Thrombophilia has been previously established as a major factor associated with recurrent in vitro fertilization-embryo transfer (IVF-ET) failures. A recent study published in the journal Human Fertility, demonstrates the safety and effectiveness of enoxaparin, a low-molecular weight heparin (LMWH), for the prophylactic treatment of women with thrombophilia and recurrent IVF-ET failures.
H Qublan and colleagues from the Infertility & IVF Center, King Hussein Medical Center, Jordan, conducted a randomized placebo-controlled study to assess the safety and efficacy of LMWH for the thromboprophylactic treatment of women with thrombophilia and recurrent IVF-ET failures. The study included women with a history of three or more IVF failures and at least one thrombophilic defect. Eighty-three patients were randomized into two groups to receive either 40 mg/day enoxaparin, or placebo. The treatments were continued from the day of embryo-transfer till delivery or diagnosis of fetal death.
Patients who had received LMWH demonstrated significant increase in implantation and pregnancy rates with 23.8% live birth as compared to the placebo group who had 2.8% live birth. Investigators observed that in spite of comparable frequency of treatment complications in both the groups, the abortion rate was considerably higher in the placebo than the heparin group. Based on their findings, the researchers concluded that the thromboprophylactic treatment using LMWH was safe and effective in patients with thrombophilia and recurrent IVF-ET failures.
Earlier, Qublan, et al. (Human Reproduction, 2006) conducted a study to analyze the incidence of undiagnosed thrombophilic factors and its association with IVF-ET failure. The study comprised of the test group (A) involving 90 women with three or more IVF-ET failures, and 2 control groups; women with successful pregnancy after first IVF-ET cycle (group B) and those with spontaneous conception following at least one uneventful pregnancy without any history of miscarriage (group C).
On testing for the presence of inherited or acquired thrombophilic factors, researchers found the increased incidence of antiphospholipid antibodies, factor V Leiden (FVL) and methylenetetrahydrofolate reductase (MTHFR) in the study group, compared to control groups. The study group demonstrated at least one inherited or acquired thrombophilic factor in 68.9% of women, compared to 25.6% and 25% in the corresponding control groups. Combined thrombophilia, the presence of two or more thrombophilic risk factors, was observed more frequently in women with history of repeated IVF failure (35.6%) than in the control groups (4.4% and 3%, respectively). The study results demonstrated that thrombophilia plays an important role in IVF-ET failure, thereby necessitating the screening of women for the disease condition.
Thrombophilia, the predisposition to development of thrombosis, can be acquired or inherited. Acquired or secondary thrombophilia may be associated with cancer, myeloproliferative disorders, pregnancy or postpartum, or with the exposure to drugs such as oral contraceptives and chemotherapy. Hereditary (familial) or primary thrombophilia may occur due to mutation of factor V Leiden, or prothrombin G20210A, and the deficiency of cystathionine beta synthase (homocystinuria), antithrombin, protein C, or protein S. Thrombophilia impairs the initial vascularization during implantation, an important process for a successful pregnancy, resulting in IVF-ET failure.
Low-molecular weight heparins, made up of short chains of polysaccharide, are used as anticoagulant or prophylactic treatment of venous thromboembolism following major orthopedic surgery and trauma victims. It demonstrates its major anticoagulant activity through the activation of antithrombin, while LMWH chains with high-affinity pentasaccharide are associated with the catalysis of factor Xa inactivation.
With the current study implicating the benefits of low-molecular weight heparins; further investigations are imperative for establishing LMWH as a potential candidate for standard thromboprophylactic treatment in patients with thrombophilia and repetitive IVF-ET failure.
1. Qublan H, Amarin Z, Dabbas M, et al. Low-molecular-weight heparin in the treatment of recurrent IVF-ET failure and thrombophilia: A prospective randomized placebo-controlled trial. Hum Fertil (Camb). 2008 Dec;11(4):246-53.
2. Qublan HS, Eid SS, Ababneh HA, et al. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum Reprod. 2006 Oct;21(10):2694-8.