Endometrium Of Infertile Patients Research Articles

Expression of HOXA10 and HOXA11 in the endometrium of infertile patients with chronic endometritis.

The study aimed to evaluate the impact of CE on the expression of HOXA10 and HOXA11 during the late proliferative phase in the endometrium of infertile women. A prospective, translational cohort study was conducted in partnership with the Hospital Universitário Antônio Pedro in Niterói and the Clínica Ginendo in Rio de Janeiro after approval by the Ethics Committee. The patients were selected to participate in the study after showing an indication for hysteroscopy. All participants were divided into three groups: infertile women with endometritis (n=10), infertile women without endometritis (n=17) and fertile women without endometritis (n=10). At hysteroscopy, two endometrial samples were obtaneid, with one sent for histopathological examination per the gynecologist's request and the other used for immunohistochemistry procedures to evaluate the expression of CD138, HOXA10 and HOXA11. CD138 was used to confirm the diagnosis of CE. The analysis of HOXA10 and HOXA11 was performed using the HScoring method for immunohistochemistry with polyclonal antibodies. Women with and without endometritis had lower HOXA10 and HOXA11 expression values than women in the control group (fertile women without endometritis). The expression of HOXA10 and HOXA11 during the proliferative phase is not significantly different between infertile women with endometritis and infertile women without endometritis. Translational studies with a larger number of patients should be performed.

Exploration of the potential roles of m6A regulators in the uterus in pregnancy and infertility

Infertility is a prevalent female reproductive disease worldwide. Currently, there are many unknown etiologies of infertility. N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic mRNA. This study intended to investigate the implications of m6A regulators in the uterus for pregnancy and infertility. Pregnant ICR mice on days (D) 0, 4, 6, 10, and 15 were used to monitor m6A methylation in the uterus by liquid chromatography-tandem mass spectrometry (LC–MS/MS), and then m6A methylation regulators were detected by real-time quantitative PCR (qPCR), western blot and immunohistochemistry (IHC). We found that m6A levels increased and that m6A regulators were expressed differently in the uterus during pregnancy. Then, we acquired expression data from endometrial tissue from women with infertility and recurrent pregnancy loss from the Gene Expression Omnibus (GEO) database. The expression of m6A regulators in infertility was significantly dysregulated according to the data mining technique. Specifically, the mRNA levels of METTL16 (p = 0.0147) and WTAP (p = 0.028) were lower and those of ALKBH5 (p = 0.0432) and IGF2BP2 (p = 0.0016) were higher in the endometrium of infertile patients. Meanwhile, many immunity-related pathways are abnormal in infertility, such as cytokine-cytokine receptor interactions, natural killer cell-mediated cytotoxicity and leukocyte transendothelial migration. In conclusion, we found that the m6A levels in the uterus increased as pregnancy progressed, and these regulators were dysregulated in the endometrium of infertility patients. These results suggest that m6A methylation may be very important in the establishment of implantation and maintenance of pregnancy and may become a new direction for research on infertility.

A Correlative Study of Endometrial Glycogen Content in Female Infertility

Infertility is a global problem. It has been viewed as a discredit and social humiliation thrust upon healthy young adults. The present detects the glycogen content in the endometrial glands of infertile women in the age group of 18 -39 years. This study aimed to compare infertility and the glycogen content in the endometrial glands of fertile women of the same age group. The endometrium is the tissue of attention because it is the site for implantation of ovum. The current study was done to evaluate the glycogen content in the endometrium of infertile patients and compare it with that of fertile patients. This study was done on 60 cases and 20 controls. Our study showed that large masses of glycogen (++++) was seen in only 7 secretory endometria in infertile cases (14.9%) when compared to 14 secretory endometria infertile subjects (77.7%). Also, endometrial glycogen grading in the secretory phase in infertile patients showed glycogen depletion (Grade 0) in 13 cases (27.7%) whereas it was nil in the fertile group. Glycogen is an essential and straight source of nutrient for the primary concepts and also helps in the successful implantation of blastocyst and continuation of pregnancy.

Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients.

BackgroundThe purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase.MethodsEndometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed.ResultsThe rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition.ConclusionThe epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation.

Deciphering biomarkers of endometriosis by proteomic analysis of eutopic endometrium in infertile patients

AimEndometriosis is associated with infertility. The aim of this study was to examine the overall proteomic changes of eutopic endometrium in infertile women with endometriosis. MethodsTandem mass tags combined with multidimensional liquid chromatography and mass spectrometry analyses were used to screen the proteomic profiles of eutopic endometrium from infertile patients with endometriosis (N = 4), compared with that from patients without endometriosis (N = 4). Quantitative proteomic analysis, functional categories and significant pathway analysis were investigated subsequently. ResultsIn total, 6.698 proteins were identified, among which 5,812 proteins were quantified. Compared with controls, proteomic analysis showed some differentially expressed proteins: 16 up-regulated proteins and 23 down-regulated proteins. Bioinformatics analysis indicated that differentially expressed proteins were involved in humoral immune response pathways, antimicrobial humoral response and regulation of nitric oxide biosynthetic process. Besides, our results showed that alpha-1-acid glycoprotein 2, complement factor B and zinc transporter Zip14 were important resources for investigating potential mechanism of infertility in infertile women with endometriosis. ConclusionsThis study provided a reference proteome map of eutopic endometrium from infertile women with endometriosis. The long-term benefits of using those markers to stratify clinical treatment warrant further investigation.

The Clinical Description of Infertile Female Patients and Immunohistochemical Evaluation of FoxP3 and CD56 Expression in the Endometrium

Objective: to evaluate the clinical features of infertile female patients and to determine the immunohistochemical parameters of the endometrium using local immunity markers. Material and methods . The clinical and anamnestic features, FoxP3 and CD56 expression in the endometrium have been studied in infertile patients. Endometrial biopsy was performed depending on the duration of the menstrual cycle on 7-9 days after ovulation using the ProfiCombi aspiration curette (Simurg, Belarus). Results. 55 female patients of the reproductive age altogether were examined. 40 (72.73 %) infertile patients were included in the main group, and the control group consisted of 15 (27.27%) patients with no reproductive malfunction who had undergone preconception checkup. The infertile patients had a high rate of intrauterine manipulation - 22.50 (c 2 = 4.04;p = 0.05), the patients of the comparison group had not undergone these surgical operations. During the immunohistological investigation, chronic endometritis was diagnosed in 37 (92.50 %) infertile patients and in 2 (13.33 %) patients of the control group (c 2 = 33.14; p < 0.001). The expression of CD56 in the endometrium was 15.30 (12.60; 18.60) in the infertile patients and 4.90 (4.00; 5.60) in the patients of the control group (z = 4.96, p < 0.001). FoxP3 expression was 3.00 (2.30; 3.70) in the main group, FoxP3 was not expressed in any patients of the control group (p < 0.001). Conclusion. The prevalence of chronic endometritis in the infertile patients was 7 times (p < 0.001) as high as that in the women in the comparison group. The women of the main group revealed higher values (p < 0.001) of local CD56 and FoxP3 immunity in the endometrium. Evidently, high FoxP3 and CD56 expression in the endometrium of infertile patients causes local disorders of the immune response, which worsens the prognosis of impregnation and carrying of pregnancy. Frequent intrauterine manipulations are a risk factor for chronic endometritis, which should be taken into account during the selection of methods of examination of infertile patients.

Clinical and morphological characteristics of the endometrium of infertile patients with HIV infection

Clinical and morphological characteristics of the endometrium of infertile patients with HIV infection

Gel-free proteomics reveals neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis

Background/aimsIndirect evidence suggests that eutopic endometrium of women suffering from endometriosis shows differential physiological characteristics as compared to normal endometrium in unaffected women. We have evaluated this issue by using hypothesis-neutral proteomics approach. MethodsIn order to examine the differential display of steady state expressed proteins between control endometrium from infertile women with no detectable endometriosis disease and that from infertile women with proven stage IV ovarian endometrioma, a large-scale gel-free 2D proteomic analysis, followed by QTOF LC-MS system and immunohistochemistry for subsequent validation was employed in the present study. ResultsWe could identify several dysregulated endometrial proteins in women suffering from stage IV ovarian endometriosis, which included proteins involved in regulating cellular redox states, cellular signaling, cytoskeletal functions, stress response, apoptosis, salt-water balance, and heme metabolism. Additionally, an overt indication of telomere maintenance and that of neoplastic potential of eutopic endometrium of infertile women with stage IV ovarian endometriosis was observed in post hoc bioinformatics-based analysis. This was further substantiated by consistent high immunopositive expression of four cancer-associated specific proteins (annexin A2, HSP90, PDGFRa, and Tubulin-a) in endometrium of infertile patients with stage IV ovarian endometriosis. ConclusionIt appears highly plausible that endometrial cells in women with stage IV ovarian endometriosis cannot adequately support embryo implantation process due to innate molecular inadequacies. Furthermore, these cells with molecular defects on their reflux into pelvic peritoneal niche may result in endometriotic lesion. Most importantly, pathognomonic characteristics showing marked indication of neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis bear a possibility of inducement of oncogenic transformation especially in the high-risk population in the course of endometriosis disease progression.

Matrix Metalloproteinases 2 and 9 and E-Cadherin Expression in the Endometrium During the Implantation Window of Infertile Women Before In Vitro Fertilization Treatment

To evaluate the expression of endometrial matrix metalloproteinases (MMPs) 2 and 9 and E-cadherin in peri-implantation phase of infertile women who have undergone in vitro fertilization (IVF) cycles. This prospective study included 51 patients who underwent endometrial biopsy during the receptive phase in a menstrual cycle prior to IVF treatment. The samples were evaluated by tissue microarray for immunohistochemical study. The expression of MMP-2, MMP-9, and E-cadherin in the endometrium prior to IVF treatment was not associated with pregnancy. There was a decrease in E-cadherin immunodetection, the higher the age of the patients, a negative relationship between E-cadherin and MMP-2, and a positive association between MMP-9 and E-cadherin. The MMP-2, MMP-9, and E-cadherin are expressed in the endometrium of infertile patients during the receptive phase of the natural menstrual cycle. However, there is no correlation between the expression of these molecules and the clinical IVF outcomes.

Clinical observations of sequential therapy with Chinese medicine and hysteroscopic mechanical stimulation of the endometrium in infertile patients with repeated implantation failure undergoing frozen-thawed embryo transfer.

To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

NF kappaB expression increases and CFTR and MUC1 expression decreases in the endometrium of infertile patients with hydrosalpinx: a comparative study

BackgroundHydrosalpinx are associated with infertility, due to reduced rates of implantation and increased abortion rates. The aims of this study were to investigate the expression of cystic fibrosis transmembrane conductance regulator (CFTR), nuclear factor kappa B (NF KappaB) and mucin-1 (MUC-1), and analyze the correlation between the expression of CFTR and NF KappaB or MUC1, in the endometrium of infertile women with and without hydrosalpinx.MethodsThirty-one infertile women with laparoscopy-confirmed unilateral or bilateral hydrosalpinx and 20 infertile women without hydrosalpinx or pelvic inflammatory disease (control group) were recruited. Endometrial biopsy samples were collected and the expression of CFTR, NF KappaB and MUC1 were analyzed using immunohistochemistry and quantitative real-time PCR.ResultsCFTR, NF KappaB and MUC1 mRNA and protein expression tended to increase in the secretory phase compared to the proliferative phase in both groups; however, these differences were not significantly different. The endometrium of infertile patients with hydrosalpinx had significantly higher NF KappaB mRNA and protein expression, and significantly lower CFTR and MUC1 mRNA and protein expression, compared to control infertile patients. A positive correlation was observed between CFTR and MUC1 mRNA expression (r = 0.65, P < 0.05); a negative correlation was observed between CFTR mRNA and NF KappaB mRNA expression (r = −0.59, P < 0.05).ConclusionsIncreased NF KappaB expression and decreased CFTR and MUC1 expression in the endometrium of infertile patients with hydrosalpinx reinforce the involvement of a molecular mechanism in the regulation of endometrial receptivity.

HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility

HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility

Expression of alpha 1 and beta 3 integrins subunits in the endometrium of patients with tubal phimosis or hydrosalpinx

To determine the expression of alpha1 and beta3 integrin subunit on the endometrium of infertile patients with hydrosalpinx and infertile patients with tubal phimosis. Case-control study. Tertiary medical center. Infertile patients with radiologic or laparoscopic diagnosis of hydrosalpinx (n = 11) or tubal phimosis (n = 12) as the only cause of infertility, and fertile controls (n = 17). Immunohistochemical analysis of alpha1 and beta3 integrin subunits was performed on endometrial biopsies obtained during the implantation window. Histologic score (HSCORE) on luminal and glandular endometrium of the patients with hydrosalpinx or tubal phimosis and the normal fertile controls. The median (+/-SEM) HSCORE for beta3 subunit expression in endometrial glands was 0.39 +/- 0.23 and 0.42 +/- 0.18 for tubal phimosis and hydrosalpinx, respectively, and 1.74 +/- 0.26 for fertile controls. The median HSCORE for beta3 subunit expression in luminal epithelium for tubal phimosis, hydrosalpinx, and fertile controls was 0.07 +/- 0.06, 0.21 +/- 0.18, and 1.03 +/- 0.31, respectively. No statistical difference was observed on the expression of alpha1 integrin subunit expression between the three groups. The endometrial expression of beta3 integrin subunit is reduced in the presence of tubal phimosis or hydrosalpinx, during the window of implantation.

The relationship of the corpus luteum and the endometrium in infertile patients

A group of 50 females undergoing an infertility work-up had measurements of serum progesterone levels in all cases, endometrial sampling in 49, and biopsy of a grossly identifiable corpus luteum in 42 cases. Of the 41 cases with three parameters available for study, 39 had correlations of all three parameters. The remaining nine cases had two of three parameters available for study. Of these, three showed a secretory endometrium but absent corpus luteum and an anovulatory progesterone level, and a patient showing a proliferative-phase endometrium at the same time had an ovulatory progesterone level and a postovulatory corpus luteum. The evidence presented suggests that, among the three parameters tested, the progesterone level as a noninvasive procedure serves as a good index of ovulation 92% of the time, and occasionally endometrial histologic sampling does not necessarily reflect ovarian function.