Low-Molecular-Weight Heparin for the Treatment of Unexplained Recurrent Miscarriage With Negative Antiphospholipid Antibodies: A Randomized Controlled Trial

Abstract

Background: Recurrent miscarriage (RM) is one of the most common clinical problems in reproduction with no definite cause in about 50% of the cases. The study aims to evaluate the effect of low-molecular-weight heparin (LMWH) in the treatment of women with RM negatively tested for antiphospholipid antibodies (APAs).

Methods: An open-labeled registered randomized controlled study (NCT 01608347) included women who attended the outpatient clinic in Assiut Women Health Hospital and Nag-Hamady Central Hospital, Egypt, with 3 or more unexplained RM. Eligible participants were randomly assigned into 2 groups. The study group included 150 patients receiving LMWH (Tinzaparin sodium 4500 IU) subcutaneous daily injection with 500 µg folic acid once daily orally started once positive pregnancy test till the 20th week of gestation. The control group included 150 patients receiving the same dose of folic acid alone. The primary outcome of the study was the rate of continuation of a viable pregnancy after 20 weeks of gestation.

Results: There was no significant difference between both groups as regards age, parity, or number of previous miscarriages. There was a significant increase in women who continued their pregnancy beyond 20 weeks in the study group compared to the control group (73.3% vs 48%, respectively; P = .002). The take-home baby rate was also significantly higher in the LMWH group compared to the control group ( P = .001).

Conclusion: Early start of LMWH decreases the incidence of miscarriage in the first 20 weeks of pregnancy in women with unexplained RM negative for APAs.

Keywords: antiphospholipid antibodies; heparin; recurrent miscarriage; unexplained pregnancy loss.