thrombotic events occur after ovulation induction 1

High-Risk Features Requiring Prophylaxis

• Severe OHSS (thrombosis risk up to 4.1%) 1, 3, 4
• Polycystic ovary syndrome 3, 4
• High antral follicle count 3, 4
• Elevated estradiol levels 3, 4
• Underlying thrombophilia 3, 4
• Antiphospholipid antibodies 3, 4
• Personal or family history of VTE 1
• Age >35 years 1
• BMI >30 kg/m² 1

Thrombosis Characteristics in IVF

• Venous events (67-75% of cases) predominantly affect upper body—neck and arm veins in 80% of venous cases 1, 4, 5
• Arterial events (25-33%) primarily involve cerebral circulation 5
• Venous thrombosis occurs later (mean 42.4 days post-embryo transfer) versus arterial events (mean 10.7 days) 1, 3
• OHSS is present in 90% of arterial cases and 78% of venous events 1, 4
• Events can occur 2 days to 11 weeks after OHSS resolution 4

Thromboprophylaxis Recommendations

For Severe OHSS (HIGHEST PRIORITY)

Initiate LMWH (enoxaparin 40 mg subcutaneously once daily) immediately upon diagnosis of moderate-to-severe OHSS and continue for at least 3 months after symptom resolution, or throughout pregnancy and postpartum if pregnancy occurs. 3, 4

• Number needed to treat is only 39 to prevent one VTE event 1, 3
• LMWH prevents approximately 26 VTEs per 1,000 women treated with severe OHSS 1, 3
• No increased risk of clinically significant bleeding with prophylaxis 1, 3
• If pregnancy ensues, continue LMWH throughout pregnancy and postpartum period 1, 3

For Patients with Pre-existing Thrombophilia or Antiphospholipid Syndrome

• Start thromboprophylaxis at beginning of ovarian stimulation 4
• For patients already on therapeutic anticoagulation for antiphospholipid syndrome, switch to therapeutic-dose LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours) 3, 4

For Standard IVF Without OHSS

Routine LMWH prophylaxis is NOT recommended for uncomplicated IVF cycles, as the baseline VTE risk is only 0.2% (NNT = 781). 1, 3, 4

• Apply standard pregnancy-based VTE risk assessment using additional risk factors (age >35, BMI >30, personal/family history VTE, thrombophilia, multiple pregnancy) 1, 2
• Consider prophylaxis only when multiple risk factors are present 2

Clinical Monitoring

Signs Requiring Immediate Evaluation

• Oliguria (indicates acute kidney injury from intravascular volume depletion) 3
• Shortness of breath (suggests pleural effusion from third-spacing) 3
• Unilateral limb swelling, particularly upper extremity or neck 1, 5
• Neurological symptoms (arterial events are predominantly intracerebral) 5

Laboratory Assessment for OHSS

• Serial hematocrit/hemoglobin (hemoconcentration) 3
• Renal function tests (creatinine, BUN) 3
• Coagulation studies 3
• Serial abdominal girth measurements 3

Prevention Strategies

Protocol Selection

• Use GnRH-antagonist stimulation protocols with GnRH-agonist trigger for final oocyte maturation in high-risk patients to reduce severe OHSS incidence 3
• Consider protocols yielding lower peak estradiol levels, such as those incorporating aromatase inhibitors 4

Cycle Management

• Freeze all embryos (elective cryopreservation) when OHSS is present, as pregnancy prolongs and worsens the syndrome 3

Common Pitfalls

• Failing to recognize that upper body venous thrombosis (neck, arm) is the predominant pattern in IVF-related VTE, not lower extremity DVT 1, 4, 5
• Discontinuing prophylaxis too early—thrombotic events can occur up to 11 weeks after OHSS resolution 4
• Using mini-dose heparin instead of standard prophylactic LMWH dosing (case reports document thrombosis despite mini-dose prophylaxis) 6
• Applying routine prophylaxis to all IVF patients rather than targeting those with OHSS or additional risk factors 1, 3