Placental inflammation is associated with poor pregnancy outcome in women with reduced fetal movements

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Abstracts / Journal of Reproductive Immunology 94 (2012) 5–130

patients, while there was no significant difference between the recurrent miscarriage patients and infertility patients, there was also no significant difference between the recurrent implantation failure patients and recurrent miscarriage patients. There were no significant differences of other immunological parameters in the three groups. CONCLUSIONS: IFN-␥ as one of the major Th1 cytokines may play a critical role in unsuccessful pregnancy, the Th1 cytokine polarization may be partly responsible for recurrent implantation failure and recurrent miscarriage. doi:10.1016/j.jri.2012.03.395 P 094 Determination of maternal serum macrophage inhibitory cytokine 1 (MIC 1) levels-is ita marker for increased risk of miscarriage in IVF patients? K. Penkova 1,2,∗ , D. Baltadzhieva 1,2 , M. Metodieva 1,2 , P. Angelova 1 1 2

SBALGAR “Dr Malinov“, Immunology, Sofia, Bulgaria Bulgaria

Imbalances in the intrauterine cytokine milieu around the time of implantation may play a causative role in early pregnancy failure. Cytokines appear to be an important component of a communication network at the fetomaternal interface. The placenta is the only tissue that expresses large amounts of MIC-1 under normal physiologic conditions MIC-1 has immunomodulatory activity and acts to maintain pregnancy by suppressing the production of proinflammatory cytokines. Recent studies have revealed the potential clinical use of serum MIC-1 levels in the monitoring of pregnancy. The aim of our study was to evaluate the prognostic value of serum MIC-1 levels in pregnant women treated with IVF. In the study, 46 women with unexplained infertility undergone IVF procedure were included at positive blood pregnancy test. Serum samples were collected from the women between 4 - 12 weeks of pregnancy andMIC-1 concentrations were measured using a sensitive enzymelinked immunosorbent assay (BioVendo, CzR). Eight women miscarried (17.39%)- 3 women in 7 g.w., 3 women in 9 g.w. and 2 women in 11 g.w. Patients were divided into 2 groups: women with miscarriage (MC)and women with successful pregnancy outcome (SPO). No difference in MIC 1 levels was observed in 3-5th weeks of gestation between the groups Serum levels of MIC-1 in 6th week of gestation were significantly higher (p = 0.02386) in the SPO group in comparison with the MC group. Maternal MIC-1 serum levels might have a clinical implication as a marker for an increased risk of miscarriage in IVF patients. doi:10.1016/j.jri.2012.03.396

P 095 Placental inflammation is associated with poor pregnancy outcome in women with reduced fetal movements E. Badger, A.E.P. Heazell, P. Dutton, R. Jones ∗ University of Manchester, MFHRC, Manchester, United Kingdom PROBLEM: Fetal growth restriction (FGR) and stillbirth are significant pregnancy complications. Women experiencing a reduction in fetal movements (RFM) are at increased risk of FGR and stillbirth. Our recent studies have found evidence of placental dysfunction in cases of RFM. The origins of placental dysfunction have not been explored. We investigated whether placental inflammation was more common in pregnancies complicated by RFM, and the relationship with poor pregnancy outcome. The involvement of inflammatory cytokines and chemokines was also examined. METHODS: Placentas of women experiencing RFM in the third trimester were collected (n = 56), and subdivided into those in normal and poor pregnancy outcome (FGR, stillbirth or admission to the neonatal intensive care unit). Leukocyte infiltration was assessed by immunohistochemistry for CD45, followed by analysis of leukocyte subtype using antibodies for CD68, CD8 and neutrophil elastase (NE). Bioplex assays for 13 cytokines/chemokines were performed on placentas and maternal serum from a subset of participants. RESULTS: 15 out of 56 (26.8%) placentas had evidence of leukocyte infiltration. This was more common in women with poor pregnancy outcome: 9/16 samples from poor pregnancy outcome contained leukocyte infiltration compared to 6/40 samples with a normal pregnancy outcome (p = 0.0055). This increase was mainly due to a significantly higher number of cytotoxic CD8+ T-lymphocytes infiltrating the villous stroma. Neutrophils were undetectable in most samples. The cytokines and chemokines examined did not differ between placentas with and without villitis. Concentrations of TNF-␣ were higher, and CXCL-10 lower, in serum of women with poor outcome (p < 0.05). CONCLUSION: This study has shown a relationship between the level of placental leukocyte infiltration, in particular CD8+ T cells, and poor pregnancy outcome in women experiencing RFM. This is a hallmark of villitis of unknown etiology (VUE), which may contribute to placental dysfunction leading to FGR/stillbirth. Failure to detect changes in pro-inflammatory cytokines may be due to the highly focal nature of VUE. Changes in circulating inflammatory cytokines have potential as screening tests, as VUE is currently only diagnosed post delivery. Studying women with RFM provides a high risk patient group in which to study placental pathology in stillbirth without confounding post-mortem effects. doi:10.1016/j.jri.2012.03.397