William B. Ley. D.V.M., M.S. D.
Phillip Sponenberg,
D.V.M., Ph.D.
Virginia-Maryland Regional College of Veterinary
Medicine
Virginia Polytechnic Institute
and
State University
Blacksburg, Virginia 24061
Twenty-one mares of light horse breeding were evaluated by endometrial cytology and biopsy and randomly assigned to either treatment or control groups. Mares in the control group were given intra-uterine infusion of sterile saline (60ml) for three consecutive days; mares in the treatment group were given were given intra-uterine infusion of 5% Dimethyl Sulfoxide (DMSO) in sterile saline (60ml) for three days. Each mare was reevaluated at 10 days and again at 30 days post-infusion therapy. The results revealed no deleterious effect upon endometrial histology. In the control group, 2 out of ten mares (20%) mares revealed improvement in biopsy grading. In the treatment group, 6 of 11 (54.5%) mares revealed improvement in biopsy grading.
Therapy of inflammatory disease of the equine endometrium has been limited to: (a) elimination of predisposing causes; (b) antibiotic therapy, (c) antiseptic solution therapy, (d) hormonal therapy and (e) therapy for the enhancement of uterine defense mechanisms (i.e. colostrum or plasma infusion)(1,2). Therapy for the degenerative changes of the of the equine endometrium are limited and have been restricted to to chemical or mechanical currettage with some success rates reported as high as 80% following endometrial regeneration (3). The use of local anti- inflammatory therapy in the equine uterus has not been extensively studied. Such adjunctive intra-uterine therapy therapy utilizing Dimethyl Sulfoxide (DMSO) has been reported, but only as a penetrating agent to carry other drugs into the endrometrium; with regard to equine intra- uterine therapy, its effectiveness and safety are unknown (!). The following trial was designed to study the effect of DMSO when used alone by intra-uterine infusion in the mare, and to evaluate histologic changes, if any, following its use.
Twenty-one non pregnant mares of light horse breeding ranging in age from 3 to 18 years were utilized in this study. Initial evaluations were performed to determine the following: (a) observations of perineal confirmation and predisposition for pneumovaginia; (b) rectal palpation of internal genitalia to determine non-gravid uterine tract and presence of palpable ovarian follicular activity; (c) collection of endometrial cytology, culture and biopsy.
Endometrial cytology was performed as previously described (a,4,5) and used in concert with culture result for interpretation of inflammatory uterine disease.
Endometrial biopsy was performed according to the technique described by Kennedy; (6) histologic interpretation was made by a singular pathologist familiar with clinical physiology and pathology of the reproductive tract of the mare as suggested by Doig and Kennedy (6,7).
Procedure as previously described was performed
Reproductive evaluations were repeated for each mare in each group at 10 and 30 days following their last respective intra-uterine infusion. Samples submitted for histopathology were not identified according to group and mare identification was coded separately to minimize subjective bias by the pathologist. Study was completed in 45 to 60 days to eliminate the effect of season
Results for the control group of mares are summarized in table 1. Ten mares were evaluated; two mares showed improvement in endometrial biopsy grading during the 30 days post-infusion vs initial. Two mares revealed a worsened biopsy grade at both the 10 and 30 day following exams; the remaining 6 mares showed no change in biopsy grading.
Results for the treatment group are presented in table 2. Eleven mares were evaluated; 6 mares showed improvement in the endometrial grading during the 30 days post treatment vs. initial. NO MARE WERE FOUND TO REGRESS OR WORSEN IN BIOPSY GRADE AS A RESULT OF THIS THERAPY. Five mares revealed no change in grading however two of these 5 were normal (i.e. grade 1) at the outset, having no room for improvement.
There was a significant difference between the treatment group vs. control group in numbers of mares improving in biopsy grade at 30 days post-therapy. These results are presented in table 3.
Dimethyl Sulfoxide use in veterinary medicine has been limited to topical and occasional intravenous routes to administration; its use in equine and small animals practice has recently been reviewed. After 20 years of research and clinical trials involving DMSO as a biological and medicinal agent, its multiplicity of effects within biological systems is known to include: an oxidant/reductant effect, a hydroxyl radical (OH-) scavenger, analgesia, anti-inflammatory, anti-collagen, diuretic, vasodilation, smooth muscle myotropic, CNS sedation, anti-psychotic/anti anxiety effect, bacteriostatic, anti-neoplastic and protective against tissue ischemia by stabilizing biological membranes. Its use in the reproductive tract in the mare has not received controlled clinical trials. however one source reported a clinical benefit of increased pregnancy rate following intravenous therapy of barren mares. Its toxicity is regarded as minimal when used within defined clinical guidelines.