Endometrial Changes Research Articles

ЭНДОМЕТРИАЛЬНЫЕ МАРКЕРЫ СИНДРОМА ПОЛИКИСТОЗА ЯИЧНИКОВ (ОБЗОР ЛИТЕРАТУРЫ)

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women and has a significant impact on
 various aspects of their health and the quality of life. The epidemiology of PCOS is well understood, while the preva-
 lence of this syndrome depends on diagnostic criteria used, the characteristics of the population sample, and vary from
 6–10 % to 15 % and higher. A number of studies suggest that the endometrium in women with PCOS differs from the
 normal endometrium morphologically and functionally. PCOS is associated with infertility problems, higher incidence
 of pregnancy complications and with increased risk of endometrial cancer, especially when obesity is present.
 The purpose of this review was to systematize the available data on molecular markers of endometrial pathology as-
 sociated with PCOS.
 The information search was conducted using Internet resources (PubMed, EMBASE); literature sources for the period
 1992–2016 were analyzed. Although the available information on the pathology of the endometrium is inconsistent,
 as a result of the analysis of published data, several mechanisms of endometrial disorders characteristic of PCOS have
 been identified: changes of hormonal effects (changes in hormone receptor expression, HOXA gene expression, changes
 in the synthesis of sex hormone binding globulin, enzymes involved in the metabolism of sex hormones in situ in the
 endometrium), hyperinsulinemia and disturbance of the glucose transport system, ratio of proinflammatory and anti-
 inflammatory factors.
 Authors conclude that the majority of analyzed studies report an increased prevalence of histologically confirmed
 hyperplasia or endometrial cancer in women with PCOS. However, there are no clinical guidelines and approaches to
 prognosis of endometrial changes women with PCOS. It is still unclear if endometrial biopsy is necessary for all women
 with PCOS. The clinical significance of endometrial markers requires further investigation.

51 Benign Endometrial Changes by Race and BMI With Ulipristal Acetate Treatment

51 Benign Endometrial Changes by Race and BMI With Ulipristal Acetate Treatment

Evaluation of endometrial changes with transvaginal power Doppler ultrasound and comparing them with endometrial sampling in breast cancer patients that are using tamoxifen

Evaluation of endometrial changes with transvaginal power Doppler ultrasound and comparing them with endometrial sampling in breast cancer patients that are using tamoxifen

The Ovarian Cycle.

The "ovarian cycle" is an exquisite and dynamic endocrine system that includes ovarian events, hypothalamic-pituitary interactions, uterine endometrial and myometrial changes during implantation and pregnancy, cervical alterations in structure, and breast development. The ovarian cycle and the steroid hormones produced by the ovary also impact epithelial cancer development in the ovary, uterus, cervix, and breast. This chapter provides a personal view of recent developments that occur in this complex endocrine environment.

Treatment of endometriosis-related chronic pelvic pain with Ulipristal Acetate and associated endometrial changes.

Aberrant progesterone signaling has been demonstrated in mechanistic studies to be a shared common pathway in fibroids and endometriosis. Progesterone receptor modulation with the selective progesterone receptor modulator (SPRM) ulipristal may decrease pain associated with endometriosis. A 25-year-old nulligravidae with endometriosis-related pelvic pain refractory to medical and surgical intervention was administered 15mg ulipristal every other day for 3 months. Daily pain scores and bleeding diary were recorded and serum chemistries and hormone levels were checked prior to, during, and after treatment. Pre-treatment and surveillance endometrial biopsy specimens were examined for histology and stained for estrogen and progesterone receptor status. During therapy, pain scores decreased to a median of 0 (P<0.05) and the patient became amenorrheic. Surveillance endometrial biopsy demonstrated SPRM-associated endometrial changes that appeared strikingly similar to simple hyperplasia and resolved with ulipristal discontinuation. Immunohistochemical evaluation demonstrated the presence of estrogen and progesterone receptors before and during ulipristal treatment. Progesterone receptor modulation with ulipristal substantially improved pain symptoms in a patient with treatment-refractory endometriosis. SPRM-associated changes in the endometrium closely mimicked hyperplasia, developed after less than three months of treatment, and resolved after discontinuation of ulipristal and induction of withdrawal bleed.

Comparison of Endometrial Changes in Uterine Leiomyoma and Adenomyosis of Uterus with Correlation of Serum Estradiol and Progesterone Levels

Comparison of Endometrial Changes in Uterine Leiomyoma and Adenomyosis of Uterus with Correlation of Serum Estradiol and Progesterone Levels

Prognostic analysis for Chinese patients with stage I ovarian endometrioid carcinoma

BackgroundThis study aimed to identify the clinical and pathological characteristics and the possible prognostic factors for Chinese patients with early-stage ovarian endometrioid carcinoma.MethodsThe present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of ovarian endometrioid carcinoma at our center. In all, 78 patients had stage I ovarian endometrioid carcinoma.ResultsIn this series, the 5-year overall survival rate and 5-year disease-free survival (DFS) rates of patients with stage I ovarian endometrioid carcinoma was 98.7% and 87.2%, respectively. Univariate analysis showed the factors that influence the DFS rates include menopausal status, FIGO stage, histological grade, lymphadenectomy, cytology of ascites. Multivariate analysis showed that grade 3 and lymphadenectomy were the independent prognostic factors of DFS for Stage I ovarian endometrioid carcinoma (P = 0.0259, 0.0276 respectively). However, the coexisting endometriosis, concomitant endometrial disorders, dissection of para-aortic lymph node and more courses of thermotherapy had no influence on DFS. Besides, it was found that 19.3% of patients in this series had synchronous early stage and well-to-moderate differentiated endometrial carcinoma.ConclusionsGrade 3 and lymphadenectomy were indicated as the independent factors of DFS for stage I patients with ovarian endometrioid carcinoma. The endometrial changes should be considered seriously when fertility-sparing surgery was planned.

P14.05: Macroscopic endometrial findings in patients with myomas treated with ulipristal acetate: ultrasonographic and hysteroscopic correlations with histologic analysis

To study the correlation between ultrasonographic, hysteroscopic and histologic findings of endometrial changes associated with a standard 3-month ulipristal acetate treatment. A prospective observational study of women undergoing treatment with ulipristal acetate was conducted in a University teaching and research hospital, tertiary referral centre. Seventy-one women with one or more symptomatic myomas were monitored after a 12-week cycle of ulipristal administration (5 mg/day). Patients underwent pre- and post-treatment transvaginal ultrasound and hysteroscopy; guided endometrial samples were collected after treatment to reveal the presence of PAEC features (Progesterone-receptor modulator associated endometrial changes). Endometrial ultrasound and hysteroscopic findings were recorded (endometrial thickness, vascularisation, appearance). Ultrasound findings were normal in most patients but in 6 (8.45%) showed patterns suggestive of endometrial changes (only one showed PAEC after histological analysis); The mean endometrial thickness did not significantly change during treatment except in 3 patients (4.2%) with a thickness ≥16 mm. Hysteroscopically, the endometrium was altered in 5 (7.04%) patients after ulipristal treatment; of these, 4 patients presented histological findings of PAEC. The mean volume of the dominant fibroid was 243 cc (95% CI, 158.71-327.28). Reductions, albeit not statistically significant, were observed in the mean dominant fibroid volume and uterine volume. Our results seem to indicate that hysteroscopic findings are better correlated with the pathological analysis than transvaginal ultrasound for detecting PAEC patterns related to ulipristal acetate treatment.

P14.07: Thickened endometrium secondary to continuous ulipristal acetate treatment

A 37 year-old nulliparous woman was referred to our centre due to hypermenorrhea and uterine leiomyomatosis. She had had two previous laparotomic multiple myomectomies in other centres. She was complaining from heavy menses as well as pelvic pain. At ultrasound examination, she had multiple intramural myomas as well as four submucous myomas of less than two centimetres. The rest of the myometrium appeared as adenomiotic (myometrial heterogenicity, ecogenic linear striation, infiltration of Junctional Zone). After trying treatment with progesterone with no symptomatic control, ulipristal acetate was prescribed. The patient took the treatment continuously for ten months (at her choice without medical agreement). The ultrasound examination at this point showed up a thickened heterogeneous endometrium (34 mm). A hysteroscopic exam was then decided, and revealed a thickened with increased vessels endometrium, compatible with PAEC (Progesterone Associated Endometrial Changes). The patient stopped the treatment and at two months follow up showed a normal echographic, hysteroscopic and histologic endometrial pattern. Since the patient wanted to preserve uterus, a hysteroscopic resection of the submucous myomas was decided. During the surgery, four myomas were resected completely and adenomyosis was confirmed.

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase

The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5′ UTR and positive correlations in the gene ‘Body’ region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.

Altered PTEN expression as a diagnostic marker for the earliest endometrial precancerous changes

Introduction: Study was planned to investigate PTEN gene expression in endometrial hyperplasia and carcinoma as analyzed by immunohistochemistry. Material and Method: This study was conducted on 80 endometrial samples in the Department of Pathology, Gandhi Medical College, Bhopal (January 2012 to August 2016) Results: 5 out of 5 cases of proliferative endometrium, 3 out of 5 cases of secretory endometrium, 37 [84%] out of 44 cases of simple and complex endometrial hyperplasia without atypia, 8 out of 15 cases of simple and complex endometrial hyperplasia with atypia and 3 out of 11 cases of endometrial carcinoma showed positive PTEN expression. Conclusion: PTEN is a major gene involved in the pathogenesis of endometrial carcinoma. Our data suggest that decreased PTEN expression was a marker of earliest endometrial pre-cancer lesion and we propose that use of PTEN immunostaining in a clinical setting may be informative in identifying premalignant lesions that are likely to progress to carcinoma.

Selective progesterone receptor modulators (SPRMs) for uterine fibroids.

Selective progesterone receptor modulators (SPRMs) for uterine fibroids.

Administration of 2.5 mg of estradiol followed by 1,500 mg of progesterone to anovulatory mares promote similar uterine morphology, hormone concentrations and molecular dynamics to those observed in cyclic mares

To test the hypothesis that the administration of 2.5 mg of estradiol benzoate (EB) followed by 1500 mg of long acting progesterone (LA P4) causes similar uterine changes and molecular dynamics in anovulatory mares to those observed in cyclic ones, we evaluated the changes of estrogen (ERα and ERβ) and progesterone receptors (PR) in anestrous, transitional and cyclic mares by RT-qPCR and immunohistochemistry. In addition, we evaluated uterine edema, tonus and estrogens and progesterone plasma profile. Endometrial biopsies were taken from anestrous and transitional mares immediately before EB injection, 48 h after EB administration and five days after LA P4 was given. In cyclic mares, biopsies were collected at estrus and at five days after ovulation. Similar estrogen peaks were achieved after the injection of the single EB dose between treated and cyclic groups, as well as maximum uterine edema. Uterine tone was increased to diestrus levels after administration of 1500 mg of LA P4. Changes in relative abundance of transcripts for PR, ERα and ERβ when progesterone stimulated endometrium was compared to estrogen stimulated endometrium were similar between cyclic and non-cyclic treated mares. However, apparent decreased PR in the endometrial glandular epithelium was not observed in non-cyclic mares five days after LA P4 administration as observed at five days after ovulation in cyclic mares. The protocol produced similar endometrial edema, uterine tonus and changes in relative abundance of PR, ERα and ERβ transcripts to those observed in cyclic mares during late estrus and early diestrus, as well as similar estradiol and estrogen conjugate plasma concentrations.

Histomorphometrics and quantitative unbiased stereology in canine uteri treated with medroxyprogesterone acetate

This article describes the effects of MPA use on the canine uterus using stereological methods. Entire reproductive tracts were removed from normal healthy canine bitches (Canis lupus familiaris) and grouped as: nulliparous (n = 11), multiparous (n = 11) and MPA-treated (n = 11; nulliparous; two treatments; 5 mg/kg). 1 cm samples were cut from the corpus, horn and uterine tube and fixed in 10% formaldehyde. Sections of each were mounted on slides and stained with hematoxylin-eosin. We assessed the fraction area for components of endometrium and myometrium and VV (volume density) and SV (surface density) of the gland and stroma using the M36 test system provided by the STEPanizer Stereological Tool. No gross histological differences were observed between study groups in the uterine tube, uterine corpus and horn. The wall of the uterine corpus and horn in MPA-treated bitches was characterized as being thicker than in the other groups. A cross-section of the uterine corpus revealed no differences between components of uterine wall in the corpus and horn; however, differences were observed in the volume density [VV; %] in variables such as: VV[str.vasc/uterus] (nulliparous vs. multiparous; p = 0.0019) and VV[str.supravasc/uterus] (multiparous vs. nulliparous and MPA; p = 0.0035). In the endometrial gland, differences were detected in SV[gland/endom] (multiparous vs. MPA, p = 0.0442). In the uterine horn, differences were only observed in the variable VV[lumen.gland/endom] (multiparous vs. MPA; p = 0.0019). This study shows quantitative changes in the architecture of the endometrium and myometrium in all the uterine segments, mainly morphological endometrial gland changes of the uterine corpus, increasing the surface area per unit of volume; however, these changes usually do not differ quantitatively from those observed in the uterus of multiparous bitches.

Safety of treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate

Introduction: During the last decade, there has been increased emphasis on the role of progesterone in the promotion of fibroid growth, as well as heightened interest in modulating progesterone pathways by use of selective progesterone receptor modulators. Among them, ulipristal acetate (UPA) has proved its efficacy in the management of symptomatic myomas by controlling bleeding and inducing amenorrhea, and reducing the size of myomas in the majority of cases.Areas covered: In this review, we summarize published scientific studies exploring evidence of the safety of selective progesterone receptor modulators and particularly UPA, a drug approved for the management of symptomatic uterine fibroids. We focus essentially on endometrial changes induced by UPA, and also evaluate other safety outcomes.Expert opinion: Data from published reports of randomized controlled trials over 5 years have demonstrated that UPA does indeed induce endometrial changes (known as progesterone receptor modulator-associated endometrial changes), but they have been shown to be both benign and reversible.Novel algorithms published very recently provide an extensive overview that may be considered as the latest expert opinion. Thus, in infertile women of reproductive age, two courses of 3 months of UPA are recommended in case of type 2 myomas or multiple myomas distorting the uterine cavity. Subsequent therapy is determined depending on the response and restoration of the uterine cavity. If there is no desire for pregnancy, long-term (four courses) intermittent therapy may be initiated. In case of a good response, treatment is stopped and restarted only if symptoms recur. In premenopausal women wishing to preserve their uterus, four courses of 3 months is the proposed strategy.Contraindications to prescribing UPA include pregnancy, breastfeeding, genital bleeding of unknown etiology of origin other than uterine fibroids, and presence of uterine, cervical, ovarian, or breast cancer.

Rationale and design of ASTEROID 2, a randomized, placebo- and active comparator-controlled study to assess the efficacy and safety of vilaprisan in patients with uterine fibroids

BackgroundUterine fibroids (UFs) may be treated with progesterone receptor modulators (PRMs), which have been shown to reduce heavy menstrual bleeding and the size of UFs. To date, one PRM (ulipristal acetate) has received regulatory approval for the treatment of UFs; therapy comprises intermittent treatment courses of up to 3months each, followed by a break to allow two menstruations to occur. We report the design of ASTEROID (Assess Safety and efficacy of vilaprisan in patients with uTERine fibrOIDs) 2, a phase 2 study examining the efficacy and safety of a novel PRM, vilaprisan, in women with UFs. Methods/designIn this randomized multi-arm study, vilaprisan (2mg daily) will be administered in different regimens: continuous treatment for 12 or 24weeks, or two 12-week treatment periods separated by a break to allow one menstruation to occur. Efficacy and safety will be compared with that of ulipristal acetate (5mg daily) and placebo. Patients randomized to receive placebo for 12weeks will also be given active treatment for 12weeks. The primary measure of efficacy will be amenorrhoea rate; secondary measures include time to normalized menstrual bleeding and percentage change in UF volume. Endometrial changes will be monitored throughout the study. DiscussionThe placebo- and active comparator-controlled trial ASTEROID 2 is the first study to evaluate systematically the efficacy and safety of different treatment regimens of PRMs in women with UFs. The findings of this study will direct the planning of future clinical trials of vilaprisan.

Place of ulipristal acetate in the management of uterine fibroids: Preoperative treatment or sequential treatment?

Symptomatic uterine fibroids affect 25% of women of childbearing potential and are responsible for various symptoms, mainly menometrorrhagia, pelvic pain and infertility. No currently available medical treatment is able to eradicate fibroids. Two treatments are indicated preoperatively to reduce bleeding and decrease the size of fibroids: GnRH agonists and ulipristal acetate. Ulipristal acetate, a selective progesterone receptor modulator, exerts an antagonist effect on fibroid tissue, inducing apoptosis. It rapidly induces amenorrhoea (after an average of seven days of treatment) and reduces fibroid volume. It causes few adverse effects and, in particular, is associated with a low rate of hot flashes compared to GnRH agonists. Due to its partial antagonist effect on endometrial tissue, endometrial thickening with no glandulocystic atypia is commonly observed during treatment and is reversible after stopping treatment. These specific histological changes are called Progesterone receptor modulator-Associated Endometrial Changes (PAEC). Since February 2012, ulipristal acetate has been approved in Europe for preoperative treatment of symptomatic fibroids for two three-month cycles. The use of ulipristal acetate facilitates surgery or allows modification of the surgical approach (due to a reduction of fibroid volume) and restores normal preoperative hemoglobin. In some cases, the reduction of menometrorrhagia induced by treatment can allow surgery to be postponed. Since May 2015, ulipristal acetate is also indicated as repeated sequential treatment for moderate-to-severe symptoms due to uterine fibroids.

Different dosages of mifepristone versus enantone to treat uterine fibroids: A multicenter randomized controlled trial.

Background:To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids.Methods:This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3.75 mg) were used. Change in volume of the largest uterine fibroid was the primary efficacy variable, and secondary efficacy variables included changes in anemia and relevant symptom. Safety evaluation included the analyses of adverse events, laboratory values, and relevant endometrial changes.Results:After three months of treatment, the mean volume of the largest leiomyoma was significantly reduced by mifepristone 10 mg or 25 mg or enantone 3.75 mg (40.27%, 42.59% and 44.49% respectively) (P < 0.0001). Percentage change from baseline in largest leiomyoma volume was not statistically significant among the three groups (P = 0.1057). Most of the patients in all groups experienced amenorrhea after the treatment. There were also significant elevations in red blood cell count, hemoglobin and hematocrit (P < 0.0001), and significant reductions in prevalence of dysmenorrhea, pelvic pressure, non-menstrual abdominal pain (P < 0.0001) in each group, while no significant difference among the three groups.All study medications are well-tolerated, and no serious adverse event was reported. Treatment-related adverse event rate was significantly lower in mifepristone 10 mg group, compared to Enantone 3.75 mg group (13.59% vs. 32.58%, P = 0.0002). In both mifepristone groups, estradiol levels were maintained in the premenopausal range, whereas patients in the enantone group had a significant reduction to postmenopausal levels (P < 0.0001).Conclusion:10mg is as effective as 25mg mifepristone and 3.75 mg enantone with minimal drug-related side effects, and may provide an alternative for clinical application, especially for patient who are in perimenopause with uterine fibroids.

Selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA) and its effects on the human endometrium.

STUDY QUESTIONWhat is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids?SUMMARY ANSWERUPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation.WHAT IS KNOWN ALREADYAdministration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes). Data on the impact of the SPRM UPA administration on endometrial sex-steroid receptor expression, progesterone (P)-regulated genes and cell proliferation are currently lacking.STUDY DESIGN SIZE, DURATIONObservational study with histological and molecular analyses to delineate impact of treatment with UPA on endometrium. Endometrial samples (n = 9) were collected at hysterectomy from women aged 39 to 49 with uterine fibroids treated with UPA (oral 5 mg daily) for 9–12 weeks. Control proliferative (n = 9) and secretory (n = 9) endometrium from women aged 38–52 with fibroids were derived from institutional tissue archives.PARTICIPANTS/MATERIALS, SETTING, METHODSStudy setting was a University Research Institute. Endometrial biopsies were collected with institutional ethical approval and written informed consent. Concentrations of mRNAs encoded by steroid receptors, P-regulated genes and factors in decidualised endometrium were quantified with qRT-PCR. Immunohistochemistry was employed for localization of progesterone (PR, PRB), androgen (AR), estrogen (ERα) receptors and expression of FOXO1, HAND2, HOXA10, PTEN homologue. Endometrial glandular and stromal cell proliferation was objectively quantified using Ki67.MAIN RESULTS AND THE ROLE OF CHANCEUPA induced morphological changes in endometrial tissue consistent with PAEC. A striking change in expression patterns of PR and AR was detected compared with either proliferative or secretory phase samples. There were significant changes in pattern of expression of mRNAs encoded by IGFBP-1, FOXO1, IL-15, HAND2, IHH and HOXA10 compared with secretory phase samples consistent with low agonist activity in endometrium. Expression of mRNA encoded by FOXM1, a transcription factor implicated in cell cycle progression, was low in UPA-treated samples. Cell proliferation (Ki67 positive nuclei) was lower in samples from women treated with UPA compared with those in the proliferative phase.LARGE SCALE DATAN/A.LIMITATIONS REASONS FOR CAUTIONA small number of well-characterized patients were studied in-depth. The impacts on morphology, molecular and cellular changes with SPRM, UPA administration on symptom control remains to be determined.WIDER IMPLICATIONS OF THE FINDINGSP plays a pivotal role in endometrial function. P-action is mediated through interaction with the PR. These data provide support for onward development of the SPRM class of compounds as effective long-term medical therapy for heavy menstrual bleeding.STUDY FUNDING/COMPETING INTEREST(S)H.O.D.C. received has clinical research support for laboratory consumables and staff from Bayer Pharma Ag and provides consultancy advice (no personal remuneration) for Bayer Pharma Ag, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc.; A.R.W.W. has received consultancy payments from Bayer, Gedeon Richter, Preglem SA, HRA Pharma; L.H.R.W., A.A.M., R.M., G.S. and P.T.K.S. have no conflicts of interest. Study funded in part from each of: Medical Research Council (G1002033; G1100356/1; MR/N022556/1); National Health Institute for Health Research (12/206/520) and TENOVUS Scotland.

Endometrial dysfunction caused by chronic endometritis: сlinical and morphological aspects

to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE). The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial receptivity to steroid hormones and glycodelin. Antibodies against CD4, СD8, and CD20 were employed to study local immunity. In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2. The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE.