Acute side-effects are comparable to those reported after intradermal vaccination for infectious diseases. Specific risks for anaphylaxis, autoimmune or graft versus host disease were not detected.
In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor–recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)]. We then examined humoral alloimmune responses in healthy females subjected to a standardized injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
ObjectivesAfter recurrent implantation failure (RIF), empirical figures on further prospects are essential for counselling but difficult to estimate within single IVF centres due to high drop-out rates. Alternatively, couples referred to a tertiary unit for RIF were evaluated.Materials and methodsMulti-centre 2-year observational trial of 1,174 eligible couples treated consecutively with adjuvant lymphocyte immunotherapy (LIT) in a university immunological department from 1999 to 2002 after three or more unsuccessful fresh embryo transfers. Acquisition of data was completed in 2005.ResultsWith another 1.5 oocyte retrievals, delivery rate per couple depended on age (39.3% at <30 years, 16.9% at >39 years, P < 0.005). Prognosis was favourable when frozen embryo transfers had been conducted before (34.4 vs. 25.8%, P < 0.005). The outcome was slightly better in ICSI couples as compared to conventional IVF (31.0 vs. 24.8%, P < 0.05). Birth rates per fresh embryo transfer from the fourth to eighth retrieval were 17.4–18.3–15.0–12.9–12.9% (decline not significant). Apart from LIT, further additional interventions were given more often to couples who had had frozen embryo transfers before (49 vs. 40%, P < 0.005).ConclusionsFemale age and ovarian response are crucial for further IVF prognosis. Previous frozen embryo transfers indicate better chances. Couples with male factor infertility may benefit from intracytoplasmatic sperm injection (ICSI) because underlying female factors are less prevalent. Cycle rank had comparatively little impact. Additional interventions are preferentially offered to couples who have a favourable prognosis anyway. Their multiple use is common practice in RIF, but its value should be considered limited.
PurposeRecurrent miscarriage (RM) is a stressful condition which gives rise to extensive diagnostic evaluation and is seen as a potentially curable maternal disease. Nevertheless, epidemiological data have shown that outcome is related to fertility. In addition to maternal age and number of preceding miscarriages, further markers derived from the past history may support counselling.MethodsObservational trial comprising 228 couples who were referred between 1996 and 2003 for immunological evaluation at maternal ages 20–39 years after three or more spontaneously conceived primary first trimester miscarriages. They were interviewed in 2005, ongoing pregnancies were followed up until birth in 2006. Past obstetric history was correlated with 2 year cumulative pregnancy and delivery rates (CPR, CDR).ResultsCPR and CDR were 206/228 (90.4 %) and 174/228 (76.4 %). Duration of infertility was associated with lower CPR (up to 3/>3 years, p < 0.01), whereas age and number of preceding losses inversely correlated with CDR (<35 years/35–39 years, p < 0.002; 3/>3 miscarriages, p < 0.002). Detection of an embryonic heart beat in 2–3 of the first three miscarriages resulted in favourable outcome (CPR: p < 0.02, CDR: p < 0.002). Prognosis was excellent in younger fertile women after three miscarriages where vital signs had been detected; under less favourable conditions not only risks for further miscarriage, but also for secondary infertility were elevated.ConclusionSecondary infertility is a feature of RM. Embryonic vital signs in preceding pregnancies are prognostic markers and should be regarded as a strong confounding factor in trials on therapeutic interventions. Prevention may be more appropriate than treatment.
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