Should I start low molecular weight heparin (LMWH) before or after egg pickup in a patient with prothrombin two heterozygous mutation?

Management of Prothrombin Gene Mutation Heterozygote During IVF Treatment

For a patient with heterozygous prothrombin gene mutation undergoing IVF treatment, prophylactic low molecular weight heparin (LMWH) should be started at the beginning of ovarian stimulation, withheld 24-36 hours prior to egg retrieval, and resumed following the procedure.

Thromboprophylaxis Timing and Protocol

• LMWH is the preferred anticoagulant for thromboprophylaxis during assisted reproductive technology (ART) procedures in patients with thrombophilias 1
• Prophylactic dosing of LMWH (e.g., enoxaparin 40 mg daily) should be started at the beginning of ovarian stimulation 1
• LMWH should be withheld 24-36 hours prior to oocyte retrieval to minimize bleeding risk 1
• Anticoagulation should be resumed following egg retrieval once adequate hemostasis is achieved 1

Rationale for Thromboprophylaxis

• Patients with prothrombin gene mutation have an increased risk of thrombosis, which is further elevated during ovarian stimulation due to high estrogen levels 1
• The increased risk of potentially life-threatening thrombosis due to elevated estrogen levels during stimulation outweighs the low risk of bleeding complications from LMWH 1
• Prophylactic anticoagulation is recommended for patients with thrombophilias undergoing ART to prevent thrombotic complications 1

Ovarian Stimulation Protocol Considerations

• Standard ovarian stimulation protocols can be used in patients with prothrombin gene mutation when appropriate thromboprophylaxis is implemented 1
• Careful monitoring of ovarian response is recommended to minimize the risk of ovarian hyperstimulation syndrome, which would further increase thrombotic risk 1
• The patient should have stable disease status before undergoing ART procedures 1

Dosing Recommendations

• Prophylactic dosing of enoxaparin is typically 40 mg daily for patients of average weight 1
• For patients weighing 50-69 kg, nadroparin 3800 IU twice daily or 3300 IU once daily can be used as an alternative 1
• For patients weighing 70-89 kg, nadroparin 5700 IU twice daily or 5700 IU once daily can be considered 1
• Dose adjustments may be needed based on the patient's weight and renal function 1

Duration of Thromboprophylaxis

• The optimal duration of prophylactic LMWH for patients with thrombophilias undergoing ovarian stimulation has not been definitively established 1
• The decision regarding duration should be made in consultation with a reproductive endocrinology specialist 1
• For patients with ongoing risk factors, prophylaxis may need to be continued throughout early pregnancy if conception occurs 1

Monitoring

• Routine platelet count monitoring is recommended every 2-4 days from days 4 to 14 of LMWH therapy to detect potential heparin-induced thrombocytopenia 2
• If the platelet count falls by 50% or more, or falls below the laboratory normal range, heparin-induced thrombocytopenia should be considered 2

Special Considerations

• Unfractionated heparin (UFH) can be considered as an alternative if LMWH is contraindicated or unavailable 1
• In patients with renal impairment, UFH may be preferred over LMWH due to the risk of LMWH accumulation 1
• The advantages of LMWH over UFH include better bioavailability, fixed dosing, decreased risk of heparin-induced thrombocytopenia, and less monitoring requirements 1, 3

By following these recommendations, the thrombotic risk associated with prothrombin gene mutation can be effectively managed during the IVF process while minimizing bleeding complications during egg retrieval.