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Journal of Feline Medicine and Surgery (2016) 18, 21–33

CLINICAL r e v i e w

Pyometra in the queen To spay or not to spay?

Fiona Hollinshead and Natali Krekeler

Introduction Practical relevance: Pyometra is a commonly occurring uterine disease Pyometra is an acute or chronic suppurative inflammation of the uter- in that often leads to loss of ine wall in intact queens. It is characterised by breeding potential and, in some cases, with cystic dilation of endometrial glands and accumulation of puru- can be life threatening. An increased lent exudate in the uterine lumen. The disease is most often observed in incidence of cystic endometrial hyperplasia (CEH) dioestrus or ‘pseudopregnancy’ in the queen, which is a phase of prog- and pyometra is seen with age. Most queens esterone dominance that lasts approximately 40 days. The relatively present with uterine lesions after 5–7 years of age long -dominated dioestrous phase occurs in queens that (average 7.6 years, range 1–20 years). Clinical signs undergo ovulation (induced or spontaneous) and predisposes them to most commonly occur within 4 weeks of the onset the development of cystic endometrial hyperplasia (CEH) and subse- of oestrus in queens that are either mated, spontaneously ovulate or are induced to ovulate Incidence of feline pyometra (mechanical stimulation or hormone induction). The disease is most often observed in dioestrus. A recent study from Sweden reported that 2.2% of intact queens were diagnosed with Clinical challenges: Queens with pyometra often pyometra by the age of 13 years.1 The incidence of pyometra is considered to be lower go undiagnosed as there may be few or only very in queens than in bitches, as queens are induced ovulators. However, underestimation mild clinical signs and laboratory changes. For of disease incidence is likely because queens often do not express clinical signs to the example, the classic sign of mucopurulent bloody same extent as seen in bitches.2 Furthermore, it seems that, despite being induced vulvar discharge often goes unnoticed. Abdominal ovulators, spontaneous ovulation is not as uncommon in queens as originally thought. is the best tool for diagnosis of There have been various reports of spontaneous ovulation in the queen, with inci- pyometra and for monitoring response to therapy. dence ranging from 30% up to 87%!3–5 Despite many hypotheses, the underlying Patient group: Classically, middle-aged/older cause of spontaneous ovulation in the queen is still unknown, but may be influenced nulliparous intact queens present with pyometra. by breed, increasing age and parity. Recently, a breed predisposition has been report- However, so-called ‘stump pyometra’ can occur ed, with Oriental purebred cats having a higher incidence of pyometra than domestic if ovarian tissue is left behind during ovariectomy and random-bred cats.1 This has also been observed by the authors. Oriental pure- or ovariohysterectomy (ovarian remnant syndrome). bred cats are additionally known to come into oestrus year-round and often have short Queens treated with exogenous steroid hormones interoestrus intervals (associated with overlapping follicular waves)6 compared with such as high doses of megestrol acetate or domestic shorthair and random-bred cats. Furthermore, Oriental queens have a higher medroxyprogesterone acetate for oestrus incidence of spontaneous ovulation than other cats. Therefore, the of Oriental prevention can also develop CEH and pyometra. queens is exposed to more frequent oestrogen priming and periods of high proges- Evidence base: There has been little published terone concentration. These two factors are hypothesised to contribute to the higher to date on CEH, and pyometra incidence of pyometra in young Oriental breed cats compared with other cats of sim- in the queen and most of the currently available ilar age. In the aforementioned large Swedish retrospective study,1 the median age of information has been extrapolated from studies diagnosis of pyometra in Oriental/exotic purebred queens (Sphynx, Siberian, Ocicat, carried out in the bitch. The queen and the bitch Korat, Siamese, Ragdoll, Maine Coon and Bengal) was significantly lower (4 years; have very different reproductive physiology; thus, P <0.05) than that reported for the general population (>7 years).2 further research and investigation into the precise aetiopathogenesis of these disease processes of Fiona Hollinshead the uterus in the queen is warranted. BVSc(Hons) MACVS PhD Diplomate ACT* Audience: This review is aimed at clinicians GlenBred, Matamata Veterinary Services, 26 Tainui Street, Matamata 3400, New Zealand working in small animal practice, especially those in countries where surgical sterilisation is not Natali Krekeler Dr Med Vet PhD Diplomate ACT practised as commonly as in the United States, Faculty of Veterinary and Agricultural Sciences, Canada or Australasia, and who will therefore see The University of Melbourne, Werribee, VIC 3030, Australia a greater proportion of intact queens. *Corresponding author: [email protected]

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quent pyometra caused by infection from could explain why we see pyometra in young bacteria ascending from the . The most cats, which are unlikely to have underlying common bacterium involved in pyometra is uterine pathology such as CEH. in bitches, it is . Similar to the bitch, regardless hypothesised that varying pathogenicity of of the underlying cause, the presence of proges - E coli strains might be responsible for the terone (endogenous or exogenous in source) development of CEH. No studies investigating facilitates the development of pyometra. the effects of bacterial pathogenicity in pyome- The incidence of feline pyometra (see box tra have been undertaken in cats. on page 21) is not well documented. The risk of Pathogenesis and aetiology: uterine disease Pivotal role of progesterone what comes first? Importantly, regardless of the underlying cause may increase of pyometra, the presence of progesterone Cats are classified as seasonally polyoestrus, with each (exogenous or endogenous) is required for coming into oestrus between spring and early pyometra to occur. This was confirmed in autumn with a seasonal anoestrus in winter non-pregnant a canine disease model where intrauterine (long-day breeders). The oestrous period or oestrous cycle, inoculation of a pathogenic strain of E coli in ‘call’ lasts 6–7 days. if ovulation (either induced oestrus or anoestrus did not result in pyometra or spontaneous) occurs but the queen does as the but inoculation of the same strain in dioestrus did.7 No comparable studies have been not become pregnant, there follows a period presence of of progesterone secretion (from the corpus published in the queen. luteum) for approximately 40 days. This is the fetuses is dioestrous phase (or so-called pseudopregnan- cy). Cats that undergo an anovulatory oestrus effectively What role do reproductive hormones play? will have an interoestrus interval of about 8–10 protective The majority of queens affected by pyometra days with baseline progesterone levels. are presented with clinical signs within 4 The pathogenesis of pyometra is incomplete- against the weeks of the onset of the latest oestrus. ly understood – both in the bitch and the Although there is no evidence that abnormal queen, but especially the queen being an development ovarian hormone concentrations are involved induced ovulator. in the bitch, pyometra is cur- of pyometra. in the pathogenesis of pyometra in queens or rently believed to be multifactorial in origin. it bitches, it has been shown that progesterone is is most likely similar in the queen. The aetiolo- necessary to initiate CEH and that oestrogen gy is similar in the two species, with proges- potentiates the effect by upregulating the terone influence predisposing the uterus to expression of progesterone receptors. ascending bacterial (most com- Therefore, pyo metra is believed monly E coli) infection. to be facilitated by an oestrogenic originally CEH and pyometra phase that is followed by a were defined as one disease enti- relatively long non-pregnant ty. it was believed that repeated pro gesterone-dominated phase exposure of the to (dioestrus caused by spon taneous high concentrations of oestrogen or induced ovulation). during proestrus and oestrus, Leukocyte inhibition, decreas - followed by high concentrations ed myometrial contractions and a of progesterone during the luteal closed in the progesterone- phase (ie, dioestrus), led to the influenced uterus facilitate bac - development of CEH (Figure 1). terial growth in a non-gravid This, in turn, predisposed the uterus from ascending infection. uterus to ascending secondary Progesterone also stimulates bacterial infection and develop- uterine stromal and glandular ment of pyometra. More recently, epithelial proliferation and the question has been raised as to increases uterine glandular secre- whether pyometra and CEH are tions, which are an important actually two separate disease source of nutrients for the early entities. Although the conditions developing embryos/fetuses in have many similarities and can pregnant queens. These effects be found as related events, they are cumulative in spontaneously also have the potential to occur ovulating cats or cats that experi- de novo. Any stimulus or irritant Figure 1 Opened uterine horn from a queen with ence repeated matings that do in a progesterone-influenced uterus can lead severe cystic endometrial not result in pregnancy. Thus, the risk of uter- to CEH,7–9 and thus the presence of CEH in changes in the uterine wall but no evidence of pyometra. ine disease may increase with each non-preg- pyometra could merely be the result of a Copyright: Dr Stephanie N nant oestrous cycle, as the presence of fetuses uterine reaction to the bacterial infection. This Simpson. Source: LORI is effectively protective against the develop-

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ment of pyometra. This finding was first dis- Endometritis covered by Dow who reported that nulli- parous bitches with pyometra outnumbered Endometritis is inflammation of the endometrium. Aside from chronic infertil- multiparous bitches with pyometra by ity, clinical signs of endometritis are rarely seen in the bitch or queen. In 10 approximately 10-fold. A similar effect is bitches, an infectious agent(s) is a common underlying cause.11 However, thought to hold true for queens. little information has been published on endometritis in either the bitch9,15 or However, it has also been shown that proges- queen. This is mainly due to the difficulty in collecting uterine samples for terone exposure alone, without prior oestrogen investigation (eg, cytology and bacteriology) using a non-invasive technique 11 priming, can lead to CEH in the queen. The and without causing further pathology. theory that progesterone is critical for the Due to these limitations, a trial of therapy should be considered development of pyometra is supported by the in young breeding queens that repeatedly fail to become pregnant despite fact that the use of exogenous steroid hormones correctly timed matings, and with any of the following history: (progestins such as megestrol acetate [MA] or < Confirmation of ovulation by either blood progesterone assay or ovarian medroxyprogesterone acetate [MPA]) for con- ultrasound; traceptive purposes has been shown to induce < Mated to more than one unrelated proven male; the disease in both bitches and queens.7,12 < No abnormalities detected on complete physical (including genital) Another observation that supports the essential examination; role of progesterone in the disease process, at < No abnormalities found after ultrasonography of the reproductive tract least in the canine species, is that the incidence (uterus and ovaries); of pyometra is similar in ovariectomised and Neutrophils observed during cytological oestrus (ie, presence of 100% 13 < ovariohysterectomised bitches. superficial or cornified epithelial cells [Figure 2]). Which bacteria are commonly involved? In most cases of pyometra, the bacteria isolated are uropathogenic E coli. Other bacteria, mostly normal vaginal commensals such as Staphy - Figure 2 Vaginal lococcus aureus, Klebsiella species, Proteus species cytology smear taken during and Streptococcus species, have also been report- oestrus in a queen ed in cases of pyometra. The uterus is presumed with endometritis. Note the presence to become infected via ascent of faecal bacteria of a cornified through the vagina during oestrus when the squamous vaginal 14 epithelial cell, a cervix is relaxed. It has been shown that E coli large number of are capable of establishing an infection in very neutrophils, red blood cells and young healthy , which are unlikely to have bacteria in the underlying CEH changes.7 This may be another background. Differential explanation for cases of pyometra in young interference queens. It is hypothesised that bacteria enter contrast microscopy, oil the uterus during proestrus and/or oestrus and immersion, x 1000 act as a mucosal irritant, thus stimulating the development of CEH under the influence of The most common infectious agents isolated in cases of endometritis are progesterone during dioestrus. normal vaginal flora. Therefore, use of a broad spectrum antibiotic with good Factors other than bacterial virulence are uterine penetration such as clindamycin (5.5 mg/kg PO q12h) or also likely involved in the pathophysiology of amoxicillin/clavulanic acid (12.5 mg/kg PO q12h) is recommended. Antibiotic pyometra in the queen, such as deficiencies in therapy should be started during oestrus and continued for approximately the innate immune response and inheritance 2–3 weeks. Abdominal ultrasound should be performed after breeding of susceptibility. (16 days after ovulation) to determine if the queen is pregnant or if there is uterine pathology, as indicated, for example, by the presence of intraluminal What is the evidence for a genetic fluid or hyper echogenicity of the endometrium. are discontinued predisposition? if the queen is pregnant or if there is no evidence of infection or inflammation. Previously, no breed predisposition for pyome- Thereafter, ongoing monitoring of fetal viability with weekly ultrasound exam- tra in queens had been reported. However, a ret- inations is recommended until parturition. 1 rospective study carried out in Sweden found If uterine fluid is present, either medical or surgical treatment is needed that Oriental purebred cats have a higher inci- depending on the age and breeding value of the queen (see pages 27–30). If dence of pyometra than other breeds, with the the queen is not pregnant but has evidence of cystic endometrial hyperplas- Sphynx breed having the highest incidence. tic changes (see page 25) then aglepristone therapy to remove progesterone Other breeds with a predisposition include the and its negative influences on a non-pregnant uterus may be beneficial to Siberian, Ocicat, Korat, Siamese, Ragdoll, Maine future fertility.16 In a valuable breeding queen, uterine biopsy for the diagnosis 1 Coon and Bengal. Furthermore, in the authors’ of endometritis (by bacterial culture and cytology) and/or CEH (by experience there are families that have a higher histopathology) could be performed at this time.15 It is important that the incidence of pyometra. These related queens queen is treated with aglepristone immediately after the biopsy procedure to are often geographically isolated, suggesting a prevent the risk of a subsequent pyometra. hereditary predisposition to pyometra.

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Diagnostic approach Laboratory findings < Haematology and biochemistry Remark - Signalment/history ably few haematological and biochemical Risk factors for pyometra in queens include: changes are seen in queens with pyometra.2 < Age Typically, middle-aged to older queens The leukogram may show a marked (>5–7 years) with a history of oestrus within neutrophilia (>35 x 109/l) with a left shift (± the previous 4 weeks are affected (although toxic changes) but this can be variable and, in pyo metra can be seen in younger queens, some cases, the leukogram may be normal. it is Table 1); not uncommon to have no other < Breed orientals and purebreeds (ie, haematological disturbances in queens with Siberian, ocicat, Korat, Siamese, Ragdoll, pyometra.2 Hyperproteinaemia, hypo kalaemia, Maine Coon, Burmese, Birman and Bengal) azotaemia and an elevation in liver enzymes are predisposed; (alanine aminotransferase and alkaline < Drug therapy A history of treatment Pyometra phosphatase), blood urea nitrogen and with progestins for prevention of oestrus should be ruled creatinine may be noted, especially if (particularly high-dose regimens of MA [>0.2 and are present. However, it is not mg/kg q24h] or MPA [>0.05 mg/kg q24h] for out in any ill, uncommon to see only mild or no biochemical durations >1 year,17 especially in older queens), changes. Queens have significantly less or pharmacological agents to induce ovulation intact queen. evidence of renal damage associated with (eg, human chorionic gonadotropin, gonado - Clinical signs pyometra than bitches. in contrast to bitches, tropin-releasing hormone [GnRH]), increases biochemical parameters are also not the risk. are non- particularly helpful as predictors of disease 2 specific, with outcome in queens with pyometra. Clinical presentation < Serum progesterone Progesterone con cen - Presenting complaints include, but are not anorexia and tration will commonly be elevated above limited to, haemopurulent vulvar discharge 2 ng/ml, depending on the length of time (if the cervix is patent), depression, listless- lethargy being since ovulation. if queens are diagnosed ness, lethargy, hyporexia/anorexia, vomiting the most with pyometra towards the end of dioestrus, and weight loss. Physical examination find- progesterone levels can be relatively low ings include abdominal distension, dehydra- common (0.5–2 ng/ml). tion and pyrexia.2,18 importantly, clinical signs < Cytology Cytological examination of the are non-specific, with anorexia and lethargy presentations. vulvar discharge is likely to reveal degenerate being the most common presentations. polymorphonuclear cells and phagocytosed Therefore, pyometra should be ruled out in bacteria (Figure 3). any ill, intact queen. in contrast to pyometra < Culture and sensitivity Bacterial culture in bitches, polyuria and polydipsia are not of vulvar discharge is not particularly helpful commonly seen in affected queens. Most in confirming a diagnosis as normal vaginal importantly, clinical signs can be few or mild flora is most likely to be isolated. However, in queens with pyometra.2 sensitivity testing is important for making in many cases the uterus will be palpably Figure 3 Cytological smear therapeutic decisions as some bacterial strains enlarged but great care should be taken during prepared from a queen with can be resistant to commonly used antibiotics. pyometra. Note the presence abdominal palpation as it can result in uterine of degenerate neutrophils, ideally, a sample collected from the uterus rupture if the cervix is closed and the uterus is epithelial cells and bacteria would be most diagnostic but obtaining in the background. friable. if the cervix is patent, the uterus may not Differential interference such samples is technically and prac tically be as enlarged and only a thickened uterine wall contrast microscopy, difficult. A sample from the cranial vagina oil immersion, x 1000 may be appreciated on palpation. using a guarded swab The presence of vulvar dis- is the next best option charge is also dependent on the for bacterial culture patency of the cervix. in open- and sensitivity testing. cervix pyometra, a haemorrhagic, Samples should be purulent vulvar discharge may be taken before antibiotic the only clinical sign. Cats can be therapy is started. Anti - fastidious with grooming, which is biotic treat ment should why a vulval discharge may not be then com mence while noticed by owners, thereby delay- awaiting results, on the ing the diagnosis. Queens with assumption that E coli closed-cervix pyometra may not is the most likely show vulvar discharge and are isolate (see later). once more commonly systemically ill; culture and sensitivity absorption of bacterial toxins in results are available, these cats can result in endotox- therapy can be modi - aemia and sometimes bacteraemia. fied if needed.

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a b

Figure 4 Lateral (a) and dorsoventral (b) radiographic images of a queen with pyometra. Arrows indicate the enlarged, fluid- filled uterus. Source: LORI

Imaging Abdominal ultrasound is the most impor- Changes that are observed on abdominal radi- tant diagnostic tool when pyometra is ography of a queen with pyometra include a suspected. Early in the disease process, the distended uterus, which can lead to displace- uterine horns typically appear distended with ment of the small intestine (Figure 4). These hypoechoic to hyperechoic fluid, with or with- changes are very similar to those seen in early out flocculation (Figure 5a). The uterine wall pregnancy prior to fetal skeletal ossification often appears thickened with irregular edges (which starts approximately 40 days after the and small hypoechoic areas consistent with luteinising hormone [LH] peak). Also, it is cystic changes to the endometrial glands often difficult to differentiate pyometra from (Figure 5b). However, many queens will other causes of uterine enlargement, such as Abdominal present more than 4 weeks after ovulation, mucometra, hydrometra, hemometra or and even late in the luteal phase or early leiomyoma, which is a further limitation of ultrasound anoestrus phase after the cervix has been radiographic examination. open for days or weeks. in these cases, there is the most may be no intraluminal fluid detectable and important only a thickened uterine wall may be seen (Figure 6). diagnostic tool Pyometra can cause diffuse or segmental when pyometra changes and there have even been occasional reports of pyometra in one uterine horn and a is suspected. pregnancy in the other horn.

a

Figure 5 Ultrasonographic images of (a) distended fluid- filled loops of uterus of different cross-sectional sizes filling the caudal in a queen with pyometra diagnosed soon after ovulation; and (b) a queen with an open pyometra diagnosed later in the disease process (approximately 4 weeks postovulation). Note the presence of intraluminal fluid in the uterus and the Figure 6 Ultrasonographic image of a cross section of a thickened endometrium with thickened uterus (with only a trace of intraluminal fluid) in a visible cystic lesions. Images queen with an open pyometra that presented during the late courtesy of Dr Cheryl Lopate, luteal phase. Note the cysts (cystic endometrial hyperplasia) Wilsonville Veterinary Clinic, b in the uterine wall. Courtesy of Dr Cheryl Lopate, Wilsonville USA Veterinary Clinic, USA

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Histopathology Table 1 Summary of clinical, laboratory and diagnostic Grossly, the uterine horns of a queen with imaging findings in feline pyometra pyometra are usually distended with some degree of annular ring formation on the sur- Comments face (Figure 7). Protuberant bands are seen Clinical presentation on the endo metrial surface, which correspond Signalment Middle-aged to older queens Also young cats, those receiving to the annular rings on the serosa. The (>5–7 years of age) exogenous hormone treatment endometrium of a uterus affected by pyo - and/or with a breed predisposition metra is classically described as ‘cobblestone’ Clinical signs Vulvar discharge, depression, Often clinical signs are very mild in appearance (Figures 1 and 8). The endome- lethargy, pyrexia, inappetence, or absent; clinical signs are trial surface is usually covered by a malodor- hyporexia/anorexia, vomiting generally non-specific ous, mucopurulent exudate, which can vary Laboratory findings in volume (Figure 8). Complete blood White blood cell count >35,000 Leukogram may be normal Histologically, thickening of the uterine wall count cells/ l, neutrophilia with left shift ±μ toxic change is caused by proliferation and dilation of Serum Hyperproteinaemia, Often only mild or no changes endometrial glands, which occurs throughout biochemistry hyperglobulinaemia the endometrium. These glands contain Progesterone >2 ng/ml Can be <2 ng/ml in anoestrus mucopurulent exudate with large numbers of concentration or at end of luteal period (poorer polymorphonuclear leukocytes (Figure 9). treatment prognosis) dense infiltration of neutrophils can also be Diagnostic imaging seen in the superficial stroma under the sur- Ultrasonography Thick-walled distended Often cystic endometrial changes face of the endometrium. in some cases, there tubular uterus filled with in the uterine wall; amount of intra- is evidence of chronic inflammation with infil- hypoechoic/hyperechoic fluid luminal fluid depends on patency of trations of predominantly plasma cells and cervix and time since ovulation histiocytes in the stroma around the dilated Radiography Fluid-dense distended tubular Consider other differentials such as 8,9 uterus in the mid-abdomen pregnancy, mucometra, hemometra cystic glands. or hydrometra

Differential diagnosis

Other causes of uterine enlargement and/or vulvar discharge include: < Mucometra, hemometra and hydrometra (these pathologies are not associated with systemic clinical signs and neutrophilia) < Pregnancy (ruled out with ultrasonography 25 days after the LH peak or by radiography 40 days after the LH peak) < Metritis, retained fetal membranes (clinical signs typically appear within the first few days postpartum) < Vaginitis due to vaginal mass/foreign body/anatomical anomalies

Figure 7 -filled uterus after surgical removal. Note the oozing of purulent material from the friable and stretched Figure 9 uterine wall. Great care is required when handling these Histopathology pus-filled uteri during ovariohysterectomy of a cross section of the uterine wall in a queen with pyometra. The uterine lumen is dilated and filled with neutrophils and necrotic debris. The is thin and stretched but the endometrium is approximately trebled in thickness. The luminal surface forms papillary structures and some of the endometrial glands are distended and also contain neutrophils and necrotic debris. Epithelial cells lining the dilated glands and the lumen are hypertrophied and Figure 8 An opened uterine horn from a queen with hyperchromatic. The pyometra. Note the degree of cystic endometrial change in endometrial stroma contains mostly plasma cells, some lymphocytes and scattered neutrophils. the resected piece of uterine wall. Courtesy of Dr Reto Fritsche, Neutrophils are particularly prominent close to the epithelium of dilated glands and the lumen. School of Veterinary Medicine, Louisiana State University, USA Courtesy of Dr Rob Foster, Ontario Veterinary College, University of Guelph

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Treatment approach

Pyometra can be treated surgically or medical- ly and, in some cases, a combination of the two approaches may be the most effective and safest solution. For example, medical treat- ment of systemically unwell or older patients to assist with uterine emptying prior to sur- gery is appropriate to reduce the morbidity and mortality that can be associated with immediate surgical treatment. Medical treat- ment can allow surgery to be delayed until a time when the queen has been stabilised with intravenous (iV) fluid therapy and iV anti - biotics and the anaesthetic risk reduced. A proportion of pyometra cases in cats Figure 10 Intraoperative spontaneously resolve after the onset of image of an enlarged, fluid- filled and friable uterus in a endogenous luteolysis and subsequent cervi- queen with pyometra cal opening, which allows drainage before the development of any systemic illness.

Surgery vs medical therapy Historically, surgery has been the treatment of choice for the majority of pyometra cases, especially for queens with a closed pyometra. However, uterine rupture is a very rare event and many cases of closed pyometra are successfully managed with careful medical therapy. Generally, medical treatment is indicated for young healthy queens (<3 years old) that are intended for breeding. However, owners of breeding animals should also be informed about the potential risk of recurrence (see text).

Surgical management ovariohysterectomy with resection of the Figure 11 Intraoperative image of an enlarged, distended, fluid-filled uterus in a queen with entire cervix is the treatment of choice in all stump pyometra secondary to ovarian remnant syndrome queens not intended for breeding. Cats that present in poor condition need to have any acid–base derangements, arrhythmias, hypo - Regardless of presentation, IV fluid therapy tension, shock, electrolyte abnormalities and and IV antibiotics should be administered. dehydration corrected before undergoing Great care should always be taken in handling anaesthesia. Fortunately, the majority of cats the uterus during surgery, as it is often very with pyometra are systemically well at pres- friable (Figures 7 and 10). Placement of saline- entation and are good anaesthetic and surgical soaked laparotomy sponges in the abdomen candidates. is recommended to prevent contamination of the abdominal cavity with purulent material. Removal of the cervix in its entirety is per- Indications for surgical treatment formed in order to avoid leakage of purulent material into the abdomen and prevent the < Queens without significant reproductive value or queens not intended risk of a stump pyometra occurring (Figure for future breeding 11) if some ovarian tissue is inadvertently left < Emergency presentations such as uterine rupture or torsion concurrent behind (ovarian remnant syndrome). with pyometra Postoperative monitoring for signs of shock, < Older queens, particularly those with significant cystic and degenerative dehydration, sepsis, electrolyte and acid–base endometrial changes detected on ultrasound examination imbalances, hypoproteinaemia, hypogly- < Pyometra that is refractory to medical treatment caemia and anaemia is required for 24–48 h following surgery.

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Medical management When considering medical treatment of a Recommended ‘low dose protocol’ pyometra, it is important to rule out any con- for natural PGF (Lutalyse) current conditions such as , kidney disease, reactive hepatitis or disseminated Start with 10–15 g/kg SC q6h for the first day intravascular coagulation (diC). A full clinical μ and ultrasound examination, as well as addi- tional haematological and biochemistry Increase to 25 g/kg q6h SC for day 2 assays, should be carried out before com- (and day 3 if toleranceμ to PGF is low) mencing treatment. All patients receiving medical treatment for pyometra need to be very carefully monitored and, if systemically well, can be treated as in-house ‘day patients’. Increase to 50 g/kg q8h SC for the next 3–5 days or until vulvar However, patients that become unwell or discharge is noμ longer observed or no fluid is detected in the require fluid therapy should be immediately uterus on ultrasound examination hospitalised. owners should also be informed of the risk of treatment failure and that, ulti- ‘Low dose protocol’ is a term now used by reproduction specialists for mately, surgery may be required. treatment with PGF. The protocol can be used on its own or, ideally, in The rationale for medical therapy is three- combination with dopamine agonists (eg, cabergoline) or progesterone fold (see box below). Pharmacological options receptor antagonists (eg, aglepristone) (PGF), include prostaglandin F2 dopamine agonists and progesteroneα receptor antago- nists or antiprogestins (Table 2). order to minimise the ecbolic effect of the Prostaglandin F2α Repeated doses of PGF result in luteolysis of drug and to reduce the risk of uterine rupture, the feline corpus luteum. The resultant as well as to reduce the side effects associated reduction in progesterone concentrations with higher doses of PGF. once luteolysis has promotes cervical relaxation and a reduction in occurred and the cervix opens, the dose can be uterine secretions. PGF also has ecbolic activity increased depending on the individual’s toler- that facilitates drainage of purulent material ance of the PGF. doses greater than 50 g/kg from the uterus. should not be required, which is significantlyμ Generally, There are two forms of PGF: its natural form less than the 200–250 μg/kg reported in the (dinoprost tromethamine [Lutalyse; Zoetis]) medical older literature. or synthetic derivatives (eg, cloprostenol). it is important to note that the corpus Neither form is registered for use in compan- treatment luteum in the queen is more resistant to the ion animals but both can be used off-label luteolytic effects of PGF than that of the bitch. in queens. Cloprostenol has been associated is indicated Furthermore, if treatment is started soon with fewer side effects and requires fewer for young after ovulation, the corpus luteum can be injections due to its longer half-life. However, refractory to the effects of PGF. often, natural PGF induces greater myometrial con- healthy queens higher doses of PGF for longer durations are tractions and therefore faster evacuation of (<3 years old) required to obtain resolution of pyometra, purulent material from the uterus compared especially if the diagnosis is made early in with synthetic PGF.19 For this reason, the that are dioestrus (before day 20 postovulation). authors recommend natural PGF for treat- during this time, low doses of PGF are poorly ment of pyometra in the cat. intended for effective in inducing complete and definitive it is paramount, especially in the case of breeding. luteolysis.2 closed-cervix pyometra, that a low starting Side effects of PGF are dose-dependent and dose of natural PGF with incremental increas- are rarely encountered with the ‘low dose pro- es is administered subcutaneously (see ‘low tocol’, mostly limited to a transient hypersali- dose protocol’ in the box above). This is in vation. individual variation in terms of toler- ance of PGF is also seen, with some queens tolerating the drug well and requiring a more Rationale for medical treatment rapid dose increase. Tolerance of PGF and reduction of side effects is also typically seen after subsequent injections. Reported side < Removal of progesterone, thus allowing cervical opening and improvement of local immune status effects include tachypnoea, vomiting, diar- rhoea, urination and restlessness. Side effects < Promotion of drainage of purulent material from the uterus and elimination of bacteria through an open cervix, aided by induction appear about 20 mins after treatment and only of myometrial contractions last 15–30 mins. Patients should therefore be Prevention of further bacterial proliferation and release of endotoxins hospitalised for at least 1 h after treatment to < observe for side effects. Systemically well

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queens can be managed as ‘day patients’ – effects of progesterone on the uterus. receiving injections throughout the day while Furthermore, initiation of aglepristone treat- under veterinary supervision but able to go ment 48 h before starting PGF treatment can home overnight when no medication is given. reduce the risk of uterine rupture in a closed- cervix pyometra by slowly opening the cervix Dopamine agonists without the stimulation of strong uterine con- dopamine agonists can be used for the tractions. Therefore, when using PGF in com- treatment of pyometra in the queen either bination with aglepristone, treatment with alone or in combination with PGF or a PGF should start on day 3; PGF is then given progesterone receptor antagonist (see below). daily as per the ‘low dose protocol’ described dopamine agonists are ergot-derived alkaloid on page 28, except on days when aglepristone compounds that act as prolactin antagonists is given. and thus have anti-luteotrophic activity. They The recommended dosage of aglepristone are effective from approximately 15–20 days If systemically in the queen is 15 mg/kg SC twice, 24 h apart, after ovulation when prolactin is present.2 and then a single injection on day 8. A higher Therefore, if a queen presents with pyometra well, cats dose rate is recommended for queens com- soon after oestrus, anti-prolactinic agents are pared with bitches due to reduced bioavail- preferred over PGF as they are very effective at receiving ability in the queen. depending on the inducing luteal arrest and luteolysis in early medical patient’s condition, additional injections of dioestrus.2 However, if a queen presents more aglepristone can be given on days 14 and 28 if than 4 weeks after oestrus or mating, use of a treatment for resolution of the pyometra has not occurred. dopamine agonist in combination with PGF in these chronic cases, treatment with aglepri- potentiates the luteolytic effect, causing more pyometra can stone weekly (mean duration of effect of rapid luteolysis and leading to cervical be managed as aglepristone is 6 days) for 2 months has been opening within 24–48 h. reported. However, the prognosis with regard There are two commonly used dopamine ‘day patients’. to fertility and recurrence rate is significantly agonists: cabergoline and bromocriptine. poorer in these cases compared with cases Cabergoline is associated with few or no side that respond after the initial three injections effects and involves only once daily adminis- on days 1, 2 and 8.16 tration, whereas bromocriptine has a number Treatment with aglepristone (15 mg/kg SC of side effects including vomiting, anorexia, q24h) in combination with trimethoprim/ depression and some behavioural changes, sulfadoxine for 7 days resulted in a success and also requires administration two to three rate of 90% (9 out of 10 cats).24 The authors times a day. The recommended dose of caber- did not note any recurrences for 2 years after goline is 5 μg/kg Po q24h; the dose of treatment. bromocriptine is 10–25 μg/kg Po q8h. Both drugs are most commonly used in combina- tion with PGF, with the duration of treatment usually being 7 days. Table 2 Dosages of commonly used luteolytic, anti- luteotrophic and antiprogestin drugs for treatment Progesterone receptor antagonists of feline pyometra or antiprogestins Drug name Dose Protocol Actions Progesterone receptor antagonists or Dinoprost 10 µg/kg SC tid–5x/day x 1day Luteolysis antiprogestins, such as aglepristone (Alizine; tromethamine 25 µg/kg SC tid–5x/day x 1 day Myometrial contractions

Virbac), are synthetic steroids that com - 2 α (Lutalyse; 50 µg/kg SC tid–5x/day x 5–7 days* Cervical opening petitively bind to progesterone receptors with Zoetis) If used in x combination with a greater (9 in cats) affinity than natural aglepristone progesterone. This results in a decrease in treatment is given progesterone activity.20,21 Aglepristone has on days 3–7

minimal side effects and is a good choice for F Prostaglandin Cloprostenol 1 µg/kg SC sid for 5–7 days or the treatment of closed-cervix pyometra as until resolution it results in cervical opening with minimal Cabergoline 5 µg/kg PO sid Anti-prolactinic uterine contractions. it also induces luteolysis. Anti-luteotrophic However, queens that present with poor liver Bromocryptine 10–25 µg/kg PO tid

and/or kidney function should not be treated agonists Dopamine with aglepristone. Aglepristone 15 mg/kg SC Days 1, 2, 8 and Progesterone receptor Aglepristone is most effective when used in weekly* antagonist Cervical opening combination with natural PGF (dinoprost) for Anti- Luteolysis

5–10 days to potentiate luteolysis and enhance progestins 22,23 uterine contractions. This is particularly *Depending on response to treatment important in cats as they are notoriously SC = subcutaneous; PO = oral; sid = once a day; tid = three times a day; resistant to luteolysis and removal of the 5x/day = five times a day

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Future treatments

Techniques are currently being developed in bitches to treat both closed- and open-cervix pyometra with non-invasive, transcervical endoscopic catheterisation. This involves flushing the uterus with sterile saline to remove the mucopurulent exudate and instilling intrauterine antibiotics and PGF. Promising results in bitches have been reported, with resolution of pyometra within 3–5 days.19 Recently, a new method for cervical catheterisation using a rigid endoscope and a specialised transcervical catheter has been developed for artificial insemination (AI) in queens.25 With this development, treatment of pyometra in queens using a transcervical flushing technique may become a viable option in the near future.

Figure 12 Ultrasonogram of a uterine horn in a queen treated medically for pyometra several weeks earlier. Note that there is no intraluminal fluid present, but there are marked cystic Antimicrobial therapy changes in the thickened Monitoring tools Antimicrobial therapy should be initiated uterine wall, indicating a Ultrasound of the uterus Ultrasound poor prognosis for future < immediately with a broad spectrum antibiotic. fertility. Courtesy of Dr Cheryl examination is the most important monitoring Culture and sensitivity testing should be Lopate, Wilsonville Veterinary tool. A decrease in uterine size by 50% should performed but therapy has to be started at Clinic, USA be seen 72–96 h after initiation of therapy. if a the time of diagnosis on the assumption that reduction in uterine size of at least 50% is not E coli is the most likely pathogen. Excellent observed after 5 days of treatment, the prognosis results have been achieved with amoxicillin/ for future fertility is poor. in cases that respond clavulanic acid (12.5–25 mg/kg Po q12h) poorly to luteolytic therapy, surgery is or cephalosporins (eg, cefazolin 22 mg/kg iV recommended to remove the fluid-filled uterus.2 or iM q8h) and potentiated sulfonamides; in bitches, treatment for longer than 7–10 days care should be taken in using cephalosporins can increase the risk of complications such as or sulfonamides if renal function is impaired. diC. This has not been reported in the queen if oral antibiotics are administered, care must but should be a consideration when undertaking be taken to give the drugs at a different prolonged treatment. Weekly ultrasound time from the PGF, which might lead to examinations are recommended to assess the vomiting. The most response to therapy. When the uterine Antimicrobial therapy should be continued important dimensions have returned to normal and there for at least 14 days after resolution of vulvar is no fluid present in the uterus, luteolytic discharge and evacuation of all fluid from the monitoring tool treatment can cease. Repeat ultrasound examination 2 weeks after resolution of clinical uterine lumen as determined by ultrasound is ultrasound examination. signs and treatment is advised to assess uterine examination health (eg, degree of CEH changes) and to Assessing the response to confirm the absence of intraluminal fluid (Figure therapy and predicting future of the uterus: 12). This is especially important when treatment fertility is started in a queen soon after ovulation or in a decrease in the early luteal phase when the corpus luteum is There are a number of parameters (see below) uterine size by more refractory to luteolysis and intrauterine that should be assessed throughout the fluid accumulation can recur. A reduction in the treatment of a queen with pyometra to 50% should be uterine wall thickness and often also in the monitor the response to treatment and deter- degree of CEH changes may be detected on mine when luteolytic treatment can cease, as seen 72–96 h ultrasound after removal of progesterone and well as to provide an indication of potential after initiation resolution of bacterial infection. future fertility. < Vulvar discharge Vulvar discharge should A clinical improvement is usually seen of medical increase in volume within the first 24 h of within 48 h of initiation of medical therapy. therapy. treatment and usually ceases about 5–7 days Ideally, resolution of all clinical signs should after the onset of treatment. However, in occur within 7–10 days. contrast to dogs, pyometra in cats is often

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Prognosis for survival and future fertility

The prognosis for survival is good with immediate medical or rates in queens after treatment of pyometra. A substantial retro- surgical treatment, provided uterine rupture has not occurred. If spective analysis of treatment and subsequent reproductive per- uterine rupture occurs, the mortality rate is high (30–50%).26,27 formance in queens treated medically for pyometra is needed. It Overall, the mortality rate for queens with pyometra has been is likely that, similar to bitches, there is high variability in pregnan- reported to range from 5.6–8%.1,2 This relatively high rate may be cy and recurrence rates after treatment. However, in the authors’ related to the fact that affected queens often show only very mild experience, the success rate for pregnancy and normal litter size and non-specific clinical signs.2 Therefore, they may sometimes after treatment for pyometra is high (pregnancy rate >80%) if: be misdiagnosed for a period of time or presented for veterinary < Good case selection for medical treatment is practised; attention late in the disease process; both scenarios result in a ie, young, healthy queens that do not have evidence of uterine less favourable outcome. pathology (eg, CEH); Following medical treatment, the prognosis for future fertility < Effective treatment is initiated immediately; and the risk of recurrence of pyometra depend on a number of < Close monitoring during treatment is performed, and factors, including the age and parity of the queen, the degree of medical treatment is ceased when parameters being monitored CEH changes detected by ultrasound, and the time taken to are not improving in a timely manner; respond to therapy and for the pyometra to resolve. Older (>6 < Good breeding management of subsequent heats (see years) nulliparous queens with severe CEH changes detectable below) is ensured. on ultrasound (Figure 12) that respond slowly to therapy and Similarly, the risk of recurrence of pyometra at the subsequent require protracted treatment (>2 weeks) have a poor prognosis oestrus is variable and depends on case selection and breeding for preservation of fertility and are likely to develop recurrence of management. Queens that do not respond to medical therapy pyometra. quickly have a poor prognosis for return to fertility and an There is very little published data on pregnancy or recurrence increased risk of pyometra at the next oestrus.

Queens with progesterone concentrations slower to resolve. The nature of the vaginal <2 ng/ml, or those that are in anoestrus, discharge will also gradually change – from purulent (and often blood-tinged) to sero - usually respond poorly to medical therapy. sanguineous, before eventually becoming serous. < Vaginal cytology The number of neutro - Management of breeding phils seen on vaginal cytology should decrease queens after medical treatment over the course of treatment. of pyometra < Leukogram Weekly complete blood cell counts should be performed to evaluate it is optimal that all queens intended for neutrophilia. in most patients, the leukogram breeding are mated or inseminated on the first will return to normal 2–3 weeks after oestrus following treatment for pyometra, as commencement of medical therapy. a pregnant queen is significantly less likely to < Serum progesterone Measurement of develop recurrence of pyometra. Therefore, it serum progesterone concentration prior to is important to manage the oestrus to optimise starting medical therapy can be helpful with the likelihood of the queen becoming preg- regard to prognosis. Queens with low nant. Using a proven, fertile, young tom cat or, progesterone concentrations (<2 ng/ml) if Ai is to be carried out, using high-quality or those that are in anoestrus are poor fresh semen, is essential, as is optimal timing candidates for medical therapy as they usually with the use of ovulation-inducing agents. respond poorly.16 Measurement of pro - observation of multiple matings and confir- gesterone at weekly intervals can help mation of ovulation by measuring pro - determine if luteolysis has occurred (indicated gesterone 48–72 h after calling has ceased by serum progesterone <2 ng/ml). This is or ovulation is induced is recommended. particularly valuable if PGF alone is used to Admin istration of a broad spectrum antibiotic treat the pyometra or in refractory cases to help (amoxicillin and clavulanic acid) during determine whether complete luteolysis has oestrus and the early luteal phase (until preg- occurred. Progesterone receptor antagonists nancy is confirmed by an early ultrasound displace the endogenous progesterone, thus examination) is indicated if neutrophils are elevating systemic levels initially. Therefore, detected on vaginal cytology during oestrus when using this drug, progesterone (Figure 2). concentrations must be interpreted with After mating, it is essential to follow queens caution to assess luteolysis. The progesterone closely with ultrasound examinations in order concentration 3 weeks after initiation of to detect any recurrence of pyometra early, aglepristone treatment should be <2 ng/ml. before clinical signs associated with systemic

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illness occur. An early ultrasound examina- Melatonin implants have been reported to tion should be scheduled for 16 days after the safely provide oestrus suppression for up to LH peak to detect either embryonic vesicles 4 months in queens.30,31 Synthetic progestins (consistent with pregnancy) or uterine fluid have been widely used for oestrus suppres- (consistent with recurrence of pyometra). sion in the queen, especially in European However, it is often not possible to breed a countries.17 Great care should be taken when queen on every oestrus subsequent to treat- using these agents (eg, MA and MPA) in a ment for pyometra. Prevention of oestrus in queen that already has cystic changes in the these queens – especially individuals that are uterus as this may predispose to recurrence of known repeatedly to spontaneously ovulate – pyometra. Use of anabolic steroids such as is something to consider to reduce the risk of mibolerone for oestrus prevention is con- pyometra recurrence. Unfortunately, safe and traindicated in cats. effective methods and pharmaceutical agents An alternative management strategy for for prevention of oestrus in queens are limited. queens with a history of pyometra is to measure GnRH analogues such as deslorelin implants serum progesterone concentration 3–4 weeks (Suprelorin; Virbac) are reversible contracep- after the end of oestrus to evaluate for sponta- tives that inhibit oestrus by downregulation of neous ovulation. if ovulation has occurred the hypothalamic–pituitary–ovarian axis.28 (indicated by progesterone concentrations The effects are not only long term but highly >2–5 ng/ml), treatment with aglepristone in an variable. A minimum of 6 months’ suppression attempt to prevent pyometra may be considered. of oestrus would be obtained from a 4.7 mg Queens no longer intended for breeding implant and a minimum of 12 months from a should undergo ovariohysterectomy. ovari - 9.4 mg implant. The timing of implantation ectomy is not recommended in a queen that with regard to season would have an effect on has had pyometra and previous pregnancies, this variability, as well as individual response. as the risk of a pyometra recurring in these in one study, the period of oestrus suppression queens is high if exogenous hormonal therapy after implantation with a 4.7 mg Suprelorin (oestrogens and progestins) is administered or implant in 20 female cats ranged from 16–37 if ovarian remnants are inadvertently left months.29 Suprelorin is not registered for use in behind after ovariectomy. queens (or bitches) due to this variability in response. importantly, in the above-mentioned study, 7/8 queens that were mated after the Queens no longer intended for breeding implant was no longer effective became preg- nant and went on to kitten naturally. should undergo ovariohysterectomy. Ovari ectomy is not recommended.

KEY Points < There are many published studies on the prevalence, pathophysiology, treatment and prognosis of pyometra in the bitch. Unfortunately this work has not yet been documented in queens and there has been much extrapolation from the bitch as a model for pyometra in the queen. < A recent large retrospective study indicates that the incidence of pyometra in the queen is potentially much higher than initially assumed. This finding opens up many questions as to the underlying pathogenesis of pyometra in the queen. < Queens are unique in that the corpus luteum is much more resistant to the currently available drugs and protocols available for the medical treatment and management of pyometra. More refractory cases are seen than in bitches and often a more aggressive approach is required to induce luteolysis. < Successful medical treatment and, more importantly, successful breeding of a queen after treatment of a pyometra is ultimately influenced by the selection of suitable candidates for medical therapy. < With the availability of new drugs and protocols for the treatment of pyometra in queens, as well as a greater understanding of appropriate selection of candidates for medical therapy, clinicians are now much more able to facilitate a successful decision by owners of queens that develop a pyometra in regard to ‘spay or not to spay?’.

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Funding 15 Fontaine E, Levy X, Grellet A, et al. Diagnosis of endometri- tis in the infertile bitch: a new approach. Reprod Domest Anim The authors received no financial support for the research, 2009; 44 Suppl 2: 196–199. authorship and/or publication of this article. 16 Romagnoli S. Practical use of aglepristone. Proceedings of the Southern European Veterinary Conference; october 1–4, Conflict of interest Barcelona, Spain, 2009. 17 Romagnoli S. Progestins to control feline reproduction. The authors declared no potential conflicts of interest with respect Historical abuse of high doses and potentially safe use of to the research, authorship and/or publication of this article. low doses. J Feline Med Surg 2015; 17: 743–752. 18 Kenney KJ, Matthiesen dT, Brown No, et al. Pyometra in References cats: 183 cases (1979–1984). J Am Vet Med Assoc 1987; 191: 1130–1132. 1 Hagman R, Ström Holst B, Möller L, et al. Incidence of pyome- 19 Verstegen J, dhaliwal G and Verstegen-onclin K. Mucometra, tra in Swedish insured cats. Theriogenology 2014; 82: 114–120. cystic endometrial hyperplasia, and pyometra in the bitch: 2 Verstegen J and onclin K. The mucometra–pyometra com- advances in treatment and assessment of future reproduc- plex in the queen. Proceedings of the North American tive success. Theriogenology 2008; 70: 364–374. Veterinary Conference; January 7–11, orlando, FL, USA, 2006. 20 Arnold S, Hubler M and Reichler i. Canine pyometra: new 3 Lawler dF, Johnston Sd, Hegstad RL, et al. Ovulation with- approaches to an old disease. Proceedings of the World Small out cervical stimulation in domestic cats. J Reprod Fertil Suppl Animal Veterinary Association Conference; october 11–14, 1993; 47: 57–61. Prague, Czech Republic, 2006. 4 Pelican KM, Brown JL, Wildt dE, et al. Short term suppres- 21 Galac S, Kooistra HS, Butinar J, et al. Termination of mid- sion of follicular recruitment and spontaneous ovulation in gestation pregnancy in bitches with aglepristone, a the cat using levonorgestrel versus a GnRH antagonist. progesterone receptor antagonist. Theriogenology 2000; 53: Gen Comp Endocrinol 2005; 144: 110–121. 941–950. 5 Gudermuth dF, Newton L, daels P, et al. Incidence of spon- 22 Gobello C, Castex G, Klima L, et al. A study of two protocols taneous ovulation in group-housed cats based on serum and combining aglepristone and cloprostenol to treat open faecal concentrations of progesterone. J Reprod Fertil Suppl cervix pyometra in the bitch. Theriogenology 2003; 60: 1997; 51: 177–184. 901–908. 6 Verstegen J. regulation, estrous induction and 23 Fieni F. Clinical evaluation of the use of aglepristone, with pregnancy termination in the queen. Proceedings of the or without cloprostenol, to treat cystic endometrial hyper - Society for Theriogenology; September 16–20, Columbus, oH, plasia–pyometra complex in bitches. Theriogenology 2006; 66: USA, 2003, pp 334–339. 1550–1556. 7 Arora N, Sandford J, Browning GF, et al. A model for cystic 24 Nak d, Nak Y and Tuna B. Follow-up examinations after endometrial hyperplasia/pyometra complex in the bitch. medical treatment of pyometra in cats with the proges- Theriogenology 2006; 66: 1530–1536. terone-antagonist aglepristone. J Feline Med Surg 2009; 11: 8 Nomura K and Funahashi H. Histological characteristics of 499–502. canine deciduoma induced by intrauterine inoculation of 25 Zambelli d, Bini C and Cunto M. Endoscopic transcervical E coli suspension. J Vet Med Sci 1999; 61: 433–438. catheterization in the domestic cat. Reprod Domest Anim 2015; 9 Schlafer dH and Gifford AT. Cystic endo metrial hyperplasia, 50: 13–16. pseudo-placentational endo metrial hyperplasia, and other 26 declue AE, delgado C, Chang CH, et al. Clinical and cystic conditions of the canine and feline uterus. immunologic assessment of sepsis and the systemic inflam- Theriogenology 2008; 70: 349–358. matory response syndrome in cats. J Am Vet Med Assoc 2011; 10 C dow. The cystic hyperplasia–pyometra complex in the 238: 890–897. bitch. Vet Rec 1958; 70: 1102–1110. 27 Ruthrauff CM, Smith J and Glerum L. Primary bacterial sep- 11 Chatdarong K, Rungsipipat A, Axnér E, et al. Hysterographic tic peritonitis in cats: 13 cases. J Am Anim Hosp Assoc 2009; 45; appearance and uterine histology at different stages of the 268–276. reproductive cycle and after progestagen treatment in the 28 Fontaine C. Long-term contraception in a small implant. A domestic cat. Theriogenology 2005; 64: 12–29. review of Suprelorin (deslorelin) studies in cats. J Feline Med 12 Hollinshead FK and Krekeler N. Pyometra in the bitch. in: Surg 2015; 17: 766–771. Monnet E (ed). Small animal soft tissue surgery. Blackwell, 29 Goericke-Pesch S, Georgiev P, Atanasov A, et al. Treatment of 2013, pp 625–635. queens in estrus and after estrus with a GnRH-agonist 13 van Goethem B, Schaefers-okkens A and Kirpensteijn J. implant containing 4.7 mg deslorelin; hormonal response, Making a rational choice between ovariectomy and ovario- duration of efficacy, and reversibility. Theriogenology 2013; hysterectomy in the : a discussion of the benefits of 79: 640–646. either technique. Vet Surg 2006; 35: 136–143. 30 Gimenez F, Stornelli MC, Tittarelli CM, et al. Suppression of 14 Wadås B, Kühn i, Lagerstedt AS, et al. Biochemical estrus in cats with melatonin implants. Theriogenology 2009; phenotypes of Escherichia coli in dogs: comparison of 72: 493–499. isolates isolated from bitches suffering from pyometra and 31 Kutzler MA. 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