Follow up ALIFE study

In over 50% of cases of miscarriage the cause remains unexplained and for women
with unexplained recurrent miscarriage, no treatment to improve the chance of
live birth in a future pregnancy is known. In the recently performed *ALIFE
study* (Kaandorp, NEJM 2010) women with 2 or more miscarriages were randomised
to anticoagulant therapy or no treatment. The results showed that treatment
with anticoagulant therapy in women with unexplained recurrent miscarriage does
not increase live birth in a subsequent pregnancy. Several studies have
suggested an association between recurrent miscarriage and a common haplotype
of the Annexin A5 gene. Knowledge of the frequency of this haplotype and
possible other DNA-variations in the ALIFE cohort could provide insight in the
causes of recurrent miscarriage and the potential effect of anticoagulants.
Mutations in the human chorionic gonadotrophin (HCG) beta/luteinizing hormone
(LH) beta gene complex might be associated with recurrent miscarriage as well.
Only few data are available on this topic and the results are conflicting. More
information is necessary about the role of HCGβ gene variants or LHβ gene
variants in recurrent miscarriage. This information may facilitate the
improvement of early and preventive treatment of recurrent miscarriage.
Moreover, several coagulation disorders are associated with recurrent
miscarriage, but the mechanisms behind these associations are unclear.

The objective of this study is to collect blood samples of women who
participated in the ALIFE trial, to test for several DNA-variations as well as
anti β2 glycoprotein antibodies, but also to perform overall coagulation
assays, such as clot lysis assay and endogenous thrombin potential, to further
investigate possible causes of recurrent miscarriage.
DNA, RNA, citrated blood, heparin blood, EDTA blood, serum and plasma will be
stored in a biobank to enable future analyses of (coagulation) parameters and
DNA variations that play a role in the pathophysiology of pregnancy
complications and cardiovascular disease, and predict the response on
anticoagulant therapy of pregnancy complications.

This study is designed as a cohort study in women with recurrent miscarriage
and post hoc analysis of the effect of intervention in the ALIFE trial on women
with Annexin A5 haplotypes, or anti β2 glycoprotein antibodies.
Furthermore, a bio bank will be established to enable future research as
described in the objectives.

Participation in this study should involve no risk.
Participating women will undergo blood withdrawal once. We anticipate that the
results of the DNA tests and coagulation assays will have no direct
consequences for health and well being of the participating women. If the
results do turn out te be relevant, participating women will be informed if
they have indicated that they wish to be informed of this.