Endometrite crônica e infertilidade / Chronic endometritis and infertility

A endometrite crônica (EC) é uma doença que, apesar de ainda pouco investigada, tem sido associada a resultados reprodutivos desfavoráveis. Estudos têm mostrado que a EC pode prejudicar a receptividade endometrial, levando a falhas de implantação e perdas gestacionais recorrentes. Os métodos padronizados para diagnóstico incluem histeroscopia, histologia para pesquisa de plasmócitos e cultura endometrial para identificação de agentes bacterianos. O tratamento com antibióticos para EC parece melhorar as taxas de gestação e nascidos vivos em pacientes com falhas de implantação e perdas gestacionais recorrentes sem causa conhecida. Esta publicação tem por objetivo fazer uma revisão da etiologia, fisiopatologia, diagnóstico e tratamento da EC, seu impacto no microambiente endometrial e sua associação com infertilidade. Esta revisão narrativa da literatura atualizada sintetiza os achados encontrados em bases de dados computadorizadas.(AU)

Chronic endometritis (CE) is a poorly investigated disease, which has been related to adverse reproductive outcomes. Published studies have shown that CE can impair endometrial receptivity, which is associated with implantation failure and recurrent pregnancy loss. The standard tools for diagnosis include hysteroscopy, histology to identification of plasma cells and endometrial culture for identification of bacterial pathogens. Effective antibiotic treatment for CE seems to improve the pregnancy and live birth rates in patients with implantation failure and unexplained recurrent pregnancy loss. This paper intends to provide an overview of etiology, pathophysiology, diagnosis and treatment of CE, its impact on endometrial microenvironment and its association with infertility. This narrative review of the current literature synthesizes the findings retrieved from searches in computerized databases.(AU)

Postpartum uterine diseases negatively impact the time to pregnancy in grazing dairy cows from high-altitude tropical herds.

Infertility is a common consequence of cows suffering from postpartum uterine diseases. Diseases from a uterine origin in early lactation affect both uterine and ovarian tissues decreasing the probability of pregnancy. The objective of the present study was to determine the impact of clinical metritis, clinical endometritis, and subclinical endometritis on days open in cows from high-altitude tropical dairy herds. A single cohort longitudinal study was conducted from January 2018 to February 2019, which included 248 cows enrolled from five commercial high-altitude tropical dairy herds in the northern region of the Department of Antioquia, Colombia. A directed acyclic graph was used to identify minimal sufficient adjustment sets for each exposure variable of interest. Based on the directed acyclic graph, three models (one for each of clinical metritis, clinical endometritis, and subclinical endometritis) were proposed to assess the impact of postpartum uterine diseases on days open. The time at risk was defined as the days elapsed from calving until pregnancy (event or censure). Observations were right-censored if cows were either culled, dead, were lost to follow up, suffered a systemic illness that required the use of parenteral drugs, or if they were not pregnant at 210 postpartum days. Three Cox proportional hazards models were proposed to estimate the Hazard Ratios (HR) at any point in the follow-up period for each exposure variable. The hazard of pregnancy was significantly lower for cows with metritis (40 %; HR = 0.60; 95 % CI: 0.43 - 0.86), clinical endometritis (69 %; HR = 0.31; 95 % CI: 0.22 - 0.45), and subclinical endometritis (76 %; HR = 0.24; 95 % CI: 0.16 - 0.36) compared to their herd mates without these conditions. These results provide evidence of the negative impact of postpartum uterine diseases on time to pregnancy in grazing lactating dairy cows from high-altitude tropical herds.

Endometritis in the bitch: Immunohistochemical localization of cyclooxygenase 2.

Background: In several mammals, subfertility or infertility associated with endometritis was reported. Although there have been studies about endometritis in bitches, the pathophysiological mechanisms are not completely known. Aim: This study aimed to evaluate the immunohistochemical expression of Cyclooxygenase 2 (COX2) in clinically healthy bitches with normal uterine tissue and bitches with endometritis. Methods: Forty-eight mixed breed bitches in diestrus were used. Uterine biopsies were collected for diagnosis [normal endometrium (n = 15; NE), cystic endometrial hyperplasia (n = 1), atrophy (n= 2), acute endometritis (n = 9; AE), subacute endometritis (n = 7; SE), and chronic endometritis (n = 14; CE)]. Immunostaining and quantification of positively stained cells was performed on full-thickness uterine biopsies. Data were analyzed by the GLIMMIX procedure of SAS. Results: COX2 immunostaining was scattered and restricted to cells in the stroma in bitches with NE. However, in bitches with endometritis, strong staining was observed in the luminal epithelium, glandular epithelium, and stromal cells. Staining was also observed in inflammatory cells localized in the stroma as well as inside of the glands. The percentage of COX2 positive stromal cells in bitches with AE, SE, and CE was significantly higher compared with NE (p < 0.005). In addition, the percentage of COX2 positive stromal cells in bitches with SE, and CE was significantly lower compared with AE (p < 0.003). Conclusion: COX2 could be involved in the pathophysiological mechanisms producing endometritis without the presence of cystic endometrial hyperplasia in bitches. However, further researches on this topic are required.

Endometrite em éguas: diagnóstico e tratamentos convencionais e/ou alternativos / Endometritis in mares: diagnosis and conventional and/or alternative treatments

A endometrite é a principal causa de redução da fertilidade em éguas, além de gerar grandes transtornos econômicos e produtivos dentro do mercado do cavalo. O objetivo desse trabalho foi realizar uma revisão sistemática sobre o tema, abordando sua etiologia e principais consequências, o estado senil dos animais acometidos assim como seus mecanismos próprios de defesa uterina quer sejam mecânicos e/ou quimiotáticos. Avaliamos ainda os principais microrganismos envolvidos na endometrite bem como sua virulência e resistência antimicrobiana, um dos problemas mais graves e preocupantes que nos deparamos nos dias atuais. A virulência está relacionada à existência de genes que participam de processos fisiológicos necessários para a sobrevivência, encontrados em microrganismos patogênicos e não patogênicos. Dentre os fatores de virulência relacionados a microrganismos patogênicos do útero equino, a formação de biofilme, é um tema de grande relevância visto que a maioria dos microrganismos encontrados são capazes de produzir biofilme in vitro. Tentamos delinear os tratamentos utilizados (convencionais ou alternativos), incluindo a combinação de medicações anti-inflamatórias e antimicrobianas associada à correção de defeitos anatômicos. Esses tratamentos vão desde a limpeza física do endométrio, ao uso de drogas antimicrobianas, ecbólicas, mucolíticas, bem como imunomoduladores, concentrado de proteínas de caráter biológico (PRP), células tronco e Ozonioterapia.

Endometritis is the main cause of reduced fertility in mares, in addition to generating major economic and productive disorders within the horse market. The objective of this work was to carry out a systematic review on the subject, addressing its etiology and main consequences, the senile state of the affected animals as well as their own uterine defense mechanisms, whether mechanical and/or chemotactic. We also evaluated the main microorganisms involved in endometritis as well as their virulence and antimicrobial resistance, one of the most serious and worrying problems that we face today. Virulence is related to the existence of genes that participate in physiological processes necessary for survival, found in pathogenic and non-pathogenic microorganisms. Among the virulence factors related to pathogenic microorganisms in the equine uterus, biofilm formation is a topic of great relevance since most of the microorganisms found are capable of producing biofilm in vitro. We tried to outline the treatments used (conventional or alternative), including the combination of anti-inflammatory and antimicrobial medications associated with the correction of anatomical defects. These treatments range from physical cleaning of the endometrium, to the use of antimicrobial, ecbolic, mucolytic drugs, as well as immunomodulators, biological protein concentrate (PRP), stem cells and ozone therapy.

Endometrite em éguas: diagnóstico e tratamentos convencionais e/ou alternativos / Endometritis in mares: diagnosis and conventional and/or alternative treatments

A endometrite é a principal causa de redução da fertilidade em éguas, além de gerar grandes transtornos econômicos e produtivos dentro do mercado do cavalo. O objetivo desse trabalho foi realizar uma revisão sistemática sobre o tema, abordando sua etiologia e principais consequências, o estado senil dos animais acometidos assim como seus mecanismos próprios de defesa uterina quer sejam mecânicos e/ou quimiotáticos. Avaliamos ainda os principais microrganismos envolvidos na endometrite bem como sua virulência e resistência antimicrobiana, um dos problemas mais graves e preocupantes que nos deparamos nos dias atuais. A virulência está relacionada à existência de genes que participam de processos fisiológicos necessários para a sobrevivência, encontrados em microrganismos patogênicos e não patogênicos. Dentre os fatores de virulência relacionados a microrganismos patogênicos do útero equino, a formação de biofilme, é um tema de grande relevância visto que a maioria dos microrganismos encontrados são capazes de produzir biofilme in vitro. Tentamos delinear os tratamentos utilizados (convencionais ou alternativos), incluindo a combinação de medicações anti-inflamatórias e antimicrobianas associada à correção de defeitos anatômicos. Esses tratamentos vão desde a limpeza física do endométrio, ao uso de drogas antimicrobianas, ecbólicas, mucolíticas, bem como imunomoduladores, concentrado de proteínas de caráter biológico (PRP), células tronco e Ozonioterapia.(AU)

Endometritis is the main cause of reduced fertility in mares, in addition to generating major economic and productive disorders within the horse market. The objective of this work was to carry out a systematic review on the subject, addressing its etiology and main consequences, the senile state of the affected animals as well as their own uterine defense mechanisms, whether mechanical and/or chemotactic. We also evaluated the main microorganisms involved in endometritis as well as their virulence and antimicrobial resistance, one of the most serious and worrying problems that we face today. Virulence is related to the existence of genes that participate in physiological processes necessary for survival, found in pathogenic and non-pathogenic microorganisms. Among the virulence factors related to pathogenic microorganisms in the equine uterus, biofilm formation is a topic of great relevance since most of the microorganisms found are capable of producing biofilm in vitro. We tried to outline the treatments used (conventional or alternative), including the combination of anti-inflammatory and antimicrobial medications associated with the correction of anatomical defects. These treatments range from physical cleaning of the endometrium, to the use of antimicrobial, ecbolic, mucolytic drugs, as well as immunomodulators, biological protein concentrate (PRP), stem cells and ozone therapy.(AU)

Effect of puerperal metritis on reproductive and productive performance in dairy cows in Argentina.

The objectives of this study were to evaluate the reproductive and productive performance of dairy cows with and without puerperal metritis and to evaluate the effectiveness of using a long-acting ceftiofur preparation. Dairy cows in one dairy farm, calving from July 2009 to January 2010, were examined between 3 and 14 days postpartum and classified on the basis of vaginal discharge into three groups: cows with normal discharge (control; C); cows with a bloody mucus purulent or pathologic nonfetid discharge (PnFD), and cows with bloody mucopurulent or purulent fetid discharge (PFD). Cows in C and PnFD groups were not treated, whereas those in the PFD group were randomly allocated to receive 2.2 mg/kg of ceftiofur subcutaneously behind the ear (PFD-T) or remain untreated (PFD-No T). From the 640 cows examined, 58.2% formed the C group, 13.4% formed the PnFD group, and 28.4% formed the PFD group. Survival curves differed between cows in the C group and PFD-No T group (P = 0.0013) and between PFD-No T versus PFD-T group (P = 0.0006). Survival curves of PnFD were intermediate and did not differ from those in the C group (P = 0.2) and PFD-T group (P = 0.1) but tended to be different from the PFD-No T group (P = 0.056). The postpartum interval to achieve a 25% pregnancy rate was 72 days for cows in the C group, 73 days for the PFD-T group, 83 days for PnFD group, and 95 days for the PFD-No T group. The chance of pregnancy in a cow in the C group was 1.98 times higher (95% confidence interval = 1.33, 3.08) and in cows in the PFD-T group was 2.16 times higher (95% confidence interval = 1.37, 3.50) than that in the PFD-No T group. Finally, the chance of pregnancy in cows in the PnFD group tended to be higher (P = 0.08) than that in the PFD-No T group but did not differ from the other two groups. Cumulative 305-day milk production was higher (P < 0.0001) in C group than those with vaginal discharge, regardless of fetidness and regardless of treatment. It is concluded that puerperal metritis affects the reproductive and productive performance of dairy cows and the treatment with ceftiofur was effective in reducing the adverse effects on reproductive performance but not on milk production.

Clinical endometritis in an Argentinean herd of dairy cows: risk factors and reproductive efficiency.

The objectives of this study were to assess the clinical and metabolic risk factors for clinical endometritis, the likelihood for having a normal vaginal discharge during postpartum, and the effects of endometritis on milk yield, reproductive efficiency, and metabolic status in Holstein cows. The study was conducted in a commercial dairy herd (Cordoba, Argentina) where 303 Holstein cows were enrolled. Cows were body condition scored (1 to 5) and tail bled on -14, 7, 21, 31, 41, and 50 d relative to parturition. Cows having a vaginal discharge with presence of pus between 21 and 41 d postpartum (dpp) were diagnosed as having clinical endometritis. Plasma blood samples were analyzed for nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and blood urea nitrogen using commercial kits and insulin-like growth factor 1, insulin, and leptin by RIA. Data were analyzed with PROC MIXED, PROC GENMOD, and PROC PHREG of SAS (SAS Institute Inc., Cary, NC). Abnormal calving and puerperal metritis increased the risk for endometritis [adjusted odds ratio (AOR)=2.21 for both]. High prepartum NEFA and high postpartum BHBA increased the risk for endometritis (AOR=1.003 and 1.001, respectively), whereas high prepartum blood urea nitrogen reduced it (AOR=0.853). Cut-offs of 456.6 µM NEFA and 402.5 µM BHBA had sensitivities of 0.69 and 0.58, and specificities of 0.88 and 0.86, respectively. The likelihood for having normal vaginal discharge increased with time (∼1% × dpp) and with normal calving. Cows with endometritis had higher milk yield than normal herdmates (27.8±0.9 vs. 25.7±0.4 kg/d), lower risk for pregnancy by 100 dpp (AOR=0.10), higher nonpregnancy risk by 200 dpp (AOR=2.87), and higher risk for culling than normal cows (AOR=2.28). Cows with endometritis had a lower hazard rate (0.44) for pregnancy and had approximately 70 d longer calving-to-conception intervals. Finally, endometritis had no effect on metabolic hormones. In conclusion, the risk for clinical endometritis increases with abnormal calving and puerperal metritis, as prepartum NEFA and postpartum BHBA concentrations increase. Prepartum NEFA and postpartum BHBA could be useful for the prediction of endometritis. Last, clinical endometritis has detrimental effects on reproductive efficiency, as affected cows take longer to get pregnant and are at higher risk for culling.

Experimental endometriosis in the rat is correlated with colonic motor function alterations but not with bacterial load.

Endometriosis commonly presents with symptoms that mimic chronic gastrointestinal disorders. The authors used the autotransplantion model of endometriosis in rats to investigate the possible underlying mechanisms. After the rats were killed, the presence of endometriotic vesicles, colonic inflammation, and white blood cell (WBC) numbers in the peritoneal fluid was determined. Sections of colon and of jejunum were collected for measurement of myeloperoxidase (MPO) activity and bacterial counts, and isometric recording in response to acetylcholine was measured in segments of longitudinal and circular smooth muscle. Experimental animals had significantly more colonic damage, MPO activity, and WBC numbers than controls did. There was no significant difference in the total bacterial load; however, experimental animals demonstrated an increased tension in the longitudinal muscle, which correlated with WBC numbers and colonic damage. In summary, this study presents evidence for a significant effect of peritoneal endometriosis on colonic function and integrity, which may help explain the gastrointestinal symptoms associated with this disease.

Endometritis, salpingitis and fertilisation rates after mating mares with a history of intrauterine lumenal fluid accumulation.

The occurrence of uterine and oviductal inflammation, and fertilisation rates, were measured on Day 3 post ovulation in inseminated mares that had either exhibited intrauterine lumenal fluid during a previous dioestrus (Experiment 1) or had acute endometritis induced by intrauterine infusion of 1% glycogen (Experiment 2). Endometritis was assessed by uterine cytology and histology whereas oviductal inflammation was measured histologically. Fertilisation rates were calculated from the percentage of cleaved ova recovered by retrograde flushing of the oviducts. Mares with or without pre-existing uterine fluid during dioestrus that were inseminated showed a higher incidence of endometritis than control mares without pre-existing uterine fluid that were not inseminated (n = 7 mares/group). However, inseminated mares with uterine fluid did not show a higher incidence of endometritis than inseminated mares without uterine fluid. Mares with or without pre-existing uterine fluid showed a higher incidence of endometritis than salpingitis and these 2 groups of mares showed equivalent rates of fertilisation and oviductal oocyte recovery. Mares inseminated with semen alone or semen following 1% glycogen treatment had a higher incidence of endometritis than control noninseminated mares (n = 17 mares/group) but mares that received semen plus 1% glycogen did not show a higher incidence of endometritis than mares that received semen alone. Both these groups of mares showed a higher incidence of endometritis than salpingitis and those that received semen plus 1% glycogen showed an equal recovery rate of recently ovulated ova but a lower fertilisation rate than the mares that received semen alone.

Factores de riesgo asociados a endometritis e infección de herida operatoria post cesárea Hospital Honorio Delgado y Hospital Goyeneche, agosto 1994 a febrero 1995

Se realizó un estudio retrospectivo de casos y controles, para determinar la incidencia de Endometritis, infección de herida operatoria, ambas infecciones combinadas y en suma de estas tres patologías, así como para determinar los factores de riesgo asociados a cada una de estas infecciones postcesárea y la frecuencia de estos factores, tanto en el Hospital Goyeneche(H.G) como en el Hospital Honorio Delgado(H.H.D), teniendo como universo a todas las pacientes cesareadas entre los meses de agosto de 1994 a febrero de 1995, cuyo número fue 688 pacientes, a todas las cuales se les aplicó una ficha encuesta. Durante el periodo mencionado se presentaron 75 infecciones postoperatorias, 41 Endometritis (21 en el H.H.D y 20 en el H.G), 17 infecciones de herida operatoria (10 en el H.H.D y 7 en el H.G) y 17 infecciones combinadas (12 en el H.H.D y 5 en el H.G), quienes constituyeron el número de casos. Se seleccionó al azar del universo de 150 pacientes cesareadas que no presentaron ninguna de las infecciones mencionadas en su postoperatorio, quienes constituyeron el grupo control. Se realizaron pruebas estadísticas pertinentes. Los factores que significativamente se asociaron a Endometritis fueron: percibir un ingreso familiar igual o menor al sueldo mínimo vital, menos de 5 controles prenatales, fecha de última menstruación anemia, desproporción fetopélvica, trabajo de parto, tener pélvis estrecha, trabajo de parto mayor de 12 horas, cesárea de urgencia, más de 4 tactos vaginales, primera cesárea, no haber recibido antibióticos en el postoperatorio inmediato. Para infección de herida operatoria, se encontraron los siguientes factores de riesgo con significación estadística: ingreso familiar igual o menor al sueldo mínimo vital, indice de masa corporal alto, anemia, desproporción fetopélvica, trabajo de parto mayor de 12 horas. Para ambas infecciones combinadas se hallaron los siguientes factores de riesgo con significación estadística: ingreso familiar igual o menor al sueldo mínimo vital, menos de 5 controles prenatales, fecha de última menstruación desconocida, anemia, desproporción fetopélvica, trabajo de parto mayor de 12 horas, cesárea de urgencia, anestesia general inhalatoria, no recibir antibióticos en el postoperatorio inmediato. Fueron comunes a los tres tipos de infecciones: ingreso familiar igual o menor al sueldo mínimo vital, anemia y trabajo de parto mayor de 12 horas. Entre los factores de riesgo determinados, los más frecuentes fueron: primera cesárea, cesárea de urgencia, trabajo de parto, no recibir antibióticos en el postoperatorio inmediato, menos de 5 controles prenatales, indice de masa corporal alto, anemia. El número de factores de riesgo promedio para Endometritis fueron 9, para infección de herida operatoria fueron 9, para ambas infecciones combinadas fueron 11, mientras que para pacientes no infectadas fueron 7

The significance of female sex steroids on the vascular permeability of the traumatised uterine serosa of rats.

Using experiments with conjugated hormones, and their influence on vascular permeability assessed by the colloidal carbon technique, we have investigated the effect of female sex steroids on the microcirculation of the uterine horn of virgin rats. We found that oestrogen inhibited vascular permeability in inflammatory conditions. Progesterone increased vascular permeability.