RESUMEN
BACKGROUND: Embryo implantation remains a critical barrier in assisted reproductive technologies. One of the main causes of unsuccessful embryo implantation is window of implantation (WOI) displacement, particularly in patients with recurrent implantation failure (RIF). Therefore, a reliable diagnostic tool for identifying the optimal WOI is essential. Previous data has suggested that a novel RNA-Seq-based endometrial receptivity testing (ERT) can diagnose WOI, guide personalized embryo transfer (pET), and improve pregnancy outcomes in patients with RIF compared to standard embryo transfer (sET). However, there is still a lack of evidence from randomized controlled trials (RCT) with sufficient power to determine whether pET based on ERT can increase the rate of live births as the primary outcome. METHODS: This trial is a prospective, single-blind, parallel-group RCT (1:1 ratio of pET versus sET). Infertile women with RIF who intend to undergo frozen-thawed embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) with the availability of at least one euploid blastocyst for transfer will be enrolled and assigned into two parallel groups randomly. Participants in the intervention group will undergo ERT and then pET based on the results of ERT, while those in the control group will undergo sET. The primary outcome is live birth rate. DISCUSSION: The findings of this study will provide evidence for the effect of pET guided by ERT on pregnancy outcomes in patients with RIF. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100049041. Registered on 20 July 2021.
Asunto(s)
Implantación del Embrión , Transferencia de Embrión , Endometrio , Nacimiento Vivo , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Embarazo , Transferencia de Embrión/métodos , Endometrio/fisiopatología , Estudios Prospectivos , Método Simple Ciego , Infertilidad Femenina/terapia , Infertilidad Femenina/fisiopatología , Adulto , Índice de Embarazo , Resultado del Tratamiento , China , Valor Predictivo de las PruebasRESUMEN
O sangramento uterino anormal é diagnóstico sindrômico comum no consultório do ginecologista e pode comprometer substancialmente a qualidade de vida. O objetivo no diagnóstico de sangramento uterino anormal é distinguir pacientes com causas estruturais (anatômicas), como pólipo, adenomiose, leiomioma, malignidade e hiperplasia, de pacientes que apresentam anatomia normal, nas quais o sangramento pode ser devido a alteração dos mecanismos de coagulação, distúrbios ovulatórios, distúrbios primários do endométrio, iatrogenia, ou ter outra causa não classificada. O diagnóstico se inicia a partir de anamnese detalhada e exame físico geral e ginecológico completos, seguidos da solicitação de exames complementares (laboratoriais e de imagem), conforme indicado. O exame de imagem de primeira linha para identificação das causas estruturais inclui a ultrassonografia pélvica. Histerossonografia, histeroscopia, ressonância magnética e amostragem endometrial para exame de anatomia patológica são opções que podem ser incluídas no diagnóstico a depender da necessidade. O objetivo deste artigo é apresentar a relevância dos exames de imagem na investigação das causas de sangramento uterino anormal.
Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office and may substantially affect quality of life. The aim in the diagnosis of abnormal uterine bleeding is to distinguish women with anatomic causes such as polyp, adenomyosis, leiomyoma, malignancy and hyperplasia from women with normal anatomy where the cause may be coagulopathy, ovulatory disorders, endometrial, iatrogenic and not otherwise classified. Diagnosis begins with a thorough history and physical examination followed by appropriate laboratory and imaging tests as indicated. The primary imaging test for the identification of anatomic causes include ultrasonography. Saline infusion sonohysterography, magnetic resonance, hysteroscopy, endometrial sampling are options that can be included in the diagnosis depending on the need. The aim of this article is to present the relevance of imaging exams in the investigation of the causes of abnormal uterine bleeding.
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Humanos , Femenino , Hemorragia Uterina/diagnóstico por imagen , Examen Físico/métodos , Pólipos/diagnóstico por imagen , Útero/patología , Cuello del Útero/patología , Endometrio/fisiopatología , Adenomiosis/complicaciones , Ginecología/métodos , Hiperplasia/complicaciones , Leiomioma/complicaciones , Anamnesis/métodosRESUMEN
RESEARCH QUESTION: What is the expression pattern of platelet-derived growth factor BB (PDGF-BB), and its receptors, across the menstrual cycle in healthy control women and those with abnormal uterine bleeding-endometrial disorder (AUB-E)? DESIGN: Immunohistochemical staining for PDGF-BB, platelet-derived growth factor receptor alpha (PDGFRα) and platelet-derived growth factor beta (PDGFRß) was performed in control and AUB-E endometrium from the proliferative, early, mid- and late secretory phases of the menstrual cycle (n = 5 each group). Control proliferative phase endometrium was cultured in PDGF-BB (0, 10 ng/ml) and vascular maturation assessed (n = 3). Endothelial cell to vascular smooth muscle cell (VSMC) association was assessed after treatment with PDGF-BB (0, 1, 10 ng/ml). Secretion of angiogenic growth factors by endothelial cells or VSMC was determined. RESULTS: Endothelial cell immunoreactivity for PDGF-BB was reduced in the mid and late secretory phases in AUB-E (P = 0.008). PDGFRα was also reduced in mid secretory phase endothelial cells, proliferative and early secretory phase glandular epithelium in AUB-E (P = 0.008). PDGFRß expression was not altered. Treatment of proliferative phase endometrium with PDGF-BB (10 ng/ml) reduced the percentage of vessels expressing contractile VSMC markers. PDGF-BB had no effect on angiogenic growth factor secretion by endothelial cells or VSMC in vitro and did not affect their association in an in-vitro endothelial cell-VSMC association assay. CONCLUSIONS: Reduced endothelial cell expression of PDGF-BB in the AUB-E endometrium may contribute to the reduced vascular maturation previously observed in these women.
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Becaplermina , Células Endoteliales , Enfermedades Uterinas , Becaplermina/metabolismo , Células Cultivadas , Endometrio/metabolismo , Endometrio/fisiopatología , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Hemorragia UterinaRESUMEN
Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).
Asunto(s)
Desogestrel/administración & dosificación , Endometrio/efectos de los fármacos , Acetato de Medroxiprogesterona/administración & dosificación , Menstruación/efectos de los fármacos , Ovario/efectos de los fármacos , Ovulación/efectos de los fármacos , Progestinas/administración & dosificación , Hemorragia Uterina/tratamiento farmacológico , Adulto , Desogestrel/efectos adversos , Método Doble Ciego , Endometrio/fisiopatología , Femenino , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Ovario/fisiopatología , Progestinas/efectos adversos , Estudios Prospectivos , Tailandia , Factores de Tiempo , Resultado del Tratamiento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/fisiopatologíaRESUMEN
The endometrium plays a critical role in embryo implantation and pregnancy, and a thin uterus is recognized as a key factor in embryo implantation failure. Umbilical cord mesenchymal stem cells (UC-MSCs) have attracted interest for the repair of intrauterine adhesions. The current study investigated the repair of thin endometrium in rats using the UC-MSCs and the mechanisms involved. Rats were injected with 95% ethanol to establish a model of thin endometrium. The rats were randomly divided into normal, sham, model, and UC-MSCs groups. Endometrial morphological alterations were observed by hematoxylin-eosin staining and Masson staining, and functional restoration was assessed by testing embryo implantation. The interaction between UC-MSCs and rat endometrial stromal cells (ESCs) was evaluated using a transwell 3D model and immunocytochemistry. Microarray mRNA and miRNA platforms were used for miRNA-mRNA expression profiling. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were performed to identify the biological processes, molecular functions, cellular components, and pathways of endometrial injury and UC-MSCs transplantation repair and real-time quantitative reverse transcription PCR (qRT-PCR) was performed to further identify the expression changes of key molecules in the pathways. Endometrium thickness, number of glands, and the embryo implantation numbers were improved, and the degree of fibrosis was significantly alleviated by UC-MSCs treatment in the rat model of thin endometrium. In vitro cell experiments showed that UC-MSCs migrated to injured ESCs and enhanced their proliferation. miRNA microarray chip results showed that expression of 45 miRNAs was downregulated in the injured endometrium and upregulated after UC-MSCs transplantation. Likewise, expression of 39 miRNAs was upregulated in the injured endometrium and downregulated after UC-MSCs transplantation. The miRNA-mRNA interactions showed the changes in the miRNA and mRNA network during the processes of endometrial injury and repair. GO and KEGG analyses showed that the process of endometrial injury was mainly attributed to the decomposition of the extracellular matrix (ECM), protein degradation and absorption, and accompanying inflammation. The process of UC-MSCs transplantation and repair were accompanied by the reconstruction of the ECM, regulation of chemokines and inflammation, and cell proliferation and apoptosis. The key molecules involved in ECM-receptor interaction pathways were further verified by qRT-PCR. Itga1 and Thbs expression decreased in the model group and increased by UC-MSCs transplantation, while Laminin and Collagen expression increased in both the model group and MSCs group, with greater expression observed in the latter. This study showed that UC-MSCs transplantation could promote recovery of thin endometrial morphology and function. Furthermore, it revealed the expression changes of miRNA and mRNA after endometrial injury and UC-MSCs transplantation repair processed, and signaling pathways that may be involved in endometrial injury and repair.
Asunto(s)
Proliferación Celular , Trasplante de Células Madre de Sangre del Cordón Umbilical , Endometrio/patología , Matriz Extracelular/patología , Regeneración , Enfermedades Uterinas/cirugía , Animales , Comunicación Celular , Técnicas de Cultivo Tridimensional de Células , Células Cultivadas , Modelos Animales de Enfermedad , Endometrio/metabolismo , Endometrio/fisiopatología , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Sangre Fetal/citología , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Transcriptoma , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Enfermedades Uterinas/fisiopatologíaRESUMEN
OBJECTIVE: To determine whether increased endometrial B-cell lymphoma 6 (BCL6) expression is associated with live birth in a normal responder in vitro fertilization (IVF) population. DESIGN: Case-control study. SETTING: University-affiliated infertility center. PATIENT(S): Two groups of women undergoing IVF with preimplantation genetic testing for aneuploidy followed by warmed, single, euploid embryo transfer. Group 1 consisted of women who failed to achieve live birth, and group 2 consisted of women who achieved live birth. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometrial BCL6 expression measured by immunohistochemistry in endometrial tissue samples. Overexpression was defined by mean HSCORE with a cutoff of positivity of >1.4, as previously described in the literature. RESULT(S): Twenty-seven patients who achieved live birth and 23 patients who failed to achieve live birth were included. B-cell lymphoma 6 expression/HSCORE and live birth rate were not associated (Odds ratio [OR], 0.78 [0.24-2.55]). Using a cutoff of >1.4 for positivity, 8 of 23 samples were positive for BCL6 in the no live birth group, whereas 7 of 27 were positive in the live birth group. There was no significant association between BCL6 positivity and live birth (OR, 0.66 [0.19-2.21]). CONCLUSION(S): The proportion of patients with BCL6 positivity did not significantly differ between those who achieved live birth and those who did not. In the population of patients at our center, who compromise of women who respond normally to IVF stimulation, BCL6 overexpression was not associated with IVF success. Physicians implementing BCL6 testing as a diagnostic tool for clinical decision making should counsel patients that results may have limited utility in predicting IVF outcomes in this population.
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Endometrio/química , Fertilización In Vitro , Infertilidad/terapia , Proteínas Proto-Oncogénicas c-bcl-6/análisis , Adolescente , Adulto , Estudios de Casos y Controles , Implantación del Embrión , Endometrio/fisiopatología , Femenino , Fertilidad , Fertilización In Vitro/efectos adversos , Humanos , Infertilidad/diagnóstico , Infertilidad/metabolismo , Infertilidad/fisiopatología , Nacimiento Vivo , Masculino , Embarazo , Índice de Embarazo , Medición de Riesgo , Factores de Riesgo , Transferencia de un Solo Embrión , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.
Asunto(s)
Aborto Habitual/genética , Metilación de ADN , Epigénesis Genética , Aborto Habitual/inmunología , Aborto Habitual/metabolismo , Aborto Habitual/fisiopatología , Animales , Citocinas/metabolismo , Metilasas de Modificación del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Implantación del Embrión , Desarrollo Embrionario , Endometrio/inmunología , Endometrio/metabolismo , Endometrio/fisiopatología , Femenino , Regulación del Desarrollo de la Expresión Génica , Impresión Genómica , Histocompatibilidad Materno-Fetal , Humanos , Linfocitos/inmunología , Linfocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Placenta/inmunología , Placenta/metabolismo , Placenta/fisiopatología , Embarazo , Transducción de SeñalRESUMEN
Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.
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Implantación del Embrión/fisiología , Transferencia de Embrión/métodos , Endometrio/fisiopatología , Insuficiencia del Tratamiento , Transferencia de Embrión/tendencias , Endometriosis/genética , Endometriosis/fisiopatología , Femenino , Fertilización In Vitro/métodos , Fertilización In Vitro/tendencias , Humanos , Embarazo , Índice de Embarazo/tendencias , RecurrenciaRESUMEN
The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable. Monoamine oxidase A (MAOA) is a key molecule that regulates neurotransmitter metabolism in the nervous system. In the present study, we demonstrated a novel role for MAOA in the establishment of endometrial receptivity in women with adenomyosis and in an adenomyotic mouse model. Attenuated MAOA impairs endometrial receptivity by promoting inappropriate proliferation of EECs via the downregulation of FOXO1 during the window of implantation. These results revealed that MAOA plays a vital role in endometrial receptivity in female reproduction.
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Adenomiosis/fisiopatología , Regulación hacia Abajo , Endometrio/fisiopatología , Proteína Forkhead Box O1/metabolismo , Monoaminooxidasa/genética , Adenomiosis/metabolismo , Adulto , Animales , Endometrio/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos ICR , Monoaminooxidasa/metabolismo , Adulto JovenRESUMEN
The purpose of this American Society for Reproductive Medicine Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled "Obesity and reproduction: an educational bulletin" last published in 2015 (Fertil Steril 2015;104:1116-26).
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Fertilidad , Infertilidad Femenina/etiología , Infertilidad Masculina/etiología , Obesidad/complicaciones , Aborto Espontáneo/etiología , Índice de Masa Corporal , Endometrio/fisiopatología , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/fisiopatología , Infertilidad Femenina/terapia , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/fisiopatología , Infertilidad Masculina/terapia , Masculino , Obesidad/diagnóstico , Obesidad/fisiopatología , Obesidad/terapia , Ovario/fisiopatología , Ovulación , Embarazo , Técnicas Reproductivas Asistidas , Factores de Riesgo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
The human endometrium plays a vital role in providing the site for embryo implantation and maintaining the normal development and survival of the embryo. Recent studies have shown that stress is a common factor for the development of unexplained reproductive disorders. The nonreceptive endometrium and disturbed early maternal-fetal interaction might lead to infertility including the repeated embryo implantation failure and recurrent spontaneous abortion, or late pregnancy complications, thereby affecting the quality of life as well as the psychological status of the affected individuals. Additionally, psychological stress might also adversely affect female reproductive health. In recent years, several basic and clinical studies have tried to investigate the harm caused by psychological stress to reproductive health, however, the mechanism is still unclear. Here, we review the relationship between psychological stress and endometrial dysfunction, and its consequent effects on female infertility to provide new insights for clinical therapeutic interventions in the future.
Asunto(s)
Implantación del Embrión/fisiología , Endometrio/fisiopatología , Infertilidad Femenina/complicaciones , Estrés Psicológico/complicaciones , Enfermedades Uterinas/complicaciones , Femenino , Humanos , Infertilidad Femenina/fisiopatología , Embarazo , Calidad de Vida , Estrés Psicológico/fisiopatología , Enfermedades Uterinas/fisiopatologíaRESUMEN
OBJECTIVE: To study whether endometrial epithelial podocalyxin (PCX) inhibits implantation of human embryos in vitro and in patients undergoing in vitro fertilization (IVF). DESIGN: We have recently identified PCX as a key negative regulator of endometrial epithelial receptivity. Podocalyxin is expressed in all epithelial cells in the nonreceptive endometrium, but is selectively downregulated in the luminal epithelium (LE) for receptivity. In the current study, we first investigated whether high levels of PCX in Ishikawa monolayer inhibit attachment and/or penetration of human blastocysts in in vitro models. We then examined PCX by immunohistochemistry in putative receptive endometrial tissues biopsied from 81 IVF patients who underwent frozen embryo transfer in the next natural cycle and retrospectively analyzed the association between PCX staining in LE and clinical pregnancy as a proxy of successful implantation. SETTING: RMIT University, Australia; Vrije Universiteit Brussel, Belgium. PATIENT(S): In vitro fertilization patients undergoing frozen/thawed embryo transfer. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Endometrial epithelial PCX inhibits implantation of human embryos in vitro and in IVF patients. RESULT(S): High levels of PCX in Ishikawa monolayer significantly inhibited blastocyst attachment and penetration. Among the 81 putative receptive tissues, 73% were negative, but 27% were heterogeneously positive for PCX in LE. The clinical pregnancy rate was 53% in those with a PCX-negative LE but only 18% in those with a PCX-positive LE. If LE was positive for PCX, the odds ratio of no clinical pregnancy was 4.95 (95% Confidence interval, 1.48-14.63). CONCLUSION(S): Podocalyxin inhibits embryo implantation. Assessment of PCX may aid the evaluation and optimization of endometrial receptivity in fertility treatment.
Asunto(s)
Blastocisto/metabolismo , Implantación del Embrión , Transferencia de Embrión , Endometrio/metabolismo , Fertilización In Vitro , Infertilidad/terapia , Sialoglicoproteínas/metabolismo , Bélgica , Línea Celular , Técnicas de Cultivo de Embriones , Transferencia de Embrión/efectos adversos , Endometrio/fisiopatología , Femenino , Fertilidad , Fertilización In Vitro/efectos adversos , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Insuficiencia del Tratamiento , VictoriaRESUMEN
Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10-7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10-7 M). GALR1/GALR2 antagonist and GAL (10-7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.
Asunto(s)
Galanina/metabolismo , Inflamación/patología , Inflamación/fisiopatología , Receptor de Galanina Tipo 1/metabolismo , Receptor de Galanina Tipo 2/metabolismo , Contracción Uterina/fisiología , Útero/fisiopatología , Animales , Endometrio/fisiopatología , Femenino , Miometrio/fisiopatología , Receptor de Galanina Tipo 2/antagonistas & inhibidores , PorcinosRESUMEN
BMI-1 is a key component of stem cells, which are essential for normal organ development and cell phenotype maintenance. BMI-1 expression is deregulated in cancer, resulting in the alteration of chromatin and gene transcription repression. The cellular signaling pathway that governs BMI-1 action in the ovarian carcinogenesis sequences is incompletely deciphered. In this study, we set out to analyze the immunohistochemical (IHC) BMI-1 expression in two different groups: endometriosis-related ovarian carcinoma (EOC) and non-endometriotic ovarian carcinoma (NEOC), aiming to identify the differences in its tissue profile. METHODS: BMI-1 IHC expression has been individually quantified in epithelial and in stromal components by using adapted scores systems. Statistical analysis was performed to analyze the relationship between BMI-1 epithelial and stromal profile in each group and between groups and its correlation with classical clinicopathological characteristics. RESULTS: BMI-1 expression in epithelial tumor cells was mostly low or negative in the EOC group, and predominantly positive in the NEOC group. Moreover, the stromal BMI-1 expression was variable in the EOC group, whereas in the NEOC group, stromal BMI-1 expression was mainly strong. We noted statistically significant differences between the epithelial and stromal BMI-1 profiles in each group and between the two ovarian carcinoma (OC) groups. CONCLUSIONS: Our study provides solid evidence for a different BMI-1 expression in EOC and NEOC, corresponding to the differences in their etiopathogeny. The reported differences in the BMI-1 expression of EOC and NEOC need to be further validated in a larger and homogenous cohort of study.
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Endometriosis/fisiopatología , Endometrio/fisiopatología , Células Epiteliales/patología , Neoplasias Ováricas/patología , Complejo Represivo Polycomb 1/metabolismo , Células del Estroma/patología , Índice de Masa Corporal , Estudios de Casos y Controles , Células Epiteliales/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/clasificación , Neoplasias Ováricas/metabolismo , Células del Estroma/metabolismoRESUMEN
Uterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of ß1-, ß2- and ß3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, ß1- and ß3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, ß2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all ß-ARs subtypes, however, ß2-ARs have the greatest importance. Given this, pharmacological modulation of particular ß-ARs subtypes can be used to increase inflamed uterus contractility.
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Endometriosis/metabolismo , Endometrio/metabolismo , Infecciones por Escherichia coli/metabolismo , Escherichia coli/metabolismo , Receptores Adrenérgicos beta/metabolismo , Contracción Uterina , Animales , Endometriosis/patología , Endometriosis/fisiopatología , Endometrio/patología , Endometrio/fisiopatología , Infecciones por Escherichia coli/patología , Infecciones por Escherichia coli/fisiopatología , Femenino , Inflamación/metabolismo , Inflamación/patología , Inflamación/fisiopatología , PorcinosRESUMEN
It is very important to investigate the expression of endometrial receptive markers in the endometrium during implantation. Therefore, we examined whether it would be possible to analyze endometrial receptivity using cells from embryo transfer catheters. A total of 81 cycles from 81 consenting patients were enrolled in this study. The tip of the embryo transfer (ET) catheter was cut and immersed in a dedicated reagent. Confirmation of cell distribution was carried out using a Papanicolaou stain and immunocytochemistry. Protein expression was carried out by immunocytochemistry. The expressions of estrogen receptor α, progesterone receptor, and homeobox A10 mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction. We analyzed the relationship between the gene expression profiles associated with pregnancy from endometrial cells. Samples collected from the ET catheter showed clear staining for endometrial cells. Most of the cells were endometrial epithelial cells. Cervical cells were not observed. The protein expression was also confirmed. Three genes were analyzed that are associated with endometrial receptivity. Progesterone receptor expression was 1.4-fold (p<0.05) and homeobox A10 was 2.8-fold (p<0.01) higher in patients who became non-pregnant group, compared to the pregnant group. Estrogen receptor α expression tended to be higher in the non-pregnant group (p=0.18). Our results suggest that endometrial receptivity can be evaluated using cells obtained from the ET catheter. This method may be useful for elucidating the cause of implantation failure by comparing a receptive and non-receptive endometrium at the time of ET.
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Catéteres , Implantación del Embrión , Transferencia de Embrión/instrumentación , Endometrio/metabolismo , Receptor alfa de Estrógeno/metabolismo , Proteínas Homeobox A10/metabolismo , Infertilidad/terapia , Receptores de Progesterona/metabolismo , Endometrio/patología , Endometrio/fisiopatología , Receptor alfa de Estrógeno/genética , Femenino , Fertilidad , Fertilización In Vitro , Proteínas Homeobox A10/genética , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Embarazo , Receptores de Progesterona/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Resultado del TratamientoRESUMEN
OBJECTIVE: To introduce a special case of endometrial cavity fluid (ECF), highlighting the application of hysteroscopy and laparoscopic surgical techniques in the treatment of cervical sinus tract. DESIGN: Narrated video featuring the diagnosis and surgical management of a case of recurrent ECF. Informed consent was obtained from the patient, and approval was granted by the ethics committee of the First Affiliated Hospital of the Wenzhou Medical University. SETTING: Academic tertiary hospital. PATIENT(S): A 36-year-old woman, gravida 0, had menstrual spotting for 13 years after abdominal myomectomy of a 104 × 86 × 111-mm myoma on the posterior uterine wall near the cervix. She failed to conceive after her marriage for 10 years, and 5 operations, including hysteroscopy and laparoscopy, were performed to increase pregnancy opportunities. She also underwent in vitro fertilization and embryo transfer procedures many times, but failed. Transvaginal sonography preoperatively suggested that ECF sometimes appeared and sometimes disappeared. The local echo of the posterior wall of the cervix was enhanced. A 40-mm cystic dark area was found beside the right ovary, which seemed to connect with the cervical hyperechoic part. Additionally, a solid mass of the right adnexa with abundant blood supply was detected. INTERVENTION(S): First, hysteroscopy was performed to explore the ECF. A deep and narrow cervical sinus with a steady stream of accumulated blood overflowed in the lower part of the cervix, and a normal uterine cavity was found. Laparoscopic adhesiolysis and enucleation of the cystic structure that connected to the sinus tract then were performed. Hysteroscopy was repeated to determine the thinnest cervical region by the light transmission test. A horizontal incision was made on the thinnest layer. Scar tissues were removed. The incision was sutured in full layer intermittently and continuously under laparoscopy. The postoperative thickness of the muscular layer in the sinus was confirmed by light transmission test of hysteroscopy. The patient was discharged on the third day after operation, uneventfully. Histopathologic examination showed that the cystic structure and scar tissue contained smooth muscle tissue and were covered by both mucinous columnar epithelium of the cervical canal and endometrial glandular epithelium. MAIN OUTCOME MEASURE(S): Restoration of normal anatomy, removal of uterine effusion, and symptomatic relief. RESULT(S): At the 6-month follow-up, the patient's menstrual cycles returned to normal without the recurrence of menstrual spotting. The ultrasound scan also showed a symmetrical uterus without ECF. CONCLUSION(S): Patients with ECF who underwent assisted reproductive surgeries were related to the poor prognosis. However, the treatment should be different according to the causes, appearance time, and accumulation amount, including expectant treatment, postponement of embryo transfer, transvaginal aspiration, laparoscopic salpingectomy, or proximal tubal occlusion. For patients with recurrent ECF and/or special appearance on ultrasound, endoscopic examination is necessary. In addition, patients with large myomas at difficult locations required a uniform strategy to reduce the intraoperative and postoperative complications, especially for the nulligravida women.
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Líquidos Corporales/fisiología , Cuello del Útero/diagnóstico por imagen , Endometrio/fisiopatología , Histeroscopía/métodos , Infertilidad Femenina/terapia , Adulto , Cuello del Útero/cirugía , Femenino , Humanos , Recurrencia , UltrasonografíaRESUMEN
Innate and adaptive immune systems have a crucial role in initiating and progressing some pregnancy disorders such as preeclampsia (PE), which is one of the pregnancy-specific disorders that could result in neonatal and maternal morbidity and mortality. The dysregulation of the spiral artery and inadequate trophoblast invasion lead to PE symptoms through producing various inflammatory cytokines and anti-angiogenic factors from the placenta. T lymphocytes play a special role in the epithelium and stroma of the human endometrium. CD4+ T helper (Th) cells, Th1/Th2, and Th17/T regulatory (Treg) balance mainly contribute to the establishment of a pregnancy-favorable environment. This review examined the dysregulation of some cytokines produced from T cells, the dysregulation of the transcription factors of Th cells, the expression of chemokine receptors on T cells, as well as the effects of some factors including vitamin D on the activity of T cells, and finally, the dysregulation of various miRNAs related to T cells, which could cause PE.
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Endometrio/inmunología , MicroARNs/inmunología , Placenta/inmunología , Preeclampsia/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Animales , Presión Sanguínea , Microambiente Celular , Citocinas/inmunología , Citocinas/metabolismo , Endometrio/metabolismo , Endometrio/fisiopatología , Femenino , Regulación de la Expresión Génica , Humanos , MicroARNs/metabolismo , Placenta/metabolismo , Placenta/fisiopatología , Preeclampsia/genética , Preeclampsia/metabolismo , Preeclampsia/fisiopatología , Embarazo , Transducción de Señal , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
RESEARCH QUESTION: Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF. DESIGN: This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF. RESULTS: Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01-97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09-17.05]), PCOS (aOR 5.72, 95%CI [2.66-12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84-14.49]). CONCLUSIONS: Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.
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Líquidos Corporales , Endometrio/fisiopatología , Fertilización In Vitro/efectos adversos , Inducción de la Ovulación/efectos adversos , Síndrome del Ovario Poliquístico/cirugía , Adulto , Estudios de Cohortes , Endometrio/cirugía , Femenino , Fertilización In Vitro/métodos , Fertilización In Vitro/estadística & datos numéricos , Humanos , Inducción de la Ovulación/métodos , Quebec , Estudios Retrospectivos , Factores de RiesgoRESUMEN
ABSTRACT: To study the efficacy of using amniotic membrane, balloon and intrauterine device (IUD) as barrier therapy to prevent re-adhesion after hysteroscopic adhesiolysis.A total of 45 patients diagnosed with intrauterine adhesions in Changzhou Maternal and Child Health Hospital from June 2014 to December 2017 were included in this retrospective case control study. According to different postoperative isolation barrier methods, the patients were divided into group A (Foley balloon + fresh amniotic membrane Day1 + IUD Day7) (22 cases) and group B (Foley balloon Day1 + IUD Day7) (23 cases). Three months after the surgery, the second hysteroscopy was performed to observe the condition of the uterine cavity and the improvement of menstruation, and to monitor the thickness of the endometrium.The efficacy of hysteroscopic procedure in group A was significantly higher than that of group B (Pâ<â.05). After 3âmonths of treatment, the improvement rate of menstruation was significantly higher in group A than in group B (Pâ<â.05). Endometrial thickness in both group A and B was significantly increased compared with that before the surgery (Pâ<â.05). The postoperative endometrium of group A was significantly thicker than that of group B (Pâ<â.05).Amniotic membrane-mediated sequential double-barrier method is clinically feasible for preventing recurrent intrauterine adhesions.