Use of enoxaparin in recurrent pregnancy loss with and without thrombophilia

Abstract

Significant advances have been made in the diagnosis and treatment of recurrent pregnancy loss (RPL), however, almost half of
couples do not receive a definitive diagnosis. The presence or absence of thrombophilia has been associated with clinical outcomes in women with RPL, and there are reports of the impact of prophylactic low-molecular-weight heparin (LMWH) therapy combined with aspirin in increasing live birth rates (LBR) and preventing miscarriages. To determine the effectiveness of enoxaparin (the most widely used and available LMWH in our setting) with or without aspirin (+/- ASA) vs. Observational (+/- ASA); a rapid literature review of prophylactic enoxaparin +/- ASA in increasing LBR and preventing miscarriage in subjects with RPL with or without thrombophilia was conducted. A total of 316 publications were identified, of which 176 met the review criteria. 22 controlled studies were ultimately selected: 10 studies (population with thrombophilia), 15 studies (population without thrombophilia), and 3 studies with a mixed population. The studies did not show homogeneity in the population involved in terms of age, body mass index, history of autoimmune disease, thromboembolic disease, type of thrombophilia, acquired, congenital, or mixed, dose of enoxaparin with ASA, and the start of pharmacological intervention. In subjects with thrombophilia, the enoxaparin +/- ASA intervention was beneficial in increasing LBR (RR 2.54, Z=2.70, p=0.007) and reducing miscarriage (RR 0.32, Z=4.59, p<0.00001). In subjects without thrombophilia, the enoxaparin +/- ASA intervention was beneficial in increasing LBR (RR 1.14, Z=2.80, p=0.005) and was not effective in preventing miscarriage (RR 0.85, Z=0.91, p=0.36). The quality of evidence for biases was significant, including: random sequence bias (45%), allocation concealment bias (81%), performance bias (86%), and detection bias (31%). Despite the heterogeneity of the studies in this rapid review, it can be observed that enoxaparin +/- ASA was effective in increasing LBR in RPL with and without thrombophilia, while it was only effective in preventing miscarriage in RPL with thrombophilia. Controlled studies with broad thrombophilia laboratory panels, similar doses of enoxaparin and ASA, monitoring, and a common starting time are needed.