Twenty years of experience with paternal immunotherapy: a role as an enhancer of the in vitro fertilization

Abstract

Unexplained Recurrent Spontaneous Abortion (URSA) is a common pregnancy complication that implies loss within the first 20 weeks of gestation. Immunological mechanisms seem to participate in their development. Unexplained infertility has also been associated with these mechanisms. Paternal immunotherapy (PIT) is used worldwide as treatment for URSA, but protocols differ mainly in amount of mononuclear cells, routes of administration, or single versus several doses. Herein we report results from the use of PIT in a cohort of 416 primary URSA, 92 secondary URSA and 298 infertile women. All patients followed a multiple intra-dermal injection of paternal mononuclear cells until detection of more than 50% blocking activity in a mixed lymphocyte reaction (MLR-Bf). Patients and controls were followed during 2 years since their first consultation. Statistical comparisons were done by two-tailed unpaired t-test and Fisher?s exact test, considering differences significant when P<0.05. Primary URSA and infertile women showed a similar pattern achieving values of MLR-Bf above 50% after 3 PIT in 46% and 49% of patients, respectively. 60% of secondary URSA patients reached the desired value after only 3 injections. When analyzing outcome as succesful pregnancies, a live birth was present in 58% (n=242) of all primary URSA treated women vs. 23% in the control group (p< 0.0001, OR: 4.7, CI 95%: 3.3-6.6). Secondary URSA showed live births in 61% of patients (n=56) vs 28% in controls (p< 0.0001, OR: 4.0; CI 95%: 2.2-7.2). 33% of Infertile patients showed live births (n=99) vs 21% in controls (p=0.0009; OR: 1.9; CI 95%: 1.3-2.8). Analysis showed that best results were obtained in women between 20-35 years old. Treated women requiring IV fertilization became pregnant after 1.37±0.67 procedures (median: 1; range: 1-3) vs controls that required 2.75±0.84 (median: 3; range: 1-5) (p=<0.0001). These results confirm and extend the success of PIT for treatment of URSA and Infertile patients.