Use of aglepristone and aglepristone + intrauterine antibiotic for the treatment of pyometra in bitches

In this study, the efficacy of aglepristone and/or intrauterine antibiotic administration for the treatment of bitches with cystic endometrial hyperplasia/pyometra complex was investigated. Twenty-four bitches (5-12 years old) with the diagnosis of pyometra were treated at the University of Kafkas and at Istanbul University. The diagnosis of pyometra was established on the basis of the results of clinical, ultrasonographic and vaginal examinations, the haematological and biochemical findings and the history data. In Group I (n = 13), aglepristone (Antiprogestin, Alizine, Virbac, France; 0.33 ml/kg, s.c.) was administered on days 1, 2, 7, and 14 (day 1: diagnosis). In Group II (n = 11), intrauterine antibiotic treatment was performed according to the antibiogram on days 1, 2, 4, 6, 8 in addition to aglepristone given as in Group I. Clinical and ultrasonographic examinations, haematological results and occurrence of oestrous cycles revealed that the ratio of effectively treated bitches was 6/13 and 9/11 in Groups I and II, respectively.     

Oestrus control in bitches with proligestone, a new progestational steroid

A study of oestrus control in bitches with a new type of progestagen, proligestone, in six Dutch and three UK practices is reported. The product was given subcutaneously, regardless of the stage of the sexual cycle and of the usual contraindications for progestagens. A 97% efficacy was obtained with dosages varying from 20–33 mg/kg for the smallest animals to 10–13 mg/kg for the largest animals, when the first treatment was given in anoestrus with repeated treatments after 3 months, 4 months and thereafter every 5 months.
Following treatment in pro–oestrus, heat symptoms disappeared in 96% of the animals within 5 days. By retreatment after 3 months, oestrus prevention could be maintained in 97% of these cases.
Where the animals had been treated only with proligestone (1608 treatments in 776 bitches) there were five cases of the cystic hyperplasia pyometra complex; none of these occurred after treatment in pro–oestrus. Of the animals previously treated with other progestagens for oestrus control (814 treatments in 307 bitches) there were 11 cases.
Forty–one out of 46 bitches which had a history of reproductive disorders did not show signs again.
Other side–effects were also negligible (<0–5%). Fertility at the first oestrus after treatment appeared normal.     

Safety and efficacy of mid-term pregnancy termination using aglepristone in dogs

O bjectives : To investigate effects and side effects of aglepristone in terminating pregnancy in bitches.
M ethods : Twenty-two bitches were treated in mid-pregnancy with subcutaneous injections of aglepristone at a total dose of 20 mg/kg. Short-term follow-up (one to two weeks after treatment) included clinical examination and abdominal ultrasonography in 18 of the dogs. Long-term telephone follow-up was recorded for all 22 dogs.
R esults : Pregnancy was terminated in 21 bitches (95 per cent). Signs of abortion occurred one to eight days after treatment. Vaginal discharge was evident in 17 (77 per cent) dogs. Obvious signs of parturition were seen in nine (41 per cent) dogs. Eight dogs (36 per cent) developed anorexia, and in two (9 per cent) of the dogs a local reaction at the injection site was evident. Two dogs developed pyometra two and four years after treatment, respectively.
C linical S ignificance : Aglepristone, when administered in mid-gestation, is effective in terminating pregnancy. Side effects are few and transient.     

Follow-up examinations of bitches after conservative treatment of pyometra with the antigestagen aglepristone

The aim of this study was to determine the therapeutic success of the medical treatment of canine pyometra with the antigestagen aglepristone and to document the recurrence rate in relation to the time interval after treatment with antigestagens. In 48 (92.8%) of the 52 treated bitches, healing could be achieved within the first 3 weeks after the treatment had been started. One bitch died as a result of renal insufficiency; in three bitches there was no emptying of the uterus, so ovariohysterectomy became necessary. In these three patients, ovarian and endometrial cysts were present. Forty-one bitches could be followed up for 3 months. Four animals developed a recurrence (9.8%). In three bitches ovarian cysts and cystic endometrial hyperlasia could be found intra operationem. The development of 37 bitches could be followed for at least 1 year. Seven animals developed a pyometra again (18.9%). Two received a repeated treatment with aglepristone and have been free from recurrence for over 12 months. In 37 animals data on the subsequent sex cycles are available. In 22 bitches next heat started at the expected time, in seven animals heat started too early. In eight bitches the period of anoestrus was prolonged. Five of the six bred bitches delivered at least one litter. The presented data show that treatment of pyometra by aglepristone results in a high healing rate. The recurrence rate can be minimized by the selection of bitches without ovarian cysts and cystic endometrial hyperplasia.     

Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.     

Successful Treatment for Subinvolution of Placental Sites in the Bitch with Low Oral Doses of Progestagen

Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro‐oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility.     

Quantity of IL‐2, IL‐4, IL‐10, INF‐γ, TNF‐α and KC‐Like Cytokines in Serum of Bitches With Pyometra in Different Stages of Oestrous Cycle and Pregnancy

The occurrence of the pyometra is most common in the first half of the dioestrus when there is decreased cellular immunity associated with increased serum concentration of progesterone in females. The aim of this study was to determine the immunological profile of bitches with pyometra, studying serum levels of IL‐2, IL‐4, IL‐10, IFN‐γ, KC‐like and TNF‐α and comparing them with those of healthy bitches in anoestrus, dioestrus and pregnant. Forty females were divided into four experimental groups: group 1 (G1): with pyometra (n = 10); group 2 (G2): bitches in the second week of gestation (n = 10); group 3 (G3): in anoestrus (n = 10); and group 4 (G4): in dioestrus (n = 10). The serum levels for IL‐2, KC‐like, INF‐γ and TNF‐α were similar for all experimental groups. The values obtained for IL‐10 were found increased (p < 0.001) in animals in dioestrus and pyometra compared with females in anoestrus and pregnant, and the levels of IL‐4 observed were significantly greater (p < 0.001) in bitches with pyometra when compared with others. The cytokine profile in animals with pyometra is similar to bitches in dioestrus for IL‐10 and had increase in IL‐4 for bitches with pyometra, which represents an anti‐inflammatory these cases. This suggests the presence of an immunosuppressive state in both cases, which may explain the propensity of bitches in dioestrus to be affected by pyometra and the severity of the disease on these animals.     

Aglepristone decreases proliferation in progesterone receptor-positive canine mammary carcinomas

Background: Progesterone receptor (PR) antagonist aglepristone (RU534) has been used successfully for pregnancy termination and therapy of pyometra, vaginal tumors, and mammary hyperplasia in bitches and queens. All of these conditions share with canine mammary carcinomas the expression of PR. Objectives: To study the effect of RU534 on proliferation and apoptosis in canine mammary carcinomas in relation to PR expression. Animals: Twenty‐seven nonspayed bitches with mammary carcinomas were treated with either 2 doses of 20 mg/kg RU534 (n = 22, RU534‐treated group) or oil placebo (n = 5, control group) on days 1 and 8. Methods: Tumor samples were collected before (day 1) and after (day 15) treatment for immunohistochemistry. PR expression, proliferation index (PI), and apoptotic index (AI) were determined using antibodies against PR, Ki67, and cleaved lamin A/C antigens, respectively. The effect of treatment on these parameters was analyzed. Results: Differential expression of PR between day 1 (59.1% PR‐positive tumors) and day 15 (36.4% PR‐positive tumors) was observed in RU534‐treated tumors exclusively. After RU534 treatment, mean PI was significantly decreased in PR‐positive but unchanged in PR‐negative RU534‐treated tumors. A reduction of ≥20% in PI was found in 61.5% of RU534‐treated tumors with PR expression. Conversely, no effect on AI was observed after RU534 treatment. Conclusions and Clinical Importance: Neoadjuvant RU534 treatment had PR expression‐related inhibiting effects on proliferation of canine mammary carcinoma cells.     

Plasma concentrations of folic acid, vitamin B12 and progesterone of cyclic bitches, bitches during pregnancy and induced abortion and bitches with pyometra

The aim of this study was to investigate the plasma concentrations of folic acid, vitamin B12 and progesterone at different stages of the sexual cycle and pregnancy, during induced abortion and in bitches with pyometra. Bitches (n = 97) were assigned to groups as follows: a) oestrous cycle (n = 42) b) pregnancy (n = 25) c) induction of abortion (n = 10 and d) pyometra (n = 20). Oestrous cycle stages were determined by vaginal inspection and cytology. Pregnancies were estimated by ultrasound (5.0 Mhz; linear transducer; Schimadzu) at days 15-25, 35-45 and 46-63 of pregnancy. Treatments for the induction of abortion were started between days 25 and 35 after mating (5 microg/kg cabergoline daily, Galastop; 5-10 microg/kg Alfaprostol every other day, Gabbrostim). Diagnosis of pyometra was confirmed by ultrasound and vaginoscopy. Folic acid and vitamin B12 concentrations did not differ among different stages of the oestrous cycle. The mean concentration of folic acid during early pregnancy (days 15-25) exceeded levels of later stages (days 46-63): 9.4 +/- 3.7 microg/ml and 4.7 +/- 1.8 microg/ml, respectively (p < 0.01). A positive correlation between folic acid and vitamin B12 was determined in pregnant dogs ( r = 0.925; p < 0.02). Before the induction of abortion, the concentration of folic acid was 9.6 +/- 5.2 microg/ml; during abortion it decreased to 5.0 +/- 3.2 microg/ml (p < 0.01). A significant correlation (r = 0.925; p < 0.02) between progesterone and folic acid was obtained in bitches with abortion. The mean concentration of folic acid in bitches with pyometra significantly differed from that of bitches at different stages of the oestrous cycle (p < 0.05). The mean concentration of folic acid was significantly lower in metoestrous bitches when compared to bitches with pyometra (p < 0.05). The decrease of serum concentrations of folic acid during pregnancy and induced abortion show that fetal growth and abortion caused higher consumption of folic acid. Concerning bitches did not show any deficiency symptoms, which is why it can be concluded that this decrease is physiological.     

Surgical uterine drainage and lavage as treatment for canine pyometra

Pyometra is a common post-oestral syndrome in bitches. Classical treatment consists of either ovariohystorectomy or medical intervention. Surgical uterine drainage and lavage via direct trans-cervical catheterisation using a 5% povidone-iodine in saline solution was performed successfully in 8 bitches with pyometra. All bitches conceived and whelped without complications subsequent to this treatment. It is concluded that this method offers an effective alternative treatment for canine pyometra with shorter recovery times as well as good clinical recovery and pregnancy rates in bitches destined for further breeding.     

Effects of the Progesterone Receptor Antagonist Aglepristone on Implantation Administered on Days 6 and 7 after Mating in Rabbits

There is no safe and accurate method for early termination of pregnancy in the rabbit. So this study was carried out to determine the effect of aglepristone administration in preventing early pregnancy before implantation in this species. Twenty‐two animals (10–12 months old, New Zealand White rabbits) were naturally mated and pregnancies were confirmed in all animals by ultrasonographic examinations on day 6 after mating (5–7.5 MHz linear array transducer Dynamic Imaging Sonostar, UK) and the animals were grouped randomly: Group I & Group III: Aglepristone (Alizin^®, Virbac; 10 mg/kg, subcutaneously) was injected twice, 24 h apart, on days 6 and 7 after mating (n = 5; n = 8). Group II & Group IV: The same volume of 0.9% NaCl solution was subcutaneously injected in the same interval and served as controls (n = 5; n = 3). Ultrasonographical examination of the uterus was performed daily from day 7 to day 11 post‐mating to test aglepristone efficiency. Blood samples were collected between days 6 and 30, centrifuged at 3070 g for 10 min and stored at ?20°C. The does in aglepristone groups (Group I, III) were not pregnant whereas all animals in control groups were pregnant (Group II, IV). The does in group I & III were examined only clinically and ultrasonographically; however, does in groups III and IV were laparomized on days 6, 7, 9 and 11 post‐mating to control countable implantation sites. No implantation sites were present in group III whereas they were seen obviously in group IV. Side effects were not observed. The mean serum progesterone (P4) concentrations were not significantly different between control and treated does (p > 0.05). The results indicate that aglepristone treatment on days 6 and 7 after mating could prevent pregnancy after unwanted matings without any side effects in the rabbit. Aglepristone treatments are possibly not affecting further fertilities before implantation.     

Foetal pulmonary maturity in dogs: Estimated from bubble tests in amniotic fluid obtained via amniocentesis

The goal of this study was to evaluate the reliability of amniocentesis during late pregnancy to assess lung maturity in puppies using a bubble test as described by Gunston and Davey (South African Medical Journal, 54, 1978, 495). Thirty‐five bitches from eight different breeds were followed during late pregnancy before undergoing elective Caesarean (C)‐section on days 61–62 after ovulation. Bubble tests were performed the day before the C‐section (n = 11 bitches) and before the administration of aglepristone on amniotic fluid samples obtained via amniocentesis and were repeated the day of the surgery on amniotic fluid samples collected via puncture of the amniotic bags before they were opened (n = 35 bitches). No complications were observed following amniocenteses and the C‐sections. The mortality rate (2.3%) was similar to the result of other studies using the same protocol for an elective C‐section. Of the non‐contaminated samples collected the day of the C‐section, 89.6% were positive in the bubble test, which was consistent with observations of clinical maturity the day of the surgery and on the following days. In contrast, 70% of the samples collected the day before the C‐section (when progesterone concentrations were still high) were negative, suggesting that the puppies were still immature at this point in the pregnancy. Additionally, we observed a significant difference in the bubble test results before and 18 hr after the administration of aglepristone, suggesting that aglepristone may act as an inducer of the final maturation of the puppies by inactivating progesterone receptors and simulating a physiological decrease in progesterone. Finally, we confirmed the need to exclude all contaminated samples, which could lead to false‐negative results.     

Comparison of the use of cabergoline and gonadotrophin to treat primary and secondary anoestrus in bitches

Objective To determine the efficacy and reliability of cabergoline and pregnant mare's serum gonadotrophin (PMSG) for induction of oestrus in bitches with primary or secondary anoestrus. Procedures We studied 39 healthy bitches of various breeds aged 2–6 years and in primary or secondary anoestrus: 20 bitches were administered 5 µg/kg/day cabergoline orally until day 2 after the onset of pro‐oestrus or for a maximum of 42 days, and 19 bitches were administered 20 IU/kg/day PMSG intramuscularly for 5 consecutive days, followed by an additional single injection of 25 IU/kg of human chorionic gonadotrophin on the fifth day. Results The rates of oestrus induction in the primary and secondary anoestrous bitches treated with cabergoline and PMSG were found to be similar. Pregnancy and whelping rates in the cabergoline group were statistically different from the rates in the PMSG group (P < 0.001). Conclusion Cabergoline is more effective and reliable for the induction of a fertile oestrus in bitches with primary or secondary anoestrous.     

Use of a low dose prostaglandin F2 alpha in bitches

The dosage of Prostaglandin F2 alpha used until the present (100, 250 and 1000 micrograms/kg bw), in order to treat pyometra in the bitch, was accompanied with side effects such as salivation, vomiting and diarrhea. In the present work, the efficiency of low dose Prostaglandin (20 micrograms/kg bw) was examined in two different groups of patients: Group 1: Included 9 bitches pregnant for a period of 5-7 weeks duration. Initially the bitches were treated 3 or 4 times per day with Prostaglandin F2 alpha. In these cases abortion took place within 4 to 11 days. Group 2: 12 dogs, suffering from pyometra, were treated 3 times per day with PGF2 alpha for 8 days. In 9 dogs the pyometra resolved and the bitches came in estrus 2-5 months after treatment. 7 bitches have been mated and 6 of these gave birth to healthy litters. During a follow-up period of at least 10 months there has not been a reoccurrence of pyometra. In 3 out of the 12 dogs the uteri were still enlarged after 8 days of treatment. These bitches underwent ovariohysterectomy and a cystic hyperplasia of the endometrium was diagnosed histologically. The low dose (20 micrograms/kg BW) Prostaglandin F2 alpha induced in all dogs the expulsion of the uterine contents. Side effects during the treatment were not observed.     

Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch

The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin (15 mg/kg body wt/48 h) and/or gentamicin (4 mg/kg body wt/day) administered as intramuscular (i.m.) injections. Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.     

Effect of Exogenous GnRH at the Time of Artificial Insemination on Reproductive Performance of Awassi Ewes Synchronized with Progestagen–PMSG–PGF2α Combination

This study was carried out to investigate the efficacy of PGF_2α for oestrus synchronization (ES) in Awassi ewes to which were administered the progestagen–PMSG combination, and to evaluate the effect of the exogenous GnRH administration immediately after the artificial insemination (AI) on their pregnancy rate and lambing performance during the breeding season. The ewes (n = 33) were treated with an intravaginal sponge impregnated with 30 mg fluorogestane acetate for 12 days and were injected with 500 IU PMSG at the time of removal of the sponge. The ewes were then divided into three equal groups of 11 ewes each. One millilitre of physiological saline (0.9% NaCl; placebo) was administered to each ewe in Group 1 at the time of second AI. Approximately 4 μg GnRH (busereline) was injected to each ewe in Group 2 immediately after second AI. A total of 150 μg PGF_2α (cloprostenole) was injected at the time of sponge removal on day 12 and 4 μg GnRH immediately after the second AI was also treated to each ewe in Group 3. Intracervical AI with diluted fresh semen was performed twice at 12 and 24 h following the onset of oestrus. The injection‐oestrus onset and injection‐oestrus‐end interval in Group 3 was significantly (p < 0.001) shorter than both Groups 1 and 2. Although the pregnancy rates of Groups 2 and 3 (81.8%; 9/11) were numerically higher than of Group 1 (63.6%; 7/11), the difference among the groups was statistically insignificant. The multiple birth rate of Group 3 was found higher than Groups 1 and 2. However, the number of single lambs of Group 1 was also higher than Groups 2 and 3 (p < 0.05). Despite the litter sizes of Groups 2 (1.27; 14/11) and 3 (1.55; 17/11) being numerically higher than Group 1 (0.73; 8/11), the differences among all the groups were statistically insignificant. In conclusion, the administration of PGF_2α at the time of removal of the sponge shortens the injection oestrus‐onset and oestrus‐end interval in Awassi ewes treated with progestagen–PMSG. Additionally, exogenous GnRH treatment immediately after the AI increases the multiple birth rate of Awassi ewes synchronized with progestagen–PMSG–PGF_2α combination.     

Induction of parturition in bitches with minimal side effects by two injections of a low dose of fenprostalene, a prostaglandin F2alpha analogue, and pretreatment with prifinium bromide.

An experiment using 16 Beagle bitches (aged 11 months to 6 years and 2 months) in their 56th to 58th day of pregnancy was carried out to investigate the effects of two injections of a low dose of fenprostalene, a long-acting prostaglandin F2alpha analogue, and pretreatment with prifinium bromide, a parasympathetic nerve blocking agent, on the induction of parturition and severity of side effects. The bitches were divided into three treatment groups: one injection of 5 microg/kg of fenprostalene (group I, n=5); one injection of 7.5 mg/head of prifinium bromide followed by one injection of 5 microg/kg of fenprostalene at 5 min after prifinium bromide injection (group II, n=6); and one injection of 7.5 mg/head of prifinium bromide followed by two injections of 2.5 microg/kg of fenprostalene, one injection at 5 min after prifinium bromide injection and the next at 1 hr after the fenprostalene first injection (group III, n=5). Following the injection of fenprostalene, side effects such as salivation, vomiting, colic symptoms, and watery diarrhea occurred most frequently (80-100% of cases) in group I bitches. Apart from colic symptoms, no side effects were observed in group III bitches. Group III bitches also showed the smallest increase in plasma cortisol concentration. No significant difference in the time to initiation of parturition was found between the three groups. The one-week survival rate of newborn puppies was highest in group III. The results showed that pretreatment with prifinium bromide and two injections of 2.5 microg/kg of fenprostalene can alleviate side effects following fenprostalene administration and have no adverse effect on the survival of newborn puppies, indicating that this method is a reliable and safe way of inducing parturition in bitches.     

Expression and Activity of Matrix Metalloproteinases in the Uterus of Bitches After Spontaneous and Induced Abortion

Aim of this study was to determine the intrauterine activity of matrix metalloproteinases (MMP)‐2 and ‐9 after cessation of the local effect of progesterone. For this purpose, pregnancy was terminated in 10 bitches at mid‐gestation with the progesterone receptor antagonist aglepristone (10 mg/kg body weight, sc, Alizine^®; Virbac, France) at two subsequent days (group IRA = induced resorption/abortion). The IRA group was divided into two subgroups (Group I, n = 5, days 25–35 of pregnancy; group II, n = 5, days 36–45). Five further bitches were introduced with beginning abortion (group SRA = spontaneous resorption/abortion). Seven healthy bitches between day 25 and 45 of gestation served as controls. After ovariohysterectomy at the end of abortion and between days 25 and 45 of gestation, respectively, the distribution and activity of collagenases were investigated by immunohistochemistry and gelatin zymography. At placental sites, MMP‐2 activity in the endometrium was significantly lower in IRA groups than in the SRA group (33.7 ± 11.8% and 39.3 ± 5.4% vs 52.2 ± 10.2%, p < 0.05); however, MMP‐2 expression was lowest in the control group (control: 21.4 ± 6.3%; p < 0.01) and similarly in the myometrium (controls: 13.1 ± 2.5%; p < 0.05). MMP‐9 activity was also lower in the endometrium and myometrium of the control group in comparison to SRA and IRA groups (11.8 ± 3.2%; p < 0.01 and 28.4 ± 32.8%; p < 0.05). At interplacental sites, the amount of active collagenases in the myometrium was significantly lower in the control group. It is concluded that the blockade of the biological progesterone effect was associated with an increase in activity of both collagenases.     

Influence of Progesterone Withdrawal on Pregnancy-Related Parameters During Post-Implantation Early Pregnancy Loss

Pharmacologically-induced luteolysis or treatment with an antiprogestin in early post-implantation pregnancy in dogs results in asynchronous death and resorption of conceptuses, indicating variable rates of response of individual conceptuses towards progesterone deficiency. This variability also seems to occur in bitches showing pregnancy failure in response to spontaneous luteal deficiency. In a total of 10 beagle pregnancies (two consecutive pregnancies of five bitches), abortifacient treatments beginning on day 24 after ovulation (ov) involved either administration of a progestin antagonist (total of six pregnancies, in three bitches) or a luteolytic regimen of prostaglandin F_2α-analogue together with a dopamine agonist (total of four pregnancies, in two bitches). The outcomes were evaluated in relation to four control pregnancies in two bitches by assay of serum progesterone, prolactin and relaxin at selected time points or within selected time periods, by ultrasound of conceptuses including measurement of uterine blood flow, and parameters of the blood fibrinolytic system including plasma fibrinogen and plasminogen. The process of embryonic death and conceptus resorption was variable in onset and duration both in bitches that received the progesterone antagonist aglepristone (AGLE) and in those under the luteolytic treatment (cloprostenol combined with cabergoline). Pregnancy termination (death of all embryos or foetuses, respectively) occurred as early as day 29 and as late as day 41 after ov in AGLE-treated bitches, and not earlier than day 37 after ov in luteolytic-treatment bitches. Impending embryonic death was not predicted by changes in relaxin concentration, parameters of the fibrinolytic system, or in the perfusion of small uteroplacental vessels.