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Topic:Equine Health

Equine health encompasses the study and management of diseases, disorders, and overall well-being of horses. It involves understanding various physiological systems, preventive care, and treatment strategies to maintain optimal health in equine populations. Common areas of focus include nutrition, infectious diseases, orthopedic conditions, and reproductive health. Research in equine health aims to advance knowledge on diagnostic methods, therapeutic interventions, and management practices that improve horse welfare and performance. This page collects peer-reviewed research studies and scholarly articles that explore the diverse aspects of equine health, offering insights into current findings and advancements in the field.
Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.
Journal of cardiovascular electrophysiology    January 28, 2019   Volume 30, Issue 4 596-606 doi: 10.1111/jce.13849
Carstensen H, Hesselkilde EZ, Haugaard MM, Flethøj M, Carlson J, Pehrson S, Jespersen T, Platonov PG, Buhl R.The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. ...
Low field magnetic resonance imaging of the equine distal interphalangeal joint: Comparison between weight-bearing and non-weight-bearing conditions.
PloS one    January 28, 2019   Volume 14, Issue 1 e0211101 doi: 10.1371/journal.pone.0211101
Evrard L, Audigié F, Bertoni L, Jacquet S, Denoix JM, Busoni V.This descriptive study aimed to compare the magnetic resonance appearance of the distal interphalangeal joint articular cartilage between standing weight-bearing and non-weight-bearing conditions. Ten forefeet of live horses were scanned in a standing low-field magnetic resonance system (0.27 T). After euthanasia for reasons unrelated to the study, the non-weight-bearing isolated feet were scanned in a vertical positioning reproducing limb orientation in live horses. The same acquisition settings as during the weight-bearing examination were used. Thickness and cross-sectional area of the dist...
Assessing pain in horses.
The Veterinary record    January 27, 2019   Volume 184, Issue 4 124 doi: 10.1136/vr.l385
Gleerup KB.No abstract available
Association of catastrophic condylar fracture with bony changes of the third metacarpal bone identified by use of standing magnetic resonance imaging in forelimbs from cadavers of Thoroughbred racehorses in the United States.
American journal of veterinary research    January 27, 2019   Volume 80, Issue 2 178-188 doi: 10.2460/ajvr.80.2.178
Peloso JG, Cohen ND, Vogler JB, Marquis PA, Hilt L.OBJECTIVE To compare bony changes of the third metacarpal bone (MC3) of Thoroughbred racehorse cadavers with (cases) or without (controls) catastrophic condylar fracture by use of standing MRI. SAMPLE 140 forelimbs from 26 case horses (both forelimbs) and 88 control horses (single forelimb). PROCEDURES Bone marrow lesions (BMLs), identified as a decrease in T1-weighted (T1W) signal and increases in T2*-weighted (T2*W) and short tau inversion recovery (STIR) signals, and dense bone volume percentage (DBVP), identified as decreases in T1W, T2*W, and STIR signals, in the distopalmar aspect of MC3...
Parasitic fauna of Polish konik horses (Equus caballus gmelini Antonius) and their impact on breeding: a review.
Animal health research reviews    January 27, 2019   Volume 19, Issue 2 162-165 doi: 10.1017/S1466252318000099
Slivinska K, Karbowiak G, Gawor J, Wróblewski Z, Jaworski Z, Jastrzębska E, Demeshkant V.The influence of internal and external parasites on the health of Polish konik horses housed in different types of management strategies in Poland is discussed. This study includes consolidated data of different authors from the past 50 years, supplemented by results of more recent research. A total of 38 species of helminths (i.e., 37 Nematoda and one Cestoda) and five Diptera species were recorded from the horses. Protozoan parasites, Cryptosporidium spp. and Theileria equi, and the Rickettsiales, Anaplasma phagocytophilum, were observed for the first time in Poland.
PNAG-specific equine IgG1 mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG4/7.
Vaccine    January 26, 2019   Volume 37, Issue 9 1142-1150 doi: 10.1016/j.vaccine.2019.01.028
Rocha JN, Dangott LJ, Mwangi W, Alaniz RC, Bordin AI, Cywes-Bentley C, Lawhon SD, Pillai SD, Bray JM, Pier GB, Cohen ND.Prescottella equi (formerly Rhodococcus equi) is a facultative intracellular bacterial pathogen that causes severe pneumonia in foals 1-6 months of age, whereas adult horses are highly resistant to infection. We have shown that vaccinating pregnant mares against the conserved surface polysaccharide capsule, β-1 → 6-linked poly-N-acetyl glucosamine (PNAG), elicits opsonic killing antibody that transfers via colostrum to foals and protects them against experimental infection with virulent. R. equi. We hypothesized that equine IgG might be more important than IgG for mediating protection...
Intraovarian spatial and vascular harmony between follicles and corpus luteum in monovulatory heifers, mares, and women.
Theriogenology    January 25, 2019   Volume 128 31-39 doi: 10.1016/j.theriogenology.2019.01.019
Ginther OJ.Heifers have two or three major follicular waves per interovulatory interval (IOI). In mares and women, the ovulatory wave is the only major wave in most (75%) IOI. The beginning of diameter deviation during follicle selection of the future dominant follicle (DF) is followed by continued growth of DF and decreasing growth of the future subordinate follicles. Diameter deviation in Bos taurus heifers, mares, and women begins when the future DF is a mean of 8.5, 22.5, and 10.5 mm, respectively. Selection of the ovulatory follicle occurs more frequently from right ovary (RO) in heifers and women...
Equestrian-related injuries, predictors of fatalities, and the impact on the public health system in Sweden.
Public health    January 25, 2019   Volume 168 67-75 doi: 10.1016/j.puhe.2018.11.023
Meredith L, Thomson R, Ekman R, Kovaceva J, Ekbrand H, Bálint A.Horse riding is a popular activity but has also been found to lead to many injuries and even fatalities. No reduction in the numbers of those being admitted to hospital for equestrian-related injuries have been seen in Sweden in recent years. The aim of this work was to examine injuries, fatalities, and predictors of fatalities in equestrian-related activities and to investigate the cost of these injuries to the public health system. Methods: The study is a retrospective analysis of hospital data. Methods: National Swedish hospital and mortality registers were retrospectively examined, inclusi...
The Effect of Core Abdominal Muscle Rehabilitation Exercises on Return to Training and Performance in Horses After Colic Surgery.
Journal of equine veterinary science    January 25, 2019   Volume 75 14-18 doi: 10.1016/j.jevs.2019.01.001
Holcombe SJ, Shearer TR, Valberg SJ.We conducted a retrospective cohort study to test the hypothesis that performing 4 weeks of core abdominal rehabilitation exercises (CARE) postoperatively would be safe and associated with faster return to training and improved performance after colic surgery. Performance horses that recovered from colic surgery performed by the same surgeon and survived ≥ 1 year from 2008 to 2017 were included. Data were obtained from a review of medical records. Information about the horses' rehabilitation and performance was obtained from owners/trainers. Data from horses that completed a 4-week CARE pr...
An economic analysis of a contingency model utilising vaccination for the control of equine influenza in a non-endemic country.
PloS one    January 24, 2019   Volume 14, Issue 1 e0210885 doi: 10.1371/journal.pone.0210885
Rosanowski SM, Carpenter TE, Adamson D, Rogers CW, Pearce P, Burns M, Cogger N.Equine influenza (EI) is an infectious respiratory disease of horses that has never been reported in New Zealand (NZ). However, the 2007 EI outbreak in Australia, previously EI free, spurred the NZ government and stakeholders into evaluating alternative EI control strategies in order to economically justify any future decision to eradicate or manage EI. To build on the policy debate, this paper presents an epinomic (epidemiologic and economic) modelling approach to evaluate alternative control strategies. An epidemiologic model to determine how alternative EI control strategies influence the d...
Use of standard diagnostic techniques to determine eradication of infection in experimental equine septic arthritis. Koziy RV, Yoshimura S, Dickinson R, Rybicka JM, Moshynskyy I, Ngeleka M, Bracamonte JL, Simko E.Septic arthritis is an important disease in horses, necessitating aggressive and prolonged therapy. In order to guide therapy, reliable methods of detecting the eradication of infection are needed. Therefore, the objective of this study was to investigate detection of eradication of infection in an experimental model of equine septic arthritis using standard diagnostic techniques. For this purpose, 17 adult horses were assigned to 3 experimental groups. The middle carpal joint of each horse was injected with (Septic group, = 8), lipopolysaccharide (LPS) (LPS group, = 6), or sterile saline (...
A preliminary study on the use of jenny colostrum to improve quality in extenders for freezing donkey semen.
Cryobiology    January 24, 2019   Volume 87 110-114 doi: 10.1016/j.cryobiol.2019.01.009
Álvarez C, Luño V, González N, Gil L.Sperm quality in donkeys (Equus asinus) after freezing thawing is still considered lower than that from other animals, including horses. The aim of this study was to test a new freezing extender supplemented with jenny colostrum on donkey sperm. After thawing, we evaluated sperm motility by means of computer-assisted analysis, viability by SYBR-14 and propidium iodide (PI), membrane functional integrity by HOS-test and acrosome integrity by isothiocyanate conjugated with peanut agglutinin (FITC-PNA) and PI. Ejaculates were collected from five fertile Donkeys. Sperm samples were pooled, diluted...
Effects of body weight gain on insulin and lipid metabolism in equines.
Domestic animal endocrinology    January 24, 2019   Volume 68 111-118 doi: 10.1016/j.domaniend.2019.01.003
Blaue D, Schedlbauer C, Starzonek J, Gittel C, Brehm W, Einspanier A, Vervuert I.The objective of this study was to illuminate the changes in serum NEFA concentrations during a combined glucose-insulin test (CGIT) and basal serum triacylglycerides (TGs) with increasing BW in Shetland ponies and warmblood horses. Therefore, basal blood samples were taken during fasting and a CGIT was performed in 19 healthy equines (10 Shetland ponies, 9 warmblood horses) (t0). After one (t1) and two (t2) year(s) of receiving 200% of their maintenance metabolizable energy requirement, procedures were repeated in the same equines. Sixteen of 19 equines had no signs of insulin dysregulation c...
Modelling of oscillatory cortisol response in horses using a Bayesian population approach for evaluation of dexamethasone suppression test protocols.
Journal of pharmacokinetics and pharmacodynamics    January 23, 2019   Volume 46, Issue 1 75-87 doi: 10.1007/s10928-018-09617-0
Held F, Ekstrand C, Cvijovic M, Gabrielsson J, Jirstrand M.Cortisol is a steroid hormone relevant to immune function in horses and other species and shows a circadian rhythm. The glucocorticoid dexamethasone suppresses cortisol in horses. Pituitary pars intermedia dysfunction (PPID) is a disease in which the cortisol suppression mechanism through dexamethasone is challenged. Overnight dexamethasone suppression test (DST) protocols are used to test the functioning of this mechanism and to establish a diagnosis for PPID. However, existing DST protocols have been recognized to perform poorly in previous experimental studies, often indicating presence of ...
Serum protein expression in Equine Glandular Gastric Disease (EGGD) induced by phenylbutazone.
The Journal of veterinary medical science    January 23, 2019   Volume 81, Issue 3 418-424 doi: 10.1292/jvms.18-0679
Tesena P, Yingchutrakul Y, Roytrakul S, Wongtawan T, Angkanaporn K.Equine Glandular Gastric Disease (EGGD) is a common disease in sport horses. This disease might be associated with usage of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating inflammatory diseases. Although gastroscopy has been an effective method for diagnosis, but a less invasive, and inexpensive method is preferred. This study used proteomic technology to identify candidate serum proteins that might be used as markers of NSAIDs induced EGGD. Five Thoroughbred horses were given high doses of NSAID, phenylbutazone to treat lameness. The experiment was divided into three periods: (i) P...
Validation of an immunoblot assay employing an objective reading system and used as a confirmatory test in equine infectious anaemia surveillance programs.
Journal of virological methods    January 23, 2019   Volume 266 77-88 doi: 10.1016/j.jviromet.2019.01.012
Equine infectious anaemia (EIA) is a blood borne disease that is listed among the notifiable diseases of the World Organisation for Animal Health (OIE). EIA is also regulated by the OIE for the international trading provisions and is generally subject to control programmes. Since 2011, Italy has been conducting a surveillance plan based on a three-tier diagnostic system, using a serological ELISA as screening test, an agar gel immunodiffusion test (AGIDT) as a confirmatory method, and an immunoblot (IB) as an alternative confirmatory assay for discordant results between the first two tests. As...
Persistence of fluorescent nanoparticle-labelled bone marrow mesenchymal stem cells in vitro and after intra-articular injection.
Journal of tissue engineering and regenerative medicine    January 23, 2019   Volume 13, Issue 2 191-202 doi: 10.1002/term.2781
Grady ST, Britton L, Hinrichs K, Nixon AJ, Watts AE.Mesenchymal stem cells (MSCs) improve the osteoarthritis condition, but the fate of MSCs after intra-articular injection is unclear. We used fluorescent nanoparticles (quantum dots [QDs]) to track equine MSCs (QD-labelled MSCs [QD-MSCs]) in vivo after intra-articular injection into normal and osteoarthritic joints. One week after injection of QD-MSCs, unlabelled MSCs, or vehicle, we determined the presence of QD-MSCs in synovium and articular cartilage histologically. In vitro, we evaluated the persistence of QDs in MSCs and whether QDs affected proliferation, immunophenotype, or differentiati...
Total intravenous anesthesia with alfaxalone, dexmedetomidine and remifentanil in healthy foals undergoing abdominal surgery.
Veterinary anaesthesia and analgesia    January 22, 2019   Volume 46, Issue 3 315-324 doi: 10.1016/j.vaa.2019.01.003
Jones T, Bracamonte JL, Ambros B, Duke-Novakovski T.To evaluate effects of anesthesia induced with alfaxalone and maintained with alfaxalone, dexmedetomidine and remifentanil infusions in foals. Methods: Prospective, experimental study. Methods: A group of six healthy foals [median (range) 11 (8-33) days] undergoing abdominal surgery. Methods: Intravenous (IV) dexmedetomidine (3-7μgkg) provided sedation for insertion of a pulmonary artery catheter. IV anesthesia was induced with alfaxalone (2mgkg) and maintained with alfaxalone (6mgkghour), dexmedetomidine (1μgkghour) and remifentanil (3μgkghour). Foals were endotracheally intubated and lung...
Intravenous infusion of magnesium sulfate and its effect on horses with trigeminal-mediated headshaking.
Journal of veterinary internal medicine    January 22, 2019   Volume 33, Issue 2 923-932 doi: 10.1111/jvim.15410
Sheldon SA, Aleman M, Costa LRR, Santoyo AC, Howey Q, Madigan JE.Trigeminal-mediated headshaking results from low-threshold firing of the trigeminal nerve resulting in apparent facial pain. Magnesium may have neuroprotective effects on nerve firing that potentially dampen signs of neuropathic pain. This hypothesis has not been investigated in horses with trigeminal-mediated headshaking. Objective: To investigate head-shaking behavior in affected horses after IV magnesium sulfate infusion. Methods: Six geldings with trigeminal-mediated headshaking. Methods: Prospective randomized crossover study. Horses were controlled for diet and infused IV with 5% dextros...
Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome.
Cells    January 22, 2019   Volume 8, Issue 2 80 doi: 10.3390/cells8020080
Smieszek A, Kornicka K, Szłapka-Kosarzewska J, Androvic P, Valihrach L, Langerova L, Rohlova E, Kubista M, Marycz K.In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC) and individuals affected by equine metabolic syndrome (EqASC). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as...
First description of a fatal equine infection with Halicephalobus gingivalis in Portugal. Relevance for public health.
Veterinary medicine and science    January 22, 2019   Volume 5, Issue 2 222-229 doi: 10.1002/vms3.142
Noiva R, Ruivo P, de Carvalho LM, Fonseca C, Fevereiro M, Carvalho P, Orge L, Monteiro M, Peleteiro MC.Halicephalobus gingivalis is a small saprophytic rhabditid nematode, represented only by females with a typical rhabditoid oesophagus and one egg in the uterus, capable of infecting vertebrates. This opportunistic parasite present in the soil, manure and decaying humus, is thought to penetrate through previous injuries to the mouth, eyes and skin of horses and migrate to various organs. The brain is one such organ, where the females lay their eggs, leading to malacia and causing a sudden onset of neurological signs, such as anorexia, ataxia, urinary incontinence, blindness, decreased menace an...
Surgical treatment of epiploic foramen entrapment in 142 horses (2008-2016).
Veterinary surgery : VS    January 21, 2019   Volume 48, Issue 3 291-298 doi: 10.1111/vsu.13161
van Bergen T, Haspeslagh M, Wiemer P, Swagemakers M, van Loon G, Martens A.To report the clinical features, outcomes, and prognostic factors associated with the surgical treatment of epiploic foramen entrapment (EFE). Methods: Retrospective study at a single referral hospital. Methods: Horses (n = 142) undergoing surgery (n = 145) for EFE. Methods: Preoperative, perioperative, and postoperative data of surgeries on horses that underwent exploratory laparotomy for EFE were obtained. The postoperative outcome was assessed by follow-up telephone calls with the owners/caregivers. Factors associated with postoperative reflux (POR), relaparotomy, hospital discharge...
Evaluation of an HMGA2 variant for pleiotropic effects on height and metabolic traits in ponies.
Journal of veterinary internal medicine    January 21, 2019   Volume 33, Issue 2 942-952 doi: 10.1111/jvim.15403
Norton EM, Avila F, Schultz NE, Mickelson JR, Geor RJ, McCue ME.Ponies are highly susceptible to metabolic derangements including hyperinsulinemia, insulin resistance, and adiposity. Objective: Genetic loci affecting height in ponies have pleiotropic effects on metabolic pathways and increase the susceptibility to equine metabolic syndrome (EMS). Methods: Two hundred ninety-four Welsh ponies and 529 horses. Methods: Retrospective study of horses phenotyped for metabolic traits. Correlations between height and metabolic traits were assessed by Pearson's correlation coefficients. Complementary genome-wide analysis methods were used to identify a region of in...
Comparison of three acute colic pain scales: Reliability, validity and usability.
Veterinary journal (London, England : 1997)    January 21, 2019   Volume 246 71-77 doi: 10.1016/j.tvjl.2019.01.004
Sutton GA, Atamna R, Steinman A, Mair TS.A valid, reliable and usable scale is needed for assessing severity of acute abdominal pain in horses. The study aim was to compare three different scales: (1) the equine acute abdominal pain scale (EAAPS); (2) a scale described by Mair and Smith (2005; M and S); and (3) a numerical rating scale (NRS). Forty brief films of horses (35 of colic cases and five of control horses) were randomly presented to 46 equine veterinarians from different countries. Participants, randomly divided into three groups, each used one scale. Five randomly selected films were shown twice for determining intra-obser...
Exome sequencing in genomic regions related to racing performance of Quarter Horses.
Journal of applied genetics    January 21, 2019   Volume 60, Issue 1 79-86 doi: 10.1007/s13353-019-00483-1
Pereira GL, Malheiros JM, Ospina AMT, Chardulo LAL, Curi RA.Among horses selected for speed, the racing line of Quarter Horses is characterized by high performance in sprint races, with these animals being considered the fastest horses in the world. However, few studies have investigated in more detail the polymorphisms and genes that act on this trait. The objective of this study was to analyze exomes and UTRs in regions previously associated with this trait by GWAS in Quarter Horse racehorses with contrasting maximum speed index (SImax), prospecting causal gene polymorphisms that are related to or are in strong linkage disequilibrium with racing perf...
Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.
Nature communications    January 21, 2019   Volume 10, Issue 1 353 doi: 10.1038/s41467-018-08081-1
Wong K, van der Weyden L, Schott CR, Foote A, Constantino-Casas F, Smith S, Dobson JM, Murchison EP, Wu H, Yeh I, Fullen DR, Joseph N, Bastian BC....Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative...
Left paralumbar fossa approach combined with mesocolon fenestration for bilateral equine ovariectomy.
Veterinary surgery : VS    January 20, 2019   Volume 48, Issue 5 735-741 doi: 10.1111/vsu.13166
Devick IF, Hendrickson DA.To describe a standing left paralumbar fossa approach combined with mesocolon fenestration for bilateral equine ovariectomy. Methods: Prospective experimental clinical study. Methods: Four healthy client-owned mares and 1 client-owned Molly mule. Methods: Mares were restrained in standing stocks and sedated with an α -agonist continuous infusion to effect. The abdominal cavity was approached via a left paralumbar fossa approach, and the contralateral right ovary was accessed through an incision in the mesocolon. The location of the window was adjusted to allow triangulation, adequate visualiz...
Buffering mepivacaine with sodium bicarbonate speeds and potentiates analgesia of median and ulnar nerve blocks performed on horses.
The Veterinary record    January 19, 2019   Volume 184, Issue 5 155 doi: 10.1136/vr.104962
Boone L, Schumacher J, DeGraves F, Cole R.The objective of this study was to determine if buffering mepivacaine HCL (mepHCl) with sodium bicarbonate (NaHCO3) would significantly decrease the time to onset of analgesia when performing median and ulnar nerve blocks in naturally lame horses. Median and ulnar nerve blocks were performed on the naturally lame limb of nine horses during two separate study periods, with a minimum washout period of three days between study periods. Nerve blocks were performed by administering mepHCl alone or mepHCl mixed with NaHCO3 (nine parts 2 per cent mepHCl to one part 8.4 per cent NaHCO3). Lameness was ...
Neuroborreliosis in a horse with common variable immunodeficiency. Pecoraro HL, Felippe MJB, Miller AD, Divers TJ, Simpson KW, Guyer KM, Duhamel GE.Common variable immunodeficiency (CVID) is a rare condition in adult horses characterized by hypogammaglobulinemia and increased susceptibility to parasitic and bacterial infections, including recurrent respiratory diseases, septicemia, and meningitis. Lyme disease is often included as a differential diagnosis in CVID horses with signs of meningitis; however, the Borrelia burgdorferi organism has not been demonstrated previously within central nervous system tissues of CVID horses with neurologic disease, to our knowledge. We report herein a case of neuroborreliosis in a CVID horse, confirmed ...
Effect of breed and other animal-related factors on conception rate to artificial insemination with frozen semen in mares in Ethiopia.
Tropical animal health and production    January 19, 2019   Volume 51, Issue 5 1173-1178 doi: 10.1007/s11250-019-01804-6
Duguma A, Lemma A, Hibste A.Equine reproduction is unique by having long behavioral estrus and differences in time of breeding between breeds and individuals of mares. An experimental study was conducted at the Balderas Sport Horses and Recreational Center, Addis Ababa, Ethiopia, from January to June, 2018, to evaluate conception rate to frozen semen in local and exotic crossbreed mares. Mares were teased to characterize estrus behavior and examined by ultrasound in determining imminent ovulation. Inseminations were done post ovulation within an average of 6-9 h using frozen-thawed semen. The overall conception rate to ...