Does autoimmunity play a role in the risk of implantation failures?

158 non-pregnant women with recurrent implantation failures after IVF/ET procedures were tested for peripheral blood autoimmune profile. The control group consisted of 76 patients after first successful IVF procedure and pregnancy outcome. The objective of this study was to investigate different autoantibodies peripheral blood profile after excluding anatomical, endocrinological, endometrial and genetic disorders and to estimate the risk of implantation failures. The study's including criteria were 1.indications for IVF/ET determined by male factor and unexplained infertility 2. absence of implantation after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles. The presence of ANA in the sera increased the risk of RIF after ET/IVF procedures, especially in older patients. Patients with RIF have a higher frequency of the presence of autoantibodies ACA IgG, IgM and anti-ß2GP I IgG in the sera than in patients with successful pregnancies after IVF/ET procedures.

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population.

Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms' association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage.

The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women's heterozygosity in -716 HLA-G (p = 0.0206) and LILRB1 (p = 0.0131) against spontaneous abortion. Surprisingly, we observed more 9A/10A genotypes of KIR2DL4 gene carriers in the group of male partners from the miscarriage group in comparison to the men from the control group (p = 0.0288). Furthermore, there was no association of women's KIR2DL4 polymorphism with susceptibility to spontaneous abortion. Multivariate analysis indicated that women's -716 HLA-G and LILRB1 and men's KIR2DL4 9A/10A are important in terms of the protection or susceptibility to miscarriage, respectively (p = 0.00968). In conclusion, a woman's heterozygosity in HLA-G and LILRB1 might be an advantage for a success of reproduction, but the partner's heterozygosity in 9A/10A KIR2DL4 alleles might not.

Trace elements in seminal plasma of men from infertile couples.

INTRODUCTION: An analysis of lead, zinc, cadmium and other trace elements in semen of men from infertile couples was performed to determine the association between abnormal semen parameters and enviromental or occupational exposure to some trace metals. MATERIAL AND METHODS: Presence of manganese, cobalt, nickel, copper, zinc, molybdenum, cadmium, tin and lead was measured in seminal plasma of 34 men from infertile couples using spectrometry with time-of-flight analysis. Correlations among sperm parameters and trace metals were determined using cluster analysis and Pearson's correlation coefficient. RESULTS: Abnormally high concentrations of lead, cadmium, zinc and cobalt were found in 23 seminal plasma of men from infertile couples. The most consistent evidence was determined for an association between high cadmium concentration in seminal plasma and sperm count, motility and morphology below reference limits (p < 0.01). A correlation of significantly increased tin level and reduced sperm count in semen of men with limited fertility potential was observed (p = 0.04). CONCLUSIONS: In our study we observed a correlation of tin level with sperm count in semen of men with limited fertility potential.

Polish experiences with paternal lymphocyte immunization in women with recurrent miscarriages.

OBJECTIVE: This study aimed to evaluate the efficacy of PLI and results of subsequent pregnancy in women with RM showing alloimmune response. MATERIALS AND METHODS: Immunological investigations were performed in patients with RM. Subsequently, PLI was administered to 241 patients at their request. Of these, 202 conceived between September 2005 and September 2012. RESULTS: Of the 202 women, 169 pregnancies resulted in term delivery; the remaining 33 resulted in subsequent miscarriages (success rate = 83.7%). During seven-years observations of 202 tested individuals, 114 women were pregnant again for the second time and 92 pregnancies of them resulted in the next term delivery (success rate =80.7%). CONCLUSIONS: Alloimmune background indicated that PLI might improve pregnancy outcome in patients suffering from RM. Long-term monitoring did not reveal any negative effects of PLI on the immunological system in the treated women or newborn babies.

The occurrence of immunological disturbances in patients with recurrent miscarriage (RM) of unknown etiology.

OBJECTIVE: The 155 patients suffering from primary RM who took part in this study were qualified after excluding known causes of abortions. METHODS: The presence of the following immunological factors was examined in serum samples: autoantibodies such as anti-cardiolipin (ACA) IgG and IgM, lupus-anticoagulant (LA), anti-thyroid (ATA): anti-thyroglobulin (anti-TG) and anti-thyroid peroxydase (anti-TPO), anti-nuclear (ANA), anti-placental (APA) antibodies and alloimmunological disturbances following HLA-class I antibody test (LCT-lymphocytotoxic test), lack of blocking proliferative activity in mixed lymphocyte reaction test (MLR), anti-sperm (ASA) antibodies, levels of extracellular interferon γ (IFN γ) and tumour necrosis α (TNFα) produced by peripheral blood lymphocytes. RESULTS: Immunological disturbances were found in 69.1% of the patients suffering from primary RM of unknown etiology. The number of RM correlated with the frequency of immunological disturbance. Among the samples from patients who underwent ≥5 RM, positive levels of TNFα were the most frequently observed risk factor (up to 27%) (p=0.05). Although the incidence of immunological factors was comparable between patients with early and late pregnancy losses, elevated ATA levels were frequently seen among late miscarriage (95% CI=36.0, p≤0.01). CONCLUSION: The heterogeneity of immunological risk factors shown in this study indicates the usefulness of detecting alloimmune factors as well as autoantibodies in patients with RM of unknown etiology. This may be helpful to analyse the therapeutical effectivity of various treatment in a better characterized group of patients and to explain unsuccessful results of treatment in patients with RM of unknown etiology.