Thrombosis Prevention in IVF

Introduction to Thrombosis Risk

• 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
• 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

Patient Assessment and Regimen Determination

• Assess thrombosis risk by considering history of thrombosis, presence of aPL antibodies or APS, known thrombophilia, and risk factors for OHSS 1
• Determine appropriate regimen based on risk factors, including no anticoagulation for no risk factors, prophylactic enoxaparin for asymptomatic aPL-positive patients, and therapeutic enoxaparin for thrombotic APS 1

Administration and Timing

• Standard prophylactic dosing: Enoxaparin 40 mg subcutaneously once daily, starting at the beginning of ovarian stimulation, withholding 24-36 hours prior to oocyte retrieval, and resuming following retrieval 1
• For patients with thrombotic APS: Therapeutic-dose LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours), transitioning from vitamin K antagonists before starting IVF, withholding for retrieval, and resuming after retrieval and continuing throughout pregnancy 1
• Duration of therapy: Continue until estrogen levels return to near-physiologic levels if no pregnancy occurs for asymptomatic aPL-positive patients, and continue throughout pregnancy for patients with obstetric APS 1

Safety and Efficacy

• Prophylactic LMWH can be safely administered during IVF cycles without increasing bleeding complications during oocyte retrieval when properly timed 1
• 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
• Aspirin use is not commonly used prior to oocyte retrieval due to concerns about prolonged action increasing bleeding risk 1
• Alternative protocols, such as ovarian stimulation protocols that yield lower peak serum estrogen levels, may benefit patients at risk for thrombosis or OHSS 1

Special Populations and Considerations

• Hospitalized medical patients at risk for VTE, including those with reduced mobility, acute illness, and multiple risk factors, should receive prophylactic enoxaparin, with a standard dose of 40 mg subcutaneously once daily, as recommended by the American College of Critical Care and the National Comprehensive Cancer Network 2, 3
• Surgical patients, such as those undergoing post-cesarean delivery with additional risk factors or major surgical procedures, should also receive prophylactic enoxaparin, with a dose of 40 mg subcutaneously once daily, as recommended by the American Journal of Obstetrics and Gynecology 4
• Critically ill patients require increased prophylactic dosing, with 40 mg subcutaneously twice daily, as suggested by some guidelines 2
• Obese patients may require intermediate dosing (40 mg subcutaneously every 12 hours) or weight-based prophylactic dosing of 0.5 mg/kg subcutaneously every 12 hours, as recommended by the American Journal of Obstetrics and Gynecology 4
• Patients with renal impairment (CrCl <30 mL/min) should receive a reduced dose of 30 mg subcutaneously once daily, according to the National Comprehensive Cancer Network 5

Dosing and Administration Guidelines

Contraindications and Precautions

• Enoxaparin is contraindicated in patients with active major bleeding or known sensitivity to enoxaparin, heparin, or pork products, as stated by the American Urological Association 8
• Use of enoxaparin should be with extreme caution in patients with active bleeding, thrombocytopenia, recent gastrointestinal ulceration, or severe hypertension, as warned by the American Urological Association 8

Monitoring and Interactions

• Routine monitoring of anti-Xa levels is not required for most patients, but may be considered in patients with severe renal impairment, extreme body weights, prolonged therapy, or critically ill patients, as suggested by various guidelines 4, 9, 6
• Concurrent use of enoxaparin with other anticoagulants, such as Unfractionated Heparin (UFH), should be avoided as it increases bleeding risk, as advised by the American Heart Association 10
• Avoid concomitant use of other medications that increase bleeding risk when possible (NSAIDs, antiplatelet agents) 6

Transitioning and Duration of Therapy

• When transitioning from apixaban to enoxaparin, the American Society of Anesthesiologists recommends starting enoxaparin at the next scheduled apixaban dose time, with no overlap period required, and ideally waiting 12-24 hours after the last dose of apixaban 11
• The duration of enoxaparin therapy should continue during hospitalization or until a percutaneous coronary intervention (PCI) is performed, as recommended by the American Heart Association 12, 9