Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.
BACKGROUND
A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable.


OBJECTIVE
To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL.


METHODS
Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387).


METHODS
14 university hospitals and perinatal care centers in Germany and Austria.


METHODS
449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography.


METHODS
Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation.


METHODS
Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications.


RESULTS
At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH).


CONCLUSIONS
Placebo injections were not used, and neither trial staff nor patients were blinded.


CONCLUSIONS
Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not recommended for preventing miscarriage.


BACKGROUND
Pfizer Pharma.
Ekkehard
E
Schleussner
Gabriele
G
Kamin
Gregor
G
Seliger
Nina
N
Rogenhofer
Susanne
S
Ebner
Bettina
B
Toth
Michael
M
Schenk
Melanie
M
Henes
Michael K
MK
Bohlmann
Thorsten
T
Fischer
Oana
O
Brosteanu
Rupert
R
Bauersachs
David
D
Petroff
D000026:Abortion, Habitual / Q000517:prevention & control*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D017985:Dalteparin / Q000627:therapeutic use; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D050498:Live Birth; D011247:Pregnancy; D014815:Vitamins / Q000627:therapeutic use
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014815:Vitamins; D017985:Dalteparin