Heparin Does Not Increase Live Births in Pregnant Women with Previous Unexplained Recurrent Miscarriages: A Systematic Review and Meta-Analysis

The impact of heparin in pregnant women with previous unexplained recurrent miscarriages remains uncertain. The use of heparin in this patient population has been increasing with the hope of improving the rate of live births. We performed a systematic review of the randomized clinical trials addressing this question.

We searched MEDLINE (searched July 1^st 2012), CENTRAL (Issue 7 of 12, July 2012), American Society of Hematology (searched July 1^st 2012), clinical trials registries (http://clinicaltrials.gov/, searched July 1^st 2012), and bibliographies of relevant studies for randomized clinical trials comparing heparin (unfractionated or low molecular weight) to other best care approaches. Use of aspirin was allowed in either study arms. Included patients were pregnant women over 18 years of age with previous recurrent unexplained miscarriages (at least two at any trimester). We performed a meta-analysis using random effects models to estimate the pooled odds ratio. Statistical heterogeneity was calculated by using the I² statistic.

Eight trials proved eligible, five of which provided data from 1141 patients that could be included in the meta-analysis and three of which remain unpublished. Only the subgroup of patients with no antiphospholipid antibodies or inherited thrombophilia was included. There was a total of 839 live births observed. Enoxaparin was used in four trials and nadroparin was used in one trial. All trials randomized patients before the 8^th week of gestation. There were 430 live births (among a total of 561 pregnancies) and 409 live births (among a total of 580 pregnancies) in the heparin and other best care treatment arms respectively. The difference between the two treatment arms was not statistically significant with a pooled odds ratio of 1.49 (95% confidence interval: 0.84, 2.66; P = 0.17). There was a substantial heterogeneity among the results of different trials (Chi² = 14.91, P = 0.005; I² = 73%).

Available evidence suggests that heparin does not increase live births in pregnant women with previous unexplained recurrent miscarriages with no evidence of antiphospholipid antibodies or inherited thrombophilia. Future trials should explore new treatment strategies.

No relevant conflicts of interest to declare.