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.

The treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is selective in that it does not apply in cases in which IgG- or IgM-related APAs are directed against PE or PS. In such cases, the addition of IVIg significantly improves the outcome.

We conclude that IVIg therapy significantly improves IVF success rates in ATA+ women.

IVF outcome is significantly improved when H/A and IVIG are administered to APA+ women with repeat IVF failures. APA- women do not seem to benefit from such treatment.

Antiphospholipid antibodies (APA) have been identified in patients with recurrent pregnancy loss and IVF failure. Of these, antiphosphatidylethanolamine (aPE) and antiphosphatidylserine (aPS) may have special significance. A link between increased natural killer cell activity (NKa+) and trophoblast cell apoptosis has also been reported. This study was undertaken to determine how the APA profile was associated with peripheral NK cell activity. We evaluated 197 female IVF candidates for APA and NKa. Eighty-nine patients (45%) were APA+ and of these, 51 (57%) were aPE/aPS+. Fifty-four patients (27%) had increased NK cell activity. Some 51% of APA+ and 78% of aPE/aPS+ patients had increased NK cell activity compared with 8% and 13% when APA and aPE/aPS tested negative respectively (P: < 0.0001). Non-male factor infertility patients were APA+ and NKa+ in 57% and 34% of cases respectively, compared with 19% and 13% if a pure male factor was present. Some 88% of aPE/aPS+, non-male factor patients had increased NK cell activity, compared with 12% who tested aPE/aPS negative (P: < 0.0001) and 25% of aPE/aPS+, isolated male factor patients (P: < 0.0001). These findings establish a direct relationship between APA (specifically aPE/aPS) and increased peripheral NK cell activity among non-male factor infertility patients. It is possible that APA do not directly cause reproductive failure but rather function as markers or intermediaries for an underlying, abnormal activation of cellular immunity.