Low Molecular Weight Heparin in Recurrent Miscarriage With Negative Antiphospholipid Antibodies
Status:
Completed
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Recurrent miscarriage (RM) is traditionally defined as three or more consecutive miscarriages
occurring before 20 weeks post-menstruation. It is one of the most common clinical problems
in reproduction, yet a definite cause can be established in only 50 percent of cases (ACOG
practice bulletin, 2002). Many etiological factors have been proposed but none of them has
been fully substantiated. RM has been directly associated with maternal thrombophilic
disorders, parental chromosomal anomalies, and structural uterine anomalies and indirectly
with maternal immune dysfunction and endocrine abnormalities.
The association between pregnancy loss and antiphospholipid antibodies (aPL) was first
noticed in the latter third of the last century. The antiphospholipid syndrome (APS) is
characterized by the presence of antiphospholipid antibodies (APLA), associated with venous
and/or arterial thrombosis, and/or pregnancy loss. The adverse pregnancy outcomes associated
with the presence of APLAs include: recurrent fetal loss, intrauterine growth restriction
(IUGR), and severe pre-eclampsia especially of early onset.
Testing the effect of Heparin in treatment of cases with RA but negative for APA has bee done
in few animal and clinical studies. Animal studies showed that the subset of cases with
disorders suspicious for APS but who had negative test results for LAC and aCL is carrying
antibodies pathogenic to murine pregnancy. Testing other immunoglobulin G may provide
additional means to identify cases with an yet uncharacterized immune condition. Moreover,
the clinical relevance of low levels of APLA in these women remains unproved.
Randomized prospective study was done to assess the efficacy of early thromboprophylaxis of
Low molecular weight heparin (LMWH) (Enoxaparin sodium 20 mg, once daily subcutaneously) in
women with a history of recurrent miscarriages without identifiable causes versus no
treatment. The results showed that, there is a significant reduction in the incidence of both
early and late miscarriages (8.8% vs 4.1%) (2.3% versus 1.1%) with or without treatment,
respectively.
Cochrane Database systemic review (2005) shows randomized comparative studies for treating
recurrent miscarriage in women without antiphospholipid syndrome. The first group treated by
low dose aspirin alone and the second group treated by low dose aspirin + LMWH. The result of
these studies shows that no significant differences between the two groups and identify the
need of large randomized controlled trial to solve this problem.
The above evidence suggests the probability of presence of untested LAC and aCL or very low
levels of APLA by commonly used methods in women with recurrent miscarriage. These antibodies
may explain recurrent miscarriage in cases with negative antiphospholipid antibodies. It
remains to test the efficacy of heparin (proven effective treatment in those with positive
antibodies) in the patients with negative antibodies. Finding a solution to this frustrating
problem may open the way for an unsolved problem.
The proposed study is an open labeled randomized controlled trial (RCT) To evaluate the
effect of LMWH versus no heparin in treatment of recurrent miscarriage that is negative for
antiphospholipid antibodies testing.