What are the effects of anticoagulants on conception and fertility?

From the Guidelines

Anticoagulants, particularly low molecular weight heparins, do not have significant negative effects on conception or fertility in most patients, but warfarin should be avoided during pregnancy planning and pregnancy itself due to its teratogenic effects. The most commonly used anticoagulants like low molecular weight heparins (enoxaparin, dalteparin) and unfractionated heparin are considered safe for women trying to conceive and during pregnancy, as they do not cross the placenta and do not appear to impact fertility 1. However, warfarin (Coumadin) should be avoided during pregnancy planning and pregnancy itself as it crosses the placenta and can cause birth defects, particularly when used between weeks 6-12 of gestation 1.

Some key points to consider when using anticoagulants in patients trying to conceive or during pregnancy include:

• Warfarin crosses the placental barrier and results in anticoagulation of the fetus, as well as the mother, and there is a higher risk of fetal intracranial hemorrhage if the mother is fully anticoagulated with warfarin during vaginal delivery 1.
• Low molecular weight heparin (LMWH) does not result in an anticoagulated fetus, but the risk of maternal hemorrhage is high if delivery occurs while the mother is on LMWH, and it is recommended that the mother be hospitalized before planned delivery, with discontinuation of long-acting anticoagulation and initiation of intravenous continuous infusion of unfractionated heparin (UFH) to keep aPTT >2 times control levels 1.
• The teratogenic effects of warfarin are dose-dependent, and the rate of warfarin embryopathy is reduced (<3%) but not eliminated if the daily dose of warfarin is ≤5 mg/d 1.
• For women requiring anticoagulation who are planning pregnancy, the typical recommendation is to use low molecular weight heparin instead of warfarin or direct oral anticoagulants (DOACs) 1.
• Men taking anticoagulants generally experience no impact on fertility, though there are limited studies specifically examining this question 1.

In terms of specific anticoagulants, low molecular weight heparin is the preferred choice for women trying to conceive or during pregnancy, as it does not cross the placental barrier and maintains effective anticoagulation for the mother without affecting the developing embryo or fetus 1. Direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, dabigatran, and edoxaban are not recommended when trying to conceive or during pregnancy due to limited safety data 1.

From the FDA Drug Label

Warfarin sodium tablets are contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy. Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and the indications critically reviewed with the patient If the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be discussed in light of those risks.

The effects of anticoagulants, specifically warfarin, on conception and fertility are not directly addressed in terms of fertility. However, the drug label highlights significant risks to the fetus if pregnancy occurs while taking warfarin, including birth malformations and fetal mortality. Therefore, women of childbearing potential should be carefully evaluated before starting anticoagulant therapy, and the potential risks should be discussed if pregnancy occurs 2.

From the Research

Effects of Anticoagulants on Conception and Fertility

• The use of anticoagulants during pregnancy is a complex issue, and the choice of anticoagulant depends on various factors, including the patient's medical history and the stage of pregnancy 3.
• Women requiring long-term vitamin K antagonist therapy who are attempting pregnancy should have frequent pregnancy tests and substitute unfractionated heparin (UFH) or low molecular weight heparin (LMWH) for warfarin when pregnancy is achieved 3.
• Anticoagulation poses unique challenges for women of reproductive age, including abnormal uterine bleeding, hemorrhagic ovarian cysts, and teratogenic risks 4.
• The subdermal implant may be considered a first-line option for those requiring anticoagulation, given its superior contraceptive effectiveness and ability to reliably reduce the risk of hemorrhagic ovarian cysts 4.
• During pregnancy, enoxaparin remains the preferred anticoagulant, and warfarin is contraindicated 4.

Anticoagulant Options for Women of Reproductive Age

• Low molecular weight heparin (LMWH) is a commonly used anticoagulant in pregnancy, and its use is recommended in certain situations, such as in women with a history of venous thromboembolism (VTE) or those with prosthetic heart valves 3.
• Fondaparinux, a selective factor Xa inhibitor, represents an improvement in anticoagulation therapy with greater efficacy and safety compared to traditional anticoagulants 5.
• The chromogenic antifactor Xa assay is a useful test for monitoring the anticoagulant activity of LMWH and other anticoagulants 6.

Considerations for Women on Anticoagulation

• Women on anticoagulation should be counseled on issues ranging from menstruation and the possibility of developing a hemorrhagic ovarian cyst to teratogenic risks and safety with breastfeeding 4.
• Tranexamic acid and endometrial ablation may be useful in managing menorrhagia and dysmenorrhea in women on anticoagulation 4.
• Breastfeeding women may use warfarin, but direct oral anticoagulants are not recommended due to limited safety data 4.