Hysteroscopic detection of chronic endometritis: Evaluating proposed hysteroscopic features suggestive of chronic endometritis.

PURPOSE: To evaluate the proposed criteria in a large sample and in additional subgroups in order to test the validity of the hysteroscopic features widely-accepted as suggestive of CE. METHOD(S): All patients (n: 2675) underwent outpatient hysteroscopy, with the vaginoscopic approach technique. Hysteroscopic features such as, stromal oedema, diffuse or focal hyperaemia, "strawberry aspect", micropolyposis and endometrial polyps, are often indicate the presence of chronic endometritis. All hysteroscopic features, alone and in combination were applied in 7 (seven) different subgroups of the sample: total sample, women in reproductive age, women with infertility issues/IVF screening, women with history of recurrent miscarriages, menopausal women, and women with hysteroscopic indication of Abnormal Uterine Bleeding (AUB) in women of reproductive age and postmenopausal bleeding (PMB). From each case, endometrial samples were obtained and immunohistochemistry, identifying CD-138, was applied in order to diagnose CE. RESULT(S): A total of 2675 patients were included of which, 1444 women were found with at least one of the proposed hysteroscopic features mentioned above. Stromal oedema, focal or diffuse hyperaemia and "strawberry aspect" in combination with micropolyposis demonstrated higher rates of diagnostic accuracy in the detection of CE correlated to histologic confirmation. Micropolyposis, stromal oedema, focal or diffuse hyperaemia and "strawberry aspect" offer great diagnostic accuracy in the hysteroscopic detection of Chronic Endometritis, regardless reproductive status and/or clinical presentation. Endometrial polyps are not valid hysteroscopic features in cases of suspected CE. CONCLUSION(S): Diagnostic hysteroscopy can accurately diagnose cases of CE, based on stromal oedema, focal or diffuse hyperaemia and "strawberry aspect", in combination with micropolyposis. In subgroups of infertile women, higher diagnostic accuracy based on the hysteroscopic features mentioned, was more likely to be achieved. Whether endometrial polyps are suggestive of CE, when identified during office hysteroscopy, remains controversial.

Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients.

BACKGROUND: The purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase. METHODS: Endometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed. RESULTS: The rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition. CONCLUSION: The epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation.

Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis.

Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken.

Comparative biochemical profiles, utero-ovarian function, and fertility of the postpartum buffalo with and without subclinical endometritis.

In postpartum buffaloes, the process of uterine involution and changes in blood metabolic profile has not been studied in relation to development of subclinical endometritis (SCE). In this study, buffaloes (n = 100) approaching calving were identified. Weekly blood samples were collected on the day of calving up to 6 weeks post-calving. The diameter of uterine horns and onset of ovarian cyclicity (corpus luteum) were recorded through ultrasonography. On the basis of polymorphonuclear cell (PMN) cell count in endometrial cytology at days 45-50 postpartum, buffaloes were divided into two groups, viz., with SCE (> 5% PMN; n = 38) and without SCE (≤ 5% PMN; n = 62). Buffaloes with SCE took longer (P < 0.05) time to complete uterine involution and had larger (P < 0.05) uterine horn diameter between 3rd and 6th weeks postpartum and lower prostaglandin F2α metabolite (PGFM) concentration on the day of calving (P < 0.05) and 1 week (P < 0.001) post-calving than without SCE group. Buffaloes with SCE had lower (P < 0.001) concentration of glucose at weeks 2 and 3, higher (P < 0.001) ß-hydroxybutyric acid (BHBA) at week 3, and lower serum albumin concentration throughout the sampling period (P < 0.05 to 0.001) except at 1 week post-calving as compared to without SCE group. The urea concentration was significantly lower (P < 0.05 to 0.001) in buffaloes with SCE from 4 weeks post-calving onwards than without SCE group. The calcium concentration was lower in buffaloes with SCE at weeks 5 (P < 0.001) and 6 (P < 0.05) postpartum, whereas the concentration of magnesium and phosphorus was uniform between the two groups. No significant (P > 0.05) difference in onset of ovarian cyclicity between the 2 groups was observed, whereas buffaloes with SCE had longer (P = 0.001) median days open (141 days) than their counterpart (117 days). The first service conception rate, cumulative pregnancy rate, and pregnancy rate at 150 days postpartum were lower (P < 0.05) in buffaloes with SCE than without SCE group. In summary, higher BHBA and lower serum concentrations of glucose, albumin, urea, and calcium control onset of subclinical endometritis which in turn has negative impact on fertility of buffaloes.

Effects of metritis treatment strategies on health, behavior, reproductive, and productive responses of Holstein cows.

Our objectives were to compare the effects of ceftiofur crystalline free acid (CCFA) and ampicillin trihydrate (AMP) treatments of cows diagnosed with metritis on uterine health, behavior, reproductive, and productive responses. A controlled randomized clinical trial was designed. Metritis was defined as vaginal discharge (VD) = 5 (fetid, watery, red/brown) within 21 d in milk (DIM) and rectal temperature (RT) <39.5°C, whereas VD = 5 and RT ≥39.5°C was defined as puerperal metritis. On the day of diagnosis (d 0), cows were paired by parity and severity of metritis (metritis vs. puerperal metritis) and assigned randomly to the AMP and CCFA treatments. Cows enrolled in the AMP (n = 308) treatment were moved to a nonsalable-milk pen, where they were treated once daily for 5 d, and were moved back to their original pen 72 h after the last treatment (d 7). Cows enrolled in the CCFA (n = 310) treatment remained in their original pen and received 2 treatments of CCFA, 72 h apart. Rectal temperature was measured daily from d 0 to 6 and on d 11. Vaginal discharge was evaluated on d 4, 6, and 11 to assess cure. Cure was defined as the absence of treatment with additional antimicrobial before experiment d 11, VD <5, and RT <39.5°C. Cows were examined at 28 ± 3 DIM for purulent VD (PVD) and at 35 ± 3 DIM for cytological endometritis. Pregnancy was diagnosed at 40 ± 3 and 60 ± 7 d after first and second artificial inseminations. Cure of metritis did not differ between treatments on d 11 (AMP = 64.6 ± 3.1, CCFA = 63.5 ± 3.1%). Cows treated with AMP had greater RT from experiment d 1 to 6 compared with cows treated with CCFA (AMP = 39.1 ± 0.02, CCFA = 39.0 ± 0.02°C). Cows in the AMP treatment had greater prevalence of PVD at 28 ± 3 DIM (AMP = 82.6 ± 2.3, CCFA = 74.4 ± 2.7%) and tended to have greater prevalence of cytological endometritis at 35 ± 3 DIM (AMP = 77.8 ± 6.2 vs. CCFA = 61.7 ± 7.5%) than CCFA-treated cows. Treatment did not affect the hazard of pregnancy among multiparous cows; however, among primiparous cows, CCFA treatment reduced the hazard of pregnancy and increased the median days to pregnancy (AMP = 145 vs. CCFA = 169 d). Finally, average daily milk yield up to 14 wk postpartum was not affected by treatment (AMP = 38.0 ± 0.4, CCFA = 37.5 ± 0.4 kg). We conclude from the current experiment that CCFA was more effective in reducing RT and improving uterine health of metritic cows; however, the improved hazard of pregnancy of primiparous cows treated with AMP is important and warrants further investigation.

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.

Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review.

PURPOSE: Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment. METHODS: The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway. RESULTS: CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua. CONCLUSION: This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

Effects of endometritis on reproductive performance of zero-grazed dairy cows on smallholder farms in Rwanda.

Endometritis is a prevalent post-partum uterine infection in dairy cows resulting in suboptimal reproductive performance. The hypothesis was that endometritis status is associated with suboptimal reproductive performance of postpartum dairy cows managed under zero-grazing feeding practice on smallholder farms. In this study, there was evaluation of effects of endometritis diagnosed at 38.5 ±â€¯14.7 days postpartum (dpp) on subsequent reproductive performance. Reproductive performance of 436 cows from 345 farms was recorded for 210 dpp. Values for reproductive performance indicators were less (P < 0.05) in cows determined to be positive compared to negative for endometritis. Cows that tested positive, as compared to negative, for endometritis had longer periods after parturition until initiation of oestrous cycles (median, interquartile range; 85.0, 57.5-127.0 and 62.6, 49.0-90.0 days, respectively), longer durations before being detected pregnant (95.5, 61.8-145.5 and 63.0, 50.0-83.0 days, respectively), lesser pregnancy rates as a result of the first breeding postpartum (16.5% and 32.7%, respectively), more natural-mating or artificial inseminations per pregnancy (1.3 ± 0.1 and 1.1 ± 0.0, respectively) and more occurrences of anoestrus postpartum (48.4% and 11.7%, respectively). These results provide evidence of a strong association between endometritis and suboptimal fertility performance in zero-grazed cows on smallholder farms in Rwanda. Considering there were 70.2% of cows in the present study were diagnosed with endometritis, this is indicative of a widespread herd health issue, warranting that field veterinary practitioners prioritise endometritis in their herd health service delivery to smallholder dairy farmers for effective disease management and herd sustainability.

Assessing endometrial receptivity after recurrent implantation failure: a prospective controlled cohort study.

RESEARCH QUESTION: What is the prevalence of disrupted markers of endometrial function among women experiencing recurrent implantation failure (RIF), and does the prevalence differ from a control cohort? DESIGN: Prospective controlled cohort study. In total, 86 women with a history of RIF and 37 women starting their first fertility treatment were recruited for this study. Endometrial and blood profiling were carried out in a hormone-substituted cycle using oestradiol and progesterone. Endometrial biopsies were analysed by histology, immune cell profiling, and the endometrial receptivity array (ERA®) test (Igenomix, Valencia, Spain). The vaginal microbiome was analysed using a NGS-based technology (ArtPRED, Amsterdam, the Netherlands). Blood tests included oestradiol, progesterone, prolactin, thyroid-stimulating hormone, vitamin D and anti-phospholipid antibody levels. RESULTS: Patients who had experienced RIF produced a range of test abnormalities. Compared with controls, women with RIF had a higher prevalence of chronic endometritis (24% versus 6%), a lower vitamin D level and a borderline lower progesterone level. Women who had experienced RIF had a more favourable vaginal microbiome compared with controls. Although the RIF cohort was older than the controls (mean age 33.8 years versus 30.2 years), no differences between the groups were observed in immune cell profiling and the ERA test. CONCLUSION: These data demonstrate that a single test or treatment for the endometrial factor in RIF is unlikely to be clinically effective. Diagnosing the endometrium in women with RIF permits targeted rather than blind interventions. Relative vitamin D deficiency, lower mid-luteal progesterone and chronic endometritis are ready targets for treatment. Understanding the role and treatment of an unfavourable vaginal microbiome in RIF needs further investigation.

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.

Relationship between plasma concentrations of IGF-I and clinical endometritis, and response to progesterone synchrony in dairy cows during early lactation.

The first aim of this study was to evaluate the relationship between the concentrations of plasma insulin-like growth factor-I (IGF-I) in the transition period and the incidence of clinical endometritis postpartum. The second aim was to evaluate the relationship between the concentration of plasma IGF-I in the transition period and the estrous synchrony response and pregnancy rate to a controlled internal drug release (CIDR) protocol. A total of 402 dairy cows, 250 multiparous and 152 primiparous, were enrolled. A blood sample was taken from all cows 2 and 1 wk precalving and wk 1, 3, 4, and 5 postcalving for subsequent analysis of IGF-I. Vaginal discharge score as a measurement of uterine health was recorded in wk 3, 4, and 5 postcalving. Estrous cycles of all cows were synchronized on ≥37 d in milk (mean = 59; range 37-93) using an 8-d CIDR protocol. All cows were scanned at 32 to 35 d after insemination to confirm pregnancy. Data were analyzed using Proc Mixed and Proc Logistic models in SAS (version 9.3; SAS Institute Inc., Cary, NC). Plasma IGF-I concentrations were significantly greater in the primiparous cows than in the multiparous cows, both before and after calving, and were therefore analyzed separately. In multiparous cows plasma IGF-I concentrations postcalving were significantly lower among cows with uterine infection than in those without infection, and multiparous cows with a plasma IGF-I concentration less than 40 ng/mL 1 wk after calving were 3 times more likely to suffer from a uterine infection 4 to 5 weeks postcalving (odds ratio 2.8; 95% confidence interval 1.0-7.6). Plasma IGF-I concentrations were significantly greater after calving in the 121 primiparous cows that exhibited estrus post-CIDR protocol (mean 125 ng/mL) than in the 25 primiparous cows that did not respond (mean 95 ng/mL). Multiparous cows with greater plasma IGF-I concentrations postcalving had a significantly greater chance of conceiving (mean plasma IGF-I concentration of conceiving cows = 86 ng/mL; nonconceiving = 70 ng/mL). These results show an association between greater concentrations of plasma IGF-I postcalving and response to CIDR protocol in primiparous animals (mean plasma IGF-I concentration of responders = 116 ng/mL; nonresponders = 95 ng/mL). In contrast no association was detected between concentrations of plasma IGF-I in relation to the response to the CIDR protocol in multiparous cows. In conclusion, changes in circulating concentrations of plasma IGF-I early postpartum may help predict reproductive status of dairy cows.

Invasive Group A streptococcal postpartum endometritis associated with multi-organ infarctions: an uncommon case presentation and literature review.

Background: Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective: To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation: This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A ß-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion: STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.

Abnormal uterine inflammation in obstetric syndromes: molecular insights into the role of chemokine decoy receptor D6 and inflammasome NLRP3.

The adaptation of the uterine environment into a favorable immunological and inflammatory milieu is a physiological process needed in normal pregnancy. A uterine hyperinflammatory state, whether idiopathic or secondary to hormonal or organic uterine disorders (polycystic ovary syndromes, endometriosis/adenomyosis and fibroids), negatively influences the interactions between decidua and trophoblast, early in gestation, and between chorion and decidua later in pregnancy. Abnormal activation of uterine inflammatory pathways not only contributes to the pathogenesis of the obstetric syndromes, i.e. recurrent pregnancy loss (RPL), pre-term delivery (PTD) and pre-eclampsia (PE), but also to correlates with severity. In this review, we summarize recent advances in the knowledge of uterine molecular mechanisms of inflammatory modulation in normal pregnancy and obstetric syndromes (RPL, PTD and PE). In particular, we focus on two regulators of uterine/placental inflammation: the NLRP3 inflammasome and the chemokines decoy receptor D6. We performed comprehensive review of the literature in PubMed and Google Scholar databases from 1994 to 2018. The available evidence suggests that: (i) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; (ii) there is a role for abnormal expression and function of D6 decoy receptor at the feto-maternal interface in cases of RPL and PTD and (iii) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets.

Endometrial CD138 count appears to be a negative prognostic indicator for patients who have experienced previous embryo transfer failure.

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.

TREM-1 deficiency attenuates the inflammatory responses in LPS-induced murine endometritis.

Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro-inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells-1 (TREM-1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM-1 expression. However, whether TREM-1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM-1 knock-out (Trem-1-/- ) mice were used to inhibit TREM-1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM-1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin-1ß (IL-1ß), IL-6, and tumour necrosis factor-α (TNF-α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM-1 on endometritis during LPS infection and indicate that blocking of TREM-1 in LPS-induced endometritis holds considerable promise for blunting excessive inflammation.

Salpingitis Impairs Bovine Tubal Function and Sperm-Oviduct Interaction.

Salpingitis is a common cause for subfertility and infertility both in humans and animals. However, the effects of salpingitis on tubal function and reproductive success are largely unknown. Therefore we set out to investigate the effects of inflammation on sperm and oocyte transport and gameto-maternal interaction in the oviduct using the bovine as a model. For this purpose, oviducts revealing mild (n = 45), moderate (n = 55) and severe (n = 45) inflammation were obtained from cows immediately after slaughter and investigated by live cell imaging, histochemistry and scanning electron microscopy. Our studies showed that endometritis was always correlated with salpingitis. Moderate and severe inflammation caused a significant increase in the thickness of tubal folds (p < 0.05). Severe inflammation was characterized by luminal accumulations of mucus and glycoproteins, increased apoptosis, loss of tight junctions and shedding of tubal epithelial cells. The mean ciliary beat frequency (CBF) in the ampulla was significantly reduced as compared to the controls (p < 0.05). The higher the grade of inflammation, the lower was the CBF (p < 0.001). In severe inflammation, spermatozoa were stuck in mucus resulting in decreased sperm motility. Our results imply that tubal inflammation impairs proper tubal function and leads to reduced sperm fertilizing capacity.

Endometritis affects chemical coding of the dorsal root ganglia neurons supplying uterus in the sexually mature gilts.

This study reports on the influence of experimentally-induced uterine inflammation on chemical phenotypes, number and distribution of neurons in the dorsal root ganglia (DRGs) innervating the uterus in sexually mature gilts. On day 17 of the first studied estrous cycle, the uterine horns were injected with retrograde tracer Fast Blue (FB). After 28 days (on an expected day 3 of third studied estrous cycle), 50 ml of either saline (group SAL) or Escherichia coli (E. coli) suspension (109 colony-forming units/ml, group E. coli) were injected into each uterine horn. In the control pigs (group CON), only laparotomy was performed. Eight days later DRGs and uteri were collected. All infected gilts developed severe form of acute endometritis. By use of double immunofluorescence labelling the numbers of uterine perikarya expressing substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) were analyzed. Injection of E. coli decreased the total number of the FB positive perykaria in the Th10-S4 DRGs. We revealed an increase in the populations of uterine perikarya coded SP+/CGRP-, SP+/NKA-, SP-/NKA+, SP+/GAL+, SP+/GAL-, SP-/GAL+, SP+/PACAP+ and SP-/PACAP+. Our results suggest that uterine inflammation affects both the spatial and neurochemical organization pattern of uterine sensory innervation. Additionally, the inflammation may affect the transmission of sensory information from uterus to spinal cord.

Changes in the blood routine, biochemical indexes and the pro-inflammatory cytokine expressions of peripheral leukocytes in postpartum dairy cows with metritis.

BACKGROUND: The aim of the present study was to clarify the changes in complete blood count, blood biochemistry, and the gene expressions of pro-inflammatory cytokines of peripheral white blood cells in postpartum dairy cows with metritis. RESULTS: The cows were assigned to the control group (n = 28) or the metritis group (n = 28), retrospectively. Blood samples were taken 7 days before the estimated parturition (- 7 d), on the day of parturition (0 d), and 7 and 30 d after parturition. There was no difference in blood indexes between the control group and the metritis group at - 7 d. The WBC, granulocytes and monocytes were generally higher at 7 and 30 d in the metritis group than the control. In comparison with the controls, all liver function parameters and triglyceride levels at 0, 7 and 30 d, and the creatinine level at 7 and 30 d were higher in cows with metritis. The concentrations of Ca and P at 0, 7 and 30 d, and of glucose at 0 d were lower for cows in the metritis group compared with cows in the control group. Among these parameters, the WBC at 30 d, the aspartate aminotransferase activity (AST) at 7 d exceeded normal ranges (WBC: 5.0 ~ 16.0 × 109/L; AST: 42.5 ~ 98 U/L), whereas the concentrations of glucose and Ca from 0 to 30 d were below normal ranges (glucose: 2.5 ~ 4.5 mmol/L; Ca: 2.2 ~ 2.5 mmol/L) in the metritis group. The gene expressions of pro-inflammatory cytokines in the metritis group were higher than those in the control group, including the IL-1α at 7d, the IL-1ß at - 7, 0 and 7 d, the IL-6 at - 7, 0, 7 and 30 d, the IL-8 at 0, 7 and 30 d, and the TNF-α at 7 and 30 d. CONCLUSION: The cows with metritis experienced systemic inflammation for 4 weeks after calving, the impaired hepatic function, and the altered metabolic status with increased triglyceride level and decreased concentrations of glucose, Ca and P.

Impact of endometritis on post-partum ovarian cyclicity in dairy cows.

Endometritis in dairy cows is a major global issue and has been associated with a decrease in reproductive performance. The aim of this study was to quantify the effect of endometritis (as defined by the presence of any abnormal vaginal discharge after 21 days post-partum) on post-partum ovarian cyclicity in dairy cows. Milk progesterone analysis was used to monitor reproductive cyclicity in 170 dairy cows across three different commercial herds. Associations between the occurrence of endometritis and the incidence risk of a variety of atypical cycle profiles during the calving to conception period were investigated to establish the importance of endometritis on post-partum ovarian activity. Endometritis increased the incidence odds of atypical ovarian profiles (P < 0.05) with prolonged luteal activity being the most affected (P < 0.05), but also showed prolonged time (3 days) to onset of luteal activity after parturition (P < 0.05). Using milk progesterone analysis, we found a relatively low incidence odds for reproductive cycle problems in healthy cows during the calving to conception period. However, the incidence odds of cycle problems, in particular prolonged luteal activity, were high in cows that had experienced endometritis, which would have significantly impaired reproductive function.