经阴道超声与宫腔镜对子宫内膜病变患者的诊断价值比较研究

目的:探讨经阴道超声与宫腔镜检查诊断子宫内膜病变的临床价值,为临床诊断子宫内膜病变提供理论依据。方法:选取2011年3月-2014年3月间我院收治的158例疑似子宫内膜病变患者,分别采用经阴道超声和宫腔镜进行检查,并以病理诊断结果为"金标准",比较两种检查方法的诊断价值。结果:病理检查结果中,143例患者被确诊为子宫内膜病变,其中子宫内膜增生23例(16.08%),子宫内膜息肉31例(21.68%),子宫粘膜下肌瘤24例(16.78%),子宫内膜癌19例(13.29%),慢性非特异性子宫内膜炎46例(32.17%)。宫腔镜对子宫内膜病变诊断的准确率为94.41%,高于阴道超声的81.12%,差异有统计学意义(P0.05),其中阴道超声和宫腔镜对子宫粘膜下肌瘤、子宫内膜癌诊断的准确率比较差异无统计学意义(P0.05),阴道超声对子宫内膜增生、子宫内膜息肉及慢性非特异性子宫内膜炎的诊断准确率均较宫腔镜降低,差异有统计学意义(P0.05)。阴道超声对子宫内膜病变诊断的特异度较宫腔镜更低(P0.05),但两者灵敏度、AUC比较差异无统计学意义(P0.05)。结论:经阴道超声诊断子宫内膜病变简单、有效,而宫腔镜诊断子宫内膜病变具有准确率以及特异度较高的特点。     

Effect of susceptibility to endometritis on specific antibody in the endometria of mares

Endometrial biopsies were collected on two occasions from mares resistant to (n = 3) and once from mares susceptible to persistent endometritis (n = 6). The endometrial tissue was minced and cultured in vitro for 24 h. No hemolytic complement activity was detected in the endometrial culture supernatant. Endometrial culture supernatant from mares with persistent endometritis contained titers of antibodies to Streptococcus zooepidemicus similar to those from resistant mares. However, the culture supernatant of biopsies from mares with endometritis was less effective (P < 0.05) at opsonizing S. zooepidemicus in vitro.     

Endometritis in the mare: A comparison between reproductive history and uterine biopsy as techniques for predicting susceptibility of mares to uterine infection

Thirty mares with no clinical signs of endometritis were categorized as being susceptible or resistant to uterine infection depending on whether or not they had a history of recurrent endometritis. The same mares were then independently classified as susceptible or resistant on the basis of their uterine biopsies; those with significant endometrial degeneration were considered to be susceptible to endometritis. The mares then received an intrauterine inoculation of pathogenic Streptococcus zooepidemicus . Those mares which eliminated bacteria by 10 d after inoculation were considered truly resistant to endometritis, whereas those still infected at 10 d were considered susceptible. The original classifications based on history or biopsy were compared to the inoculation results. A history of recurrent endometritis provided a more sensitive (0.90) and specific (0.95) indication of susceptibility to uterine infection than a uterine biopsy with significant endometrial degeneration (sensitivity 0.5, specificity 0.75).     

Prevalence of endometritis and its effects on reproductive performance of dairy cows

Hostein cows (n=141) in five commercial dairy herds in central New York were examined for endometritis by examination of endometrial aspirates for presence of inflammatory cells, principally neutrophils, by endometrial cytology at 40-60 days postpartum. The prevalence of cytologically-diagnosed endometritis was 53%; within herds the prevalence varied from 37 to 74% (P=0.02). There was excellent agreement between two examiners (Kappa=0.864; P<0.0001). Parity did not influence prevalence of endometritis (P=0.53). Cytologically diagnosed endometritis was associated with profoundly impaired reproductive performance; Kaplan-Meier survival analysis revealed lower overall pregnancy rate (P<0.0001). Median days open was 206 for cows with endometritis and 118 for cows free of the condition. Overall, 76% of cows in this study became pregnant by 300 days postpartum; 63% of cows with endometritis and 89% of cows without endometritis were confirmed pregnant by 300 days postpartum (P<0.003). (For these two groups, 69, and 90% respectively, became pregnant during the duration of the study). Pregnancy to first service percentage was lower (11 versus 36%; P=0.001) for cows with than without endometritis, and these cows required more services before 50% became pregnant (3 versus 2; P=0.006). In a second study using 22 cows in a university-owned herd, the prevalence of cytological evidence of inflammation was 100% at 2 weeks postpartum, and dropped to 89, 58, and 41% at 4, 6, and 8 weeks, respectively. Endometritis diagnosed by endometrial cytology late in the voluntary waiting period was highly prevalent and exerted a profoundly detrimental effect on subsequent reproductive performance, making this condition potentially extremely costly to the North American dairy industry.     

Involvement of the plasminogen activation system in cow endometritis

The objectives of this study were to investigate the: (a) presence and activity of components of the "plasminogen activators/plasmin" system in dairy cows with or without endometritis; (b) variations in enzyme activity according to the degree of endometritis; and (c) associations between these enzymes and changes in endometrial histology after intrauterine antibiotic treatment. Endometrial biopsies were collected from anestrus (no palpable ovarian structures and milk progesterone <1 ng/ml) Holstein cows, 30-40 days postpartum. On the basis of a vaginoscopic examination, rectal palpation of the cervix and uterus, and endometrial histology, there were 92 cows with endometritis and 20 cows without endometritis. After biopsy collection, each cow was given an intrauterine infusion of 1.5x10(6) IU of procaine penicillin G. In cows with endometritis, genital tract examinations and biopsies were repeated 2 weeks later. Both plasminogen activators (PAs), tissue type (t-PA) and urokinase (u-PA), were immunologically identified in all uterine biopsies. Plasminogen activator activity (PAA) increased, whereas plasminogen activator inhibition (PAI) and plasmin inhibition (PI) decreased in proportion to the degree of inflammation. Two weeks after intrauterine treatment, PAA had decreased significantly in all cows that had reduced severity of endometrial inflammation and had increased significantly in all cows with increased severity of inflammation. The change in the degree of inflammation depended upon plasminogen activator activity; cows with higher PAA were more likely to improve. In conclusion, there was evidence for a role of the plasminogen activation proteolytic system in bovine endometritis.     

Exosome-derived uterine miR-218 isolated from cows with endometritis regulates the release of cytokines and chemokines

As an inflammation of the endometrium, endometritis can affect fertility and lead to serious economic losses in the dairy industry. Widely found in various tissues and body fluids, exosomes and exosome micro (mi)RNAs have been shown to play an important regulatory role in the immune responses. As one of differentially expressed exosome miRNAs, miR-218 is involved in the pathogenesis of bovine endometritis. The mechanisms of miR-218 in regulating the release of cytokines and chemokines in endometritis, however, are poorly understood. Exosomes were isolated from bovine uterine cavity fluid and verified by transmission electron microscopy. An in vitro lipopolysaccharide-treated cell model for bovine endometritis was then established to evaluate the correlation between exosome-derived miR-218 and the immune responses. We demonstrated that exosomes could be used to deliver miR-218 from endometrial epithelial cells (EECs) into the uterine microenvironment and adjacent recipient cells to modulate local immune responses. miR-218 packaged in the exosomes secreted from EECs acts as an inhibitor by blocking immune factors such as interleukin (IL)-6, IL-1β, tumour necrosis factor-α, the chemokines macrophage inflammatory genes (MIP)-1α and MIP-1β to maintain the immune balance in the uterus. However, uterine inflammation altered the immunoregulatory mechanism of exosome miR-218. MiR-218 is a potential biomarker for the detection of endometritis. Our findings also revealed a new mechanism for the development of endometritis in cows.     

Post-breeding inflammation and endometrial cytology in mares

Endometritis has been reported to be the third most common medical condition of horses. Timely diagnosis and treatment of endometritis in mares increases the chance of pregnancy. Exfoliative endometrial cytology is often used as a clinical tool to evaluate endometrial inflammation through detection of neutrophils. There is a lack of information on the time frame for changes in endometrial cytologic parameters following breeding. The main objectives of this article are to use current information to describe systematic analysis of endometrial cytology using standardized methods for sample collection and interpretation, and discuss how these parameters change in relationship to post-breeding interval and mare susceptibility.     

High concentrations of myeloperoxidase in the equine uterus as an indicator of endometritis

Intraluminal fluid and excessive abnormal hyperedema are regularly used for the diagnosis of endometritis in the mare, which is routinely confirmed by the presence of neutrophils on endometrial smears. Studies show a relation between neutrophils and myeloperoxidase (MPO), an enzyme contained in and released by neutrophils during degranulation or after cell lysis. This enzyme has been found in many fluids and tissues, and associated with different inflammatory pathologies in the horse. The aims of this study were to assess the presence and concentration of MPO in the equine uterus, and to investigate its relation with neutrophils, and other clinical signs of endometritis. Mares (n = 51) were evaluated for the presence of intraluminal fluid and excessive endometrial edema before breeding, and a small volume lavage and cytology samples were obtained. From 69 cycles, supernatant of the uterine flushes was analyzed with a specific equine MPO ELISA assay to measure MPO concentration. Cytology samples were used for the diagnosis of endometritis. Myeloperoxidase was present in the uterus of all estrus mares in highly variable concentrations. Myeloperoxidase concentrations were significantly (P < 0.05) higher in samples with positive cytologies and in the presence of intraluminal fluid. Occasionally, some samples with negative cytologies showed high MPO concentration, but the opposite was never observed. Cycles presenting hyperedema weren't associated with high concentration of MPO, intraluminal fluid, or positive cytology, making it a poor diagnostic tool of endometritis.     

The effects of Arcanobacterium pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo

Uterine bacterial infection after parturition causes endometritis, perturbs ovarian function and leads to infertility in cattle. Although endometritis is caused by mixed infections, endometrial pathology is associated with the presence of Arcanobacterium pyogenes. The aims of the present study were to determine the effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Heat-killed A. pyogenes did not affect the production of prostaglandin F2alpha (PGF) or prostaglandin E(2) (PGE) from endometrial explants, or purified populations of endometrial epithelial or stromal cells. However, the explants produced more PGF and PGE than controls when treated with a bacteria-free filtrate (BFF) cultured from A. pyogenes. Similarly, BFF stimulated PGF and PGE production by epithelial and stromal cells, respectively. So, BFF or control PBS was infused into the uterus of heifers (n=7 per group) for 8 days, starting the day after estrus. Emergence of the follicle wave, dominant follicle or corpus luteum diameter, and peripheral plasma FSH, LH, estradiol, progesterone, PGFM, or acute phase protein concentrations were unaffected by the BFF infusion. In the live animal it is likely that the intact uterine mucosa limits the exposure of the endometrial cells to the exotoxin of A. pyogenes, whereas the cells are readily exposed to the toxin in vitro.     

A comparison of diagnostic techniques for postpartum endometritis in dairy cattle

Holstein cows (n=221) from eight commercial dairy herds were examined for endometritis between 28 and 41 days postpartum using 5 diagnostic techniques: (1) vaginoscopy; (2) ultrasonographic assessment of uterine fluid volume; (3) ultrasonographic assessment of endometrial thickness; (4) endometrial cytology collected by cytobrush; and (5) endometrial cytology collected by uterine lavage. Concordance correlation was used to evaluate the reliability of cytobrush and lavage cytology. Cytobrush cytology was found to have the greatest intraobserver repeatability (cytobrush, rho(c)=0.85 versus lavage, rho(c)=0.76) and was chosen as the reference diagnostic test. Pregnancy data at 150 days postpartum was available for 189 cows. Survival analysis was used to determine the lowest percentage of polymorphonuclear cells associated with time to pregnancy. The sensitivity and specificity of the diagnostic techniques was determined using pregnancy status at 150 days and cytobrush cytology as the diagnostic standards. The risk of non-pregnancy at 150 days was 1.9 times higher in cows with more than 8% PMNs identified using cytobrush cytology than in cows with less than 8% PMNs (P=0.04). Twenty-one cows of 189 cows (11.1%) had >8% PMNs and were considered to be positive for endometritis. Cows with endometritis had a 17.9% lower first service conception rate (P=0.03) and a 24-day increase in median days open (P=0.04). The sensitivities of all five diagnostic tests relative to 150-day pregnancy status ranged from 7.1 to 14.3% and the specificities from 84.0 to 93.3%. Relative to cytobrush cytology, the respective sensitivity and specificity values are as follows: vaginoscopy (53.9%, 95.4%); lavage cytology (92.3%, 93.9%); ultrasonographic assessment of uterine fluid (30.8%, 92.8%); and ultrasonographic assessment of endometrial thickness (3.9%, 89.2%). Endometritis impaired reproductive performance. Cytobrush cytology was the most reliable method of diagnosing endometritis in cattle.     

Endometritis in the mare: a diagnostic study comparing cultures from swab and biopsy

The objective of this study was to compare results from endometrial culture swabs with results from culturing of endometrial biopsies. The culture results were related to cytological findings (polymorphonuclear; PMN-cells) and histological observations (PMN-cells). Biopsy and swab samples were smeared on the surface of a blood agar petri dish, and examined for growth of bacteria. Cytology samples were obtained from endometrial biopsies, stained and examined under microscopy for the presence of PMN-cells. Endometrial biopsies were examined for the presence of PMN-infiltration of the endometrial luminal epithelium and the stratum compactum. Using the presence of PMNs in a tissue specimen as the "best standard" for diagnosing endometritis, the sensitivity of bacterial growth from an endometrial biopsy was 0.82. The sensitivity for cytology was 0.77, and the sensitivity of bacterial growth from an endometrial surface swab was 0.34. The specificity for biopsy cultures, swab cultures, and cytology to diagnose endometritis were 0.92, 1.0, and 1.0 respectively. The positive predictive value for biopsy cultures, swab cultures, and cytology were 0.97, 1.0, and 1.0 respectively. The negative predictive value for biopsy cultures, swab cultures, and cytology were 0.67, 0.44, and 0.62 respectively. In conclusion, bacteriological culture and cytology from an endometrial biopsy provide the practitioner with the most accurate results regarding both sensitivity and positive predictive value.     

Endometritis Increases Pro-inflammatory Cytokines in Follicular Fluid and Cervico-vaginal Mucus in the Buffalo Cow

Emerging evidence shows that some of the pro-inflammatory cytokines are elevated not only in the endometrium but also in the follicular fluid of cows with endometritis. Developing a cervico-vaginal mucus (CVM) based test has the potential for becoming a pen-side test because of the ease of sample collection. The present study describes the results of two different experiments. The first experiment was conducted to investigate the influence of endometritis on the proinflammatory cytokines of follicular fluid based on the reproductive tracts of buffalo collected at a slaughter house Buffalo genitalia were categorized into purulent endometritis (PE), cytological endometritis (CE), and non-endometritis (NE) based on the white-side test and endometrial cytology, respectively (n?=?14/group). Each group was subdivided into follicular and mid-luteal stage (n?=?7/stage) and the follicular fluid was collected from the largest follicle. Second experiment was done to study the difference in the levels of proinflammatory cytokines in the CVM of repeat breeders with subclinical endometritis presented to the clinic. CVM was collected from the repeaters (n?=?10) and non-repeaters (n?=?10) through aseptic trans-vaginal aspiration. The pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNFα were quantitated through bovine specific ELISA kits. Significantly higher concentrations of pro-inflammatory cytokines (IL-1β, IL-8, IL-6, and TNFα) along with low intra-follicular estradiol in buffaloes of PE and CE groups suggest that endometritis impedes the follicular steroidogenesis. Significantly higher concentration of IL-1β and TNF-α in the CVM of repeaters indicate their potential as a pen-side diagnostic test for CE.     

Effect of a povidone-iodine intrauterine infusion on progesterone levels and endometrial steroid receptor expression in mares

Background  

Intrauterine infusions have been widely used for the treatment of endometritis in the mare. Nevertheless, their consequences on endocrine and endometrial molecular aspects are unknown. We studied the effect of a 1% povidone-iodine solution intrauterine infusion on progesterone levels, endometrial histology and estrogen (ERα) and progesterone (PR) receptor distribution by immunohistochemistry.     

Endometrial expression of selected transcripts involved in prostaglandin synthesis in cows with endometritis

Several cytokines and prostaglandins play an important role in preparing the endometrium for implantation and mediating pro-inflammatory events. The aim of the present study was to examine mRNA expression of interleukin 1α (IL-1α), interleukin receptor antagonist (IL-1-RN), cytosolic prostaglandin E synthase (cPGES), microsomal PGES (mPGES-1 and mPGES-2) and lipocalin-type PGDS (L-PGDS) in the bovine endometrium. Endometrial epithelium samples were collected ex vivo from cows with different status of health at day 21-27 postpartum on a dairy farm. Three groups (n = 9 animals each) were defined: (1) healthy cows with no signs of endometritis (control group), (2) cows with subclinical endometritis, and (3) cows with signs of clinical endometritis. Oestrous cycle-dependent mRNA expression pattern was investigated using bovine endometrial epithelial cells from healthy uteri collected at the abattoir. These uteri were classified into post-ovulatory, early-to-mid luteal, late luteal or pre-ovulatory phase (n = 8 animals for each cycle phase). After collecting endometrial epithelium using the cytobrush-method, mRNA analysis was performed by real-time RT-PCR. L-PGDS, IL-1α and IL-1-RN mRNA were expressed significantly higher (P < 0.05) in the endometrium of cows with subclinical or clinical endometritis compared with healthy cows. A twofold lower cPGES mRNA expression (P < 0.05) was detected in cows with subclinical endometritis compared to healthy cows. L-PGDS and IL-1-RN mRNA expression was increased (P < 0.05) after ovulation compared with the pre-ovulatory or luteal phase, respectively. These results support the hypothesis that a dys-regulated cytokine and/or prostaglandin profile in the uterus could be induced by subclinical endometritis or clinical endometritis.     

Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic

In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes in bitches with endometrial hyperplasia were lower than those of normal bitches both before and after treatment with postmating antibiotic (P = 0.04 and < 0.01, respectively). Mating-induced endometritis in bitches with endometrial hyperplasia appears to affect fertility by reducing the uterine vasodilatory response to mating and delaying clearance of uterine fluid as a result of decreased uterine contractions but the effect can be ameliorated in part by the postmating administration of antibiotic.     

Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows

The objectives of the study were to validate the use of endometrial cytology (EC) and ultrasonography (US) to diagnose subclinical endometritis in clinically normal postpartum dairy cows, and to measure the impact of subclinical endometritis on reproductive performance. Holstein cows from two dairy farms were examined at Visit 1 (V1) at 20-33 days in milk (DIM), and clinically normal cows (n = 228), based on the absence of abnormal discharge on external inspection and vaginoscopy, were selected. The reproductive tract of selected cows was evaluated by transrectal palpation, US and EC. All cows in the study were re-examined at Visit 2 (V2) at 34-47 DIM (2 weeks after V1) and were subsequently followed for a minimum of 8 months (until pregnant or culled). Survival analysis was used to derive a case definition of subclinical endometritis, based on factors associated with decreased relative pregnancy rate. Positive EC at V1 (>18% polymorphonuclear leukocytes; PMN) or fluid in uterus at V1 (FIU1) were associated with a significant reduction in the relative pregnancy rate and identified cows with subclinical endometritis. Similarly, a positive EC (>10% PMN) at V2 or fluid in the uterus at V2 (FIU2), identified cows with subclinical endometritis. Cows with subclinical endometritis at V1 and at V2 had a relative pregnancy rate of 41 and 51% (hazard ratio for pregnancy of 0.59 and 0.49), respectively, compared to cows without subclinical endometritis. Given EC or US findings, no diagnostic criteria based on transrectal palpation of the uterus had predictive value for risk of pregnancy. In conclusion, subclinical endometritis, diagnosed by EC or US, was associated with reduced relative pregnancy rate.     

A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows

Clinical endometritis in dairy cows is defined as mucopurulent or purulent vulvar discharge 21 days or more after parturition. The diagnosis of clinical endometritis is commonly based on vaginal examination. Techniques to reduce the proportions of false negative findings have been described. This paper discusses a clinical approach to determine the proportion of false positive findings that might occur by vaginal inspection. The consequences of false positive findings in dairy practice are unnecessary or inadequate treatments. In research, incorrect diagnoses have an impact on the interpretation of studies on the diagnosis and treatment of clinical endometritis. The objective of the present study was to compare intrauterine bacteriology and endometrial cytology in cows diagnosed with clinical endometritis with findings obtained by vaginoscopy. Clinical endometritis was defined as mucopurulent or purulent vulvar discharge. On two commercial dairy farms, cows were examined 21 to 28 d postpartum. Uterine samples (n = 230) were collected from cows with clinical endometritis with the cytobrush technique to determine the proportion of polymorphonuclear neutrophils (PMN) and to culture smears for aerobic bacteria. Two threshold values for the proportion of PMN (5 and 18%) were chosen as possible indicators for an inflamed endometrium. Common uterine pathogens A. pyogenes and E. coli were found in 33.5 and 10.4% of the samples, respectively. With increasing vaginal discharge score, proportion of samples positive for A. pyogenes increased significantly. The proportion of cows exceeding the thresholds for PMN increased with vaginal discharge score and the presence of A. pyogenes.Considering only the presence of aerobic uterine pathogens and a proportion of PMN above the threshold values of 5 and 18% as indicative for endometritis, a proportion of 17.3 and 28.5%, respectively, of diagnoses by vaginoscopy were false positive.     

The characteristics of local immunity in Chlamydia-associated chronic inflammatory diseases of the organs of the lesser pelvis in women

Local immune reactions in 107 women with Chlamydia-associated chronic endometritis and salpingo-oophoritis were studied on endometrial biopsy specimens. Of these women, group 1 consisted 45 patients with Chlamydia-associated chronic endometritis and salpingo-oophoritis and group 2 consisted of 62 such patients having, in addition, bacterial vaginosis and candidiasis. Among associated bacteria, epidermal staphylococci, Escherichia coli and their combinations prevailed. Pathomorphologically, in the biopsy specimens taken from the patients of group 1 a decrease in the activity of mononuclear phagocytes, secondary SIgA deficiency with the level of IgA-producing plasmocytes relatively unchanged, the moderate intensity of the synthesis of IgG and a shift in the ratio of T-helpers/T-suppressors towards the latter were observed. In the biopsy specimens of the uterine mucosa obtained from group 2 a decrease in the phagocytic activity of neutrophil granulocytes and macrophages, the pronounced suppression of IgA production by IgA plasmocytes with a sharp decrease in the amount of SIgA and an essential increase in the number of IgG-producing cells were noted. Disturbances of local immunity, observed in the presence of associated Chlamydia infection, gives grounds for the inclusion of immunomodulating preparations into the complex of therapeutic measures.