Immunological mechanisms might contribute to the repeated implantation failure in the in-vitro fertilization program. AI might be a valuable therapeutic option in this situation. Here we summarize our extensive experience with this immunotherapy. We conducted a retrospective analysis of all couples who were referred to our outpatients department from 1996 to 1998 for AI after two or more embryo transfers (ET). Six hundred and eighty-six couples (89%) continued IVF/ICSI and were followed up for 2–3 years. On average patients entered AI after 3–4 IVF–ET at an age of 33 years and completed IVF/ICSI treatment after another 2 ET; 2.6 embryos per ET were transferred according to the German embryo protection law. The cumulative birth rate war 38% after IVF transfer and 42% when spontaneous pregnancies were included. Until the age of 36 years the rates of viable pregnancies and birth were improved by a quarter in the first 6 months as compared to the second half year (33.3% versus 26.3%, 26.0% versus 19.6%) and to the German IVF Registry of 1998. Couples who had undergone more than three ET before AI seemed to benefit most. Our data suggest that AI is a valuable adjuvant therapy with a temporary effect when 3–4 IVF/ICSI transfers have been unsuccessful. The underlying immunomodulatory mechanisms require further investigation.