Immunology: High fecundity rates following in− vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin

Abstract

This study was undertaken to explore whether intervention with heparin and aspirin (H/A) in selected patients undergoing in-vitro fertilization (IVF) and embryo transfer could improve fecundity rates. Specifically, it explored the possibility that women diagnosed with organic pelvic disease who demonstrated antiphospholipid antibodies (APA) could benefit from H/A administration in a similar manner to that used in patients with recurrent pregnancy loss. We used an enzyme-linked immunosorbent assay for six different phospholipids to identify patients who expressed APA before they underwent IVF/embryo transfer. This study was confined to the first IVF/embryo transfer cycle that followed assessment of APA status and accordingly, the number of IVF/embryo transfer cycles corresponds with the number of patients treated. APA seropositive patients were treated with aspirin, 81 mg orally q.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 of controlled ovarian stimulation. The endpoint for success was a live birth or an ultrasound confirming fetal cardiac activity (a viable pregnancy). The prevalence of APA in patients diagnosed with organic pelvic disease (53%) was much higher than in those without female pathology (14%). The administration of H/A to APA seropositive patients significantly (P < 0.05) improved the viable pregnancy rate (49%) compared to the untreated APA seropositive group (16%). The viable pregnancy rate for APA seropositive women treated with H/A was also significantly (P < 0.001) higher than for untreated APA seronegative patients (27%). We conclude that all women undergoing IVF/embryo transfer should be tested for APA prior to initiating ovarian stimulation and those with APA seropositivity should be treated with H/A.

Is there a Role for Antithrombotic Therapy in the Prevention of Pregnancy Loss?

“…Kutteh et al [40] reported a higher implantation rate in the group of women treated with heparin and aspirin (25 vs. 19.4%) but no statistically significant differences were detected in implantation, pregnancy and ongoing pregnancy rates between those who received standard therapy and those treated with heparin and aspirin. In contrast, Sher et al [41] reported that treatment with aspirin and heparin was associated with a significant beneficial effect (rate of ongoing pregnancy: 49 vs. 16%, respectively). Similarly, in a retrospective study by Hasegawa et al [42], treatment with aspirin (81 mg/day) and prednisone (10 mg/ day) improved the implantation rate in women with antinuclear antibodies, with or without aPL, who were undergoing IVF.…”

Roles of Antiphospholipid Antibodies, Antithyroid Antibodies and Antisperm Antibodies in Female Reproductive Health

“…The administration of heparin/aspirin to APA-seropositive patients significantly improved the clinical pregnancy rate (49%) compared to the untreated APA-seropositive group (16%). This suggested that all women who chose IVF should undergo APA testing prior to initiating ovarian stimulation and those with APA seropositivity should be treated with heparin/aspirin [33,34. ]…”

Anticoagulation and in vitro fertilization and ovarian stimulation

“…1,6,15 The effect of unfractionated heparin (with aspirin therapy) on in vitro fertilization outcome has been evaluated in several studies, with inconsistent results. [16][17][18][19][20][21] Most of these studies enrolled women with antiphospholipid or other auto-antibodies and were observational in nature. 16,[18][19][20][21] However, one single-center double-blind randomized crossover trial that compared unfractionated heparin 5000 units subcutaneously twice daily and aspirin from the day of embryo transfer with negative pregnancy test or week 14 of pregnancy with placebo in women with recurrent implantation failure and at least one auto-antibody (antiphospholipid antibody or antinuclear antibody) reported no significant difference in pregnancy or implantation rates between treated and placebo cycles (Table 3).…”

“…[16][17][18][19][20][21] Most of these studies enrolled women with antiphospholipid or other auto-antibodies and were observational in nature. 16,[18][19][20][21] However, one single-center double-blind randomized crossover trial that compared unfractionated heparin 5000 units subcutaneously twice daily and aspirin from the day of embryo transfer with negative pregnancy test or week 14 of pregnancy with placebo in women with recurrent implantation failure and at least one auto-antibody (antiphospholipid antibody or antinuclear antibody) reported no significant difference in pregnancy or implantation rates between treated and placebo cycles (Table 3). 17 The results of 3 recent meta-analyses that investigated whether low-molecular-weight heparin (LMWH) administered around the time of implantation improves clinical outcomes in women undergoing assisted reproduction are shown in Table 2.…”