Vet Res Commun DOI 10.1007/s11259-014-9619-9

ORIGINAL ARTICLE

Effectiveness of a modified administration protocol for the medical treatment of canine pyometra Alberto Contri & Alessia Gloria & Augusto Carluccio & Stefania Pantaleo & Domenico Robbe

Received: 25 March 2014 / Accepted: 2 October 2014 # Springer Science+Business Media Dordrecht 2014

Abstract Pyometra is one of the most common diseases in intact bitches. The aim of this study was to evaluate the effectiveness of a modified aglepristone protocol for the medical treatment of pyometra in the bitch. Of these, 73 bitches affected by pyometra of different breeds and age (2–14 years old) were enrolled. They were randomly assigned to a control group (CTG - 26 bitches) treated with classical protocol (aglepristone at 0, 1 and 6 days - day 0=day of the diagnosis) and a modified treated group (MTG - 47 bitches) treated with a different administration protocol (aglepristone at 0, 2, 5 and 8 days). The classical protocol with the anti-progestagen aglepristone was effective in 88.5 % (23/26) of CTG bitches while the modified protocol was effective in all (47/47) of MTG bitches. One of the 23 CTG bitches received a further administration on day 14, which resolved the pyometra, while in the three cases of CTG bitches, in which the treatment was ineffective, an ovariohysterectomy was carried out. The modified protocol showed a success rate of 100 %, compared with the classical protocol proposed in the literature, and no recurrence of the disease was recorded in the 24 months follow up. After treatment, the oestrus onset was earlier than expected (interoestrus of 128±32 days). In this study, the modified treatment protocol showed high efficacy and lack of recurrence within 24 months, suggesting a complete recovery of reproductive function in the bitch, with a normal fertility.

Keywords Bitch . Pyometra . Medical treatment . Aglepristone . Follow up

A. Contri : A. Gloria (*) : A. Carluccio : S. Pantaleo : D. Robbe Department of Veterinary Clinical Sciences, University of Teramo, Viale Crispi 212, 64100 Teramo, Italy e-mail: [email protected]

Introduction Canine pyometra is a reproductive infectious and inflammatory disorder that affects the bitch’s uterus most frequently in the dioestrus phase (Lesboyries and Berthelon 1936), although some anoestrous bitches can be diagnosed with pyometra (Noakes et al. 2001). The symptoms of pyometra may follow cystic endometrial hyperplasia (CEH) (De Bosschere et al. 2001; De Bosschere et al. 2002), and thus, the disease is currently defined as CEH/ pyometra complex. Historically, many protocols have been proposed for the treatment of pyometra such as the use of antibiotics alone (Querol 1981; Threlfall 1995), which was frequently unsuccessful, or the parenteral (subcutaneous – SC) (Renton et al. 1993; Corrada et al. 2006a, b; England et al. 2007) or intravaginal (Gabor et al. 1999) administration of prostaglandin F2α (PGF). However, natural prostaglandins showed severe adverse side effects, including panting, salivation, vomiting, straining, diarrhoea, pyrexia (Hubler et al. 1991) and the risk of uterine rupture in closed-cervix pyometra (Jackson 1979). Recently, a synthetic prostaglandins F2α analogue (cloprostenol) used for the treatment of pyometra in the bitch showed limited side effects when administered at small doses and in combination with the prolactin-inhibitor cabergolin (Corrada et al. 2006a, b; England et al. 2007). The use of the anti-progestagen aglepristone (RU534) either alone (Trasch et al. 2003) or in combination with cloprostenol (Fieni 2006) was proposed for the treatment of pyometra. The classical protocol proposed for aglepristone consisted of 3 administrations at days 1, 2 and 7 (Trasch et al. 2003) or 8 (Fieni 2006) (day 1=day of the diagnosis), with variable effectiveness (92.3 and 60 %, respectively). Compared with aglepristone alone, the association aglepristone-cloprostenol increased the recovery rate at day 90 from 60 to 84 % (Fieni 2006). The recurrence rate reported

Vet Res Commun

in literature was 18.9 % (Trasch et al. 2003) and 19 % (Fieni 2006) in bitches treated with aglepristone. The aim of the present study was to evaluate the effectiveness and safety of a modified administration protocol, consisting of four subcutaneous injections of aglepristone at days 0 (diagnosis), 2, 5 and 8, for the medical treatment of pyometra. Furthermore, the reproductive efficiency and the possible recurrence of the disease were monitored for a follow up period of 24 months. Pyometra is considered an emergency in canine reproduction, and ovariohysterectomy is considered the treatment of choice. However, surgery cannot be performed in all situations, such as in breeding females.

Materials and methods In this study, 73 bitches affected by pyometra were included. Bitches with systemic signs of illness, uterine liquid content, neutrophil leucocytosis with left shift, and progesterone over 2 ng/ml, were classified as being affected by pyometra and enrolled. At admission, a clinical examination of the bitch was performed, and each systemic sign of illness (lethargy, depression, anorexia, polyuria and polydipsia, vomiting, fever) was recorded. Enlargement of the uterus and the liquid content of the uterine lumen were evaluated and measured using ultrasound (Toshiba PVM-375AT multi-frequency convex 6 MHz probe). Eight cross-sections for both the right and left uterine horns were recorded and averaged. A complete blood count was performed on 1 ml of a whole blood sample using an ADVIA 120 haematology system (Siemens, Milan, Italy). A clinical biochemistry profile (Olympus AU400, Olympus, Milan, Italy) considering the following parameters was performed: ALT, AST, ALP, urea, and creatinine. Progesterone was measured in blood serum using a radioimmunoassay (RIA) evaluation (Hoffmann and Schneider 1993). The assay sensitivity was 0.09 ng/ml, and the assay specificity was 98.2 %. Serum progesterone higher than 2 ng/ml was considered indicative of dioestrus phase. Pyometra was classified as open or closed based on the presence or lack of a purulent vulvar discharge. Bitches were randomly assigned to two treatment protocols: a classical treatment group (CTG) (26 bitches), in which a subcutaneous injection of 10 mg/kg body weight of aglepristone (Alizine®; Virbac, Carros; France) was performed at d0 (diagnosis) and at d1 and d6, and a modified treatment group (MTG) (47 bitches), in which the same dosage was administered at d0, d2, d5, and d8 after diagnosis. In both groups, support therapy was performed by the administration of 20 mg/kg/day of amoxicillin-clavulanic acid from d0 to d5 (Synulox®; Pfizer, Paris, France), and perfusion

support was provided by intravenous lactated Ringer’s solution (4–10 ml/kg/h) from d0 to d2-3. On d0, d7 and d14, a clinical examination, uterine ultrasound, complete blood cell profile, biochemistry profile, and progesteronaemia test were performed. If anechoic areas were still present in the uterine lumen at d14, a further ultrasound examination was performed at d21. If the pyometra was not resolved (based on clinical signs and uterine lumen reduction), a further administration of aglepristone was performed at d14. Then, if ineffective, the bitches were submitted to ovariohysterectomy. The follow-up consisted of an anamnestic interview of the owner, a clinical examination and uterine ultrasonography, which were performed 6, 12 and 24 months after the treatment. Interoestrus, defined as the time (days) between the end of the clinical signs of oestrus (oestrus defined as: vulvar discharge, vaginal superficial cells >90 % in the vaginal smear, and acceptance of the male) pretreatment and the end of the sign of the first oestrus posttreatment, was also recorded. At clinical examination, information about mating, pregnancy, and whelping were recorded. The pregnancy rate (bitches pregnant/bitch mated*100), estimated by ultrasound on d25 after ovulation, and whelping rate (bitches whelped/bitches mated*100) were calculated.

Statistical analyses In this study, all data are reported as means±standard deviations (SDs). Data related to uterine diameter and CBC values were evaluated using a general linear model (GLM) with univariate analysis of variance (UniANOVA), in which the time (d0, d7 and d14) and the type of pyometra (open or closed pyometra) were the fixed variables. When appropriate (time), a post-hoc evaluation was performed using Scheffè’s multiple-comparison test. The recovery rate, recurrence rate, pregnancy rate, and whelping rate were compared in CTG and MTG by a Fisher exact test. Differences were considered significant when p ≤0.05. Statistical analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA).

Results The 73 bitches enrolled in this study were randomly assigned to CTG (26 bitches) and MTG (47 bitches). The age of the bitches at diagnosis was 6.2±2.4 years, with no difference between the age of occurrence of open (6.1±2.2 years) and closed (6.4±2.7 years) pyometra. The CEH/pyometra complex showed a wide range of symptoms at diagnosis. In several cases, unspecific signs were reported by the owners, such as lack of appetite (63 %) or lethargy (69.9 %), and in most cases, these were the only symptoms reported. Polyuria/ polydipsia was recorded in the 50.7 % of the bitches.

Vet Res Commun

Hyperthermia (over 39.0 °C) was present in 19 patients (26 %). Other signs were vomiting (31.4 %) and weakness (27.4 %). Based on the diagnosis and the presence of vaginal discharge, bitches with open pyometra (OP) comprised 46.2 % (12/26) of the CTG and 42.6 % (20/47) of the MTG, while bitches with closed pyometra (CP) comprised 53.8 % (14/26) and 57.4 % (27/47) of the CTG and MTG, respectively. An improvement of the general condition, in terms of food ingestion and wakefulness, was recorded within 24 h in most animals. Vaginal discharge was present in 44.7 % (46.2 and 42.6 % in CTG and MTG, respectively) of the bitches at diagnosis (d0), in 93 % (92.1 and 94 % in CTG and MTG, respectively) at 24 h after treatment (d1) and in 100 % within 36 h. Significant decrease in the sizes of the uterine horn and the uterine lumen were present at d7 (p ≤0.05) and at d14 (p ≤0.01) after the first administration in both treatment groups (Table 1). Most of the bitches (69.2 %-18/26 in CTG and 76.6 %-36/47 in MTG) showed abnormal levels of serum alkaline phosphatase (SAP). A moderate non-regenerative anaemia was detected in 5 bitches in the CTG and 8 in the MTG, and this condition was resolved by d14 in all animals. The CBC examination revealed a clear leucocytosis in 22 bitches in the CTG (84.6 %) and in 41 bitches (87.2 %) in the MTG, with values of 42,368.8±7,829 cells/μl and 39,968 ± 14,486 cells/μl in CTG bitches with closed and open pyometra, respectively, and 45,177.5±6,615.6 cells/μl and 33,669.7±15,136.3 cells/μl, in MTG bitches with closed and open pyometra, respectively. Neutrophilia was reported in the same animals, with segmented neutrophil values of 32,823± 8,930 cells/μl and 24,582±10,329 cells/μl in CTG bitches with closed and open pyometra, respectively, and 35,310.5± 12,717.8 cells/μl and 21,240.7±7,893.6 cells/μl in MTG bitches with closed and open pyometra, respectively. The evaluation of CBC at d7 showed a non-significant reduction in white blood cell count values and segmented neutrophils in both groups, while the values were significantly reduced and were within the normal ranges (Lumsden et al. 1979) at d14 in

Table 1 Uterine diameter and lumen detected by ultrasound in treated bitch with open and closed pyometra the day of the start of the treatment (d0), at day 7 and at day 14

d0 d7 d14

Open pyometra

Closed pyometra

Uterine diameter (cm) Uterine lumen (cm)

2.7±0.5a 2.4±0.7a

3.8±0.8b 3.1±0.9b

Uterine diameter (cm) Uterine lumen (cm) Uterine diameter (cm) Uterine lumen (cm)

a

b

2.6±0.5 1.3±0.5 1±0.2 0

2.1±0.6 1.5±0.6 0.8±0.2 0.2±0.3

In the same row, values with different superscript (a/b) differ significantly (p ≤0.05)

most animals (CTG: 73.1 %, 19/26 bitches; MTG: 76.6 %, 36/ 47 bitches). The plasma concentration of progesterone was high in all bitches at the time of the admission (34.1±10.7 ng/ml), confirming the dioestrus status. No differences were found in the progesterone concentration between CTG and MTG bitches. No differences were found between open and closed pyometra cases at d0 (33.8±15.2 ng/ml and 34.3±13.7 ng/ml, respectively), d7 (26.7±12.4 ng/ml and 29.3±11.4 ng/ml), or d14 (25.7±13.7 ng/ml and 24.3±13.9 ng/ml). The treatment protocol with the anti-progestagen aglepristone allow the recovery of the disease in 88.5 % (23/ 26) of CTG bitches and in 100 % (47/47) of MTG bitches, with significant difference between groups (p ≤0.05). One of the 23 CTG bitches received a further administration on d14, which resolved the pyometra, while in two cases of 26 CTG, the treatment was ineffective and bitches were submitted to ovariohysterectomy. Six months after treatment, all treated bitches in the CTG and MTG were healthy. In the CTG, 19 bitches (82.6 %, 19/ 23) showed signs of oestrus at the 12-month examination, with an interoestrus of 151±21 days. In the MTG, 42 bitches (89.4 %) showed the signs of post-treatment oestrus for the first time in the period between treatment and examination or, in some cases, at examination. The overall interoestrus was 128±32 days. Four of the successfully treated CTG bitches showed a recurrence of the pyometra (17.4 %) following the first (2 bitches) or second (2 bitches) oestrus after treatment. In the MTG, none of the treated animals showed a recurrence of the pyometra within 24 months after treatment. The recurrence was significantly higher in CTG than in MTG (p ≤0.05). The pregnancy rate and the whelping rate were similar in the treatment groups (Table 2). Some of the treated bitches were mated at the oestrus following the therapy (4, 57.1 % in CTG; 16, 69.6 % in MTG), and some were mated at the second oestrus (3, 42.9 % in the CTG; 7, 30.4 % in the MTG).

Discussion Several medical treatments for pyometra have been proposed in the dog, and all of them are aimed at reducing the effect of progesterone on the reproductive tract. To achieve this goal, Table 2 Fertility results after treatment with the modified protocol with aglepristone (MTG) compared with the classical protocol (CTG) CTG group Insemination/mating Pregnancy rate Whelping rate

30.4 % 85.7 % 85.7 %

MTC group 7/26 6/7 6/7

48.9 % 82.6 % 78.3 %

23/47 19/23 18/23

Vet Res Commun

two different therapeutic approaches can be undertaken. One is the reduction of the circulating progesterone due to the luteolytic effect of the prostaglandin F2alpha or its analogue (Romagnoli et al. 1996) in combination or without dopamine agonists (Corrada et al. 2006a, b; England et al. 2007). The second method of treatment is to reduce the effect of the progesterone on the affected uterus by the use of aglepristone. This molecule is a high-affinity progesterone receptor antagonist (Hoffmann and Schuler 2000). The classical protocol for the treatment of pyometra with aglepristone involves three subcutaneous doses at d1, d2 and d7 of 10 mg/kg (Hoffmann et al. 2000). The use of aglepristone as a single drug for the treatment of pyometra is controversial because the use of only progestagen antagonists could be partially ineffective, as the drug blocks the receptors but does not have any effect on uterine contractility (Verstegen et al. 2008). Furthermore, a previous paper showed that an increased success of the medical treatment could be achieved by the use of aglepristone, in day 1, 2, and 8, in combination with cloprostenol from day 3 to day 7 (Fieni 2006). As previously reported (Trasch et al. 2003) the treatment of the pyometra using aglepriston was effective even without prostaglandin The administration of aglepristone increased the contraction of the myometrial fibres stimulated by oxytocin and the prostaglandin F2alpha (Gogny et al. 2010), suggesting that progesterone could play a role in the inhibition of uterine contractility during the metaoestrus in both pregnant and nonpregnant bitches. Thus, it is possible that blocking progesterone receptors enhances myometrial contractility in the presence of relatively low levels of the endogenous prostaglandin F2alpha, which is released as a consequence of the inflammation. Our results substantially confirmed the findings previously reported for the classical treatment method (Trasch et al. 2003; Fieni 2006), although better results were recorded using the modified treatment. This protocol reached a significant higher success rate (100 % of cases) and a significant reduction in the recurrence of pyometra in the following oestrus within 24 months (0 % in the MTG; 17.4 % in the CTG). The recurrence rate of the treated bitch in the classical protocol was very close to other reported in literature with a comparable protocol (Trasch et al. 2003). These results could be explained by the protocol proposed here, which potentially allows a higher dose of the drug to be delivered for a longer period. Several studies on orally administered mifepristone have reported rapid absorption (1 h) and an inverse relationship between the elimination time and the dose. Furthermore, the pharmacokinetic parameters also suggest that mifepristone can be retained in tissues and released slowly (Heikinheimo et al. 1989; Shi et al. 1993). As for mifepristone, aglepristone seemed absorbed relatively slowly after subcutaneous injection, and the excretion is very slow. Only 60 % of the administered dose is excreted during the first 10 days and about

80 % over 24 days after administration at a dose rate of 10 mg/kg, as stated by the Manufactorer. The subcutaneous administration suggests slower absorption of the drug, and thus, the inhibitory effect on the progesterone receptors could be more durable. This explanation could be corroborated by the low recurrence of pyometra in the following oestrus. However, this suggestion should be confirmed with specific studies on the pharmacokinetics of the subcutaneously administered aglepristone. In both CTG and MTG group a reduced interestrus was recorded, and this could be the result of a central effect of the anti-progestagen on the hypothalamic receptors (Galac et al. 2004). The values of the parameters recorded by the CBC evaluation confirmed other reports on the typical picture of pyometra in the bitch. We found a smaller decrease in white blood cells compared with affected bitches treated by ovariohysterectomy (Bartoskova et al. 2007). In that study, the altered haematological parameters returned to their normal ranges by d7 after hysterectomy. In our cases, the normalization of the altered CBC parameters was completed within 14 days, confirming other studies in which the medical treatment of pyometra resulted in a recovery of the normal parameters within 10–15 days after treatment (England et al. 2007; Verstegen et al. 2008; Gobello et al. 2003). In this study, a significant reduction in the circulating progesterone was not detected. This finding could be masked by a widely different behaviour of the decline in progesterone among the bitches. These data are similar to those reported in a previous study (Fieni 2006), in which aglepristone did not affect the concentration of the circulating progesterone, although a wide standard deviation among the bitches was found. These differences could be related to the luteal phase in which the treatment was performed. The lack of a significant reduction in progesteronaemia was detected when aglepristone was administered at d12-d13 after ovulation (Galac et al. 2004), while a significant and progressive reduction was reported when the administration was performed at d29-d30 after ovulation (Polisca et al. 2010). In conclusion, the modified administration protocol for the medical treatment of pyometra in bitches with aglepristone proposed here showed an higher effectiveness (100 %) compared with the classical protocol (85.3 %), healing the clinical signs presented by the bitch within 24–48 h. The treatment also induced a complete evacuation of the uterus in 95.7 % of the subjects within d14 and 100 % within d21 as well as a recovery of the blood cell count within d21 after treatment. The recurrence of the pyometra in the bitches treated with the modified protocol were lower (0 %) compared with the classical protocol (17.4 %) The pregnancy rate (82.6 %) and the whelping rate (78.3 %) in the treated animals were similar to those reported for monitored healthy bitches using fresh semen (Linde-Forsberg and Forsberg 1989; England 1992;

Vet Res Commun

Linde-Forsberg and Forsberg 1993), suggesting a recovery of normal reproductive function.

Conflict of interest The authors declare that they have no conflict of interest.

References Bartoskova A, Vitasek R, Leva L, Faldyna M (2007) Hysterectomy leads to fast improvement of haematological and immunological parameters in bitches with pyometra. J Small Anim Pract 48:564–568 Corrada Y, Arias D, Rodriguez R, Tortora M, Gobello C (2006a) Combination dopamine agonist and prostaglandin agonist treatment of cystic endometrial hyperplasia-pyometra complex in the bitch. Theriogenology 66:1557–1559 Corrada Y, Rodríguez R, Tortora M, Arias D, Gobello C (2006b) A combination of oral cabergoline and double cloprostenol injections to produce third-quarter gestation termination in the bitch. J Am Anim Hosp Assoc 42:366–370 De Bosschere H, Ducatelle R, Vermeirsch H, Van Den Broeck W, Coryn M (2001) Cystic endometrial hyperplasia- pyometra complex in the bitch: should the two entities be disconnected? Theriogenology 55: 1509–1519 De Bosschere H, Ducatelle R, Tshamala M (2002) Is mechanically induced cystic endometrial hyperplasia (CEH) a suitable model for study of spontaneously occurring CEH in the uterus of the bitch? Reprod Domest Anim 37:152–157 England GCW (1992) Ultrasound evaluation of pregnancy and spontaneous embryonic resorption in the bitch. J Small Anim Pract 33: 430–436 England GCW, Freeman SL, Russo M (2007) Treatment of spontaneous pyometra in 22 bitches with combination of cabergoline and cloprostenol. Vet Rec 160:293–296 Fieni F (2006) Clinical evaluation of the use of aglepristone, with or without cloprostenol, to treat cystic endometrial hyperplasiapyometra complex in the bitch. Theriogenology 66:1550–1556 Gabor G, Silver L, Szenci O (1999) Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch. Acta Vet Hung 47:103–108 Galac S, Kooistra HS, Dieleman SJ, Cestnik V, Okkens AC (2004) Effects of aglepristone, a progesterone receptor antagonist, administered during the early luteal phase in non-pregnant bitches. Theriogenology 62:494–500 Gobello C, Castex G, Klima L, Rodríguez R, Corrada Y (2003) A study of two protocols combining aglepristone and cloprostenol to treat open cervix pyometra in the bitch. Theriogenology 60:901–908 Gogny A, Mallem Y, Destrumelle S, Thorin C, Desfontis JC, Gogny M, Fiéni F (2010) In vitro comparison of myometrial contractility induced by aglepristone-oxytocin and aglepristone-PGF2alpha combinations at different stages of the estrus cycle in the bitch. Theriogenology 74:1531–1538

Heikinheimo O, Haukkamaa M, Lahteenmaki P (1989) Distribution of RU486 and its demethylated metabolites in human. J Clin Endocrinol Metab 68:270–275 Hoffmann B, Schneider S (1993) Secretion and release of luteinizing hormone during the luteal phase of the oestrous cycle in the dog. J Reprod Fertil 47:85–91 Hoffmann B, Schuler G (2000) Receptor blockers — general aspects with respect to their use in domestic animal reproduction. Anim Reprod Sci 60-61:295–312 Hoffmann B, Lemmer W, Bostedt H, Failing K (2000) Die anwendung des antigestagens aglepristone zur konservativen behaundlung der pyometra bei der hundin. Tierarztl Prax 28:323–329 Hubler M, Arnold S, Casal M, Flückinger M, Hauser B, Corboz L (1991) Anwendung von niedrig dosiertem Prostaglandin F2a bei Hundinnen. Schweiz Arch Tierheilkd 133:323–329 Jackson PGG (1979) Treatment of canine pyometra with dinoprost. Vet Rec 105:131 Lesboyries G, Berthelon D (1936) Pathogenie et traitement de l’endometrite chronique de la chienne et de la chatte. Bull Acad Vet France 9:346 Linde-Forsberg C, Forsberg M (1989) Fertility in dogs in relation to semen quality and the time and site of insemination with fresh and frozen semen. J Reprod Fertil Suppl 39:299–310 Linde-Forsberg C, Forsberg M (1993) Results of 527 controlled artificial inseminations in dogs. J Reprod Fertil Suppl 47:313–323 Lumsden JH, Mullen K, McSherry BJ (1979) Canine haematology and biochemistry reference values. Can J Comp Med 43:125–131 Noakes DE, Dhaliwal G, England GCW (2001) Cystic endometrial hyperplasia/pyometra in the dog: a review. J Reprod Fertil 57: 395–406 Polisca A, Scotti L, Orlandi R, Brecchia G, Maranesi M, Zerani M, Boiti C (2010) Aglepristone (RU534) administration to non-pregnant bitches in the mid-luteal phase induces early luteal regression. Theriogenology 74:672–681 Querol M (1981) Die behandlung der pyometra der hundin mit dem mastitis und metritispraparat ubrocelan, entamast und entamast uterino. Tierarztl Umsch 36:359–360 Renton JP, Boyd JS, Harvey MJ (1993) Observations on the treatment and diagnosis of open pyometra in the bitch (Canis familiaris). J Reprod Fertil Suppl 47:465–469 Romagnoli S, Camillo F, Novellini S, Johnston SD, Cela M (1996) Luteolytic effects of prostaglandins F2alpha on day 8 to 19 corpora lutea in the bitch. Theriogenology 45:397–403 Shi YE, Ye ZH, He CH, Zhang GQ, Xu JQ, Van Look PF, Fotherby K (1993) Pharmacokinetic study of RU 486 and its metabolites after oral administration of single doses to pregnant and non-pregnant women. Contraception 48:133–149 Threlfall WR (1995) Diagnosis and medical management of pyometra. Semin Vet Med Surg 10:21–29 Trasch K, Wehrend A, Bostedt H (2003) Follow-up examinations of bitches after conservative treatment of pyometra with the antigestagen aglepristone. J Vet Med A Physiol Pathol Clin Med 50:375–379 Verstegen J, Dhaliwal G, Verstegen-Onclin K (2008) Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: advances in treatment and assessment of future reproductive success. Theriogenology 70:364–374

Effectiveness of a modified administration protocol for the medical treatment of canine pyometra.

Pyometra is one of the most common diseases in intact bitches. The aim of this study was to evaluate the effectiveness of a modified aglepristone prot...
151KB Sizes 0 Downloads 4 Views