Anticoagulants for the treatment of recurrent pregnancy loss in women without antiphospholipid syndrome.
BACKGROUND
Since hypercoagulability might result in recurrent pregnancy loss, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained pregnancy loss.


OBJECTIVE
To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias.


METHODS
We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2004), the Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966 to March 2004), and EMBASE (1980 to March 2004). 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 spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias were eligible. Interventions included aspirin, unfractionated heparin, and low molecular weight heparin for the prevention of birth loss. 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. Data were entered into the Review Manager software and double checked.


RESULTS
Two studies (242 participants) were included in the review and for both of them data were extracted for the subgroups of women fulfilling the inclusion criteria of the review. In one study, 54 pregnant women with recurrent spontaneous abortion without detectable anticardiolipin antibodies were randomised to low-dose aspirin or placebo. Similar live-birth rates were observed with aspirin and placebo (relative risk (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In another study, a subgroup of 20 women who had had a previous fetal loss after the 20th week and had a thrombophilic defect were randomised to enoxaparin or aspirin. Enoxaparin treatment resulted in an increased live-birth rate, as compared to low-dose aspirin, RR 10.00, 95% CI 1.56 to 64.20).


CONCLUSIONS
The evidence on the efficacy and safety of thromboprophylaxis with aspirin and heparin in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias is too limited to recommend the use of anticoagulants in this setting. Large, randomised, placebo-controlled trials are urgently needed.
Di Nisio
M
M
Peters
Lw
L
Middeldorp
S
S
D000026:Abortion, Habitual / Q000188:drug therapy* / Q000209:etiology; D000925:Anticoagulants / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000150:complications; D005260:Female; 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