Endometrial Receptivity In Patients Research Articles

Рецептивность эндометрия у больных доброкачественными заболеваниями матки в сочетании с бесплодием до и после оперативного лечения

Рецептивность эндометрия у больных доброкачественными заболеваниями матки в сочетании с бесплодием до и после оперативного лечения

Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization

IntroductionRecurrent implantation failure (RIF) is a challenging problem of assisted reproductive technology that arises mainly due to inadequate endometrial receptivity and its pathogenesis is still unclear. ObjectivesIn this study, we conducted the first investigation of the effect of decreased PIBF1 expression in mid-secretory phase on endometrial receptivity in patients with RIF. MethodsMicroarray assay, reverse transcriptase-quantitative polymerase chain reaction, western blot, and in-vitro experiments were conducted. ResultsThe results showed that progesterone-induced blocking factor 1 (PIBF1) expression was highest in the mid-secretory endometrium in control subjects, but was significantly lower in RIF patients. In Ishikawa and human endometrial stromal cells (HESCs), rather than human endometrial epithelial cells, PIBF1 knockdown significantly downregulated cell proliferation and the levels of interleukin 6 (IL6) and phosphorylated signal transducer and activator of transcription-3 (p-STAT3). Besides, in HESCs, the levels of IL6, p-STAT3, prolactin and insulin-like growth factor binding-protein-1 (IGFBP1) decreased after PIBF1 knockdown during in-vitro decidualization. All these cellular changes could be notably restored by PIBF1 or IL6 overexpression. Consistent with our findings with PIBF1, the levels of IL6, p-STAT3, ki-67, prolactin, and IGFBP1 in the mid-secretory endometrium were notably lower in patients with RIF compared with controls. ConclusionIn summary, in the mid-secretory phase, decreased expression of PIBF1, IL6, and p-STAT3 inhibited HESC proliferation and decidualization, which is of theoretical and clinical importance for future research and clinical-treatment strategies.

La réceptivité endométriale en aide médicale à la procréation : Une piste à ne pas oublier devant un échec d’implantation

Infertility affects between 8 and 12% of reproductive-age couples worldwide. Despite improvements in assisted reproductive techniques (ART), live birth rates are still limited. In clinical practice, imaging and microscopy are currently widely used, but their diagnostic effectiveness remains limited. In research, the emergence of innovative techniques named OMICS would improve the identification of the implantation window, while progressing in the understanding of the pathophysiological mechanisms involved in embryo implantation failures. To date, transcriptomic analysis seems to be the most promising approach in clinical research. The objective of this review is to present the results obtained with the different approaches available in clinical practice and in research to assess endometrial receptivity in patients undergoing ART.

Changes in Tissue Endometrial Receptivity under the Influence of High Intensity Focused Ultrasound during Ablation of Uterine Fibroids in Patients of Reproductive Age

Objective: To investigate the influence of the MRI-guided high-intensity focused ultrasound ablation (HIFU) of uterine fibroids on the endometrial receptivity in patients planning pregnancy. Material and Methods: A prospective comparative controlled study of 95 reproductive age women planning a pregnancy with symptomatic uterine fibroids was conducted. 32 patients receiving HIFU treatment and 35 women receiving surgical treatment under laparoscopic myomectomy were examined. A control group was existing 28 healthy fertile women, examined voluntarily. The endometrium obtained with pipelle biopsia on days 20-22 of the menstrual cycle was examined by immunohistochemistry before and three months after the treatment. Statistical analysis of the results was carried out using SPSS 22.0. Results: It was established that the focusing ultrasound rays passing through the endometrium do not cause changes in the maturation rate and do not affect the state of intercellular contacts. At the same time, a significant increase in the frequency of asynchronous maturation of pinopodia was found to be 50.00% (16) versus 14.28% (4); p=0.021 and the number of heteromorphic secretory cells 53.33% (8) versus 5.88% (1); p=0.002 in implantation endometrium. Conclusions: The study did not reveal any significant negative effects of focused ultrasonic waves during FUSMRI ablation of uterine fibroids on endometrial receptivity in women of reproductive age. MRg HIFU ablation of uterine fibroids might be considered as an alternative treatment in patients of reproductive age with uterine fibroids planning a pregnancy. Content: A prospective comparative controlled study of 95 women planning a pregnancy with symptomatic uterine fibroids, who received treatment by HIFU ablation and laparoscopic myomectomy.

Application of ultrasound multimodal score in the assessment of endometrial receptivity in patients with artificial abortion

BackgroundThis study aimed to evaluate the value and feasibility of ultrasound multimodal score in the evaluation of endometrial receptivity in patients with artificial abortion (AA).MethodsSixty-eight patients with AA (AA group) and 70 women of the childbearing age without any history of abortion (control group) were recruited between January 2018 and December 2018. All subjects received the examination of endometrium in the middle luteum phase (7–9 days after ovulation) with two-dimensional gray-scale ultrasound, two-dimensional color Doppler ultrasound, and three-dimensional ultrasound, and the quantitative scores were obtained and compared between two groups.ResultsThe quantitative score of endometrial receptivity was 10.46 ± 2.99 in the AA group and 13.49 ± 2.21 in the control group showing significant difference (p < 0.05).ConclusionsUltrasound multimodal quantitative scores can be used to evaluate the endometrial receptivity of patients with AA.

Влияние энергии фокусированного ультразвука при проведении аблации миомы матки под контролем магнитно-резонансной томографии на рецептивность эндометрия у пациенток репродуктивного возраста

Objective. To study the impact of the energy of focused ultrasonic waves during focused ultrasound ablation of uterine fibroids guided by magnetic resonance imaging (MRI-FUS) on the parameters of endometrial receptivity. Patients and methods. A prospective cohort study of 67 reproductive-age women suffering from uterine fibroids. The treatment group comprised 32 patients, who underwent treatment for a uterine fibroid by MRI-FUS ablation. The comparison group consisted of 35 women, who underwent laparoscopic myomectomy. The control group included 28 fertile healthy women. The endometrial tissue obtained with the use of pipelle biopsy pipelle biopsia on the 20–22th day of the cycle was examined by the method of light and scanning electron microscopy before and three months after treatment. Results. The ultrastructural parameters of endometrial receptivity in patients with uterine fibroids were characterised by a phase delay in the pinopode development rates (88.57 vs. 21.42% in control; р &lt; 0.05), a high incidence of tight junctions (34.29 vs. 7.14% in control; р = 0.021) and atypical cells of the microenvironment (54.29 vs. 7.14%; р = 0.005). No significant changes in the pinopode development rates were noted after myomectomy, the incidence of their asynchronous development significantly decreased (54,29 vs. 20.00%; р = 0.011). No significant changes in the pinopode development rates were noted after MRI-FUS ablation of uterine fibroids either, conversely, a significant increase of their asynchronous development was established (50.00 vs. 14.28%; р = 0.021) as well as a higher number of heteromorphic secretory cells (53.33 vs. 5.88%; р = 0.002) in the endometrium. Conclusion. The use of non-invasive methods of treatment of uterine fibroids in patients who are planning a pregnancy should be well grounded and take into consideration the character and causes of previous reproductive failures. Key words: magnetic resonance imaging, uterine fibroids, myomectomy, pinopodes, focussed ultrasound ablation, endometrium

Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis.

Endometriosis is frequently related to infertility and little is known about the mechanisms underlying this association. Some studies point to an endometrial factor involved in this condition, which could compromise embryo implantation. Progesterone plays crucial role in endometrial receptivity by acting through progesterone receptor (PGR) isoforms PR-A and PR-B whose expression is epigenetically regulated by DNA methylation, in a specific promoter region for each isoform. Epigenetic changes in PGR-A and PGR-B may be related to progesterone resistance of endometriosis-related infertility. In order to better understand the mechanisms involved in endometrial receptivity, this case-control study aimed to compare the methylation pattern of PGR-A and PGR-B in eutopic endometrium from infertile women with and without endometriosis during the secretory phase. Endometrial biopsies from 19 patients (10 infertile women with endometriosis and 9 infertile controls) with regular cycles were performed during the secretory phase and were dated according to Noyes' criteria. The percentage of DNA methylation at PGR-A and PGR-B was carried out by high-resolution melting assay. The PGR-A gene showed 0% of DNA methylation (unmethylated) in both control and endometriosis groups. However, PGR-B gene showed a partially methylated pattern in majority of the patients (n = 7), with methylation percentage corresponding to 50%, while in the control group the percentage of methylation was 20% (hypomethylated; P = .04). The increased percentage of methylation at PGR-B may be related to reduced gene expression, which could compromise the endometrial receptivity in patients with endometriosis.

Integrated miRNA-seq analysis reveals the molecular mechanism underlying the effect of acupuncture on endometrial receptivity in patients undergoing fertilization: embryo transplantation.

Endometrial receptivity (ER) is the main factor affecting in vitro fertilization (IVF) and embryo transplantation. Previous studies have shown that acupuncture might be useful for increasing ER. However, the underlying microRNA (miRNA) molecular mechanisms deserve to be further elucidated. In this study, we performed small RNA sequencing of endometrial samples from infertile women who either underwent acupuncture therapy or did not. Differentially expressed microRNAs (DEmiRNAs) were identified and used to predict target genes. Then, the functional and pathway were analyzed for the target genes. Moreover, quantitative reverse transcription PCR (qRT-PCR) was performed to validate the RNA-seq results. Finally, the miRNA-gene network was conducted by Cytoscape. A total of 39 DEmiRNAs were identified between the acupuncture group and the control group. The functional enrichment analysis suggested that the target genes of the DEmiRNAs were significantly enriched in GO biological process (BP) terms associated with transcription, such as regulation of DNA-templated transcription and positive regulation of DNA-templated transcription. The pathway analysis showed that DEmiRNAs might be involved in acupuncture therapy via Endocytosis, Axon guidance, Oxytocin signaling, the Hippo pathway, and Estrogen signaling pathways. Significant downregulation of hsa-miR-449a and hsa-miR-449b-3p, and significant upregulation of hsa-miR-3135b and hsa-miR-345-3p in the RNA-seq results were validated by qRT-PCR. Besides, these four DEmiRNAs and their 34 target genes conducted a miRNA-gene network. Our results predict that hsa-miR-449a, hsa-miR-3135b and hsa-miR-345-3p may underly mechanisms by which acupuncture therapy help increase ER and promote endometrium receptivity in preparation for in vitro fertilization and embryo transplantation.

Current Therapies to Improve the Endometrial Receptivity of Patients with Repeated Implantation Failure in IVF-ET

Repeated implantation failure (RIF) implies at least 3 consecutive treatment cycles of failed in vitro fertilization-embryo transfer (IVF-ET), in which 1 or 2 quality embryos...

Endometrial but not Ovarian Response is Associated With Clinical Outcomes and can be Improved by Prolonged Pituitary Downregulation in Patients With Thin and Medium Endometrium.

The aim of this study is to investigate the effect of ovarian and endometrial response on live birth rates (LBRs) in young normal and high responders and prolonged pituitary downregulation on endometrial receptivity and clinical outcomes in patients with different endometrial thickness. Between January 2013 and December 2017, 9511 patients underwent first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with age ≤35 years, follicle stimulating hormone < 10 IU/l, and ≥4 retrieved oocytes were conducted. The estradiol (E2) levels on the human chorionic gonadotropin (HCG) day were classified into 4 groups: group 1 (<3000 pg/mL); group 2 (3000-5000 pg/mL); group 3 (5000-7000 pg/mL), and group 4 (≥7000 pg/mL). Logistic regression analysis was performed to predict the independent variables for live birth. Clinical outcomes between gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-a prolonged protocol in patients with different endometrial thickness (EMT) were compared. There were no significant differences among the 4 groups in implantation rates, clinical pregnancy rates, and LBRs (P > .05). Binary logistic regression analysis suggested that EMT but not E2 levels was one of the independent predictive factors of LBRs (odds ratio 0.889, 95% confidence interval, 0.865-0.914, P < .001). The prolonged protocol had significantly higher implantation rates and clinical pregnancy rates in patients with medium (7 < EMT < 14 mm), especially thin endometrium (≤7 mm) compared to short GnRH-a long protocol. Our study showed that endometrial response but not ovarian response was associated with LBRs in young normal and hyper responders. Prolonged pituitary downregulation was an effective treatment to improve endometrial receptivity in patients with medium, especially thin endometrium.

Clinical pregnancy and live birth increase significantly with every additional blastocyst up to five and decline after that: an analysis of 16,666 first fresh single-blastocyst transfers from the Society for Assisted Reproductive Technology registry

To study the association between the number of blastocysts available and pregnancy outcomes in first fresh autologous single blastocyst transfer cycles. Retrospective cohort study. Not applicable. Patients from the Society for Assisted Reproductive Technology reporting fertility clinics (n=16,666). None. Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of blastocysts and each outcome. When comparing fresh single blastocyst transfer rates, the odds of a positive pregnancy outcome (CP) increased significantly with each additional supernumerary blastocyst up to five and declined by 2% for every additional blastocyst after five. Similarly, the odds of an LB was 17% higher for each additional blastocyst up to five and declined by 2% for every additional blastocyst after five. There was no significant association between blastocyst number and miscarriage rate. Odds of positive pregnancy outcomes (CP, LB) increased significantly with every additional blastocyst up to five, but declined after that, in first fresh autologous cycles with single-blastocyst transfer. The decline after five may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes or inadequate selection of the best embryo for transfer based on morphology alone.

Ultrastructural markers of tissue endometrial receptivity in patients with recurrent implantation failure

The scanning electron microscopy of the endometrial surface epithelium during the ‘implantation window’ was performed in 119 patients with uterine factor of infertility or recurrent miscarriage due to endometrial hypoplasia. Ultramorphological picture of the surface endometrial epithelium was characterized by aplasia and hypoplasia of pinopodes (67.39%), dense cell – cell contacts (69.53%), heteromorphy of secretory cells (15.22%) in combination with atypia of microenvironment cells (50%) in patients with infertility. The asynchronous development of pinopodes (46.67%) and the absence of intercellular contacts separation during the ‘implantation window’ (84.44%) was observed in patients with recurrent miscarriage. The revealed disturbance determines the mechanisms of the blastocyst adhesion violation and trophoblast invasion in the different stages of implantation in patients with uterine factor of infertility and recurrent miscarriage.

Circular RNA sequencing reveals the molecular mechanism of the effects of acupuncture and moxibustion on endometrial receptivity in patients undergoing infertility treatment.

The present study aimed to determine the profile of differentially expressed circular RNAs (circRNAs) in infertile patients treated with acupuncture and moxibustion and verify the role of acupuncture and moxibustion in altering endometrial receptivity (ER). High‑throughput RNA sequencing and bioinformatics analysis of samples from six pairs of patients treated with or without acupuncture and moxibustion were conducted. The reliability of high‑throughput RNA sequencing was validated using reverse transcription‑quantitative PCR. The most significant circRNA functions and pathways were selected by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA‑miR‑mRNA interaction network was constructed to determine the connection between circRNAs, microRNAs (miRs), and mRNAs. High‑throughput RNA sequencing identified 2,653 circRNAs. A total of 86 circRNAs was differentially expressed, of which 57 were upregulated and 29 were downregulated, between the acupuncture and moxibustion group and the control group. In the GO analysis, the identified BP terms were chromatin modification, positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response, oxidative DNA demethylation, regulation of transcription from RNA polymerase II promoter in response to hypoxia, and regulation of smooth muscle cell differentiation. The identified CC terms were nucleoplasm, nucleolus, nucleus, histone acetyltransferase complex, and annulate lamellae. The identified MF terms were methylcytosine dioxygenase activity, chromatin binding, zinc ion binding, histone binding, and protein binding. In the KEGG pathway analysis, the identified pathways were protein processing in endoplasmic reticulum, degradation of aromatic compounds, shigellosis, mTOR signaling pathway, bacterial invasion of epithelial cells, and prostate cancer. Circ‑SFMBT2, circ‑BACH1, and circ‑LPAR1 were significantly upregulated (P<0.05) and associated with numerous miRs and mRNAs. Acupuncture and moxibustion could impact ER by regulating the expression of circRNAs.

Uses of Ultrasound and Doppler in Assessment of Endometrial Receptivity in Patients of Unexplained Infertility

Background:although the majority of infertile couples was found to have an identifiable male or female factor, 15–30% was categorized as having ‘‘unexplained infertility’’. The endometrium is considered to be a key determinant in successful implantation. Endometrial receptivity is regulated by many factors including endometrial perfusion. Aim of the Work: this study aimedto detect the role of the two dimensional ultrasound and Doppler ultrasonographic uterine markers of implantation in patients of unexplained infertility compared to fertile participants. Patients and Methods: the study was performed on 50 patients presented to the outpatient clinic in Al-Hussein, Bab El-Shearia (Sayed Galal) Hospitals, Al-Azhar University from October 2017 to August 2018 and they were categorized into two groups: Group A (Patients group): it was included 30 participants presented with unexplained infertility. Group B) (Control group) who included 20 fertile women coming for contraception. Results: there was a significant statistical difference as regard the endometrial thickness between cases and controls, and the controls had a thicker endometrium. Lower pulsatility index (PI) in uterine artery in the controls compared to the infertile group. Increased sub endometrial vascularization in the controls compared to the infertile group. Conclusion:ultrasound as well as Doppler studies of the endometrial and subendometrial vascularization had a role in predicting endometrial receptivity. Uterine artery Doppler study and the endometrial thickness measurement had a role in detection of uterine receptivity.

Uses of Ultrasound and Doppler in Assessment of Endometrial Receptivity in Patients of Unexplained Infertility

Background:although the majority of infertile couples was found to have an identifiable male or female factor, 15–30% was categorized as having ‘‘unexplained infertility’’. The endometrium is considered to be a key determinant in successful implantation. Endometrial receptivity is regulated by many factors including endometrial perfusion. Aim of the Work: this study aimedto detect the role of the two dimensional ultrasound and Doppler ultrasonographic uterine markers of implantation in patients of unexplained infertility compared to fertile participants. Patients and Methods: the study was performed on 50 patients presented to the outpatient clinic in Al-Hussein, Bab El-Shearia (Sayed Galal) Hospitals, Al-Azhar University from October 2017 to August 2018 and they were categorized into two groups: Group A (Patients group): it was included 30 participants presented with unexplained infertility. Group B) (Control group) who included 20 fertile women coming for contraception. Results: there was a significant statistical difference as regard the endometrial thickness between cases and controls, and the controls had a thicker endometrium. Lower pulsatility index (PI) in uterine artery in the controls compared to the infertile group. Increased sub endometrial vascularization in the controls compared to the infertile group. Conclusion:ultrasound as well as Doppler studies of the endometrial and subendometrial vascularization had a role in predicting endometrial receptivity. Uterine artery Doppler study and the endometrial thickness measurement had a role in detection of uterine receptivity.

Modern methods of influence at endometrial receptivity in patients with recurrent implantation failure (review)

Objective. To carry out an analysis of the data available in scientific literature on modern methods of influence at endometrial receptivity in patients with recurrent implantation failure. Materials and methods. The review includes the data of foreign and Russia papers published on PubMed during the last 7-10 years. Results. There are studies described the role of endometrial scratching, infusion granulocyte colony stimulating factor, autologous peripheral blood mononuclear cells, autologous platelet-rich plasma, the endometrial receptivity array in treatment for patients with repeated implantation failure. Conclusion. Several adjuvant therapies and diagnostic tests have been used along with IVF to increase the pregnancy rates for women with repeated implantation failure. Perhaps a new test-system to find personal predictors of endometrial receptivity can tern up a positive effect at patients with RIF.

The Efficiency of Intrauterine Irrigation of the Cavitated Drug Solutes in Patients with Endometrial Receptivity Disorders

Evaluate the efficiency of intrauterine irrigation of cavitated low-frequency sonication drug solution in restoring of endometrial receptivity in patients with uterine infertility. 92 women with uterine infertility due to endometrial hypoplasia were examined in the dynamics of therapy including irrigation of the uterine cavity with cavitated low-frequency ultrasound with drug solutions. The control group consisted of 28 healthy fertile women. An ultrasound examination of the pelvic organs with color dopplerogragy, histological and immunohistochemical study of the endometrium was performed on the "implantation window" LH + 7, in dynamics before the start of therapy and in the next cycle after the end of treatment. After cavitation irrigation of the uterine cavity, 62 (67.39%) women with infertility in the endometrial specimens had adequate vascularization of the stroma (before treatment, 36.95%, p=0.017, in control 78.57%), in 68 (73, 91%) women - a decrease in the density of the stromal matrix, in 64 (69.56%) - according to light microscopy data, mature pinopodia were determined (initially 28.26%, p=0.0015). On the background of therapy, the ratio of ERα / PR expression in the stroma of the implantation endometrium was normalized, which was characterized by the prevalence of the PR pool (1.01±0.34 before treatment, 0.36 ± 0.03 after therapy, p = 0.040, in control 0.34±0.06, p> 0.05). The parameters of stromal expression of natural uterine killers CD56 + bright against the background of treatment in patients with infertility come in accordance with the indices of healthy fertile women (from 35.21 ± 2.14 cells in l/s to 45.75±3.18 cells l/s; in the control 47.8±2.13 cells in l/s; p> 0.05). A significant decrease in stromal expression of CD3+ is noted: 78.17±6.89 cells in l/s versus 23.83±3.63 cells in l/s; p=0.004. The expression level of CD34 in the endometrial stroma after the treatment was significantly increased (20.88±0.77 cells in l/s versus 33.83±3.63 cells in l/s, p=0.035). The use of G-CSF cavitaion solutions for irrigation of the uterine cavity appears to be effective in restoring tissue and molecular endometrial receptivity in patients with uterine infertility due to endometrial hypoplasia.

New aspects of the diagnosis of endometrial receptivity in patients with reproductive failure

New aspects of the diagnosis of endometrial receptivity in patients with reproductive failure

New aspects of the diagnosis of endometrial receptivity in patients with reproductive failure

New aspects of the diagnosis of endometrial receptivity in patients with reproductive failure

Effects of hypoxia‑inducible factor‑1α on endometrial receptivity of women with polycystic ovary syndrome.

Embryo implantation is associated with an hypoxic endometrial microenvironment. Hypoxia‑inducible factor‑1α (HIF‑1α) is activated under hypoxic conditions. In the present study, the expression pattern of HIF‑1α in endometrial tissue was investigated and its effects on endometrial receptivity in patients with polycystic ovary syndrome (PCOS) were examined. A total of 81patients were enrolled for invitro fertilization and embryo transfer. They were divided into PCOS (n=40) and Control groups (n=41); both groups were further divided based on body weight (overweight and normal weight subgroups). The expressions of HIF‑1α, vascular endothelial growth factor (VEGF) and glucose transporter protein (GLUT)‑1 and GLUT4 were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. The results demonstrated that mRNA and protein expression levels of HIF‑1α and VEGF in the PCOS group were significantly lower compared with expression levels in the Control group. However, there were no statistically significant differences in the expression levels of GLUT1 and GLUT4 between groups. In patients with PCOS, GLUT1 and GLUT4 were mainly localized in the nuclei and cytoplasm, but not in the cell membrane. Overweight patients had the lowest expression levels of HIF‑1α, VEGF and GLUT1 expression compared with normal weight patients. In conclusion, HIF‑1α may be involved in the molecular mechanisms of endometrial dysfunction in women with PCOS, particularly in those who are overweight. HIF‑1α might therefore be a novel target for improving the endometrial receptivity and successful embryo implantation in PCOS women.