Objective: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).

Design: Randomised controlled trial.

Setting: Specialist clinic for recurrent miscarriages.

Subjects: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.

Intervention: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks9 gestation.

Main outcome measures: Rate of live births with the two treatments.

Results: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks9 gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks9 gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).

Conclusion: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

The prognosis for pregnancies in women with recurrent miscarriage associated with phospholipid antibodies is poor

This randomised controlled trial found that the prognosis improved with low dose aspirin and was further improved with the addition of low dose heparin to the aspirin

This combination may promote successful embryonic implantation in the early stages of pregnancy and protect against thrombosis of the uteroplacental vasculature after successful placentation

Most miscarriages occurred before 13 weeks9 gestation

Nearly a quarter of the successful pregnancies were delivered prematurely (before 37 weeks9 gestation), so close surveillance is necessary

Long term use of low dose heparin was associated with few complications