[Show abstract][Hide abstract]ABSTRACT: Persistent endometritis in the mare is associated with hypersecretion of mucus by endometrial epithelium and migration of neutrophils into the uterine lumen. This study examines the relationships between N-acetylcysteine (NAC), a mucolytic agent with anti-inflammatory properties, and endometrial architecture, serum neutrophil function, post-breeding therapy, and reproductive performance of NAC-treated mares in a clinical setting. In study 1, endometrial biopsies from mares receiving intrauterine saline (fertile-control, n = 6) or 3.3% NAC (fertile-treatment, n = 6; barren-treatment, n = 10) were evaluated by histology and image analysis. In study 2, phagocytic activity of serum-derived neutrophils was measured after adding 0.5% or 3% NAC. In study 3, pregnancy rates of repeat breeders (n = 44) receiving an intrauterine infusion of 3.3% NAC 24-36 hours before mating (group 1) was recorded, as was first cycle of the season pregnancy rates of reproductively normal mares (group 2, n = 85), and mares treated for bacterial endometritis the cycle before mating (group 3, n = 25). Intrauterine NAC did not adversely affect endometrial histology. Extracellular mucus thickness and staining intensity were reduced in fertile-treatment mares (P < 0.03). Neutrophil function was inhibited by 3% NAC solution, but not by 0.5% NAC (P < 0.05). In study 3, for groups 1, 2, and 3, respectively, the first-cycle pregnancy rates were 77%, 74%, and 56%, and early embryonic death rates were 15%, 13%, and 7%. In group 2 mares treated with uterine lavage and oxytocin post-mating, the pregnancy rate was 89% (39/44), whereas in mares treated with uterine lavage and 1 g ceftiofur, it was 60% (24/40). Of the oxytocin-treated mares, 18% (8/44) had ≥1 cm of intrauterine fluid or marked uterine edema, whereas 80% (32/40) of the antibiotic-treated mares did. In conclusion, intrauterine infusion of a 3.3% solution of NAC was not irritating and inhibited the oxidative burst of neutrophils. Repeat breeder mares, with evidence of mucus hypersecretion, but no uterine pathogens, when treated with NAC followed by post-mating uterine lavage and oxytocin (and in some cases intrauterine antibiotics), achieved a pregnancy rate of 77%.
[Show abstract][Hide abstract]ABSTRACT: Reasons for performing studyMares diagnosed with twin vesicles at 13-17 days after ovulation commonly have one of 2 vesicles manually reduced. It is not known whether vesicle location (adjacent vs. nonadjacent), mare age, mare reproductive status, parity, month of breeding or mare plasma progesterone concentration affects live foal rates. Objectives
To determine factors associated with a positive outcome (live foal) in mares undergoing manual twin reduction between 13 and 17 days post ovulation when performed by a single operator. Study designRetrospective case-control study. Methods
Breeding records and the Jockey Club records of registered Thoroughbreds were used to evaluate factors affecting the outcome of pregnancies in mares undergoing twin elimination and mares with singleton pregnancies. Thoroughbred mares with twin pregnancies (n = 129) were matched by age, parity, farm location and month bred with mares diagnosed with a singleton pregnancy (n = 127). The effects of location of embryonic vesicles, mare age, reproductive status, parity, month of breeding, vesicle size and plasma progesterone concentration at pregnancy diagnosis on live foal rate were examined. ResultsPosition of embryonic vesicles at time of manual elimination, parity and month bred had no effect on live foal rate. Live foal rates in mares >9 years of age were lower (71.8%) than in all mares 9 years (87.1%; P<0.05). Mares >9 years of age that had a twin reduced lost more pregnancies (34.8%) than age-matched control mares (20.0%; P<0.005). Mean plasma progesterone concentration of twin-reduced mares was greater than in control mares when compared on the same day post ovulation. Plasma progesterone concentrations did not differ between mares that lost their pregnancy and those that delivered a live foal. Conclusions
Mare age of >9 years is associated with decreased pregnancy rate after twin reduction. Potential relevanceFurthering the understanding of factors that affect live foal outcome following manual twin elimination in mares. The Summary is available in Chinese - see Supporting information.
[Show abstract][Hide abstract]ABSTRACT: Supplementation with L-arginine can increase uterine arterial blood flow and vascular perfusion of the preovulatory follicle in mares. Increased vascular perfusion of the preovulatory follicle has been correlated to successful pregnancy in mares. The objective of this study was to determine if supplemental L-arginine would increase ovarian arterial blood flow, vascular perfusion of the preovulatory follicle and embryo recovery rates in mares. Mares were blocked by age and breed and assigned at random within block to L-arginine supplementation or control groups. Mares were fed L-arginine beginning 17 d prior and through the duration of the study. Transrectal Doppler ultrasonography was used to measure ovarian arterial blood flow and vascular perfusion of the preovulatory follicle daily once it reached 35 mm and subsequent corpus luteum on Days 2, 4 and 6. Mares once achieving a follicle ≥ 35mm follicle were bred via artificial insemination and an embryo collection was attempted 7 d after ovulation. Treatment did not affect interovulatory interval (arginine treated: 18.1 ± 2.6 d, control: 20.7 ± 2.3 d) or embryo recovery rate (arginine-treated: 54%, control: 48%). Mares treated with L-arginine had a larger follicle for the 10 d preceding ovulation than control mares (30.4 ± 1.2 and 26.3 ± 1.3 mm, respectively; P < 0.05) and vascular perfusion of the dominant follicle tended (P = 0.10) to be greater for the 4 d prior to ovulation. No differences were observed between groups in diameter or vascular perfusion of the corpus luteum. Resistance indices, normalized to ovulation, were not significantly different between groups during the follicular or luteal phase. Oral L-arginine supplementation increased the size and tended to increase perfusion of the F1, but had no effect on luteal perfusion or embryo recovery rates in mares.
Full-text available · Article · Jan 2013 · Theriogenology
[Show abstract][Hide abstract]ABSTRACT: Objective-To assess survival-to-discharge rates of mares and foals and postoperative complications and fertility in mares following cesarean section (C-section). Design-Retrospective case series. Animals-95 mares. Procedures-Medical and breeding records of mares that underwent C-section were reviewed; signalment, surgical technique, complications, survival-to-discharge rate, and pregnancy and foaling rates were recorded and evaluated. Foaling rates in the 3 years after C-section were compared with the cumulative foaling rate before C-section. Results-C-section was performed because of dystocia (n = 71) or concurrent maternal disease (20) or was elective (4). Overall survival-to-discharge rate was 84% (80/95) for mares and 35% (28/80) for foals. Six of 15 mares that had partial fetotomies prior to C-section did not survive. Mares that had dystocia for < 90 minutes had the fewest complications. Cumulative foaling rate before C-section was 77% (394/509). Overall foaling rate for the 3 years after C-section was 52% (30/58) and 68% (13/19) when duration of dystocia was ≥ 90 minutes and < 90 minutes, respectively, and was 31 % (9/29) for mares ≥ 16 years old. Foaling rate was significantly lower for mares bred in the same year as C-section than for mares bred in later years. Conclusions and Clinical Relevance-Breeding in the same year as C-section, dystocia for ≥ 90 minutes before C-section, and mare age ≥ 16 years were associated with poor foaling rates. Prognosis for delivery of a live foal in years following C-section was good if duration of dystocia was < 90 minutes and the mare was < 16 years old at the time of surgery.
Article · Oct 2012 · Journal of the American Veterinary Medical Association
[Show abstract][Hide abstract]ABSTRACT: Ascending placentitis results in premature birth and high foal mortality. By understanding how placentitis induces premature delivery, it may be possible to develop diagnostic markers and to delay premature delivery pharmacologically, thereby decreasing perinatal foal mortality.
To identify relationships between bacterial infection, inflammation and premature parturition in mares with experimentally induced placentitis.
Experiment 1: Concentrations of allantoic fluid prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical inoculation with Streptococcus equi ssp. zooepidemicus (at Days 285-291 of gestation) until parturition and compared with controls (n = 4). Experiment 2: mRNA expression of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-8 in the chorioallantois from inoculated mares in Experiment 1 were compared with 7 mares that foaled normally.
Bacterial inoculation resulted in 7 aborted fetuses and birth of one premature, viable foal. Infection was associated with inflammation of the chorioallantois in the region of the cervical star, isolation of bacteria and high concentrations of PGE2 and PGF2alpha in allantoic fluid obtained within 48 h of delivery (P = 0.04). Chorioallantois from all mares expressed mRNA for IL-8, TNF-alpha, IL-6 and IL-1beta. Experimentally infected mares expressed more mRNA for IL-6 (P = 0.003) and IL-8 (P = 0.009) in the cervical star region and more mRNA for IL-6 (P = 0.004) in tissues from placental horns than control mares.
Bacterial placentitis may result in liberation of cytokines from the chorioallantois and prostaglandin formation leading to abortion or birth of a precociously mature foal.
Full-text available · Article · Feb 2012 · Equine Veterinary Journal
[Show abstract][Hide abstract]ABSTRACT: The objective was to determine if long-term treatment with trimethoprim sulfamethoxazole (antimicrobial), pentoxifylline (anti-inflammatory/anti-cytokine) and altrenogest (synthetic progestin), would improve pregnancy outcome in mares with experimentally induced placentitis. Seventeen normal, pregnant pony mares were enrolled in the study at 280-295 d of pregnancy. Placentitis was induced in all mares by intra-cervical inoculation of Streptococcus equi subsp. zooepidemicus (10(7) CFU). Five mares served as infected, untreated control animals (Group UNTREAT). Twelve mares (Group TREAT) were infected and given trimethoprim sulfamethoxazole (30 mg/kg, PO, q 12h), pentoxifylline (8.5 mg/kg, PO, q 12h) and altrenogest (0.088 mg/kg, PO, q 24h) from the onset of clinical signs to delivery of a live foal or abortion. Blood samples were cultured from all foals at delivery and fetal stomach and thoracic contents were obtained for culture from dead fetuses. More mares in Group TREAT delivered viable foals (10/12; 83%; P < 0.05) than mares in Group UNTREAT (0/5; 0%). Ten of 12 foals (83%) in Group TREAT had negative blood cultures at birth. All foals in Group UNTREAT (5/5; 100%) had positive cultures from one or more samples (blood, stomach contents, and thoracic fluid). Bacteria were recovered from uterine culture samples in both groups. Streptococcus equi subsp. zooepidemicus was the predominant organism recovered from fetal/foal or mare culture samples. The authors inferred that administration of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest may improve the viability of foals from mares with experimentally induced placentitis.
Full-text available · Article · Aug 2010 · Theriogenology
[Show abstract][Hide abstract]ABSTRACT: Contents:
Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cytokines. It must be instituted early if a pregnancy is to be saved. Treatments include antibiotics, tocolytics and immunomodulators. Prompt, aggressive treatment with antibiotics has improved foal viability in experimental models of placentitis.
Article · Jun 2010 · Reproduction in Domestic Animals
[Show abstract][Hide abstract]ABSTRACT: Contents:
Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post-mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response.
Article · Jun 2010 · Reproduction in Domestic Animals
[Show abstract][Hide abstract]ABSTRACT: Antibiotics are infused into the uterine lumen, added to semen extenders and given systemically for infections of the reproductive tract of the mare and stallion. Evidence-based guidelines for determining treatment length and route of administration are limited and use is frequently based on convenience or tradition. Current recommended antibiotic use for the treatment of bacterial and fungal endometritis, placentitis and metritis in the mare and genital infections of the stallion are presented. Antibiotic classes used for reproductive problems are also reviewed.
[Show abstract][Hide abstract]ABSTRACT: Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA-Tris), mucolytics (DMSO, kerosene, N-acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes).
Article · Sep 2009 · Reproduction in Domestic Animals
[Show abstract][Hide abstract]ABSTRACT: Placental insufficiency is regarded as the primary factor contributing to late-term abortion and perinatal death of foals. Often when problems associated with late-term pregnancy in the horse are manifest the condition is well-advanced and therapeutic intervention may not be effective in rescuing the pregnancy. If a compromised pregnancy due to placental insufficiency could be identified early, the pregnancy might be sustained through medical intervention. Because the placenta is the sole source of circulating relaxin in the mare, we hypothesized that systemic relaxin may serve as a biomarker of placental function and fetal well-being and a predictor of pregnancy outcome at delivery. To test this hypothesis we monitored plasma relaxin in mares (light breeds) with normal and problematic pregnancies from clinical cases presented to the veterinary hospital and in pregnant mares experimentally inoculated with Streptococcus equi zooepidemicus to induce uterine infection. Upon establishment of placentitis, mares were assigned to different therapeutic strategies and responsiveness was monitored. Blood was collected during the third trimester of pregnancy, and relaxin content was determined using a homologous equine relaxin radioimmunoassay. The results reported here show a positive relationship between low circulating relaxin and poor pregnancy outcome in mares with compromised placental function. While relaxin may have value as a diagnostic assay for identifying mares with high-risk pregnancies associated with placental dysfunction, the variable results obtained from mares undergoing drug treatment for experimentally induced placentitis make it difficult to determine the reliability of relaxin for evaluating therapeutic efficacy.
Article · May 2009 · Annals of the New York Academy of Sciences
[Show abstract][Hide abstract]ABSTRACT: Reproductive problems in the perinatal period can adversely affect a mare's future fertility or, worse, may be life threatening to her or her foal. A number of abnormalities can occur, including uterine torsion, uterine artery or uterine hemorrhage, retained fetal membranes, metritis, rectovaginal injuries, and necrotic vaginitis. Because hemorrhage, retained placenta, metritis, and necrotic vaginitis can happen after a normal delivery or after dystocia, all mares should be monitored closely in the first days after parturition for signs of lethargy, depression, colic, sore feet, or anorexia. Methods for diagnosing, managing, and treating these conditions and the possible complications are discussed.
Article · Nov 2008 · Journal of Equine Veterinary Science
[Show abstract][Hide abstract]ABSTRACT: Most equine infertility cases can be solved with a methodical, thorough physical and reproductive examination and appropriate diagnostic laboratory aids. Repeated examinations may be needed in some cases to identify subtle anatomical abnormalities or irregularities between hormonal and physiological relationships of the reproductive tract. For pregnancy to occur, hormonal signaling must be exquisitely synchronized with physical changes of the reproductive tract and deposition of fertile semen in the uterus. Asynchrony of these events, infection, inflammation, previous trauma to the reproductive tract or "stress" can interfere with conception or maintenance of pregnancy. Infertile mares are presented for three common problems: (1) accumulation of intra-uterine fluid during or immediately after estrus; (2) long standing infection and/or chronic inflammation; or (3) irregular or no estrous cycles. By defining the problem, diagnostics can be chosen to determine the cause. Treatment protocols should be designed around the diagnosis and antibiotics, ecbolics or steroids should not be used indiscriminately. In all cases of mare infertility, semen quality needs to be determined to be satisfactory as a subfertile stallion bred to a subfertile mare greatly decreases the likelihood of pregnancy.
[Show abstract][Hide abstract]ABSTRACT: Equine follicle stimulating hormone (eFSH) has been used to induce follicular development in transitional mares and problem acyclic mares, as well as superovulate cycling mares. The most efficacious protocol is to administer 12.5 mg eFSH, intramuscularly, twice daily beginning 5 to 7 days after ovulation when the diameter of the largest follicle is 20 to 25 mm. Prostaglandins are to be administered on the second day of eFSH therapy. Treatment with eFSH is continued for 3 to 5 days until follicle(s) are >or=35 mm in diameter. The mare is subsequently allowed to 'coast' for 36 h, after which human chorionic gonadotropin is administered to induce ovulation.
[Show abstract][Hide abstract]ABSTRACT: Low-volume uterine flush (n=401) was performed in 308 infertile mares to diagnose endometritis. Mares evaluated were either barren after three or more breedings or had two or more unsuccessful embryo recovery attempts during consecutive cycles. Culture results were compared with cytological and histological findings, efflux clarity and pH to substantiate that the micro-organisms recovered were truly pathogens. Cytological specimens were evaluated for presence of epithelial and inflammatory cells, bacteria, yeast and debris. Endometrial biopsies (n=110) were examined for the presence of neutrophils in the stratum compactum. Micro-organisms were recovered in 282/401 (70%) of low-volume flushes; E. coli was most frequently isolated (42.2%), followed by beta hemolytic Streptococcus (37.6%). Efflux clarity of 318 flushes was clear (n=109), cloudy (n=149), or mucoid (n=60). Isolation of micro-organisms was highly associated with cloudy and mucoid effluxes (P<0.001), debris on cytological specimens (P<0.001), increased efflux pH (P<0.003), and neutrophils on endometrial biopsy (P<0.01). E. coli was associated with debris on cytological smear (P<0.002), whereas beta hemolytic Streptococcus was associated with increased efflux pH (P<0.002). Using the presence of neutrophils in a tissue specimen as the "best standard" for diagnosing endometritis, the sensitivity of flush culture was 0.71 and for flush cytology was 0.8, whereas the specificity was 0.86 and 0.67, respectively. Neutrophils in uterine flushes under-reported inflammation; only 86/282 positive cultures were positive on cytology. The clinical estimate of a contaminated (false positive) flush culture was 11%, if a false positive was defined as positive culture with clear efflux and no debris or neutrophils on cytology (26/228). In conclusion, a low-volume uterine flush was a rapid, accurate method for identifying mares with chronic endometritis. When micro-organisms were recovered, endometritis was confirmed by efflux clarity, pH and cytological findings of debris, bacteria, or neutrophils. E. coli was most commonly isolated and it appeared to differ in pathogenicity from beta hemolytic Streptococcus.
[Show abstract][Hide abstract]ABSTRACT: Endometrial cytology and culture specimens (n=2123) were collected concurrently with a guarded uterine culture instrument from 970 mares (738 barren, 1230 foaling and 155 maiden mares) during three breeding seasons (2001-2004). Results were compared to the 28-d pregnancy rate for the cycle from which the samples were taken. Cytological smears were evaluated for inflammation at x100 and graded as: not inflammatory (0-2 neutrophils/field), moderate inflammation (2-5 neutrophils/field), severe inflammation (>5 neutrophils/field), or hypocellular (scant epithelial cells and no neutrophils). Uterine culture swabs were plated within 6h, incubated for 72 h and results determined at 24, 48, and 72 h. Approximately, 20% (n=423) cytology samples were positive for inflammation (>2 neutrophils), whereas approximately 11% (n=231) of cultures had microorganisms recovered. A majority (64%) of the positive cultures (147/231) had inflammation on cytology smears. Streptococcus equi subsp. zooepidemicus was associated with more positive cytology results than coliforms (P<0.01). Mares with positive cytology or culture had lower pregnancy rates than mares with normal findings (P<0.01). Lowest pregnancy rates were recorded for mares with severe endometrial inflammation (21%, versus moderate inflammation 48%). Isolation of a microorganism from mares with endometrial inflammation was not associated with a further reduction in pregnancy rates. In barren, foaling and maiden mares, cytology was positive in 28, 17, and 5%, respectively, and culture was positive in 12.2, 11.1, and 3.2%. Foaling and maiden mares had higher pregnancy rates than barren mares (62, 69, and 44%, respectively, P<0.001). In conclusion, a positive cytology was twice as common as a positive culture, and isolation of microorganisms was associated with reduced pregnancy rates, even in the apparent absence of inflammation.