Secretory Endometrium Research Articles

Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility? MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples. Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility. MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells. MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10-13), early-secretory (cycle days 14-19) or mid-secretory (cycle days 20-24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25-28) secretory phases. MSX1 transcript increased 5-fold (P < 0.05) between the late-proliferative and early secretory phase and was then down-regulated (P < 0.05) prior to receptivity for implantation. In fertile patients, MSX1 protein displayed strong nuclear localization in the luminal epithelium and glands, while it was weakly expressed in nuclei of the stroma. MSX1 protein levels accumulated throughout the secretory phase in all endometrial cellular compartments. MSX1 protein decreased (P < 0.05) in the glands between mid- and late-secretory phases. However, infertile patients demonstrated a broad reduction (P < 0.001) of MSX1 accumulation in all cell types throughout the secretory phase that was most pronounced (∼3-fold) in stroma and glands. Infertility was associated with persistent co-localization of E-cadherin and β-catenin in epithelial cell junctions in the mid- and late-secretory phases. Details of the infertility diagnoses and other patient demographic data were not available. Therefore, patients with uterine abnormalities (Mullerian) could not be distinguished from other sources of infertility. Antibody against human MSX2 is not available, limiting the study to MSX1. However, both RNAs in the human endometrium are similarly regulated. In mice, Msx1 and Msx2 are imperative for murine embryo implantation, with Msx2 compensating for genetic ablation of Msx1 through its up-regulation in a knockout model. This investigation establishes that the MSX1 homeobox protein accumulation is associated with the secretory phase in endometrium of fertile couples, and is widely disrupted in infertile patients. It is the first study to examine MSX1 protein localization in the human endometrium, and supported by genetic findings in mice, suggests that genes regulated by MSX1 are linked to the loss of epithelial cell polarity required for uterine receptivity during implantation. This research was supported by the NICHD National Cooperative Reproductive Medicine Network grant HD039005 (M.P.D.), NIH grants HD068524 (S.K.D.), HD071408 (D.R.A., M.P.D.), and HL128628 (S.D.), the Intramural Research Program of the NICHD, March of Dimes (S.K.D., S.D.) and JSPS KAKENHI grant 26112506 (Y.H.). There were no conflicts or competing interests.

Clusterin immunoexpression is associated with early stage endometrial carcinomas

Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184–15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression.

Wilms' tumor 1 protein expression in endometrial adenocarcinoma and endometrial intra-epithelial neoplasia.

To investigate the expression of Wilms' tumor 1 (WT1) protein in endometrial adenocarcinoma (EC) and endometrial intra-epithelial neoplasia (EIN). WT1 protein expression was determined on immunohistochemistry in 30 EC patients and in 20 EIN patients. WT1 protein expression in proliferative (n = 7), secretory (n = 9) and atrophic endometrium (n = 9) and benign endometrial polyps (n = 28) was used as the control group. Cellular and vascular WT1 staining was scored semiquantitatively. Cellular WT1 staining was 67% and vascular positivity was 73% in the EC group. In the EIN group the cellular staining was 100% and vascular staining was 85%. Although all EIN samples were positive for cellular WT1 staining, median cellular staining score was similar to that of EC (median, 2; range, 1-3; IQR, 1.75 vs 2, 0-3, 0.75, respectively). Increasing EC grade and stage were not associated with cellular or vascular WT1 staining score. WT1 is expressed in EIN.

Histopathological analysis of endometrial biopsies in dysfunctional uterine bleeding

Background: It is estimated that 9-30% of women of reproductive age suffer from menorrhagia. Because most cases are associated with anovulatory menstrual cycles, adolescent and perimenopausal women are particularly vulnerable to this particular condition. The aim of this study was to evaluate the histopathological pattern of endometrial biopsy from patients presenting with dysfunctional uterine bleeding.Materials and Methods: This is a cross-sectional observational study done in Nobel Medical College, Biratnagar, Nepal for a period of three years from June 2012 to June 2015. All the patients presenting with dysfunctional uterine bleeding and who underwent endometrial biopsy were included in this study. Distribution of various histopathological patterns was observed in the different age groups.Results: A total of 300 cases were included in my study. The commonest pattern in these patients was proliferative endometrium 61 (%). The commonest pathology was simple cystic hyperplasia (13.3%). Other patterns identified were secretory endometrium, chronic endometritis and pill endometrium. Malignant lesion comprised of 8 (2.7%) of patients and the majority was in &gt;50 years followed by in between 41-50 years of age. Atrophic endometrium was the commonest finding in post menopausal bleeding, comprising of 11 cases (3.6%), followed by endometrial carcinoma of 8 cases (2.7%).Conclusion: As observed from the study, there is an age specific association of endometrial bleeding, with highest incidence in perimenopausal age group. Hence, dilatation and curettage is helpful for diagnosis, to assess therapeutic response and to know the pathological incidence of organic lesions in cases of dysfunctional uterine bleeding.

A shift in the balance of T17 and Treg cells in menstrual blood of women with unexplained recurrent spontaneous abortion

To determine usefulness of menstrual blood for assessment of differential frequency of T cell subsets, peripheral blood (PB) and menstrual blood (MB) from healthy fertile (n=15), unexplained recurrent spontaneous abortion (URSA) women (n=15) and unexplained infertile women (n=8) were collected in the second day of menstrual bleeding. Frequency of T cell subsets was measured by flow cytometry. URSA and unexplained infertile patients had higher frequency of TCRαβ+CD3+CD56− and CD45RO+ T cells as well as CD45RO+/CD45RO− ratio in PB as compared to MB. Frequency of CD3+TCRγδ+ cells in PB of unexplained infertile and MB of URSA patients were significantly lower than that in fertile group. In all groups MB contained higher percentage of CD4+CD25+Foxp3+ regulatory and lower percentages of CD16+ T cells compared to PB. T17 cells (CD3+CD56−IL-17+) was found to be significantly higher in MB of only fertile and unexplained infertile subjects and not URSA patients in comparison with PB. Compared to PB, only fertile women had higher T17:Treg ratio in their MB. URSA women had significantly lower MB T17 cells and T17:Treg ratio compared to those in fertile and unexplained infertile women. Based on the findings presented here, we speculate that MB has its own unique immune milieu which is not solely continuation of the immune environment of secretory endometrium. Indeed, immunophenotyping of MB immune cells could potentially be a useful tool for investigation of immunological disturbances in pregnancy-related disorders.

Parallel Expression of Enzyme Inhibitors of CD8T Cell Activity in Tumor Microenvironments and Secretory Endometrium.

The divergent requirement for tolerance to support conception and protective response against sexually transmitted infections defines the unique immunological dynamics in the female reproductive tract (FRT). In part, these requirements are achieved by the cyclic modulation of cytolytic CD8T cell function in the FRT that underlie the respective immunosuppressive and immunocompetent milieus during the secretory and proliferative phases of the menstrual cycle. The CD8T cell function can be dampened by exposure to indoleamine 2,3-dioxygenase and/or arginase enzymes. Indeed, these 2 enzymes are known as primary inducers of immune suppression in tumor microenvironments. This review discusses the intriguing parallel expression of these 2 enzymes in tumor microenvironments and in the secretory endometrium. We surmise that investigating the underlying natural mechanisms that suppress and restore the immunocompetence of CD8T cells in the FRT each month may provide valuable insights into ways to artificially recapitulate these mechanisms and inhibit immune suppression in tumor microenvironments.

Expression and Significance of WNT4 in Ectopic and Eutopic Endometrium of Human Endometriosis.

The objective was to investigate the expression of the WNT4 gene in ectopic endometrium and eutopic endometrium (EU) during endometriosis and the relationship of WNT4 expression with the menstrual cycle. Ectopic endometrium and EU tissues were collected from 30 women with pathologically confirmed endometriosis and 30 women without endometriosis. The WNT4 protein and messenger RNA (mRNA) expression levels were measured by fluorescence-based quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot methods. The expression of WNT4 was not significantly correlated with the menstrual cycle, and there were no significant differences when WNT4 expression in proliferative endometrium was compared with that in secretory endometrium within each group. There were no significant differences between the protein and mRNA expression of WNT4 in ectopic endometrium and in EU from participants with endometriosis. The WNT4 expression level in EU was significantly reduced compared with that in normal endometrium of the control group, even when analyzed by the menstrual cycle phase. WNT4 was also downregulated in ectopic lesions. This study provides further evidence supporting the theory of "EU determinism" in the pathogenesis of endometriosis.

CAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.

Correlation between transvaginal ultrasound measured endometrial thickness and histopathological findings in Turkish women with abnormal uterine bleeding.

The present study aims to determine how transvaginal ultrasonography and histopathological examination findings are correlated in a cohort of premenopausal and postmenopausal Turkish women with abnormal uterine bleeding. This is a retrospective review of 350 Turkish women who underwent transvaginal ultrasonography and suction curettage as a result of abnormal uterine bleeding. Sonographic appearance of the endometrium was normal in 244 patients (69.7%), while homogeneous thickening was detected in 47 patients (13.4%) and cystic thickening in 21 patients (6.0%). A sonographic diagnosis of endometrial polyp was made in 38 patients (10.9%). Histopathological analysis of endometrial samplings revealed proliferative endometrium (36%), secretory endometrium (24.6%), decidualization (10.9%), endometrial polyp (8.3%), endometritis (6.8%), endometrial hyperplasia (4.6%), irregular shedding (3.7%), atrophic endometrium (3.1%), endometrial cancer (1.1%) and placental retention (0.9%). The sonographic and histopathological findings correlated significantly (χ(2) = 122768, P = 0.001; r = 0.215, P = 0.001). Approximately 51% of the women with homogeneous endometrial thickening had proliferative endometrium. Only 44.7% of the women with ultrasonographically visualized endometrial polyps had histopathologically diagnosed endometrial polyps. Nearly 57% of the women with cystic endometrial thickening had proliferative endometrium. If there is no facility for hysteroscopy or hysteroscopy-guided endometrial biopsy for women with abnormal uterine bleeding, transvaginal ultrasonography findings can be efficiently used to make a preliminary diagnosis and, thus, notify the pathologists.

Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma

Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma

Expression of ERα and PR in Various Morphological Patterns of Abnormal Uterine Bleeding-Endometrial causes in Reproductive Age Group.

Abnormal Uterine Bleeding (AUB) is most common gynaecological problem but its management is not well defined. So FIGO/PALMCOEIN classification was developed to provide clear management options as treatment is different in PALM and AUB-E group. FIGO/PALM-COEIN classification and immunohistochemistry with ERα and PR expression in AUB-E group will be helpful in management of these patients, thus preventing surgical interventions. To study histomorphological classification according to FIGO/PALM-COEIN classification in patients presenting with AUB into PALM and AUB-E group. To study the receptor expression of ERα and PR in AUB-E group. This cross sectional study was performed in patients presenting with AUB in reproductive age group (15-45 years). Six hundred endometrial specimens were stained with H&E for histolomorphological examination and classified as per FIGO/PALM-COEIN classification of AUB in non-gravid women in reproductive age group. Fifty endometrial biopsies were of pregnancy and pregnancy related complications and were excluded from study. A total of 550 samples were evaluated in present study. IHC for quantification of ERα and PR expression was carried out in AUB-E (100) cases and control group endometrium (20) cases due to technical constraints. Unpaired student t-test was performed. p-value ≤ 0.05 was taken as critical level of significance. Endometrial (58.19%) (AUB-E) causes were most common cause of AUB. Most common morphology was AUB-E (Proliferative endometrium), AUB-L (Leiomyoma) and AUB-E (Secretory endometrium) respectively. Statistically significant expression of ERα and PR was found in AUB-E endometrium as compared to control group endometrium. In Non secretory/Proliferative endometrium AUB-E group. Proliferative endometrium and hyperplasia without atypia had significant expression of ERα and PR in glands and stroma when compared with proliferative phase control group endometrium. But disordered proliferative endometrium had only significant PR expression in stroma. When secretory phase endometrium was compared with control group secretory phase significant expression for PR was noted only in stroma. FIGO/PALM-COEIN classification will be helpful in deciding treatment of AUB cases. Study of receptor expression in AUB-E group will help in providing evidence based treatment and prevent from surgical procedures like hysterectomy and endometrial ablation.

Management of Proliferative Endometrium on Biopsy in Post-Menopausal Women

Post-menopausal bleeding (PMB) is usually caused by several endometrial conditions (hyperplasia and carcinoma) for which there are evidence-based treatments. However, there is little literature and no evidence-based treatments for a finding of proliferative endometrium without atypia on Pipelle endometrial biopsy in women presenting with PMB. Our aim is to explore management and treatment options for this subset of women. This is a retrospective, observational case series review of women presenting with PMB to a gynaecology rapid access clinic at a District General Hospital in Manchester, UK over a period of three weeks. Four women who were found to have a proliferative or secretory endometrium on endometrial Pipelle biopsy were chosen. Their history, examination findings, investigations, treatment and follow-up findings were then analysed. This case series has identified the management dilemma posed by patients with proliferative endometrium with no atypia on endometrial sampling. The four patients were followed-up with a repeat Pipelle endometrial biopsy six weeks after presentation to the specialist gynaecology unit. They were subsequently counselled or treated with oral progesterone therapy for six to eight weeks. The management options included the Mirena intrauterine system (IUS), oral progesterone therapy and discharging the patient back to primary care. There is no consensus on the importance of oral progesterone or the duration of follow up necessary to monitor for the development of endometrial hyperplasia or cancer in this subset of patients. Further research is needed to develop evidence-based, management guidelines for proliferative endometrium in women with PMB.

Pattern and frequency of endometrial changes and pathologies among pregnant and nonpregnant women presented with abnormal uterine bleeding in rural inhabitants of north India: A retrospective secondary data analysis

Background: Abnormal uterine bleeding i.e., dysfunctional uterine bleed is one of the most frequent problems that occur in women of all ages. It occurs due to various disorders. Endometrial biopsy remains a preferred sampling procedure for the diagnosis of endometrial pathology. This study was conducted to determine the type, frequency of endometrial pathologies in women presenting with AUB, and their association with different age groups. Materials and Methods: This was retrospective study conducted in Histopathology Section of the Pathology Department of the Rural Institute of Medical Science and Research, Saifai, Etawah. Five hundred and forty seven (547) patients who have undergone endometrial biopsies and who clinically presented with AUB were included in this study. The pattern of endometrial pathologies was diagnosed, classified, and it was compared in terms of age. Result: Out of the 563 patients who have undergone endometrial biopsies and who presented with AUB, 547 were included in study and others were discarded because of scanty tissue. The patients were aged between 15 years and 72 years, and most of the patients were aged between 41 years and 50 years (36.56%). The common clinical presentation was menorrhagia (42.96%). The most common pattern on histopathology was secretory endometrium (28.33%). Pregnancy related pathology was also forming a bulk (17.36%), whereas incidence rate of malignancy was low (1.09%). Conclusion: AUB is the common clinical complaint interfering with the quality of life in healthy women. Endometrial sampling therefore, biopsy or curettage, is an important diagnostic procedure for the evaluation of AUB with special preference above 35 years of age to rule out malignancy.

A two year histopathological study of endometrial biopsies in a teaching hospital in Northern India

Introduction: Endometrial biopsies and curettings constitute an important tool for diagnosis of endometrial pathology; whether benign, pre-malignant and malignant, and help the gynecologist to decide appropriate therapeutic strategy. The present study was carried out to document the histopathological appearances seen in endometrial biopsies, and their age–wise distribution in patients with infertility and abnormal (irregular, excessive or continuous) uterine bleeding due to endometrial causes. Materials and Methods: A total of 214 specimens of endometrial curettings and biopsies from patients with abnormal uterine bleeding due to endometrial causes and inability to conceive, received in the Pathology department, Gian Sagar Medical College and Hospital, Banur, Rajpura, over a period of two years from January 2012 upto December 2013, were retrieved and analyzed retrospectively, and their findings were documented. The tissue had been received in 10% formalin, processed routinely, and the slides had been stained with Hematoxylin and Eosin. Results and Conclusion: The most common histopathological diagnosis was proliferative endometrium seen 33% cases. Products of conception were confirmed histologically in 12% cases. Endometrial hyperplasias were seen in 09% cases, and disordered proliferative endometrium in 06%. Secretory endometrium was seen in 07% cases. 02% biopsies showed atrophic endometrium. Luteal phase defects were seen in 07% of the specimens. 01% cases showed tubercular endometritis and adenocarcinoma each. The most common finding in patients of infertility was proliferative endometrium indicating anovulatory cycles. Endometrial biopsy is a valuable tool in assessment of endometrial status in infertility, as well as benign and malignant pathology in abnormal uterine bleeding due to relative ease and accessibility of procedure and rapid availability of results. Keywords: Abnormal uterine bleeding, Infertility, Dysfunctional uterine bleeding, Hyperplasia, Ca

ENDOMETRIAL HYPERPLASIA: CONTROVERSIAL ISSUES OF PATHOGENESIS AND THERAPY

Traditional attitude towards the role of hyperestrogenia in endometrial hyperplasia pathogenesis can be considered cogent only in case of simple endometrial hyperplasia (SEH). In case of complex endometrial hyperplasia (CEH) and atypical endometrial hyperplasia (AEH) excessive proliferation occurs only in endometrial glands not diffusely but as pockets. The signs of atrophy are often registered outside these pockets that reflects the state of hypoestrogens. The aim. To justify a differentiated approach to treatment tactics of patients with EH. Material. Pathological changes adjacent to the lesions AEH in 274 patients have been studied. Results. The structure of the endometrium outside the foci of the CEH and the AEH represents a wide spectrum of pathological changes – SEH, proliferative and secretory endometrium, polyps, atrophic endometrium, that's not confirms the role of hyperestrogenic in the pathogenesis of the CEH and AEH. Conclusion. SEH, as a result of imbalance of estrogen and progesterone, is subject to cyclic hormone therapy with progestin for the prevention of acyclic bleeding. In the case of the absence of abnormal uterine bleeding after uterine curettage under SEH and CEH without atypia valid only observation with regular control. At AEH surgical treatment is required.

Endometrial aspiration cytology in gynecological disorders.

Context:Endometrial aspiration is not a popular modality for the study of the endometrium despite its simplicity and potential utility.Aim:The present study was aimed at evaluating the utility of endometrial aspiration in various gynecological disorders.Materials and Methods:In this diagnostic accuracy study, 55 prospectively registered women with various gynecological disorders were evaluated clinically and subjected to endometrial aspiration cytology and study of endometrial histology. Endometrial aspiration was performed by infant feeding tube in 10 cases and intra cath cannula in 45 cases. The slides were stained with rapid Papanicolaou (PAP) stain and Leishman stain.Results:Endometrial aspiration cytology showed 90% and 94.6% sampling adequacy with infant feeding tube and intra cath cannula, respectively. Intra cath cannula was very convenient to handle and superior to infant feeding tube in aspirating the endometrium. Of the two stains used, rapid PAP stain was less time-consuming and superior to Leishman stain in studying the nuclear details. Leishman stain was helpful in detecting cytoplasmic vacuoles of secretory endometrium. Overall diagnostic accuracy of endometrial cytology was 90.4% while that for morphological hormonal evaluation was 97.6%. It enjoyed a sensitivity of 91.66%, a specificity of 88.23%, positive predictive value of 94.28%, and negative predictive value of 83.33%.Conclusion:Intra cath cannula emerged as an inexpensive, effective, and convenient device for endometrial aspiration. Endometrial aspiration proved to be a fairly effective, simple, and informative diagnostic modality.

P27 and its ubiquitin ligase Skp2 expression in endometrium of IVF patients with repeated hormonal stimulation

This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3–21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.

Endometrial Expression of Estrogen Receptors and the Androgen Receptor in Women With Polycystic Ovary Syndrome: A Lifestyle Intervention Study.

Polycystic ovary syndrome (PCOS) is a common cause of anovulation. It may also negatively affect the endometrium, which could lead to implantation failure and proliferative aberrations. Our objective was to study sex hormone receptors in the endometrium of women with PCOS. This is a cross-sectional study and lifestyle intervention. Clinical and laboratory research unit was undertaken at a university hospital. Twenty overweight/obese women fulfilling all three PCOS criteria (anovulation, hyperandrogenism, and polycystic ovaries), 10 body mass index-matched regularly menstruating controls, 11 normal-weight women with PCOS, and 11 normal-weight controls. Intervention for this study included dietary management and physical exercise. mRNA levels and immunostaining of estrogen receptor α (ERα) and β (ERβ), nongenomic estrogen receptor α36 (ERα36), and G-protein-coupled estrogen receptor-1 (GPER), and the androgen receptor (AR) on cycle days 6-8 and cycle days 21-23. Before intervention, mRNA levels of ERα, ERα36, and the ERα/ERβ mRNA ratio were lower in proliferative endometrium of overweight/obese PCOS women compared with controls (P < .05). After intervention, ERα protein and the ERα/ERβ protein ratio in proliferative endometrium increased and were higher in PCOS women with improved menstrual function than in those without improvement (P < .05). In the subgroup of PCOS women with restored ovulation, only higher protein levels of GPER were found in secretory endometrium (P < .01). However, PCOS women who remained anovulatory had higher protein levels of ERα, GPER, and AR on cycle days 21-23 than controls (P < .05). Lifestyle intervention alters, but does not fully restore, ER and AR expression in proliferative and secretory endometrium of obese women with PCOS.

Uterine pathologies to be considered before uterus-preserving surgery in cases of uterine prolapse

Objective: Investigation of unpredictable risks due to abnormal uterine pathology after the choice of uterus-preserving reconstructive surgical procedure for women who have uterine prolapse and no other complaints was aimed. Methods: The data of 121 women (105 postmenopausal and 16 premenopausal) who underwent vaginal hysterectomy due to pelvic organ prolapse was examined and the post-hysterectomy histopathology results were evaluated. Results: Senile cystic atrophy was the most common endometrial pathology result among postmenopausal women (63.5%). However, proliferative and secretory endometrium was the most common endometrial pathology finding among premenopausal women (81.3%). There were statistically significant differences between postmenopausal and perimenopausal women in terms of these pathology results (p 0.05), myoma uteri was significantly more common in patients with perimenopause (p=0.01). Conclusion: The uterus must be evaluated in terms of endometrial pathologies in asymptomatic women with pelvic organ prolapse before uterus-preserving reconstructive surgical procedure, especially in postmenopausal period. J Clin Exp Invest 2015; 6 (4): 443-446 Key words: Pelvic organ prolapse, vaginal hysterectomy, endometrium

Progesterone administration for luteal phase deficiency in human reproduction: an old or new issue?

Luteal phase deficiency (LPD) is described as a condition of insufficient progesterone exposure to maintain a regular secretory endometrium and allow for normal embryo implantation and growth. Recently, scientific focus is turning to understand the physiology of implantation, in particular the several molecular markers of endometrial competence, through the recent transcriptomic approaches and microarray technology. In spite of the wide availability of clinical and instrumental methods for assessing endometrial competence, reproducible and reliable diagnostic tests for LPD are currently lacking, so no type-IA evidence has been proposed by the main scientific societies for assessing endometrial competence in infertile couples. Nevertheless, LPD is a very common condition that may occur during a series of clinical conditions, and during controlled ovarian stimulation (COS) and hyperstimulation (COH) programs. In many cases, the correct approach to treat LPD is the identification and correction of any underlying condition while, in case of no underlying dysfunction, the treatment becomes empiric. To date, no direct data is available regarding the efficacy of luteal phase support for improving fertility in spontaneous cycles or in non-gonadotropin induced ovulatory cycles. On the contrary, in gonadotropin in vitro fertilization (IVF) and non-IVF cycles, LPD is always present and progesterone exerts a significant positive effect on reproductive outcomes. The scientific debate still remains open regarding progesterone administration protocols, specially on routes of administration, dose and timing and the potential association with other drugs, and further research is still needed.