This study presents sample size considerations derived from the Efficacy of Thromboprophylaxis as an Intervention during Gravidity (EThIGII) trial (ClinicalTrials.gov: NCT00400387) to address the question of
low-molecular-weight heparin (
LMWH) treatment in women with recurrent pregnancy loss (RPL) depending on the M2/ANXA5 haplotype. To evaluate the possible influence of such treatment on
miscarriage rates of trial participants, a post hoc analysis of ANXA5 promoter genotypes in the light of M2/ANXA5 (RPRGL3) distribution was performed using logistic models.
DNA for genotyping was available from 129
LMWH and 95 control patients, 44 (19.6%) of whom were M2/ANXA5 carriers.
Miscarriages occurred in 1 (4.0%) of 25 M2/ANXA5 carriers from the
LMWH group compared to 4 (21.1%) of 19 in the control group, resulting in an odds ratio (95% confidence interval) for
miscarriage of 0.16 (0.016-1.5) for women treated with
LMWH. In noncarriers,
miscarriage rates were 6 (5.8%) of 104 versus 7 (9.2%) of 76 for the
LMWH and the control groups, respectively, corresponding to an odds ratio for
miscarriage of 0.60 (0.19-1.9). The apparent beneficial effects of
miscarriage rate reduction in M2/ANXA5 carriers with RPL concur with
biological considerations about improvement in reduced ANXA5 function through
LMWH treatment in an adequate murine model. The data obtained were instrumental to design proper assessment of the existence and magnitude of this effect.