A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies

Objective: To investigate whether heparin and low-dose aspirin increase the pregnancy rate in antiphospholipid antibody or antinuclear antibody-seropositive women with IVF implantation failure. Design: A double-blind, randomized, transfer-by-transfer of fresh or cryopreserved embryos, crossover trial. Setting: A hospital infertility clinic and associated IVF service. Patient(s): Women seropositive for at least one antiphospholipid (APA), antinuclear (ANA), or beta(2) glycoprotein I autoantibody and greater than or equal to10 embryos transferred without achieving pregnancy (n = 143). Intervention(s): Subcutaneous unfractionated heparin (5,000 IU b.i.d.) and aspirin (100 mg daily) (158 transfers of 296 embryos) or placebo (142 transfers of 259 embryos) from the day of embryo transfer. Main Outcome Measure(s): Fetal heart per embryo transferred (implantation rate). Result(s): There was no significant difference in pregnancy rates or implantation rates between treated and placebo cycles; for example, fetal hearts per embryo transferred implantation rates were 6.8% (20/296) and 8.5% (22/259), respectively, and the generalized estimating equation covariate adjusted relative pregnancy rate was 0.65 (95% confidence interval, 0.33-1.28). The implantation rate for seropositive trial participants (42/555, 7.6%) compared favorably with that for IVF implantation-failure patients continuing treatment outside the trial (147/3237, 4.5%). Conclusion(s): Heparin and aspirin did not improve pregnancy or implantation rates for APA-positive or ANA-positive patients with IVF implantation failure. (C) 2003 by American Society for Reproductive Medicine.