LMWH in IVF – Biomarkers and benefits

There is biological plausibility that coagulation activation underlies a proportion of in vitro fertilisation IVF failures and recurrent early clinical pregnancy loss (RPL). However, low-molecular-weight heparin (LMWH) use, based upon previous clinical outcome alone, is not effective in preventing RPL. RPL is heterogeneous in mechanism. Identifying those with an underlying thrombotic mechanism would allow stratification for LMWH treatment. Annexin A5 is an anticoagulant protein expressed on the trophoblast surface. The annexin A5 M2 haplotype (ANXA5 M2) is associated with several placenta mediated pregnancy complications (PMPC) and poor IVF outcome. It is transmitted equally by males and females. A pragmatic observational study of IVF couples screened for M2 carriage and treated with LMWH achieved a 37.9% live birth rate, similar to an unscreened and untreated group with fewer adverse risk factors for conception and a better prognosis from assisted conception. This suggests that LMWH may counteract the adverse effects of M2 carriage. Using this biomarker to stratify IVF and PMPC patients for LMWH treatment merits further evaluation.