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Problem: The humoral immune response to phospholipids was investigated in women with reproductive failure [1073 women after one in vitro fertilization (IVF), 853 women after two and more IVF, 627 women after three and more repeated spontaneous miscarriages or missed abortions, 412 women after diagnostic laparoscopy] and compared with that of 391 healthy fertile women., Method of Study: Sera from all women in the study were tested by enzyme-linked immunosorbent assay (ELISA) for the detection of IgG, IgA, and IgM isotypes of antibodies against seven phospholipids (aPLs), i.e. cardiolipin, L-phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylacid as well as against beta2-glycoprotein I., Results: Patients after two and more IVF (48 and 50%, respectively), patients with three and more repeated spontaneous miscarriages (50 and 46.5%, respectively) are associated with significantly higher serum levels of aPLs against inositol, and L-serine (P < 0.01). A quarter of them were positive for three and more aPLs., Conclusion: It seems that determination of aPLs only against cardiolipin in reproductive failure is not sufficient for obstetric-gynecology diagnosis as the primary anti-phospholipid syndrome. Our long-ranging study (from 1998 to 2003) shows the necessity to test for a complete aPLs profile. Sera from patients after two and more IVF procedures, and sera from women after three and more repeated abortions are immunologically more active than sera from women after one unsuccessful IVF and sera from women after diagnostic laparoscopy. This important result is very significant for future treatment.