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1.
Life Sci ; 260: 118439, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950574

RESUMO

AIMS: This study aims to investigate the effects of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) on a thin-endometrium rat model. MAIN METHODS: Twenty rats in two groups of 10 were used. Group I was perfused with normal saline (NS) in the right uterine horn and 95% ethanol in the left one. Group II was bilaterally perfused with 95% ethanol into the uterine horns. After three estrous cycles, Group II was perfused with NS in the right uterine horn and G-CSF (30 µg/kg) in the left one. Hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining were used to detect changes in endometrial thickness and expression of cytokeratin 19 (CK19) and vimentin (Vim). The relative expression levels of vascular endothelial growth factor (Vegf) and leukemia inhibitory factor (Lif) were also tested via reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and Western-blot analyses. KEY FINDINGS: G-CSF treatment significantly increased the thickness of the endometrium in the 95% ethanol-induced thin-endometrium rat model. The expression levels of endometrial glandular epithelial cell marker for CK19 and stromal cell marker Vim were augmented in the G-CSF-treated group compared with the control group. Moreover, G-CSF treatment stimulated the expression of VEGF and LIF in the 95% ethanol-induced thin-endometrium rat model. SIGNIFICANCE: G-CSF intrauterine perfusion improved endometrial receptivity in the thin-endometrium rat model by stimulating endometrial proliferation and angiogenesis.


Assuntos
Endométrio/efeitos dos fármacos , Endométrio/fisiopatologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Animais , Endométrio/fisiologia , Etanol/toxicidade , Feminino , Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Inibidor de Leucemia/genética , Perfusão , Ratos Sprague-Dawley , Útero/fisiologia , Fator A de Crescimento do Endotélio Vascular/genética , Vimentina/metabolismo
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 936-941, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701227

RESUMO

OBJECTIVE: To observe the expression of HELQ and RAD51C in normal endometrial and endometrial stromal sarcoma (ESS) and analyze their correlation with the clinical features of the patients. METHODS: The expressions of HELQ and RAD51C proteins were detected by immunohistochemical staining in normal endometrial tissues (14 cases) and tumor tissues from patients with ESS (37 cases) treated in Hunan Provincial Cancer Hospital from January, 2013 to December, 2016. The correlations of the expressions of the two proteins with the patients'age, FIGO staging, tissue type, tumor size, and lymph node metastasis were analyzed. RESULTS: Immunohistochemical staining showed that the expressions of HELQ and RAD51C were both decreased in ESS patients compared with the normal group, and there was a positive correlation between HELQ and RAD51C expression (P < 0.05). HELQ expression in ESS was correlated with the tumor size and type. The expressions of HELQ and RAD51C were not correlated with the patients' age, FIGO stage and status of lymph node metastasis (P > 0.05). CONCLUSIONS: Homologous recombination- directed DNA repair involving HELQ and RAD51C may participate in the occurrence and progression of ESS.


Assuntos
DNA Helicases , Proteínas de Ligação a DNA , Neoplasias do Endométrio , Regulação Neoplásica da Expressão Gênica , Sarcoma do Estroma Endometrial , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/fisiopatologia , Endométrio/fisiopatologia , Feminino , Humanos , Metástase Linfática/fisiopatologia , Sarcoma do Estroma Endometrial/fisiopatologia
3.
Nat Rev Endocrinol ; 16(9): 479-494, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32601352

RESUMO

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Placentação/fisiologia , Pré-Eclâmpsia/fisiopatologia , Complicações na Gravidez/fisiopatologia , Biomarcadores , Decídua/fisiopatologia , Desenvolvimento Embrionário , Endométrio/fisiopatologia , Feminino , Desenvolvimento Fetal , Feto/irrigação sanguínea , Humanos , Placenta/irrigação sanguínea , Doenças Placentárias/fisiopatologia , Gravidez , Transdução de Sinais , Trofoblastos/fisiologia
4.
Medicine (Baltimore) ; 99(12): e19111, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195931

RESUMO

BACKGROUND: Thin endometrium, defined as <7 mm of the endometrial thickness around ovulation period, had been identified as a negative factor on pregnancy rate of infertile women. It was considered to be the toughest part in treatment of infertility, because there was a lack of significant effect, although many drugs had been already used. Icariin was one of the major bioactive pharmaceutical constituent extracted from the Chinese herb "Ying Yang Huo," in the genus of Epimedium, and some randomized controlled trials reported its application for thin endometrium. There is no systematic review focusing on the effective of icariin in treating infertile women with thin endometrium, so our review aims to explore it. METHODS: The bibliographic database and electronic library will be systematically searched online, such as MEDLINE, EMBASE, Web of Science, Clinicaltrails.org., China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, and Cochrane Library. And the reference listed for potential literatures of included studies will be scanned additionally. Related randomized controlled trials (RCTs) will be collected and selected before January 4, 2020. Trials will be screened by independent reviewers, and the literature will be search in English or Chinese, with the search terms as "Icariin," "Epimedium," "infertile women," "female infertility," "endometrium," "pregnancy rate." The software for Systematic review and Meta-analysis is RevMan 5.3. The protocol and the systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. RESULT AND CONCLUSION: The efficacy of icariin to treat thin endometrium will be evaluated, and the conclusion will be published to help clinicians determine treatment strategy for infertile women with thin endometirum by providing medical evidence. REGISTRATION INFORMATION: PROSPERO CRD42019148977.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endométrio/fisiopatologia , Flavonoides/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , China , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Flavonoides/administração & dosagem , Flavonoides/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Reprod Sci ; 27(2): 561-568, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32046396

RESUMO

This study aimed to investigate the efficacy of the transplantation of autologous adipose-derived stromal vascular fraction (AD-SVF) containing adipose stem cells (ASCs) in regenerating functional endometrium in patients with severe Asherman's syndrome (AS). This was a prospective clinical study involving six infertile women aged 20-44 years who were diagnosed with severe AS by hysteroscopy. Autologous AD-SVF were isolated from patient's adipose tissue obtained by liposuction and then transplanted into uterus by transcervical instillation using an embryo transfer catheter followed by estrogen hormone therapy. Endometrial growth and pregnancy outcomes were assessed after fresh or frozen embryo transfer. Of the five patients who remained in the study, two women who had amenorrhea resumed their menstruation with irregular scant bleeding. Three women with oligomenorrhea had increased menstrual amount. Before therapy, the maximum EMT measured ultrasonographically was 3.0 ± 1.0 mm (range: 1.7 to 4.4 mm), which significantly increased to 6.9 ± 2.9 mm (range: 5.2 to 12.0 mm, p = 0.043) after cell transplantation and hormone therapy. Five women had embryo transfer after therapy: one fresh and four frozen-thawed. One woman conceived but aborted spontaneously at 9-week gestation. AD-SVF is a safe and easily available cell product containing adipose-derived stem cells. Autologous transplantation of AD-SVF may regenerate damaged human endometrium and increase endometrial receptivity. Our study showed the feasibility of AD-SVF in restoring endometrial function and increasing endometrial thickness. This cell therapy may become a promising treatment for infertile women with endometrial dysfunction and needs further investigation.


Assuntos
Tecido Adiposo/fisiologia , Endométrio/fisiopatologia , Ginatresia/terapia , Regeneração , Transplante de Células-Tronco/métodos , Células-Tronco/fisiologia , Transplante Autólogo , Tecido Adiposo/citologia , Adulto , Feminino , Ginatresia/complicações , Humanos , Infertilidade Feminina/complicações , Projetos Piloto , Resultado do Tratamento
6.
Gynecol Obstet Invest ; 85(2): 107-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31968333

RESUMO

The junctional zone endometrium (JZE) is a compacted layer of smooth muscle cells with little extracellular matrix. The innermost myometrium adjacent to the endometrium, JZE is best visualized and evaluated on T2-weighted magnetic resonance imaging (MRI) and two-dimensional/three-dimensional transvaginal ultrasound (TVUS) scanning. Increased thickness of JZE >12 mm on MRI images has been associated with myometrial and subendometrial pathologic conditions, such as, adenomyosis, and is considered a poor prognostic factor for implantation. Gonadotrophin-releasing hormone analogue (GnRHa) has been proposed as a treatment for adenomyosis and fibroids larger than 7 cm, and overall improvement in symptoms and disease progression were attributed to JZE thinning after GnRHa treatment. JZE contractility and frequency of contractions are affected by ovarian hormone cyclic activity and pathologic changes adjacent to JZE, such as fibroids and polyps. However, JZE contractility is not evaluated by TVUS during gynecological examinations because guidelines do not exist and the process is time consuming. The present data indicate that JZE is an important part of the nongravid uterus anatomy, structure, and functionality. When more evidence is available, the morphologic features, thickness, and contractility of JZE may potentially be used as markers for diagnosis and prognosis of normal and abnormal uterine function, for early stages of pregnancy, and possibly for early detection of endometrial cancer. A new tool for JZE measurements should be further investigated to fill this clinical gap. Key Message: JZE is an important component of the nongravid uterus anatomy, structure, and functionality. The thickness and contractility of JZE could potentially be used as markers for diagnosis and prognosis of normal and abnormal uterine function, early stages of pregnancy, and early detection of endometrial cancer. A new tool for JZE measurements should be further investigated.


Assuntos
Endométrio/patologia , Endométrio/fisiopatologia , Adenomiose/diagnóstico por imagem , Adenomiose/patologia , Adulto , Implantação do Embrião , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Endométrio/diagnóstico por imagem , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Leiomioma/fisiopatologia , Imagem por Ressonância Magnética/métodos , Miométrio/diagnóstico por imagem , Miométrio/patologia , Miométrio/fisiopatologia , Gravidez , Ultrassonografia/métodos , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/fisiopatologia , Útero/diagnóstico por imagem , Útero/patologia
7.
Biomater Sci ; 8(3): 988-996, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31868868

RESUMO

Intrauterine adhesions caused by damage to the basal layer of the endometrium have a serious impact on women's fertility. Currently, there is no effective treatment to promote the regeneration of the endometrium. Urinary bladder matrix (UBM) is a derivative extracellular matrix biomaterial that has a complete basement membrane and provides a basis for the body to achieve complete self-functional repair. In this study, UBM was transplanted into the uterine horns of intrauterine adhesions in Sprague-Dawley rats to test whether UBM could improve endometrial regeneration in rats with intrauterine adhesions. Thicker endometria, increased numbers of glands, fewer fibrotic areas and increased proliferation of cells and blood vessels were found in the UBM group compared to the injury group. Transplantation of UBM reduced the mRNA levels of proinflammatory cytokines (tumor necrosis factor α) and increased those of anti-inflammatory cytokines (basic fibroblast growth factor) compared to the injury group. In the UBM group, the mRNA expression of endometrial receptivity factors (leukemia inhibitory factor and integrin αVß3) was higher than that in the injury group, but it was lower than that in the normal group and the sham-operated group. More embryos were seen in the UBM group than in the injury group, although the UBM group had fewer embryos than the normal and sham-operated groups. Therefore, UBM may contribute to endometrial regeneration and may improve endometrial receptivity and fertility.


Assuntos
Endométrio/fisiopatologia , Matriz Extracelular/metabolismo , Aderências Teciduais/fisiopatologia , Bexiga Urinária/metabolismo , Doenças Uterinas/fisiopatologia , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Endométrio/metabolismo , Feminino , Humanos , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/metabolismo , Ratos , Ratos Sprague-Dawley , Regeneração , Aderências Teciduais/genética , Aderências Teciduais/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Doenças Uterinas/genética , Doenças Uterinas/metabolismo
8.
Fertil Steril ; 112(6): 1015-1021, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843072

RESUMO

OBJECTIVE: To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures. DESIGN: A nonblinded multicenter randomized clinical trial. SETTING: Fertility clinics. PATIENT(S): Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153). INTERVENTION(S): Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and prenatal and birth data. RESULT(S): There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86-1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05-2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups. CONCLUSION(S): Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups. CLINICAL TRIAL REGISTRATION NUMBER: NCT01963819.


Assuntos
Endométrio/cirurgia , Fertilização In Vitro , Infertilidade/terapia , Adolescente , Adulto , Dinamarca , Endométrio/fisiopatologia , Feminino , Fertilidade , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas , Resultado do Tratamento , Adulto Jovem
9.
Fertil Steril ; 112(6): 1103-1111, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843086

RESUMO

OBJECTIVE: To explore the predictive value of endometrial CD138 expression in the natural cycle preceding frozen embryo transfer in patients with normal endometrial dating and histopathologic features, who previously failed the transfer of two high-quality fresh embryos. DESIGN: Retrospective analysis. SETTING: University-affiliated hospital. PATIENT(S): Women with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos, and who then underwent an endometrial scratching operation preceding a natural cycle. INTERVENTION(S): Paraffin-embedded endometrial samples cut into sections for immunohistochemistry staining of CD138 (syndecan-1) expression, then clinical information for these patients reviewed and analyzed. MAIN OUTCOME MEASURE(S): Clinical rates of pregnancy and implantation. RESULT(S): A total of 141 women met the inclusion criteria. Of these patients, about 31.2% (44 of 141) were positive for CD138 expression, with CD138 counts ranging from 0 to 33. Receiver operating characteristic (ROC) curves were analyzed to determine whether the number of cells expressing CD138 (CD138+ cells) predicted a successful pregnancy. The areas under the ROC curves based on CD138+ cell density and CD138+ cell count were 0.660 and 0.658, respectively. The clinical pregnancy and embryo implantation rates in patients not expressing CD138 (80.04% and 64.9%, respectively) were statistically significantly higher than rates in CD138+ patients (52.7% and 46.8%, respectively). In addition, the higher the number of cells expressing CD138, the worse the outcome of the pregnancy. Finally, clinical data showed that free pelvic fluid on the day of endometrial sampling (identified using transvaginal ultrasound) might be a risk factor for CD138 expression. CONCLUSION(S): Endometrial CD138+ count might be a valuable marker predicting pregnancy outcomes after frozen embryo transfer in patients with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos.


Assuntos
Transferência Embrionária , Endometrite/imunologia , Endométrio/imunologia , Infertilidade/terapia , Sindecana-1/análise , Adulto , Biomarcadores/análise , Contagem de Células , Endometrite/diagnóstico , Endometrite/fisiopatologia , Endométrio/patologia , Endométrio/fisiopatologia , Feminino , Fertilidade , Fertilização In Vitro , Humanos , Imuno-Histoquímica , Infertilidade/diagnóstico , Infertilidade/imunologia , Infertilidade/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Adulto Jovem
10.
Fertil Steril ; 112(6): 987-993, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843098

RESUMO

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade/uso terapêutico , Fertilidade/efeitos dos fármacos , Fertilização In Vitro , Infertilidade/terapia , Endométrio/fisiopatologia , Medicina Baseada em Evidências , Feminino , Fármacos para a Fertilidade/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(47): e17841, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764781

RESUMO

BACKGROUND: Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation. OBJECTIVE: To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity. METHODS: We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation. RESULTS: This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms. CONCLUSIONS: This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M85VT.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Endométrio/fisiopatologia , Feminino , Humanos , Infertilidade Feminina/etiologia , Fitoterapia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Int J Mol Sci ; 20(21)2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31717776

RESUMO

Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.


Assuntos
Aborto Habitual/imunologia , Decídua/imunologia , Endométrio/imunologia , Citocinas/metabolismo , Decídua/fisiopatologia , Células Dendríticas/imunologia , Embrião de Mamíferos/imunologia , Embrião de Mamíferos/metabolismo , Endométrio/fisiopatologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Gravidez , Linfócitos T Reguladores/imunologia
13.
Reprod Biol Endocrinol ; 17(1): 94, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729993

RESUMO

BACKGROUND: Although thyroid dysfunction caused by Hashimoto's thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice. METHODS: Female NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot. RESULTS: HT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin ß3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found. CONCLUSIONS: These findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.


Assuntos
Biomarcadores/metabolismo , Implantação do Embrião , Endométrio/fisiopatologia , Doença de Hashimoto/fisiopatologia , Animais , Endométrio/metabolismo , Endométrio/ultraestrutura , Estradiol/sangue , Feminino , Expressão Gênica , Doença de Hashimoto/sangue , Humanos , Integrina beta3/genética , Integrina beta3/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Masculino , Camundongos Endogâmicos NOD , Microscopia Eletrônica de Varredura , Gravidez , Testosterona/sangue , Tireotropina/sangue
14.
Rev Assoc Med Bras (1992) ; 65(9): 1144-1150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618328

RESUMO

OBJECTIVE: In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS: A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS: The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION: The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Muco do Colo Uterino/efeitos dos fármacos , Clomifeno/farmacologia , Quimioterapia Combinada , Endométrio/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Proteína de Ligação a Elemento Regulador de Esterol 1/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto Jovem
15.
J Assist Reprod Genet ; 36(11): 2217-2231, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502111

RESUMO

Human endometrium has a key role in implantation process. The measurement of endometrial thickness is the most commonly used in clinical practice. Managing patients with thin endometrium still represents a major challenge for clinicians. The objective of this systematic review was to investigate all available interventions to improve endometrial thickness (EMT) in women with history of thin endometrium undergoing fresh or frozen-thawed embryo transfers (ET). We performed a comprehensive search of relevant studies from January 1978 to February 2018. The different strategies were categorized as hormonal, vascular, and growth factor approaches and specifically analyzed according to the type of ET. Thirty-one studies were included. Overall, quality of the evidence ranged from very low to moderate, with only few randomized controlled trials that support the use of either GnRH analogues in fresh ET or sildenafil in frozen ET for enhancing endometrial growth. Besides, intensified estradiol administration is a common approach that might improve EMT in frozen ET. The present review evidences the paucity of reliable data regarding the efficiency of different interventions aiming at increasing EMT before fresh or frozen-thawed ET. Robust and high-quality randomized controlled trials are still needed before guidelines can be established.


Assuntos
Transferência Embrionária/métodos , Endométrio/fisiopatologia , Infertilidade/terapia , Implantação do Embrião/fisiologia , Feminino , Humanos , Gravidez , Taxa de Gravidez
16.
Res Vet Sci ; 126: 164-169, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31499425

RESUMO

Endometritis is one of the most common reproductive diseases caused by bacterial infection in the cow. Ferulic acid is a major effective component extracted from Ligusticum wallichii. Ferulic acid displays pharmacological effects such as anti-inflammation and antioxidation. The aim of the present study was to investigate the protective effects of ferulic acid on inflammation induced by lipopolysaccharide (LPS) in bovine endometrial epithelial cells (BEECs). BEECs were pretreated with ferulic acid followed by LPS treatment. QRT-PCR analysis showed the mRNA expression of LPS-induced proinflammatory cytokines (IL1B, IL6, TNFA, and IL8) was decreased with ferulic acid pretreatment. Western blot analysis showed that ferulic acid inhibited the degradation of IκB and phosphorylation of NF-κB p65. Ferulic acid suppressed the phosphorylation of MAPKs, including p38 and JNK. All of these results indicated that ferulic acid may be considered as a potential anti-inflammatory drug for curing endometritis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Doenças dos Bovinos/tratamento farmacológico , Ácidos Cumáricos/administração & dosagem , Endometrite/veterinária , Inflamação/veterinária , Animais , Bovinos , Doenças dos Bovinos/induzido quimicamente , Endometrite/induzido quimicamente , Endometrite/tratamento farmacológico , Endométrio/efeitos dos fármacos , Endométrio/fisiopatologia , Células Epiteliais/efeitos dos fármacos , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Medicina (Kaunas) ; 55(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450870

RESUMO

Background and Objectives: Assisted reproductive techniques today have helped many infertile couples achieve their desired pregnancy. However, unsuccessful implantation is usually the key failure in in vitro fertilization cycles. Many factors are now being studied to improve the implantation rate, one being endometrial artificial injury (endometrial scratching). The purpose of this study was to assess whether local endometrial artificial injury improved pregnancy rate, in long agonist and antagonist protocols. Materials and Methods: A retrospective analysis was carried out at the JSC Baltic American Clinic from January 1, 2016 to December 31, 2018. Women who were undergoing in vitro fertilization treatment were enrolled in the study. Medical data including demographic factors, menstrual history, and anamnesis of infertility were collected from medical records. Subjects were divided into intervention and control groups. The outcome of this study was clinical pregnancy rate (CPR). Results: A total of 137 women presenting with primary or secondary infertility were enrolled in the study. Clinical pregnancy was observed in 44/71 (61.9%) patients in the intervention group and 33/66 (50%) in the group without endometrial scratching (p value = 0.16). CPR in the intervention group was significantly higher in the patient group that had undergone ovarian stimulation with a long agonist protocol rather than the antagonist protocol (73.8% vs. 41.4%; p value = 0.006). In the multivariable logistic regression model, previously failed in vitro fertilization (IVF) (odds ratio (OR) = 0.07, 95% confidence interval (CI) 0.01-0.47), stimulation with the long agonist protocol (OR = 19.89, 95% CI 3.57-18.63), antagonist protocol (OR = 0.05, 95% CI 0.01-0.34), number of embryos (OR = 1.37, 95% CI 1.05-1.38), and number of blastocysts (OR = 2.96, 95% CI 1.43-8.36) remained important independent prognostic factors for clinical pregnancy. Conclusions: Our study findings indicate that randomized controlled studies are required to define patients for this procedure and to prove the effect and safety of local endometrial injury, before it is introduced to routine clinical practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/lesões , Fertilização In Vitro/métodos , Infertilidade Feminina/tratamento farmacológico , Adulto , Implantação do Embrião/fisiologia , Endométrio/fisiopatologia , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Infertilidade Feminina/fisiopatologia , Lituânia , Modelos Logísticos , Razão de Chances , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
18.
PLoS One ; 14(7): e0219294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291298

RESUMO

BACKGROUND: Abnormal uterine bleeding needs surgical treatment if medical therapy fails. After introduction of non-hysteroscopic endometrial ablation as alternative to hysteroscopic endometrial resection, we aimed to compare short and long-term outcomes for women treated with these two minimally-invasive procedures. A secondary goal was comparing the present cohort to a previous cohort of women treated with hysteroscopic resection only. MATERIALS AND METHODS: Historical cohort study of women treated for abnormal uterine bleeding with hysteroscopic resection or endometrial ablation at Haukeland University Hospital during 2006-2014. Similar patient file and patient-reported outcome data were collected from 386 hysteroscopic resections in a previous cohort (1992-1998). Categorical variables were compared by Chi-square or Fisher´s Exact-test, linear variables by Mann-Whitney U-test and time to hysterectomy by the Kaplan-Meier method. RESULTS: During 2006-2014, 772 women were treated with endometrial resection or ablation, 468 women (61%) consented to study-inclusion; 333 women (71%) were treated with hysteroscopic resection and 135 (29%) with endometrial ablation. Preoperative characteristics were significantly different for women treated with hysteroscopic resection compared to endometrial ablation in the 2006-2014-cohort and between the two time-cohorts regarding menopausal, sterilization and myoma status (p≤0.036). The endometrial ablation group had significantly shorter operation time, median 13 minutes (95% Confidence Interval (CI) 12-14) and a lower complication rate (2%) versus operation time, median 25 minutes (95% CI 23-26) and complication rate (13%) in the hysteroscopy group, all p ≤0.001. The patient-reported rate of satisfaction with treatment was equivalent in both groups (85%, p = 0.955). The endometrial ablation group had lower hysterectomy rate (8% vs 16%, p = 0.024). Patient-reported satisfaction rate was higher (85%) in the 2006-2014-cohort compared with the 1992-1998-cohort (73%), p<0.001. CONCLUSIONS: Endometrial ablation has similar patient satisfaction rate, but shorter operation time and lower complication rate and may be a good alternative to hysteroscopic resection for treatment of abnormal uterine bleeding.


Assuntos
Técnicas de Ablação Endometrial , Endométrio/cirurgia , Histeroscopia , Metrorragia/cirurgia , Adulto , Estudos de Coortes , Endométrio/fisiopatologia , Feminino , Humanos , Metrorragia/fisiopatologia , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Gravidez , Resultado do Tratamento
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