Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome.
BACKGROUND
Since hypercoagulability might result in recurrent miscarriage, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained recurrent miscarriage.


OBJECTIVE
To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two miscarriages without apparent causes other than inherited thrombophilia.


METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 1), MEDLINE (January 1966 to March 2007), and EMBASE (1980 to March 2007). We scanned bibliographies of all located articles for any unidentified articles.


METHODS
Randomised and quasi-randomised controlled trials that assessed the effect of anticoagulant treatment on the live-birth rate in women with a history of at least two miscarriages (up to 20 weeks of amenorrhoea) without apparent causes other than inherited thrombophilia were eligible. Interventions included aspirin, unfractionated heparin, and low molecular weight heparin for the prevention of miscarriage. One treatment could be compared with another or with placebo.


METHODS
Two authors assessed the trials for inclusion in the review and extracted the data. We double checked the data.


RESULTS
Two studies (189 participants) were included in the review. In one study, 54 pregnant women with recurrent miscarriage (RM) but no detectable anticardiolipin antibodies were randomised to low-dose aspirin or placebo. RM was defined as three or more consecutive miscarriages (occurring before 22 weeks' gestational age (based on last menstrual period)). Similar live-birth rates were observed with aspirin and placebo, both 81% (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In the other study, 107 women with consecutive recurrent miscarriage without any apparent cause and no hereditary thrombophilia were randomised between enoxaparin and aspirin. Here RM was stated as three or more consecutive first trimester miscarriages or at least two consecutive second trimester miscarriages. Similar live birth rates were observed with enoxaparin and aspirin, respectively 82% and 84% (RR 0.97, 95% CI 0.81 to 1.16).


CONCLUSIONS
There is a paucity in studies on the efficacy and safety of aspirin and heparin in women with a history of at least two miscarriages without apparent causes other than inherited thrombophilia. The two reviewed trials studied different treatments and only one study was placebo-controlled. Neither of the studies showed a benefit of one treatment over the other. Therefore, the use of anticoagulants in this setting is not recommended. However, large randomised placebo-controlled trials are still urgently needed.
Kaandorp
Stef
S
Obstetrics and Gynaecology, Academic Medical Center, Meibergdreef 9, P.O. Box 22660, Amsterdam, Netherlands, 1100 DD. s.p.kaandorp@amc.uva.nl
Di Nisio
Marcello
M
Goddijn
Mariette
M
Middeldorp
Saskia
S
D000026:Abortion, Habitual / Q000188:drug therapy* / Q000209:etiology; D000925:Anticoagulants / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000150:complications; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin