Implantation Window In Women Research Articles

Correlation between Serum Levels of HLA-G and Recurrent Implantation Failure During Implantation Window in Women Undergoing In Vitro Fertilization

Background: Recurrent implantation failure (RIF) during artificial reproductive techniques (ARTs) remains a health problem. Many physiopathological pathways have been proposed for RIF, but the causes are not yet clear. Thus, the purpose of the current study was to evaluate the possible correlation between human leucocyte antigen-G (HLA-G) serum levels and recurrent implantation failure during the implantation window in women undergoing In vitro fertilization (IVF). Materials and Methods: In this prospective case-control study, 39 patients with RIF and 20 cases with successful implantation were enrolled as the control group. HLA-G serum levels were measured using the sandwich ELISA method in both groups. Results: HLA-G serum levels in the RIF group were significantly higher than in controls (0.085 ± 0.019 compared to 0.073 ± 0.005, p = 0.024). Furthermore, by grouping patients based on age and BMI, we found that in the cases with ages above 30 years and with BMI more than 25 (kg/m2), HLA-G serum levels in the RIF group were remarkably greater than controls (0.088 ± 0.019 compared to 0.072 ± 0.004, p = 0.002 and 0.083 ± 0.012 compared to 0.072 ± 0.003, p = 0.021, respectively). Conclusion: Serum levels of HLA-G increase in the RIF patients, especially in cases of patients above 30 years old and those with BMI ≥ 25, which remains significant after eliminating confounding variables. These results may indicate the involvement of physiopathological pathways of HLA-G in the increasing risk of RIF.

Endometrial expression of FOX proteins (FOXA1 and FOXA2) in women of reproductive age with different endometrial thickness: prospective cohort comparative study

Aim. To evaluate the expression of FOX proteins (FOXA1 and FOXA2) in the endometrium during the implantation window in women with a history of reproductive dysfunctions with different thickness of the endometrium.
 Materials and methods. The prospective cohort comparative study was conducted. The main group included patients with "thin" endometrium (7 mm according to ultrasound on preovulatory days; n=52), the comparison group consisted of women with normal endometrial thickness (7 mm according to ultrasound; n=62; women of both groups with reproductive dysfunctions of unknown reason), the control group included 16 healthy fertile women. Aspiration biopsy of the endometrium was performed on the 68 days after ovulation, as well as venipuncture to obtain a sample of peripheral blood to determine the levels of sex steroids (estradiol E2 and progesterone P). A combined histological and immunohistochemical study of endometrial biopsies was performed.
 Results. All women had ovulatory values of progesterone P16.1 nmol/l (68 days after ovulation) and normoestrogenemia (E2, pmol/l) in the blood. E2/P was similar in all groups (p0, 05). A pronounced expression of FOXA1 was noted in women with thin endometrium significantly more often (p0.05) with various hormone-receptor characteristics of the endometrium (42% n=22 out of 52) compared with healthy participants (0%; n=0). Reduced FOXA2 expression in the uterine mucosa was significantly more often detected on 68 days after ovulation in women with "thin" endometrium (56% n=29 of 52) than in women with normal endometrial thickness, both in women from the comparison group and in healthy women from the control group (p0.05). In a generalized analysis of the expression of FOX proteins in the endometrium on days 68 after ovulation, it was generally found that every second (50%; n=57 out of 114) women with a history of reproductive disorders (with a reduced and normal M-echo value) expression of proteomic markers differed from healthy women. In the case of "thin" endometrium, more than two thirds of patients (71%; n=37 out of 52) showed differences in endometrial expression of FOX proteins compared with women without a burdened reproductive history.
 Conclusion. In the majority of women (71%) with a thin endometrium and a history of reproductive dysfunctions, the expression of FOX proteins in the endometrium differed from the control group. Overall, endometrial expression of FOX proteins, which is likely to be different from healthy women, in patients with reproductive dysfunctions of unknown origin is a significant predictor of reproductive failure. At the same time, such an isolated indicator as M-echo value 7 mm according to ultrasound data is not an absolute prognostic marker of endometrial receptivity disorders.

Intrauterine administration of autologous peripheral blood mononuclear cells regulates the endometrium estrogen and progesterone receptor expression: An RCT.

Repeated implantation failure (RIF) affects 15% of women of reproductive age. There is a high endometrial expression of both estrogen receptors and progesterone receptors (PRs) during the window of implantation in women with RIF. To evaluate the effects of intrauterine administration of human peripheral blood mononuclear cells (PBMC) on estrogen receptor α (ERα) and PRs expression in the endometrium of women with RIF during the implantation window. This randomized clinical trial study was conducted on 22 women with RIF history from January 2018 to August 2019 in Erfan hospital, Tehran, Iran. Participantswere divided into 2 groups (PBMC-treated group [n = 11] and control group [n = 11]). Endometrial tissue samples were collected at the implantation window time, during the mid-secretory phase (luteinizing hormone surge +7 days) of each menstrual cycle. The quantitative real-time polymerase chain reaction technique was used to measure the mRNA levels of ERα and PRs isoforms (PR-A and PR-B) in endometrial tissues. Furthermore, the protein expression of ERα and PRs was investigated using immunohistochemical staining. PBMC treatment significantly decreased the mRNA expression of endometrial ERα and PRs isoforms at the time of the implantation window (p 0.001). Moreover, the endometrial ERα and PRs protein localization were significantly lower in PBMC-treated women compared with controls (p = 0.01, and p 0.001 respectively). The intrauterine administration of PBMC decreased the endometrial ERα and PRs expression during the window of implantation in women with RIF. This local response to PBMC therapy could promote endometrial receptivity and embryo implantation.

Uterine NK cells underexpress KIR2DL1/S1 and LILRB1 in reproductive failure.

A significant proportion of recurrent miscarriage, recurrent implantation failure and infertility are unexplained, and these conditions have been proposed to have an etiology of immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) comprise three subsets and are the most numerous immune cells found in the uterine mucosa at the time of implantation. They are thought to play an important role in successful pregnancy by regulation of extravillous trophoblast (EVT) invasion and spiral artery remodelling. Here, we examine the frequency, phenotype and function of uNK1-3 from the uterine mucosa of 16 women with unexplained reproductive failure compared to 11 controls with no reproductive problems, during the window of implantation. We report that KIR2DL1/S1 and LILRB1 expression is lower in the reproductive failure group for both uNK (total uNK, uNK 2 and 3) and pNK. We also show that degranulation activity is significantly reduced in total uNK, and that TNF-α production is lower in all uNK subsets in the reproductive failure group. Taken together, our findings suggest that reproductive failure is associated with global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G on EVT during early pregnancy, leading to reduced uNK activation. This is the first study to examine uNK subsets during the window of implantation in women with reproductive failure and will serve as a platform to focus on particular aspects of phenotype and function of uNK subsets in future studies. Further understanding of uNK dysregulation is important to establish potential diagnostic and therapeutic targets in the population of women with unexplained reproductive failure.

Gene pathway analysis of the endometrium at the start of the window of implantation in women with unexplained infertility and unexplained recurrent pregnancy loss: is unexplained recurrent pregnancy loss a subset of unexplained infertility?

This study aims to understand differences/similarities in the genetic profile of the endometrium at the start of window of implantation (WOI) in women with unexplained infertility (UI) and unexplained recurrent pregnancy loss (uRPL). Differentially expressed genes (DEGs) from the endometrium were evaluated using gene expression array and pathway enrichment analysis was performed to analyse gene expression pathways involved in both conditions. We found 2,171 genes arranged in 117 pathways and 730 genes arranged in 33 pathways differentially expressed in endometrium of patients in UI and uRPL, respectively. Complement-coagulation cascades, morphine addiction pathway, and PI3K-Akt signalling pathway were predominantly differentially expressed in UI. Cancer pathways, NF-κB signalling pathway, and actin cytoskeleton regulation pathway showed significant changes in uRPL. Forty-eight percent of DEGs and 84% of differentially expressed pathways in uRPL were found in the endometrium of UI patients. Unexpected close association in gene expression pathways between UI and uRPL is observed supporting the hypothesis ‘uRPL is a clinical subset of UI’. Yet 100% DEGs overlap wasn’t found suggesting the endometrium has still some different gene expression patterns at start of WOI in UI and uRPL. Lastly, diagnostic tools may be developed for uRPL because more specific genes-pathways are involved compared with UI, which shows broader genetic expression profile.

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endometrium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

The strong association between endometriosis and infertility is of high clinical significance. High proliferative bias in eutopic endometrium during the secretory phase is a hallmark of endometriosis, which may result in high occurrence of implantation failure and resultant infertility in endometriosis. The ErbB family of proteins regulates the proliferation capacity in the endometrium, potentially causing endometrial hostility to the implantation process in endometriosis. However, our knowledge regarding the involvement of the ErbB family in human endometrium during the window of implantation (WOI) in endometriosis-associated infertility is scant. In the present study, the cellular profiles of immunopositive ErbBs-1 to -4 in the endometrium of endometriosis-free, infertile women (Group 1; n = 11) and in eutopic endometrium of infertile women diagnosed with stage IV ovarian endometriosis (Group 2; n = 13) during the mid-secretory phase were compared using standardized guidelines. Computer-aided standardized combinative analysis of immunoprecipitation in different compartments revealed an overexpression of ErbB-1 in the epithelial, stromal and vascular compartments, along with marginally higher ErbB-3 expression (p < 0.06) in the vascular compartment and ErbB-4 expression (p < 0.05) in the glandular epithelium and stroma in the endometrium during the WOI in women with primary infertility associated with stage IV ovarian endometriosis compared with disease-free endometrium of control infertile women. It appears that changes in ErbBs in the eutopic endometrium during WOI induce anomalous proliferative, inflammatory and angiogenic activities in it, which can antagonize endometrial preparation for embryo implantation in endometriosis. This knowledge appears usable in strategizing methods for the treatment of endometriosis-associated infertility, as well as preempting the oncogenic potential of endometriosis.

Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome.

ObjectiveNumerous studies have reported on ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). However, relevant data on endometrial receptivity are limited. This study was conducted to compare endometrial receptivity during implantation windows among letrozole (LE), clomiphene citrate (CC), and natural cycle, and to assess the predictive value for pregnancy of observed indicators.MethodsThis randomized controlled trial study enrolled 270 patients with PCOS. Patients were given LE (n=90) at a dose of 2.5mg/day or CC (n=90) at a dose of 50 mg/day on cycle days 5–9 for ovulation induction. Patients in the natural cycle group (n=90) did not receive any drug for ovulation induction. Endometrial ultrasonic parameters, integrin αvβ3, and vascular endothelial growth factor (VEGF) concentrations in uterine secretion were detected during the implantation window. The endometrial receptivity, ovulation rate, pregnancy rates, and predictive value of observed indicators for pregnancy were analyzed.ResultsThe successful ovulation rate did not differ between the LE group and CC group (P>0.05). Endometrial ultrasonic parameters [endometrial thickness (ET), endometrial volume (EV), vascularization index (VI), flow index (FI), vascularization flow index (VFI)], integrin αvβ3, and VEGF concentrations in uterine fluid were significantly higher in the LE group compared with the CC group and natural cycle group (P<0.05). The clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than in the CC group (P<0.05). Endometrial ultrasonic parameters (VI, FI, and VFI), integrin αvβ3, and VEGF concentrations in uterine fluid of all pregnancy groups were significantly higher compared with the no pregnancy group (P<0.05), and the above parameters in ongoing pregnancy were significantly higher than in biochemical pregnancy (P<0.05). The endometrial FI during the implantation window had the highest predictive value for pregnancy (AUC=0.889). The integrin αvβ3 in uterine fluid had better predictive value (AUC=0.876) than VEGF.ConclusionsEndometrial receptivity during the implantation window of LE is superior to CC in PCOS women, which may be related to higher clinical pregnancy and ongoing pregnancy rates. Endometrial FI examined by 3-D power Doppler, and integrin αvβ3 in uterine secretion during the implantation window, could be preferable non-invasive predictor markers for pregnancy.Clinical Trial Registration www.chictr.org.cn, ChiCTR1900023423.

Нарушения экспрессии эстрогеновых и прогестероновых рецепторов в период окна имплантации в эутопическом эндометрии женщин с бесплодием, ассоциированным с наружным генитальным эндометриозом

Study Objective: To study impaired expression of estrogen (ER) and progesteron (PR) receptor isoforms during the implantation window in eutopic endometrium of infertile women associated with endometriosis genitalis externa (EGE). Study Design: open perspective comparative study. Materials and Methods. The study included 32 patients with endometriosis-associated infertility and implantation failures within the scope of assisted reproductive technology programme (study group), and 33 fertile women with EGE rAFS (stages I to IV) (comparison group). We performed morphological and immunohistochemical examination of endometrium biopsy samples (pipelle biopsy) during an expected implantation window. Study Results. Eutopic endometrium of women with EGE and infertility during the implantation window demonstrated statistically higher (р &lt; 0.05) expression of ERα (19-fold), ERβ (2.3-fold) in stroma and PR-B in glands (1.7-folds) as compared to fertile women win EGE with lower PR-A expression in stroma (2.5-fold). Conclusion. The morphofunctional condition of endometrium and its receptive properties during the implantation window in women with endometriosis-associated infertility reflect the nature of ER (α and β) and PR (А and В) isoforms expression, the abnormalities underlying the endometrium receptivity disorders, with clinical manifestations being absent pregnancy. Keywords: endometriosis-associated infertility; implantation window; endometrium receptivity

Annexin A7 Regulates Endometrial Receptivity.

A limited window of receptivity is a prerequisite of reproductive success. Indispensable receptivity genes include cyclooxygenase 2 (COX2), an enzyme accomplishing formation of prostaglandin E2 (PGE2). A powerful regulator of PGE2 formation is Annexin A7 (ANXA7). The present study thus explored whether ANXA7 impacts on implantation and fertility. Here we show that ANXA7 is expressed in endometrial tissue and increases upon decidual transformation of human endometrial stromal cells (HESCs) in a time-dependent manner. Silencing ANXA7 significantly decreased the expression of PRL and IGFBP1, canonical decidual marker genes, but enhances COX2 and PGE2 levels. Genetic knockout of AnxA7 in mice significantly increases the number of implantation sites and litter sizes. Further, analysis of human endometrial biopsies showed that ANXA7 transcript and protein levels are decreased during the midluteal window of implantation in women suffering from recurrent pregnancy loss (RPL) when compared to subfertile patients. Taken together, the data indicate that ANXA7 has a conserved role in regulating endometrial receptivity and implantation.

Assessment of endometrial receptivity during implantation window in women with unexplained infertility

This study aimed to assess the endometrial receptivity during implantation window in women with unexplained infertility. A prospective study recruited 168 women with unexplained infertility and 169 fertile women. Ultrasonic parameters and biomarkers in the uterine fluid were detected. The endometrial vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly higher in fertile women as compared with unexplained infertile women, and the integrin αvβ3, vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and leukemia inhibitory factor (LIF) levels in uterine fluid were significantly higher in fertile women. The biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate in fertile women were 20.12%, 18.34%, and 17.75%, respectively, which were significantly higher compared with unexplained infertile women (7.14%, 5.36%, and 4.17%, respectively). Endometrial thickness (ET), endometrial volume (EV), VI, FI, and VFI measured by ultrasound, and the integrin αvβ3, VEGF, TNF-α, and LIF levels in uterine fluid were all significantly higher in pregnant women as compared with nonpregnant women. The best parameters of ultrasonic indicators for predicting endometrial receptivity in women with unexplained infertility were FI(AUC = 0.894, sensitivity 93.8%, and specificity 83.1%). Integrin αvβ3 had the best predictive value for endometrial receptivity among biomarkers in the uterine fluid (AUC = 0.921, sensitivity 96.7%, and specificity 89.5%). Women with unexplained infertility present declined endometrial receptivity. Endometrial ultrasonic parameters detected by three-dimensional power Doppler and biomarkers in the uterine fluid may be effective indicators to predict endometrial receptivity.

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.

Overexpression of Endometrial Estrogen Receptor-Alpha in The Window of Implantation in Women with Unexplained Infertility.

BackgroundFailure in the endometrial receptivity may account for a significant number of infertility cases including unexplained infertility in women. Reduction in the endometrial estrogen receptor-alpha (ER-α) expression during implantation may be a critical event that coincides with the expression of specific genes and the formation of a receptive endometrium. The aim of the present study was to assess the expression of ER-α in the mid-secretory phase in the endometrium of women with unexplained infertility.Materials and MethodsThis case-control study was carried out on randomly selected fertile (n=10) and infertile (n=16) women whose source of infertility remained unexplained. We evaluated the expression of ER-α and glycode-lin-A (GdA) through mRNA level measurement with real-time polymerase chain reaction (PCR) in the endometrium of fertile women and patients suffering from unexplained infertility and fertile women. Endometrial biopsies of each subject were collected during a single menstrual cycle 7 days after the peak of luteinizing hormone (LH+7).ResultsEndometrial expression level of ER-α was significantly (P<0.05) higher in the patients with unexplained infertility compared to the control. Significantly (P<0.05) lower levels of GdA expression were seen in women with unexplained infertility. A statistically non-significant negative correlation was observed between ER-α and GdA mRNA expression.ConclusionOur findings demonstrate that reduction in the endometrial GdA expression is associated with elevated expression of ER-α in mid-luteal phase. Disruption in the endometrial ER-α expression, which leads to defects in uterine receptivity, may contribute to unexplained infertility.

Expression of the mRNA of the inflammatory component of the immune response in the period of the expected window of implantation in women with recurrent pregnancy loss in the programs of assisted reproductive technologies

The aim of study. To reveal the peculiarities of mRNA expression of the inflammatory component genes of the immune response in the expected window of the implantation in women with RPL in ART programs.Material and methods. 240 patients with RPL in ART programs and 100 conditionally healthy fertile women in the control group with the presence in history of at least one childbirth in time and the absence of episodes of miscarriage were examined. The average age of the examined women of the main group was 29.80 ± 0.30 years, the control group – 30.09 ± 0.32 (p &gt;0.05). The average number of cases of involuntary termination of pregnancy after conduction of ART in main group was 3.24 ± 0.11, the average term of termination of pregnancy was 8.15 ± 0.65 weeks.All women had a paipel-biopsy of the endometrium during the expected implantation window. Samples were frozen at t = -70 °C. until the study. Reverse transcription -polymerase chain reaction was used to study mRNA expression of IL-1β, IL-2, IL-10, Foxp3, TLR9, IL-2Rα cytokine genes in endometrial biopsy obtained on the day of the implantation window.Results. It was found that the relative level of mRNA expression of IL-1β, IL-2, Foxp3, TLR9, IL-2Rα genes did not differ significantly in patients with RPL in the cycles of VRT and control group. A statistically significant decrease in mRNA expression of the IL-10 gene was noted.Conclusion. RPL in the treatment of infertile women in ART programs is associated with changes in the transcription profile of the endometrium during the intended implantation window and with a decrease in the expression level of the IL-10 gene mRNA.

Endometrial expression of β3 integrin, calcitonin and plexin-B1 in the window of implantation in women with unexplained infertility

Endometrial receptivity plays a key role in the establishment of successful implantation and its impairment may contribute to subfertility and limit the assisted reproduction techniques (ART) success. The aim of present study was to investigate endometrial receptivity in terms of β3 integrin, calcitonin and plexin-B1 expression in women with unexplained infertility. We evaluated expression of β3 integrin, calcitonin and plexin-B1 through mRNA level measurement with real-time RT-PCR, in the endometrium of 16 infertile women with unexplained infertility and 10 fertile women. Endometrial biopsies were collected during a single menstrual cycle on postovulatory day LH+7 in each subject. Significant differences regarding β3 integrin and calcitonin expression levels found between patients with unexplained infertility and the fertile women. Endometrial plexin-B1 expression levels showed no significant difference between fertile and infertile women. There were significant correlations between expression of β3 integrin with calcitonin and plexin-B1 in fertile and infertile women. Reduced in endometrial expression of β3 integrin and calcitonin alone or together may contribute to unexplained infertility and these genes could account as the potential molecular markers of infertility.

HOXA-11 mediated dysregulation of matrix remodeling during implantation window in women with endometriosis

To investigate the Homeobox genes HOXA-10 and HOXA-11 mediated endometrial molecular defects during implantation window in endometriosis-associated infertility cases. Endometrial biopsies were obtained during implantation window from 31 infertile women with endometriosis (age < 35 years) and 26 age and BMI-matched infertile women without endometriosis were included in the study for comparison purposes. Endometrial expression of HOXA-10 and HOXA-11 genes, MMP-2, -9, α(v)β(3) integrin, leukemia inhibitory factor and surface characteristics including average roughness and topology were assessed. A significantly lower expression of HOXA-10 and HOXA-11 were observed in endometriotic women compared to non-endometriotic controls. Further, a significantly higher endometrial expression of MMP-2 and -9 were observed in women with endometriosis when compared with controls. Interestingly, endometrial surface were observed to be grossly affected in terms of average roughness and topology in women with endometriosis compared to controls. The findings suggest that aberrant expression of HOXA-10 and -11 genes adversely affects endometrial remodelling and expression of receptivity markers.

Proinflammatory cytokines induced altered expression of cyclooxygenase-2 gene results in unreceptive endometrium in women with idiopathic recurrent spontaneous miscarriage

To investigate the expression pattern of proinflammatory, anti-inflammatory, and angiogenic cytokines and their effect on various mediators of endometrial receptivity in women with idiopathic recurrent spontaneous miscarriage (IRSM). A prospective study. Tertiary care hospital and reproductive health research unit. Thirty-six women with IRSM (<35 years) and 30 fertile women as controls matched by age and body mass index undergoing sterilization. Endometrial biopsies in all women corresponding to the window of implantation. Assessment of endometrial expression of proinflammatory, anti-inflammatory, and angiogenic cytokines, mediators of matrix turnover and angiogenesis, markers of receptivity. A statistical significantly higher level of proinflammatory cytokines, mediators of matrix turnover and angiogenesis, and a reduced expression of anti-inflammatory and angiogenic cytokines were observed in women with IRSM. Additionally, the markers of endometrial receptivity were poorly expressed in women with IRSM. Aberrant expression of proinflammatory, anti-inflammatory, and angiogenic cytokines during implantation window in women with IRSM is one of the key factors that adversely affect endometrial development, as evidenced by the inadequate expression of various endometrial receptivity markers.

Endometrial Indian hedgehog expression is decreased in women with endometriosis

Nuclear and cytoplasmic endometrial expression of Indian hedgehog increased from the late proliferative to mid and late secretory phases in 26 healthy volunteers compared with 30 women with endometriosis. The abnormal expression of Indian hedgehog protein in women with endometriosis suggests a resistance to P action.

Is there a uniform basal endometrial gene expression profile during the implantation window in women who became pregnant in a subsequent ICSI cycle?

To understand which genes are really involved in the implantation process, we planned to study the gene basal expression profile during the window of implantation (WOI) of patients who became pregnant in a subsequent ICSI cycle. Women attending their first ICSI cycle at ANDROS Day Surgery for severe male factor infertility were included in the study. An endometrial biopsy was performed during the WOI, in one of the last two cycles before the ICSI cycle. Forty-seven selected gene profiles were analyzed using Low Density Array technology. Only biopsies from women who subsequently became pregnant were evaluated, to exclude any bias regarding embryo viability and embryo transfer difficulties. Fifteen patients were included in the analysis as they became pregnant after ICSI procedure. Four of 47 selected genes were excluded from the analysis. Of the 43 genes analyzed, only 6 genes (VEGFA, PLA2G2A, ALPL, LIF, NNMT and STC1) showed a statistically uniform expression among patients who subsequently became pregnant. For all the other genes analyzed there were considerable differences in their expression levels amongst women who subsequently became pregnant. Our data suggest that very few genes, which change their expression level during the WOI, show a quantitative homogeneous expression in endometrially-receptive patients. In conclusion, in this study only six genes showed a homogeneous expression, and are probably involved in embryo implantation mechanisms.

Reduced expression of biomarkers associated with the implantation window in women with endometriosis

To evaluate the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis. Prospective observational study. Clinical research center. Twenty-four women with endometriosis and 23 healthy volunteers of similar age. Secretory phase endometrial biopsy. Expression of immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 in eutopic endometrium. Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are P dependent, these findings suggest the possibility of reduced endometrial P action in this population.