Implantation Window In Patients Research Articles

Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study

BackgroundThe oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF).MethodsThis descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανβ-3 and HOXA10 in endometrium were collected.ResultsThirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27–40 years) completed the research. The median number of embryo transfer cycles was three (range 3–8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0–13.5) to 0.65 (range 0–6), P = 0.035; additionally, the H-score of expression of ανβ-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%).ConclusionsThese results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανβ-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

P-483 Application of RNA-sequencing based predictive model for endometrial WOI in patients with recurrent implantation failure: a prospective cohort study

Abstract Study question Is intrauterine pregnancy rate following a FET timed by the rsERT with hour precision higher than the conventional FET among patients with recurrent implantation failure? Summary answer Personalized embryo transfer (pET) guided by this newly optimized rsERT significantly improved pregnancy outcomes of patients with recurrent implantation failure (RIF). What is known already Asynchrony between blastocyst and endometrium is responsible for implantation failures. Hence, accurate prediction for endometrial window of implantation (WOI) would maximize the effectiveness of assisted reproductive technology (ART). Previously, we have established a predictive model for endometrial WOI (rsERT) by three-time points sampling from the same patient at 48-hour intervals during one menstrual cycle. To avoid multiple sampling and build a more efficient WOI prediction tool, estimation method with hour precision by single time point sampling is urgently needed. Study design, size, duration This was a two-phase strategy involving model optimization and benefit evaluation with a prospective controlled trial. The study was performed in a tertiary hospital setting between September 2018 and December 2021. In the first phase (September 2018-June 2020), 91 participants were recruited to optimize the rsERT. In the second phase (June 2020-December 2021), 176 patients with RIF were enrolled to valida the clinical efficacy of this newly optimized rsERT. Participants/materials, setting, methods First phase: endometrium samples were obtained from sampling on LH + 5, +7, +9 or P + 3, +5, +7 respectively. Samples were predicted by the rsERT. Only those in agreement with theoretical WOI timing and from whom successfully obtained intrauterine clinical pregnancy after subsequent FET were eligible. Second phase: 88 patients in the experimental group underwent pET timed by rsERT after sampling at LH + 7 or P + 5. 88 patients in the control group performed standard embryo transfer without sampling. Main results and the role of chance This newly optimized predictive model could provide hour-based results of endometrial WOI and have an average accuracy of 94.51% by using 10-fold cross validation. In the second phase, a total of 88 NGS were constructed for RNA-sequencing by using endometrial biopsy samples from RIF patients in the experimental group (n = 88). The results indicated WOI displacement in 40 of 88 (45.45%). Among them, advanced WOI occurred in two patients (2/40, 5.00%), and delayed WOI occurred in 38 patients (38/40, 95.00%). The baseline clinical parameters, including age, BMI, infertility duration, types of infertility, number of previous failed cycles, main aetiology of infertility, the prevalence of pre-implantation genetic screening/diagnosis (PGS/PGD), endometrial thickness, endometrial types, the percentage of transferred blastocysts, good-quality embryo transferred rate and number of transferred embryos were all comparable between the two groups (P &amp;gt; 0.05). The intrauterine pregnancy rate (IPR) and implantation rate (IR) of the experimental group were significantly improved compared to those of the control group (for IPR: 61.36% vs. 31.82%, RR 3.630, 95%CI 1.958-6.732, P = 0.000; for IR: 42.86% vs. 24.66%, RR 2.292, 95%CI 1.392-3.772, P = 0.001). Moreover, in the experimental group, pregnancy outcomes did not exhibit remarkable differences between the natural cycle and hormone replacement (HRT) cycle. Limitations, reasons for caution Caution is warranted due to the non-randomized design and limited sample size of the study. Besides, embryonic factors should be taken into consideration as well. Hence, a multi-center randomized controlled trial of rsERT combined with PGT is needed to further validate its clinical efficacy. Wider implications of the findings These data add a new alternative of predictive model for endometrial WOI among Chinese women. Trial registration number the National Key Research and Development Program of China

Impact of body mass index on peripheral and uterine immune status in the window of implantation in patients with recurrent reproductive failure

This study aimed to investigate whether maternal obesity affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure classified according to their body mass index (BMI). A total of 228 repeated implantation failure (RIF) and 266 recurrent miscarriage (RM) patients were enrolled in the study and further subdivided into three groups according to their BMI: (i) normal weight (18.5≤ BMI <23); (ii) overweight (23≤ BMI <25); and (iii) obese (BMI ≥25). Peripheral blood and endometrium samples were collected in the mid-luteal phase before IVF treatment or natural pregnancy. Peripheral immunocytes were analyzed by flow cytometry, while uterine immune cells were subjected to immunohistochemistry. In RM patients, significantly increased peripheral helper T cells and decreased cytotoxic T cells, NK cells were observed in the obese group compared with the normal-weight group. Meanwhile, in the endometrium, the percentage of NK cell, macrophage cell, M2 macrophage cell, and Treg cell significantly reduced with increased BMI in RIF patients, and the percentage of NK cell and M2 macrophage cell significantly decreased with increased BMI in RM patients. In conclusion, obesity may cause endometrial immune disorder in recurrent reproductive failure women, but was only associated with the peripheral immune change in RM patients.

Имплантационная несостоятельность эндометрия в циклах экстракорпорального оплодотворения у пациенток с хроническим эндометритом

Introduction. Chronic endometritis is one of the most frequent gynecological diseases which negatively impacts the main pathogenetic links in the morphogenesis of secretory and gestational endometrial transformation. These links determine implantation failure. The study aimed to verify the expression of estrogen receptors (ER) and progesterone receptors (PR), progesterone-induced blocking factor (PIBF) and stromal cell-derived factor-1 (SDF-1) in the endometrium of patients having chronic endometritis with ineffective IVF cycles or undeveloped pregnancies occurred after assisted reproductive technologies in their histories. Materials and methods. We formed 3 study groups: group I included samples of the endometrium of patients with ineffective IVF cycles (n=50); group II contained samples received from patients with a history of undeveloped pregnancy after IVF (n=50); and group III (the control group) included endometrial tissue from healthy patients (n=25). We carried out routine histological evaluation followed by an immunohistochemical assay with ER, PR, PIBF, and SDF-1 in the endometrial glands and stroma in the middle secretion phase. esults. The middle stage of the secretion phase of the menstrual cycle in endometrial samples of groups I and II was detected in only 46% and 42% of cases, respectively. We showed a decrease in the ER and PR expression in more than 92% of cases. Statistically significant decrease was detected in PIBF and SDF-1 expression in the endometrial glands and stroma within the implantation window in patients with a history of reproductive loss. Conclusion. Violation of implantation viability with an imbalance of chemokines, cytokines, cellular factors, and structural and functional characteristics of the endometrium was found in patients with revealed chronic endometritis and history of ineffective IVF cycles and miscarriage after ART. Keywords: endometrium,IVF, missed abortion after IVF, estrogen receptor, progesterone receptor, progesterone-induced blocking factor, stromal cell-derived factor-1

Рецептивность эндометрия пациенток с повторными неудачами имплантации

Study Objective: To broaden the understanding of the pathogenesis of impaired receptivity in patients with repeated implant failures (RIF) in in vitro fertilisation programs. Study Design: Open perspective comparative study. Materials and Methods. 57 women aged 27 to 42 years old (mean age: 36 ± 6.2 years old) with clinically verified RIF. A morphological control group included 30 fertile women. The subject of the study was endometrium biopsy material obtained on day 5–7 of menstruation, following the peak blood concentration of luteinizing hormone (implantation window). Study Results. During the implantation window, patients with RIF have statistically significant (р &lt; 0.05) changes: 1.5- and 1.4-fold increase in gland and stromal expression of estrogen α receptors, respectively; 2.3-fold increase in expression of progesterone A and B receptors with simultaneous reduction in stromal expression by 1.6 times; focal reduction in MUC1 expression in apical surface of endometrium; 1.3-fold increase in pinopods density in apical surface of endometrium and 2.3-fold increase in stromal expression of CD56+ NK-cells; 2-fold reduction in CD4+ cell expression, and 2.2-fold increase in CD8+ expression vs morphological controls. During the implantation window, von Willebrand factor and CD34+ levels in endometrial stroma did not demonstrate statistically significant differences when expressed in blood-vessel endothelium. Conclusion. Pathogenesis of impaired receptivity in patients with RIF can be explained with impaired expression of sex hormone receptors in stroma and glandular component and reduced MUC1 expression, increased density and reduced amount of mature and maturating pinopods in apical surface of endometrium. An increased number of expressed CD56+ NK-cells during the implantation window in patients in both groups (in patients with RIF, CD56+ expression is significantly higher) in combination with the found imbalance between Т-lymphocytes can be a cause of the immunological component of impaired implantation pathogenesis. Keywords: repeated implant failures, pinopods, MUC1, CD56+, CD4+, CD8+, von Willebrand factor, CD34+, estrogen α receptors, progesterone A and B receptors.

Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window

BackgroundPoor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.MethodsEndometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.ResultsThe presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.ConclusionsMiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.

P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures

Abstract Study question Is ERA testing different between RIF patients with control group? Summary answer In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits. Study design, size, duration This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020. Participants/materials, setting, methods 181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test. Main results and the role of chance The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%). Limitations, reasons for caution This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors. Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results. Trial registration number 18MMHISO70e

Evaluation of glycan expression in endometrial epithelial structures as a predictive factor for endometrial receptivity

Aim. To evaluate the endometrial glyotype in the implantation window in patients with infertility in assisted reproductive technologies (ART) programs and to develop criteria for assessing endometrial receptivity based on the analysis of complex changes in the functional groups of glycans in the main endometrial epithelial to use in clinical practice.&#x0D; Materials and methods. The study included 32 infertile patients who took part in ART programs. Pipelle endometrial biopsy was performed during the implantation window in the cycle preceding the cycle of ovarian stimulation and embryo transfer. Using lectin histochemistry and immunohistochemistry, glycans levels in the glycocalyx of endometrial surface epithelium (SE) and glandular epithelium (GE) was studied.&#x0D; Results. Differences in the expression of mannose-rich glycans in SE and N-acetylgalactosamine--terminated glycans in the GE of the endometrium were revealed, as well as the link between the expression of lectin staining glycans: ConA, VVL, UEA-I, SNA, MAL-II, ECL and monoclonal antibodies: anti-MECA -79 mAb and anti-LeY mAb in SE and GE of the endometrium was assessed in patients with infertility, depending on the outcome of the ART program. The estimated threshold levels in glycan expression and the odds ratio for pregnancy occurrence allow to characterize the diagnostic value for the studied glycomarkers and to develop criteria for assessing endometrial receptivity.&#x0D; Conclusion. Based on a comprehensive evaluation of glycans in the main endometrial epithelial structures in the cycle preceding the ART cycle, criteria for assessment of the likelihood of pregnancy have been developed, which can increase the effectiveness of ART programs in patients with infertility.

Lipid Profiling of Peri-implantation Endometrium in Patients With Premature Progesterone Rise in the Late Follicular Phase.

Late follicular phase elevation in serum progesterone (P) during controlled ovarian hyperstimulation negatively affects the outcome of assisted reproductive technology by contributing to endometrial-embryo asynchrony. There are still no data on lipid metabolite alterations during this process. To investigate alterations in the lipid profile during the window of implantation in patients with premature P rise. Lipidomic variations in the endometrium were evaluated by ultrahigh-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry. University assisted reproductive medicine unit. Forty-three patients undergoing in vitro fertilization/intracytoplasmic sperm injection because of a tubal factor or male factor infertility were included in this study. The patients were divided into a high P group (P ≥ 1.5 ng/mL, 15 patients) and a normal P group (P < 1.5 ng/mL, 28 patients) on the day of human chorionic gonadotropin administration. The endometrial tissues were obtained by Pipelle biopsy 7 days after human chorionic gonadotropin administration. Alterations in lipid metabolites. A total of 1026 ions were identified, and 25 lipids were significantly upregulated. The endometrial lipid profile was characterized by substantial increases in the concentrations of phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, diacylglycerol, ceramide, phosphatidylinositol, and phosphatidylserine in patients with a premature P rise at the end of the follicular phase. The correlation analysis between P levels and lipids showed a stronger negative correlation between phosphatidylethanolamine or phosphatidylserine and P levels. Premature P elevation disrupts the lipid homeostasis of the endometrium during the peri-implantation period. The altered lipid levels may impair endometrial receptivity and early embryo implantation.

Endometrial miR-543 Is Downregulated During the Implantation Window in Women With Endometriosis-Related Infertility.

Differentially expressed microRNAs (miRNAs) and their target mRNAs may lead to alterations in normal physiological status of the tissues and initiate pathological processes. The aim of this study was to investigate the expression of the most relevant miRNAs in the eutopic endometrial tissue during the window of implantation in women with endometriosis-related infertility. In the study, 76 infertile women with a regular menstrual cycle were recruited from the Center for Reproductive Medicine, Peking University Third Hospital between January 2014 and June 2016. We performed a combined messenger RNA and miRNA microarray and bioinformatics analysis of eutopic endometrium in 6 women with and without endometriosis-related infertility at the time of implantation window. Quantitative real-time polymerase chain reaction arrays were utilized to examine the expression levels of selected miRNAs (from 35 patients with endometriosis and 35 disease-free individuals at different menstrual stages). Five differentially expressed miRNAs (miR-142-5p, miR-146a-5p, miR-1281, miR-940, and miR-4634) were significantly upregulated, whereas miR-543 was significantly downregulated in the eutopic endometrium during the window of implantation in patients with endometriosis. Further analysis showed that miR-543 was significantly upregulated at the peri-implantation phase compared with that at proliferative phase in the endometrium of disease-free patients (P < .05). However, the expression level of miR-543 was significantly decreased in patients with endometriosis (P < .05), especially downregulated at the window of implantation phase (P < .05). miR-543 plays an important role during embryo implantation process and is associated with endometrial receptivity. Downregulation of miR-543 may affect embryo implantation, resulting in the pathogenesis of endometriosis-related infertility.

Endometrial MIR-543 is down-regulated during the implantation window in women with endometriosis-related infertility

Differentially expressed microRNAs (miRNAs) have been shown to be associated with endometriosis-related infertility. The aim of this study was to investigate the expression of the most relevant miRNAs in the eutopic endometrial tissue during the window of implantation in women with endometriosis-related infertility. All the infertile patients (76 women with a regular menstrual cycle) received treatment between January 2014 and June 2016. The study group included 38 patients with endometriosis related-infertility (n=38, with 26 at the proliferative phase and 12 at the time of implantation window (mid-secretory phase)). The control group included 38 patients with tubal factors (n=38, with 24 at the proliferative phase and 14 at the time of implantation window). Human miRNA microarray and mRNA microarray were used to examine the expression levels of miRNA and mRNA, respectively (from 3 endometriosis patients and 3 control cases). Quantitative Real-time PCR (RT-qPCR) arrays were utilized to examine the expression levels of 6 selected miRNAs (from 35 endometriosis patients and 35 disease-free individuals). Five differentially expressed miRNAs (miR-142-5p, miR-146a-5p, miR-1281, miR-940 and miR-4634) were significantly upregulated, whereas miR-543 was significantly down-regulated in the eutopic endometrium during the window of implantation in patients with endometriosis. RT-qPCR results showed that miR-543 was significantly down-regulated in patients with endometriosis (p=0.002), especially down-regulated at the window of implantation phase (p= 0.012). The area under the receiver operator characteristics curve was 0.72 [95% confidence interval (CI):0.594-0.846] in discriminating endometriosis from controls. miR-543 is down-regulated in the eutopic endometrial tissue during the window of implantation in women with endometriosis. Dysregulated expression of miR-543 may affect embryo implantation by disturbing the endometrial receptivity, which results in the pathogenesis of endometriosis-related infertility.

Современные методы оценки «окна имплантации» у пациенток, проходящих лечение в программе экстракорпорального оплодотворения

Современные методы оценки «окна имплантации» у пациенток, проходящих лечение в программе экстракорпорального оплодотворения

Diverse endometrial mRNA signatures during the window of implantation in patients with repeated implantation failure

High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups. The majority of these mRNAs were found to encode membrane proteins by Gene Ontology (GO) analysis. The major functional biological pathways associated with the down-regulated mRNAs were cytokine-cytokine receptor interaction, the p53 signalling pathway and the complement and coagulation cascades. Up-regulated mRNAs were found mainly to participate in pathways such as PPAR signalling, hematopoietic cell lineage, phosphatidylinositol signalling system, ECM-receptor interaction and notch signalling. AQP3, DPP4 and TIMP3 whose expression patterns were down-regulated in RIF patients both by microarray and real-time PCR had a high correspondence with previous studies demonstrating that these genes may contribute to the defects in endometrial receptivity in RIF patients. Overall, these RIF-associated mRNAs may help devise new diagnostic tools for endometrial receptivity.

Osteopontin and Integrin αvβ3 Expression during the Implantation Window in IVF Patients with Elevated Serum Progesterone and Oestradiol Level.

Background: To explore whether endometrial receptivity is determined by osteopontin (OPN) and integrin αvβ3 expression in women with elevated serum progesterone (P) and/or oestradiol (E2) who are undergoing in vitro fertilisation (IVF). Methods: According to serum hormone levels on the day of HCG administration, 33 infertile women were divided into 3 groups: the high E2, high P, and high E2 and P groups. The control group included 11 fertile, healthy women. Endometrial biopsy was performed on ovulation day + 7 to + 8 for all study participants, and the mRNA and protein expression levels of OPN and integrin αvβ3 were analyzed. Result: No statistically significant differences regarding OPN and integrin αvβ3 expression were found between infertile patients in the high P, high E2, high E2 and P and control groups. There was no significant correlation between OPN and integrin αvβ3 staining intensity during the implantation window biopsy in any of the groups studied. Conclusion: Endometrial OPN and integrant αvβ3 expression/co-expression is not impaired during the window of implantation in patients with high P, high E2, or high E2 and P levels. The clinical value of assessing endometrial receptivity with OPN and integrin αvβ3 seems to be uncertain.

Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure.

Telomerase plays a critical role in cell proliferation and senescence, but the exact involvement of endometrial telomerase in recurrent implantation failure (RIF) is unknown. We collected endometrial biopsies from RIF patients (N = 30) and fertile women (N = 30). Real-time PCR was performed for detecting changes in telomerase reverse transcriptase (Tert), ER alpha, and PR expression at the transcript level, and the correlation between the variable expressions of these genes was tested using regression analysis. Then, western blot and immunohistochemistry were used to analyze the expression profiles of TERT and ER alpha at the protein level. Compared to the control, Tert expression was substantially increased, whereas ER alpha expression significantly decreased in the endometrium with RIF. No change was observed in PR expression. Tert expression was inversely associated with ER alpha expression. TERT protein expression in RIF patients was also clearly elevated, and was localized to both the endometrial epithelium and stromal cells. However, the signals for ER alpha in the stromal cells were weaker than those in the control. Expression of endometrial telomerase was substantially enhanced as ER alpha decreased in RIF patients during the implantation window.

Clinical and morphological determinants of infertility associated with inflammatory diseases of the pelvic organs

There is a violation of the secretory transformation of the endometrium during the implantation window in patients with the infertility associated with inflammatory diseases of the small pelvic organs, against the background of a high incidence of chronic endometritis and salpingitis. The impact of inflammatory changes in the small pelvic organs leads to disruption of morphological and functional state of the endometrium and also to receptor imbalance.

Expression pattern of osteopontin and v 3 integrin during the implantation window in infertile patients with early stages of endometriosis

To study endometrial receptivity in terms of osteopontin (OPN) and αvβ3 integrin expression and co-expression in infertile women with early stages of endometriosis. We investigated the immunohistochemical expression and co-expression of OPN and αvβ3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject. No statistically significant differences regarding OPN and αvβ3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvβ3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied. Endometrial OPN and αvβ3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.

Expression of GPR30, ERα and ERβ in endometrium during window of implantation in patients with polycystic ovary syndrome: a pilot study

Women with polycystic ovary syndrome (PCOS) exhibit a lower pregnancy rate, which may be related to decreased estrogen receptor (ER) expression or endometrial receptivity. We measured expression of ERα, ERβ and the novel G protein-coupled ER (GPR30) in endometrium during window of implantation (WOI) in PCOS patients. Fifteen Chinese women with PCOS were compared to 15 normal subjects. Serial trans-vaginal ultrasonic scanner (TVUS) examinations detected follicular development, and endometrial thickness and pattern were assessed via TVUS on the day of ovulation. GPR30 expression was detected in the cytoplasm of endometrial epithelial cells, and was significantly lower in the PCOS group (p < 0.05). ERα and ERβ expression was lower in the PCOS group, and was detected mainly in the nucleus of endometrial epithelial cells. There was no significant difference in endometrium thickness (p > 0.05), but there was a significant difference in the ultrasonic pattern (p < 0.05). Endometrial expression of GPR30, ERα and ERβ was decreased during WOI in PCOS patients, and was accompanied by poor endometrial receptivity, low pregnancy rate and higher spontaneous abortions. We propose that restored receptor expression might improve endometrial receptivity and help lower infertility associated with PCOS.

Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) have lower pregnancy and higher miscarriage rates, possibly due to decreased endometrial receptivity. In this study, endometrium was processed for RNA extraction and hybridization of chemically fragmented, biotinylated, complementary RNA on high-density oligonucleotide microarrays, and screened for 21,571 genes. Real-time polymerase chain reaction (PCR) was used to verify the result. Genes found to be down-regulated in the endometrium during the implantation window in PCOS patients included those whose activity was integral to membrane function, adhesion, invasive growth and the cytoskeleton. Among these genes, some have previously been associated with endometrial receptivity (by microarray research or other methods) and some have never previously been associated with endometrial receptivity. Using real-time PCR, expression of transmembrane 4 superfamily member 4 ( TM4SF4) and matrix metalloproteinase 26 ( MMP26) was found to be significantly decreased during the implantation window in patients with PCOS ( P = 0.003). TM4SF4 has been demonstrated to be associated with adhesion; MMP26 has been shown to be related to degradation of extracellular matrix. It is suggested the down-regulated gene expression during the implantation window in patients with PCOS indicates differential gene expression in the endometrium between PCOS and normal women during the implantation window. This might affect endometrial receptivity.