Follicular proinflammatory cytokines and chemokines as markers of IVF success.

Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1ß, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF), chemokines (MIP-1α, MIP-1ß, MCP-1, RANTES, and IL-8), and other biomarkers (sAPO-1/Fas, CD44(v6)) in 153 women undergoing in vitro fertilization (IVF). Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6) were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6) but lower IL-ß and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6) characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1ß were associated with successful IVF-induced pregnancy.

Sequencing and annotated analysis of an Estonian human genome.

In present study we describe the sequencing and annotated analysis of the individual genome of Estonian. Using SOLID technology we generated 2,449,441,916 of 50-bp reads. The Bioscope version 1.3 was used for mapping and pairing of reads to the NCBI human genome reference (build 36, hg18). Bioscope enables also the annotation of the results of variant (tertiary) analysis. The average mapping of reads was 75.5% with total coverage of 107.72 Gb. resulting in mean fold coverage of 34.6. We found 3,482,975 SNPs out of which 352,492 were novel. 21,222 SNPs were in coding region: 10,649 were synonymous SNPs, 10,360 were nonsynonymous missense SNPs, 155 were nonsynonymous nonsense SNPs and 58 were nonsynonymous frameshifts. We identified 219 CNVs with total base pair coverage of 37,326,300 bp and 87,451 large insertion/deletion polymorphisms covering 10,152,256 bp of the genome. In addition, we found 285,864 small size insertion/deletion polymorphisms out of which 133,969 were novel. Finally, we identified 53 inversions, 19 overlapped genes and 2 overlapped exons. Interestingly, we found the region in chromosome 6 to be enriched with the coding SNPs and CNVs. This study confirms previous findings, that our genomes are more complex and variable as thought before. Therefore, sequencing of the personal genomes followed by annotation would improve the analysis of heritability of phenotypes and our understandings on the functions of genome.

Serum sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) associates negatively with embryo quality in infertility patients.

PROBLEM: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker of infection and inflammation. METHOD OF STUDY: We studied serum and follicular fluid sTREM-1 in infertile patients (N = 110) utilizing enzyme-linked immunosorbent assay. RESULTS: Serum and follicular sTREM-1 were in good correlation (Pearson's correlation 0.56, P < 0.0001) with higher values in follicular fluid (140.4 ± 34.4 and 115.6 ± 35.1 pg/mL, t-test, P < 0.0001). Endometriosis associated with lower follicular and serum sTREM-1 compared with male factor infertility patients (age-adjusted r = -25.7 pg/mL, P = 0.018; r = -22.1 pg/mL, P = 0.030). No associations between follicular or serum sTREM-1 and clinical parameters were found, except higher serum sTREM-1 associated with lower embryo quality in all patients (adjusted r = -0.3%, P = 0.033), with a cutoff value between 111.5 and 113.3 pg/mL (OR = 0.38, P = 0.048; OR = 0.34, P = 0.028) predicting that more than 39% of embryos would be with good quality. CONCLUSION: Serum sTREM-1 could represent a prognostic marker for female fecundity, probably indicating impaired inflammatory reaction of immune system.

Serum anti-endometrial antibodies in infertile women - potential risk factor for implantation failure.

PROBLEM: Female infertility patients with diverse etiologies show increased production of autoantibodies. METHOD OF STUDY: Immunoblot analysis of sera from patients with endometriosis and tubal factor infertility (TFI) and mass spectrometry identification of candidate antigens. RESULTS: The immunoblot results demonstrated the presence of IgA and IgG anti-endometrial antibodies (AEA) to various antigens at molecular weights ranging from 10 to 200 kDa. Differences were detected in certain AEA reactions between the patients' groups and particular AEA were associated with in vitro fertilization (IVF) implantation failure. IgA AEA to a 47-kDa protein were more prevalent in TFI patients and were associated with unsuccessful IVF treatment. This antigen was subsequently identified as alpha-enolase. CONCLUSION: Determination of the presence and spectra of AEA in patients with endometriosis and TFI undergoing IVF may be a useful marker to predict their pregnancy outcome.

Controlled ovarian hyperstimulation changes the prevalence of serum autoantibodies in in vitro fertilization patients.

PROBLEM: Autoimmune mechanisms are involved in etiology of female infertility, the medical problem frequently treated by in vitro fertilization (IVF). Controlled ovarian hyperstimulation (COH) with supraphysiological levels of sex hormones is achieved by IVF. METHODS OF STUDY: Anti-human-ovary and eight common autoantibodies [nuclear (ANA-H, ANA-R on human HEp-2 cell line and rodent antigen, respectively), smooth muscle (SMA), parietal cell, thyroid microsomal, mitochondrial, beta2-glycoprotein-I, cardiolipin antibodies] found in IVF patients (n = 129) were analyzed with regard to the number of previous IVF procedures and the age of the patient. The changes in autoimmune reactions caused by the COH were determined. RESULTS: Endometriosis and polycystic ovary syndrome were associated with a higher number of common serum autoantibodies compared with the tubal factor infertility (Proportion test, P < 0.05). ANA-R was associated with unexplained infertility [adjusted odds ratio (aOR) 8.79, P = 0.038]. SMA correlated with endometriosis (aOR 37.29, P = 0.008), male factor infertility (aOR 20.45, P = 0.018) and with the previous IVF procedures (aOR 2.87, P = 0.013). There was an overall decrease in the number of detectible autoantibodies after COH (Proportion test, P < 0.05). CONCLUSION: COH may have a suppressive effect on the humoral immunity by the time of embryo transfer but more conclusive studies are needed.