Репозиторий Университета

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

© 2018 Dynasty Publishing House. All rights reserved. The objective: To enhance the efficacy of diagnosis and treatment of various kinds of intrauterine pathology in women with infertility using minimally invasive hospital-substitute methods. Patients and methods: We made a complex examination and treatment of 226 female patients with infertility and various intrauterine pathologies aged 22 to 45 years. Minimally invasive interventions were performed using an office hysteroscope, without cervical fixation or dilation of the cervical canal, and in some cases without anaesthesia, which permitted to reduce traumatization of patients during highly informative diagnostic screening and surgical treatment of the diagnosed intrauterine pathology. Results: According to the findings of office hysteroscopy, all patients were divided into 3 groups: group 1 included 110 (49%) women with endometrial polyps, group 2 - 30 (13%) women with polyps of the cervical canal, group 3 - 86 (38%) women with intrauterine synechiae. All women were treated in outpatient settings, laser destruction of intrauterine synechiae and polypectomy of the cervical canal and uterine cavity were performed. 22 (10%) patients with complete or almost complete obliteration of the uterine cavity by fibrinous adhesions and 12 (5%) women with multiple small endometrial polyps were hospitalised. 148 (65%) patients 3-6 months after intervention underwent control office hysteroscopy. No pathology was found in 129 of them, in 5 patients single adhesions were found after complete obliteration, in 2 - endocervical polyps and in 12 - endometrial polyps. Pregnancy occurred in 51 (22%) patients from group 1, in 19 (9%) and 34 (15%) from groups 2 and 3, including pregnancies after assisted reproductive technologies. Conclusion: Office hysteroscopy as a hospital-substitute method of examination and treatment of female patients with infertility conditioned by intauterine pathology has demonstrated its high efficacy.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II - 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7-10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II - 5.5±0.06 years and 2.4±0.07 years, respectively (p<0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p<0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p<0.001). Immunohistochemical analysis of the endometrium on the 18th-24th day of the cycle established high expression of CD16, CD20, CD56, and HLADRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p<0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p<0, 05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16, CD20, CD56 and HLA-DRII .

© 2018 Sankt Peterburg. All rights reserved. The purpose of this study was to assess the level of apoptosis in cells of human seminiferous tubules in normal and pathological spermatogenesis by revealing the proportion of immunostaining cells for caspase-9 and -3 and by comparing the expression of pro-apoptotic (BAK and BAX) and anti-apoptotic genes (BCL2 and BCLW). A retrospective study involved men (n = 42) who complained of childlessness in marriage for 2 years with a diagnosis of idiopathic infertility, established after physical, genetic, biochemical (hormones) and cytological (spermogram) analyzis. The biopsies of the testes as well as the autopsy material of men 22—35 (n = 10), 64—75 (n = 10) and 75—90 (n = 10) years were studied using the immunohistochemical method (caspase-9 and -3) and PCR-RT. The marking level for caspase-9 in spermatogonies with normal spermatogenesis is approximately at the same level (the proportion of stained spermatogonies is 39.5 0.33 % in young men, 35.6 0.44 % in the elderly, and 32.2 0.28 % in man of senile age), and increases when the maturation is blocked and in the case of focal variant of Sertoli-cell-only syndrome (64.3 0.39 and 72.0 0.41 %, respectively). When using antibodies to caspase-3, the percentage of immunopositive spermatogonia in normal spermatogenesis was 60.1 0.44 % in young men, 78.2 1.2 % in the elderly, and 87.3 0.9 % in men of senille age, and with idiopathic infertility, a sharp increase in the proportion of labeled spermatogonia was observed (an average of 91.4 1.1 %). In the case of hypospermatogenesis and the blocking of maturation, a significant increase in the relative level of expression of the proapoptotic genes of the internal pathway of apoptosis of BAX and BAK was observed against the background of a decrease in the expression of the anti-apoptotic genes BCL2 and BCLW, compared to men of the same age but with normal spermatogenesis. Based on the results, we can conclude that in the elderly’s testes the receptor-mediated pathway of apoptosis predominates over the mitochondrial (internal) pathway. In the idiopathic form of male infertility the internal pathway of apoptosis is dominant. An increase in the activity of apoptosis markers can be associated with impaired maturation of the germ cells in the meiosis block and with the depletion of the germ cell pool in Sertoli-cell-only syndrome.

© 2018, Dynasty Publishing House. All rights reserved. The objective. A quantitative analysis of the levels of environmental contaminants from the class of polychlorinated diben-zoparadioxins, furans (PCDD/F) and polychlorinated biphenyls (PCB) as sensors of chemical alteration in the reproductive system in idiopathic infertility. Patients and methods. The examination included 122 women diagnosed with «idiopathic infertility». The levels of ecopollutants were determined by a combination of high-performance capillary gas chromatography and high-resolution gas chromatography/ mass spectrometry according to the standard protocol. Results. In follicular fluid of patients, the total content of dioxins/furans did not exceed 15.7 pg/g of lipids, i.e. was at the sensitivity threshold of the employed method. PCB concentrations were also low (not more than 28.6 pg/g of lipids), but PCB153 and PCB180 congeners associated with fertility disorders have not been found. Conclusion. As has been hypothesized, this class of xenobiotics does not play a leading role in the genesis of environmentally-conditioned reproductive pathologies in women.

© Bionika Media Ltd. Objective. To study the features of sexual functioning and the psychopathological pattern of sexual dysfunctions in women with infertility in assisted reproductive technology programs to elaborate treatment and rehabilitation measures and to improve quality of life in a couple. Subjects and methods. An open-label continuous comparative cross-sectional study of sexual functioning and psychopathological and personality characteristics was conducted in 589 women visiting the V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, for infertility. Clinical, psychopathological, clinicosexological, and psychometric studies were used. Results. 58.9% of the examined patients were found to have non-psychotic mental disorders, among them there was a predominance of anxiety disorders (28.0%); 18.34% had sexual dysfunctions, among which a libido disorder was prevalent (25.0%). There was a high comorbidity of sexual dysfunctions and borderline mental disorders (100.0%). The personal and psychopathological characteristics were revealed in patients with sexual dysfunction (p < 0.05). Conclusion. The studied features of the psychopathological pattern of sexual dysfunctions in infertile women are needed to elaborate differentiated tactics for the treatment and rehabilitation measures and to improve quality of life in a married couple.

© 2018, SPb RAACI Search for novel prognostic criteria predicting successful in vitro fertilization remains a nonresolved problem at the present time. The aim of our study was to analyse a predictive role of IL-1? as an additional marker of pregnancy after in vitro fertilization (IVF). The study included 120 women with tubo-peritoneal infertility subjected to the IVF procedure. Retrospectively, two groups were formed of this cohort, dependent on efficiency of in vitro fertilization. Group I included 40 women with successful pregnancy whereas group II comprised 80 women with failed pregnancy. IL-1? concentrations in serum were detected by ELISA technique. A polymorphic rs1800587 marker at 5`UTR region has been amplified by PCR followed by Sanger sequencing. We have shown IL-1? hyperproduction in the women from group I. The women with effective IVF outcome exhibited positive correlation between IL-1? and luteinizing hormone, prolactin, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate levels. The women with ineffective in vitro fertilization have detected a negative correlation between IL-1? levels and anti-Muellerian hormone, a positive correlation of IL-1? with 17-hydroxyprogesterone. The women with T allele of the polymorphic rs1800587 marker at 5`UTR region have shown a 2.5-fold higher chance to become pregnant after IVF than the women carrying C allele (95% CI = [1.45-4.35], ? = 0.0009). The women with T/T genotype exhibited a positive correlation between IL-1? and estradiol, testosterone; the subjects with heterozygous C/T genotype showed correlation with estradiol, and those harboring C/C genotype exhibited correlation with follicle-stimulating hormone. The revealed changes suggest a potential involvement of IL-1? into regulation of cyclic processes in the ovary including ovulation. Moreover, IL-1? may participate in formation of pro-inflammatory environment for successful blastocyst implantation.

© 2018 Stavropol State Medical University. All rights reserved. Male fertility is based on complex intracellular signaling during spermatogenesis. Effect of Interleukin-1 (IL-1) and its homologues on spermatogenesis is actively studied. Nevertheless, its role in idiopathic infertility has not been sufficiently studied, especially in the phase of hypospermatogenesis. Aim: Evaluation of the expression of IL-1α, IL-1β and IL-1ra in human seminiferous tubules in idiopathic infertility. A retrospective study involved men (n=54) who complained of childlessness in a marriage for 2 years with the diagnosis of idiopathic infertility, established after a physical, medico-genetic, biochemical (hormone) and cytological (spermogram) analysis. The biopsy specimens obtained from the operation, as well as the autopsy material of men aged 22-35 years (n=10), were studied using the immunohistochemical method (antibodies: IL-1α, IL-1β and IL-1ra). At hypo-spermatogenesis, the maturation block, and Sertoli-cell syndrome, Leydig cells are marked to IL-1α, IL-1β labeling with a decrease in IL-1ra. Sertoli cells and germ cells show weak responses to IL-1α, IL-1β and their absence on IL-1ra. Thus, the different levels of expression of IL-1α, IL-1β and IL-1ra indicate that these cytokines control spermatogenesis and are one of the triggers in the formation of male infertility form-phases.

© 2018 Media Sphera Publishing Group. All rights reserved. Objective - to study endometrial receptivity in infertile women with external genital endometriosis (EGE). Subject and methods. Clinical, morphological, immunohistochemical, and molecular genetic examinations of endometrial aspiration pipelle biopsy specimens obtained on days 22-24 of the menstrual cycle from 94 infertile women with endometriosis: 50 women with Stage I-II EGE and 44 women with ovarian endometrioid cysts (OEC). A control group consisted of 54 women with tubal peritoneal factor of infertility (TPFI) and a successful attempt at IVF. Hematoxylin and eosin-stained sections were found to contain a number of endometrial surface epithelial cells containing mature pinopods. The expression levels of leukemia inhibitory factor (LIF), HOXA-10, glycodelin A, avβ3 integrin, estrogen receptors (ER) and progesterone receptors (PR), aromatase in the superficial epithelium, glandular epithelium and endometrial stroma were immunohistochemically revealed. Forty-four patients, including 17 with Stage I-II EGE and 27 with TPFI, showed mRNA expression levels of leukemia inhibitory factor receptor (LIFR), LIF, ER1, PgR, HOXA-10, and PTEN by real-time quantitative polymerase chain reaction (PCR) with a preliminary reverse transcription PCR assay. Results. It was established that in the infertile women with Stage I-II EGE and those with OEC, endometrial receptivity was impaired, which was manifested by a decline in the number of superficial epithelial cells containing mature pinopods, as well as a decrease in the endometrial level of the key receptivity markers: αvβ3 integrin, LIF, glycodelin A, and HOXA10 and increases in the synthesis of aromatase and in the imbalance of endometrial stromal expression of ER and PR detected by immunohisto chemistry (IHC). Molecular genetic study showed lower mRNA expression levels of the HOXA-10, LIFR, and PgR genes, which confirms the data obtained by IHC. Conclusion. To assess the role of the endometrium in the development of infertility in women with EGE, it is necessary to conduct morphological and IHC studies of the molecular markers of receptivity, by determining the status of pinopods of the endometrial surface epithelium during the window of implantation.

© Bionika Media Ltd. The article highlights the clinical and pathogenetic relationships between endometriosis/adenomyosis and chronic endometritis (CE) within reproductive failures. It describes a cause-and-effect relationship between endometriosis/ adenomyosis and CE by the example of its clinical symptomatology and the pathogenic mechanisms involving an autoimmune process, aseptic inflammation, and altered endometrial receptivity. Endometriosis/adenomyosis and CE have a number of common pathogenetic mechanisms of development and clinical manifestations (infertility, miscarriages, and assisted reproductive program failures). This implies the necessity to qualitatively assess the endometrium in women with endometriosis and adenomyosis during pregravid preparation, as well as the search for new therapeutic ways to correct autoimmune disorders. The use of sodium desoxyribonucleate (derinat) showing the pharmacological properties of an activator of the cellular and humoral immune system and a stimulator of reparative and regenerative processes is a promising approach to drug therapy.