Background: RECURRENT SPONTANEOUS ABORTION (RSA) is usually defined as three or more consecutive pregnancy losses before 20th week of gestation. Although different factors are considered as etiology of RSA but in some cases, despite of extensive work up, the cause of RSA remains unknown which called UNEXPLAINED RSA. Immunological factors are suggested as etiological factors of UNEXPLAINED RSA. On the other hand, pattern recognition receptors (PRRs) are one of the most imperative components of innate immunity which can recognize ligands derived from various pathogens. Toll like receptors (TLRs) as a main group of PRRs consist of at least 10 functional proteins in human. After ligand recognition, TLRs activate intracellular signaling cascade which induce inflammatory and / or anti-viral responses. TLR5 is one of the cell surface TLRs which recognizes bacterial flagellin. In present study, the expression of TLR5 gene was tested in endometrium of women suffering from UNEXPLAINED RSA.Materials and Methods: Endometrial samples were obtained between day 19th and 24th of menstrual cycle (window of implantation) from 10 women with UNEXPLAINED RSA and 6 fertile women who had at least one successful pregnancy (control group). TLR5 gene expression was studied by RT-PCR and then quantified by real time PCR.Beta actin was used as housekeeping gene.Results: TLR5 gene expression was detected in endometrium of patients with UNEXPLAINED RSA and normal women. The mean relative expression of TLR5 gene was higher in endometrium of women with UNEXPLAINED RSA in compare to normal ones at significant level.Conclusion: This finding suggests that TLR5 might play important role in the pathogenesis of UNEXPLAINED RSA since TLR5 signaling could result in inflammatory cytokine production. It has been also proposed that increased inflammatory microenvironment of endometrium may lead to implantation failure.

BACKGROUND AND OBJECTIVE: Chronic endometritis is one of the most specific, but not the most common causes of infertility, which reduces the amount of pregnancy and poor results of pregnancy, such as preterm labor and ABORTION. The aim of this study was to evaluate the role of chronic endometritis in RECURRENT SPONTANEOUS ABORTIONs (RSA) and to determine the bilateral relationship between the histological and pathological findings of this inflammation. METHODS: A case controlled-prospective observational study was performed on one hundred women 20-35 years in the Fatemeh Zahra infertility center and Rohani hospital. Patient group include forty patients with UNEXPLAINED RSA and control group include 60 women that underwent hysteroscopy due to vaginal bleeding or other causes except RSA. All of the women underwent endometrial biopsy and examined by pathologist for presence plasma cells in stroma. FINDINGS: In all patients endometritis rate was 8%. Patients with RSA had a significantly higher incidence of CE both hysteroscopically (30% vs. 6. 7%; p<0. 005) and pathologically (27. 5% vs. 6. 7%; p < 0. 005). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of hysteroscopy in the diagnosis of CE were 93. 3%, 97. 6%, 87. 5% and 98. 8% respectively. Also the PPV and NPV of hysteroscopy, sensitivity, specificity in the diagnosis of endometrial polyp were 100%, 87. 3%, 76. 3% and 100% respectively. CONCLUSION: Based on the results, there was a significant association between CE and UNEXPLAINED RSA. Due to high sensitivity and acceptable specificity of hysteroscopy in diagnosis of CE and endometrial polyp, we recommended hysteroscopic evaluation of patients with UNEXPLAINED RSA.

Background: Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus.Objective: This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with RECURRENT SPONTANEOUS ABORTION (RSA).Materials and Methods: Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using c2 test.Results: There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA.Conclusion: Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women.

Background: RECURRENT SPONTANEOUS ABORTION (RSA) is caused by multiple genetic and non-genetic factors. Around 50% of the RSA cases have no known etiology and are considered as UNEXPLAINED RSA (URSA). Estrogens, via binding to their receptors, play an important role in female reproduction. This study aimed to investigate whether single nucleotide polymorphisms (SNPs; +1082G/A, +1730G/A and rs1256030 C/T) in the estrogen receptor beta (ESR2) gene are associated with susceptibility to URSA in a population of Iranian women.Methods: In this case-control study, the study groups consisted of 240 subjects with a history of URSA and 102 fertile women as controls. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured on day 2-3 of menstrual cycle. Two functional SNPs, +1082G/A (a silent mutation in exon 5) and +1730G/A (3' untranslated region of the exon 8),and one intron,rs1256030C/T, in the ESR2 gene were genotyped, using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis.Results: Serum levels of LH were significantly increased in URSA women. No significant differences in distribution of +1082G/A, +1730G/A and rs1256030C/T between URSA and control groups were observed.Conclusion: Our findings suggest that the studied SNPs on ESR2 gene may not be associated with URSA.

Background: The aim of this study was to examine the possible relationship between sperm DNA integrity and chromatin packaging evaluated by cytochemical assays, traditional sperm parameters and RECURRENT SPONTANEOUS ABORTION (RSA) of unknown origin.Materials and Methods: In this cohort study, 40 couples with a history of RSA and 40 couples with proven fertility were considered as case and control groups respectively.The semen samples of all husbands were analysed for sperm parameters and also sperm chromatin and DNA integrity assessed using cytochemical tests including aniline blue (AB), chromomycin A3 (CMA3), toluidine blue (TB), acridine orange (AOT) and nuclear chromatin stability assay.Results: Among different sperm parameters, only slow motility was significantly different between the two groups. In sperm chromatin evaluations, there were significant differences between the two groups in all of the tests. In addition, the majority of semen samples in RSA patients exhibited upper percentages of abnormal spermatozoa than the cut-off values regarding different cytochemical assays.Conclusion: Our study showed that in the cases of RSA, slow motility had a significant reduction in comparison with controls and also spermatozoa of men from RSA group had less chromatin condensation and poorer DNA integrity than spermatozoa that obtained from fertile men with no history of RSA.

objective: To Determine the incidence of diminished ovarian reserve in UNEXPLAINED RECURRENT ABORTION. Materials and methods: among 116 women with complaint of RECURRENT ABORTION who referred to Ghaem hospital, after evaluation, 25 women with UNEXPLAINED RECURRENT ABORTION were chosen as the test group and the control group (n=25) were women with a history of normal pregnancy. Mean age, day 3 serum FSH and E2 levels, presence or absence of a history of infertility and menstrual cycle lengths were compared between two groups. Results: Day 3 FSH and E2 Levels were higher in the UNEXPLAINED RECURRENT ABORTION group compared with the control group (61% VS 16%) P<0.005. Other factors did not differ between two groups. Conclusion: Women with UNEXPLAINED RECURRENT ABORTION have a greater incidence of elevated day 3 serum FSH and E2 levels than do women with a normal pregnancy history. Therefore diminished ovarian reserve may contribute to RECURRENT pregnancy loss and should be considered as a part of the work – up for UNEXPLAINED RECURRENT ABORTION.  

Introduction RECURRENT SPONTANEOUS ABORTION (RSA) is one of the most common complications in reproductive ages. Several factors such as genetic, anatomical, and endocrine disorders, infection, and environmental and immunological factors have been involved in RSA. In cases of ABORTIONs, whose reasons are known, the chance of success in pregnancy can be increased after the elimination of the defective factors; but, in women with a history RSA with an unknown reason, there is an imbalance in the regulatory mechanisms of immune cells, and even the pattern of immunological cells changes in these women. Actually, an inappropriate immune response is often associated with pregnancy loss. Immunologic factors involved in patients with RSA have gradually been identified, using diagnostic methods and several studies. The present study was conducted with the aim of reviewing RSA immunology and new findings in this field. In this study, more than 40 articles on immunologic factors involved in RSA were reviewed. Conclusion Based on the current findings related to the immunology of pregnancy, due to the extensive role of the immunologic factors in this disorder, more accurate identification of the functional role of each immunologic factor becomes more important. Also, new therapeutic approaches will be addressed to the researchers in this field based on the changes in the function of immune system.