Management of Heterozygous Factor V Leiden in Assisted Reproductive Technology
Antithrombotic Prophylaxis During IVF
- The American Society of Hematology (ASH) 2018 guidelines recommend against routine antithrombotic prophylaxis for unselected women undergoing assisted reproduction (conditional recommendation, low certainty of evidence) 1.
- This recommendation applies to women who are heterozygous for Factor V Leiden and have no prior venous thrombo‑embolism (VTE), because their thrombotic risk during ovarian stimulation is not high enough to justify prophylaxis 1, 2.
- Exception: if severe ovarian hyperstimulation syndrome (OHSS) occurs, ASH suggests initiating antithrombotic prophylaxis (conditional recommendation, low certainty) 1, 2.
Antepartum Management (Pregnancy Obtained)
- The ASH 2018 guidelines advise against ante‑partum prophylaxis with low‑molecular‑weight heparin (LMWH) to prevent a first VTE event in women who are heterozygous for Factor V Leiden and have no prior VTE, even when there is a family history of VTE (conditional recommendation, very low certainty) 1, 2.
- This conservative approach is justified because the absolute risk of VTE during pregnancy in this population remains below the 2 % threshold that would warrant systematic prophylaxis 3.
Risk Assessment and Surveillance
- Clinicians should re‑evaluate the thrombotic risk profile if additional risk factors arise, such as prolonged immobilization, cesarean delivery, obstetric complications, or extended ante‑partum hospitalization 3.
Common Pitfalls to Avoid
- Do not equate heterozygous Factor V Leiden with high‑risk thrombophilias (e.g., antithrombin deficiency, homozygous Factor V Leiden, combined thrombophilias) that require ante‑partum prophylaxis 1, 2, 3.
- Do not start systematic antithrombotic prophylaxis during IVF solely based on heterozygous Factor V Leiden status, except in the setting of severe OHSS 1, 2.
Management of Pregnant Women with Factor V Leiden Mutation
Risk Stratification and Management
- For pregnant women with heterozygous Factor V Leiden mutation and no prior history of VTE, clinical vigilance during pregnancy is recommended rather than LMWH prophylaxis, according to the American College of Chest Physicians 4, 5, 6
- Postpartum prophylaxis with LMWH for 6 weeks is suggested for pregnant women with heterozygous Factor V Leiden mutation and no prior history of VTE, as recommended by the American College of Chest Physicians 4, 5, 6
- For pregnant women with homozygous Factor V Leiden mutation and a positive family history of VTE, antepartum prophylaxis with prophylactic- or intermediate-dose LMWH is suggested, according to the American College of Chest Physicians 4, 5
- The American College of Chest Physicians recommends against screening for inherited thrombophilia in women with pregnancy complications and against using antithrombotic therapy in this setting 5, 6