Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes / 中华妇产科杂志

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Isthmocele: an overview of diagnosis and treatment

SUMMARY An isthmocele, a cesarean scar defect or uterine niche, is any indentation representing myometrial discontinuity or a triangular anechoic defect in the anterior uterine wall, with the base communicating to the uterine cavity, at the site of a previous cesarean section scar. It can be classified as a small or large defect, depending on the wall thickness of the myometrial deficiency. Although usually asymptomatic, its primary symptom is abnormal or postmenstrual bleeding, and chronic pelvic pain may also occur. Infertility, placenta accrete or praevia, scar dehiscence, uterine rupture, and cesarean scar ectopic pregnancy may also appear as complications of this condition. The risk factors of isthmocele proven to date include retroflexed uterus and multiple cesarean sections. Nevertheless, factors such as a lower position of cesarean section, incomplete closure of the hysterotomy, early adhesions of the uterine wall and a genetic predisposition may also contribute to the development of a niche. As there are no definitive criteria for diagnosing an isthmocele, several imaging methods can be used to assess the integrity of the uterine wall and thus diagnose an isthmocele. However, transvaginal ultrasound and saline infusion sonohysterography emerge as specific, sensitive and cost-effective methods to diagnose isthmocele. The treatment includes clinical or surgical management, depending on the size of the defect, the presence of symptoms, the presence of secondary infertility and plans of childbearing. Surgical management includes minimally invasive approaches with sparing techniques such as hysteroscopic, laparoscopic or transvaginal procedures according to the defect size.

RESUMO A istmocele ou nicho uterino é representada por uma descontinuidade miometrial ou um defeito anecoico triangular na parede uterina anterior, com a base se comunicando com a cavidade uterina no local de uma cicatriz anterior de cesárea. O defeito pode ser classificado como pequeno ou grande, dependendo da espessura da parede miometrial deficiente. Embora geralmente assintomático, seu principal sintoma é o sangramento uterino anormal ou pós-menstrual; a dor pélvica crônica também pode ocorrer. Infertilidade, placenta acreta ou prévia, deiscência de cicatriz, ruptura uterina e gravidez ectópica em cicatriz de cesárea prévia também podem aparecer como complicações dessa condição. Os fatores de risco para desenvolvimento da istmocele comprovados até o momento incluem útero retroverso e múltiplas cesarianas. No entanto, fatores como localização mais inferior de uma cesárea prévia, fechamento incompleto da histerotomia, aderências precoces na parede uterina e predisposição genética também podem contribuir para o desenvolvimento de um nicho. Como não existem critérios definitivos para o diagnóstico de uma istmocele, vários métodos de imagem podem ser usados para avaliar a integridade da parede uterina e, assim, diagnosticar uma istmocele. Entretanto, ultrassonografia transvaginal e sono-histerografia com infusão salina surgem como métodos específicos, sensíveis e custo-efetivos para o diagnóstico de istmocele. O tratamento inclui manejo clínico ou cirúrgico, dependendo do tamanho do defeito, da presença de sintomas, da presença de infertilidade secundária e de planos de gravidez. O manejo cirúrgico inclui abordagens minimamente invasivas como histeroscopia, laparoscopia ou transvaginal, de acordo com o tamanho do defeito.

Isthmocele: from risk factors to management / Istmocele: de fatores de risco ao manejo

Abstract Objective The aim of the present study was to perform a comprehensive review of the literature to provide a complete and clear picture of isthmocele-a hypoechoic area within themyometriumat the site of the uterine scar of a previous cesarean section-by exploring in depth every aspect of this condition. Methods A comprehensive review of the literature was performed to identify the most relevant studies about this topic. Results Every aspect of isthmocele has been studied and described: pathophysiology, clinical symptoms, classification, and diagnosis. Its treatment, both medical and surgical, has also been reported according to the actual literature data. Conclusion Cesarean section is the most common surgical procedure performed worldwide, and one of the consequences of this technique is isthmocele. A single and systematic classification of isthmocele is needed to improve its diagnosis and management. Further studies should be performed to better understand its pathogenesis.

Resumo Objetivo O objetivo do presente estudo foi realizar uma revisão abrangente da literatura a fim de fornecer um quadro completo e claro da istmocele-uma área hipoecoica dentro domiométrio no local da cicatriz uterina de uma cesariana anterior- aprofundando todos os aspectos desta condição Métodos Uma revisão abrangente da literatura foi realizada para identificar os estudos mais relevantes sobre este tema. Resultados Todos os aspectos da istmocele foram estudados e descritos: fisiopatologia, sintomas clínicos, classificação e diagnóstico. Os tratamentos médico e cirúrgico também foram relatados de acordo com os dados reais da literatura. Conclusão A cesárea é o procedimento cirúrgico mais comum realizado em todo o mundo, e uma das consequências desta técnica é a istmocele. Uma classificação única e sistemática da istmocele é necessária para melhorar seu diagnóstico e manejo. Novos estudos devem ser realizados para melhor entender sua patogênese.

Evaluation of embolization for periuterine varices involving chronic pelvic pain secondary to pelvic congestion syndrome

OBJECTIVES: To evaluate the clinical response and success rate after periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome and to report the safety of endovascular treatment and its rate of complications. METHODS: Retrospective cohort of patients undergoing endovascular treatment of pelvic congestion syndrome in our department from January 2012 to November 2015. Data were analyzed based on patient background, imaging findings, embolized veins, rate of complications, and clinical response as indicated by the visual analog pain scale. RESULTS: We performed periuterine varices embolization in 22 patients during the study, four of which required a second embolization. Seventeen patients reported a reduction in pelvic pain after the first embolization and three patients reported a reduction in pelvic pain after the second embolization. Minor complications were observed in our patients, such as postural hypotension, postoperative pain, and venous perforation during the procedure, without clinical repercussion. CONCLUSION: Periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome appears to be an effective and safe technique.

Citología endometrial en pacientes posmenopáusicas con terapia hormonal / Endometrial cytology in postmenopausal women under hormonal therapy

Demostrar la utilidad de la toma de muestra con Uterobrush® y compararlo con la biopsia endometrial, en pacientes posmenopáusicas con terapia hormonal. Estudio prospectivo durante un lapso de seis meses, en el cual se incluyeron 30 pacientes, de las cuales 15 referían sangrado genital anormal y 15 no referían sintomatología. A cada paciente se le realizó citología endometrial con Uterobrush® y posteriormente se le realizó biopsia de endometrio con cureta de Novak. El diagnóstico citológico se comparó con el diagnóstico biópsico, para obtener la sensibilidad y especificidad de la técnica con Uterobrush®. Consulta externa del Servicio de Ginecología del Instituto Autónomo Hospital Universitario de Los Andes (IIAHULA) Mérida. El procedimiento fue fácil en un 73,3 por ciento de las pacientes, no refiriendo dolor. No se presentó sangrado posterior a la introducción del Uterobrush® en un 53,33 por ciento. Las muestras fueron adecuadas en el 70 por ciento de los casos. La principal causa de limitación fue la mala preservación de las células. Al comparar los diagnósticos citológicos con la biopsia encontramos una sensibilidad del 71 por ciento y una especificidad del 75. La citología endometrial con Uterobrush® es un procedimiento aceptable, fácil de usar, económico, y bien tolerado por las pacientes; siendo útil para la valoración endometrial en mujeres posmenopáusicas y en aquellas que así lo ameriten, pero no se pretende desplazar a la biopsia endometrial sino sugerir estudios más extensos.

Hidatidosis uterina: una localización excepcional / Uterine hydatid cyst: an exceptional location

La hidatidosis es una zoonosis de distribución mundial producida por helmintos del género Echinococcus. En Chile representa un problema de salud pública no resuelto aún en su totalidad. La localización ginecológica es poco frecuente, pero debe considerarse en el diagnóstico diferencial de masas pélvicas, sobre todo, en pacientes con infertilidad. Se presenta un caso clínico de hidatidosis pélvica primaria de origen uterino como hallazgo operatorio. Se discute el manejo y seguimiento.

The hydatid disease is a worldwide distribution zoonotic infection caused by a tapeworm of the genus Echinococcus. In Chile, it is a public health probiem that hasn't been completely solved yet. It is very unlikely to be found in ginecology. Still it has to be considered within pelvic mass study, mostly between infertile patients. We now discuss a surgical finding of a pelvic primary hydatid disease of uterine origin clinical case, the management and follow-up.

Gestaçäo em pacientes com síndrome de Asherman tratadas por histeroscopia / Pregnancy in patients with Asherman's syndrome submitted to hysteroscopic treatment: case reports

Os autores revisam os principais aspectos da fisiopatologia da síndrome de Asherman dando ênfase à classificaçao e seqüelas para o padrao menstrual e à capacidade reprodutiva. Tecem comentários com referência à curetagem uterina, colocaçao de dispositivo intra-uterino (DIU) e estrogenioterapia e, mais recentemente, à lise de aderências por vídeo-histeroscopia. Relatam três casos que foram tratados com vídeo-histeroscopia evoluindo com gravidez a termo, mostrando resultados favoráveis com este método terapêutico.

Gravidez e útero encarcerado / Incarcerated uterus and pregnancy

É reportada a ocorrência de dois casos de encarceramento uterino e gravidez, diagnosticados e conduzidos na Clínica Obstétrica do Hospital Geral de Fortaleza (ex-INAMPS), num total de 41.037 gestaçoes. O primeiro foi solucionado através de laparotomia exploradora, com lise das aderências que aprisionavam o útero retrovertido na pequena pélvis, combinada com compressao bidigital do fórnice vaginal posterior. Isso foi em decorrência do insucesso da intervençao conservadora. No segundo, conseguiu-se a liberaçao do útero gravídico retrovertido fixo, através do toque combinado. As abordagens só foram levadas a efeito, após debelaçao do quadro de infecçao urinária que acometia ambas as pacientes e postas em prática sob analgesia perdural. As gravidezes atingiram o termo, com nascimento de fetos vivos e saudáveis.

A histerectomia no ciclo grávido puerperal: estudo crítico a propósito de 99 casos / Hysterectomy in the puerperal pregnancy cycle: critical study apropos of 99 cases

Reviram-se as observaçöes de 99 histerectomias, praticadas no decurso do Ciclo Grávido-Puerperal, na Clínica Obstétrica da Faculdade de Medicina da Universidade de Säo Paulo, nos períodos de 1931-1945, 1951-1983. Foram indicaçöes de histerectomia, no ciclo grávido-puerperal: infecçäo puerperal, na rotura uterina, moléstia trofoblástica, atonia uterina, acretismo placentário, descolamento prematuro da placenta, mioma uterino, placenta prévia, câncer cervical e a necrose uterina puerperal. No período de 1951-1961 a real incidência de histerectomia foi: na rotura uterina 9,6%, no mioma 3,4%, na perfuraçäo uterina 1,9%, no deslocamento prematuro da placenta 0,9% e, na moléstia trofoblástica, no período 1973-1984, foi de 10,4%. No período 1931-1945 pontificaram as causas hemorrágicas, totalizando 83,2% das indicaçöes de histerectomias. Entre 1951-1961 e 1974-1983 esse número declinou para 45,1% e 24,0%, respectivamente. No período 1974-1983 foi flagrante a elevaçäo do índice de histerectomias, por moléstia trofoblástica (19,2%) e infecçäo puerperal (56,0%) pós-aborto. Entre os 28 casos de histerectomia praticada por infecçäo puerperal, em 11, tratava-se de pacientes com menos de 26 anos, das quais 5 eram nulíparas e 6 primíparas. Entre essas 11 observaçöes, em 8 havia, inclusive, perfuraçäo uterina. Chama a atençäo que incidência de pacientes jovens (menos de 26 anos) e idosas (mais de 36 anos) foi, nitidamente, maior no período 1974-1983, quando, por razöes sociais (jovens) e, possivelmente, econômicas (idosas), a configuraçäo de gestaçäo indesejada obrigou a prática do aborto. A histerectomia sub-total foi mais freqüente no período 1931-1945. Progressivamente , sua indicaçäo declinou, à medida em que a técnica total se elevava até atingir 74,0% de intervençöes, no período 1973-1984 ...