Why is Enoxaparin (low molecular weight heparin) used before In Vitro Fertilization (IVF) transfer?

Enoxaparin Use Before IVF Transfer: Thrombosis Prevention in High-Risk Patients

Enoxaparin (low molecular weight heparin) is primarily used before IVF transfer to prevent potentially life-threatening thrombosis in patients at high risk for thromboembolic events, particularly those with antiphospholipid antibodies or a history of thrombosis. 1

Primary Indications for Enoxaparin in IVF

• Elevated thrombosis risk during ovarian stimulation: The high estrogen levels produced during ovarian stimulation significantly increase thrombosis risk 1
• Prevention of ovarian hyperstimulation syndrome (OHSS) complications: OHSS can lead to severe complications including arterial and venous thrombosis 1
• Protection for patients with thrombophilia: Particularly those with antiphospholipid antibodies (aPL) or antiphospholipid syndrome (APS) 1

Dosing and Administration Protocol

For patients undergoing IVF with risk factors for thrombosis:

1. Standard prophylactic dosing: Enoxaparin 40 mg subcutaneously once daily 1, 2

   • Start at the beginning of ovarian stimulation
   • Withhold 24-36 hours prior to oocyte retrieval
   • Resume following retrieval

2. For patients with thrombotic APS: Therapeutic-dose LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours) 1, 2

   • Transition from vitamin K antagonists before starting IVF
   • Withhold for retrieval
   • Resume after retrieval and continue throughout pregnancy

3. Duration of therapy:

   • For asymptomatic aPL-positive patients: Continue until estrogen levels return to near-physiologic levels if no pregnancy occurs 1
   • For patients with obstetric APS: Continue throughout pregnancy 1

Evidence for Efficacy and Safety

The risk of venous thromboembolism (VTE) after IVF is approximately doubled compared to the background pregnant population, with a 5-10 fold increased risk during the first trimester 3. This risk is dramatically higher (up to 100-fold) in patients who develop OHSS 3.

Studies have demonstrated that:

• Prophylactic LMWH can be safely administered during IVF cycles without increasing bleeding complications during oocyte retrieval when properly timed 4
• Reports of thrombosis in aPL-positive patients undergoing IVF are uncommon when empiric anticoagulation is used 1
• Thrombotic events have occurred in patients who discontinued LMWH after oocyte retrieval 1

Special Considerations and Cautions

• Aspirin use: Not commonly used prior to oocyte retrieval due to concerns about prolonged action increasing bleeding risk 1
• Alternative protocols: Patients at risk for thrombosis or OHSS may benefit from ovarian stimulation protocols that yield lower peak serum estrogen levels 1
• Monitoring: While routine anti-Xa monitoring is not required for most patients, it may be considered in patients with severe renal impairment or extreme body weights 2
• Contraindications: Active major bleeding or known sensitivity to enoxaparin, heparin, or pork products 2

Algorithm for Enoxaparin Use in IVF

1. Assess thrombosis risk:

   • History of thrombosis
   • Presence of aPL antibodies or APS
   • Known thrombophilia
   • Risk factors for OHSS

2. Determine appropriate regimen:

   • No risk factors: No anticoagulation needed
   • Asymptomatic aPL-positive: Prophylactic enoxaparin (40 mg daily)
   • Obstetric APS: Prophylactic enoxaparin (40 mg daily)
   • Thrombotic APS: Therapeutic enoxaparin (1 mg/kg every 12 hours)

3. Time administration appropriately:

   • Start at beginning of stimulation
   • Hold 24-36 hours before retrieval
   • Resume after retrieval
   • Continue based on pregnancy outcome and risk profile

By following this approach, the risk of potentially life-threatening thrombotic complications during IVF can be significantly reduced while maintaining the safety of the procedure.