What are the effects of Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA), and Direct Oral Anticoagulants (DOACs) on conception, implantation, and fertility?

From the Guidelines

Low molecular weight heparins (LMWHs) are the preferred anticoagulant for women planning pregnancy or who are pregnant, while vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) should be avoided due to potential risks to the fetus. The effects of LMWHs, VKAs, and DOACs on conception, implantation, and fertility are a critical consideration in the management of women of childbearing potential. Key points to consider include:

• LMWHs, such as enoxaparin, do not cross the placenta and have not been associated with adverse effects on fertility or implantation, making them a safe choice during conception and pregnancy 1.
• VKAs, like warfarin, should be avoided during pregnancy planning and pregnancy itself, particularly between weeks 6-12, due to their ability to cross the placenta and cause embryopathy 1.
• DOACs, including rivaroxaban, apixaban, dabigatran, and edoxaban, are not recommended during pregnancy planning or pregnancy due to insufficient safety data and potential reproductive toxicity 1.
• Women taking DOACs who wish to conceive should transition to LMWH before attempting pregnancy, and those who become pregnant while on DOACs should discontinue the medication and commence LMWH immediately 1.
• The safety concerns associated with VKAs and DOACs stem from their ability to cross the placenta and affect the developing embryo, whereas LMWHs work by enhancing antithromatin activity and remain in the bloodstream 1. In terms of dosing, LMWHs are typically administered based on weight, with examples including enoxaparin 1mg/kg twice daily or 1.5mg/kg once daily 1. It is essential to note that the use of LMWHs during pregnancy requires monitoring of plasma anti-Xa levels to ensure adequate anticoagulation and minimize the risk of bleeding complications 1. Overall, the choice of anticoagulant in women of childbearing potential should prioritize the safety of the fetus and the mother, with LMWHs being the preferred option due to their favorable safety profile 1.

From the Research

Effects of Anticoagulants on Conception, Implantation, and Fertility

• The effects of Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA), and Direct Oral Anticoagulants (DOACs) on conception, implantation, and fertility have been studied in various contexts, including pregnancy and thrombophilia treatment 2, 3, 4, 5, 6.
• LMWH has been shown to be effective in treating thrombophilia during pregnancy, with a significantly higher live birth rate when combined with low-dose aspirin compared to aspirin or LMWH alone 2.
• The use of LMWH in patients at risk for thrombosis during IVF cycles has been found to be safe, with no bleeding or thromboembolic complications noted 3.
• VKAs, such as warfarin, have been associated with embryopathy and fetal complications, particularly when used at high doses or with high INR levels 4.
• DOACs have been increasingly used in the prevention of recurrent venous thromboembolism, including in patients with thrombophilia, although their efficacy in severe thrombophilia or triple positive antiphospholipid syndrome remains controversial 5, 6.

Anticoagulation Therapy in Pregnancy and Thrombophilia

• The choice of anticoagulant therapy in pregnancy and thrombophilia depends on various factors, including the risk of thromboembolic events, the presence of mechanical valve prostheses, and the patient's individual characteristics 4.
• LMWH is often recommended as the anticoagulant of choice during pregnancy, due to its safety profile and effectiveness in preventing thromboembolic events 2, 3.
• VKAs, such as warfarin, may be used in certain situations, such as in patients with mechanical valve prostheses, but require careful monitoring of INR levels to minimize the risk of embryopathy and fetal complications 4.
• DOACs, such as rivaroxaban, dabigatran, and apixaban, have been used in patients with thrombophilia, although their use in pregnancy is still limited and requires further study 5, 6.

Fertility and Anticoagulation Therapy

• The impact of anticoagulation therapy on fertility is not well understood, although some studies suggest that LMWH may improve fertility outcomes in patients with thrombophilia 2, 3.
• The use of VKAs, such as warfarin, has been associated with reduced fertility in some studies, although the evidence is limited 4.
• DOACs have been found to be effective in preventing recurrent venous thromboembolism in patients with thrombophilia, although their impact on fertility is still unknown 5, 6.