Practical use of a combination of a dopamine agonist and a synthetic prostaglandin analogue to terminate unwanted pregnancy in dogs

The combination of a dopamine agonist, caber-goline, and a synthetic analogue of prostaglandin F_2a, cloprostenol, was used to induce termination of pregnancy from day 25 after the estimated luteinising hormone surge (day 27 ± 4 after the first mating) in five mature beagle bitches. Caber-goline was administered orally at 5 μg/kg daily and cloprostenol was injected subcutaneously at 1 μg/kg every other day. Treatment efficacy, in terms of pregnancy termination, was 100 per cent. Termination always took place by resorption of the fetuses. No side effects were observed. A mean of three injections of cloprostenol and nine days of cabergoline treatment was necessary to eliminate all signs of gestation. Termination was in each case accompanied by a decline in plasma progesterone (to less than 1 ng/ml) within 72 hours of initiation of treatment. In a control group of five, untreated bitches, plasma progesterone remained elevated throughout a corre-     

Comparisons of different combinations of analogues of PGF2 alpha and dopamine agonists for the termination of pregnancy in dogs.

Groups of five pregnant bitches were treated to terminate the pregnancy with four combinations of drugs, starting 28 days after the estimated surge of luteinising hormone (LH), 22 to 28 days after the first mating. The treatments were: cabergoline administered orally for 10 days at a dose of 5 micrograms/kg and a single subcutaneous injection of 2.5 micrograms/kg cloprostenol at the start of the treatment; the same dose of cabergoline plus two doses of 1 microgram/kg cloprostenol administered on days 28 and 32 after the LH surge; bromocryptine administered orally at a dose of 30 micrograms/kg three times a day for 10 days plus a single dose of 2.5 micrograms/kg cloprostenol; the same dose of bromocryptine plus two doses of 1 microgram/kg cloprostenol; and a group of five pregnant bitches was left untreated. The pregnancies were terminated in all but one of the treated bitches, in each case by resorption of the fetuses. There were few side effects in the bitches treated with two doses of 1 microgram/kg cloprostenol, and were present but acceptable in those treated with one dose of 2.5 micrograms/kg. Plasma progesterone concentrations decreased to less than 1 ng/ml within 72 hours of the start of treatment and remained low except in the bitch in which pregnancy was not terminated. In the five untreated bitches, plasma progesterone remained high and they whelped normally. In the treated groups, the intervals between successive displays of oestrus were reduced by approximately 70 days in comparison with previous cycles or with the control group, but the fertility of the dogs was not affected adversely.     

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.     

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.     

Retrospective analysis of the efficacy of different hormone treatments of cystic ovarian disease in cattle

Cystic ovarian disease in cows was treated either with a single intramuscular injection of 500 micrograms cloprostenol, a prostaglandin F2 alpha analogue, in 77 cases of luteal cysts or with 500 micrograms gonadorelin or 20 micrograms buserelin, gonadotrophin releasing hormone or its analogue (GnRH), in 116 cases of follicular cysts. Recovery was defined as the absence of cysts and the formation of a corpus luteum either with or without observed oestrus within 10 days after treatment with cloprostenol and 15 days after treatment with GnRH. Recovery occurred in 65 per cent and 52.6 per cent of cases, respectively, in average times of 4.9 and 19 days. Fifteen days after treatment with GnRH, 20 cows with luteinised cysts were treated with cloprostenol and 15 recovered in a mean of 20.4 days, while 10 which still had follicular cysts, were given GnRH and one recovered 31 days after the beginning of treatment. Another 27 cows, in which cysts became luteinised, were treated with cloprostenol seven days after treatment with GnRH to give quicker (average 11.5 days) but poor (48 per cent) recovery and with a higher rate (33 per cent) of recurrence of cysts. A progesterone releasing intrauterine device was used in 25 cases of cystic ovarian disease, some of which had been previously treated. Sixty-eight per cent recovered in an average of 15 days. The proportions of cows becoming pregnant to one to three inseminations after the different methods of treatment were similar (77 to 94 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)     

A combination of oral cabergoline and double cloprostenol injections to produce third-quarter gestation termination in the bitch

To assess the efficacy and safety of a combined cabergoline and cloprostenol protocol to terminate third-quarter pregnancy, 22 pregnant bitches that ranged from 35 to 45 days after mating were randomly assigned to a treatment group (n=13) or to an untreated control group (n=9). The animals were monitored for 12 days, and pregnancy termination was confirmed by ultrasound examination. Twelve of the 13 treated bitches aborted within 9 days of the initiation of treatment (mean 4.6 days). Only mild side effects were observed. The control animals had normal gestational courses, as did the bitch that did not respond to the therapy. This combination of drugs appeared to be a practical, safe, and efficient abortifacient when used in third-quarter pregnancies.     

Treatment of pseudopregnancy in the bitch with cabergoline, an ergoline derivative

Cabergoline, a new prolactin inhibitor, was evaluated clinically in 143 bitches with pseudopregnancy and, or, false lactation, 14 cases of lactation after ovariohysterectomy for the removal of dead fetuses, 12 cases of persisting lactation after early weaning, and five cases of eclampsia. The drug was administered as a once-daily oral treatment (on food) in 139 cases or as subcutaneous injections at 48 hour intervals (maximum four injections) at a dose of 5, 2–5 or 1–5 μg/kg bodyweight in 35 cases. Improvement was evident within three to four days, and in 80 per cent of the cases clinical signs (abnormal behaviour, mammary gland swelling. milk secretion) had been significantly reduced or had disappeared within seven days. Treatment was successful in 95 per cent of the cases. Emesis was the only objectionable clinical side effect, being seen in 3 per cent of orally treated animals and necessitated withdrawal of one dog from the study. Vomiting occurred after the first (65-7 per cent) and second (22-9 per cent) injection only.     

Evaluation of a new non-hormonal substance for terminating pregnancy in bitches in clinical trials

A new non-hormonal contragestational agent (DL 717-IT), the 2-(4 chlorophenyl)-s-triazole |5,1-a|-isoquinoline, was tested in clinical trials to determine its efficacy for interrupting the pregnancy in the bitch. Five hundred and sixty-five bitches were given a single intramuscular injection of the drug between the first and 15th day after the mating. Of the 475 bitches that received 2–5 mg/kg, 430 (90-5 per cent) did not whelp at all, 15 (3-2 per cent) delivered a few stillborn or weak puppies that died some hours after birth, and 30 (6-3 per cent) delivered at least one normal live pup. Of 90 bitches treated with 3–5 mg/kg, 87 (96-7 per cent) did not whelp at all, two (2-2 per cent) delivered a few stillborn or weak puppies that died some hours after birth, and one (1 1 per cent) delivered normal live puppies. DL 717-IT, owing to the high effectiveness and minimal side effects, must be considered a very reliable drug for the interruption of pregnancies in the bitch.     

The use of cloprostenol for the termination of pregnancy and the expulsion of mummified fetus in cattle

Misalliance and mummification are two indications for treatment with cloprostenol. Of 56 animals mated accidentally that were treated with 0-5 mg cloprostenol, 12 were more than 150 days pregnant and of those, nine required more than one treatment. The animals treated early in pregnancy aborted promptly and completely whereas two, considered to be 200 days pregnant at the first treatment, failed to respond at all. There were no reports of retained fetal membranes or any adverse side effects. Eight cases of fetal mummification were also submitted for treatment. All aborted within three to five days, the fetus being removed manually per vaginam in each case. Serial blood progesterone assays indicated that successful treatment was associated with leutolysis in all cases. It was concluded that cloprostenol may successfully be used for the treatment of misalliance and mummification of the fetus.     

Effects of prostaglandin F2 alpha-analogue administration on luteal function, implantation of embryos and maintenance of pregnancy in bitches

The present experiment was carried out to clarify the effect of administration of the prostaglandin F2 alpha (PGF2 alpha)-analogue on the luteal function and the maintenance of pregnancy in bitches. Fifty-one bitches received a single inoculation of PGF2 alpha-analogue by intramuscular injection. The effect of this agent was observed by monitoring progesterone (P) levels and the state of the uterus by laparotomy, the occurrence of abortion, and the state of parturition. As a result, when bitches were administered with 100-400 micrograms at the beginning of the luteal phase, the decrease in the P level was temporary. In bitches inoculated with 100-800 micrograms of PGF2 alpha-analogue at the functional luteal stage, the P level began to decrease as early as on the following day after injection. In those treated with 100-200 micrograms of PGF2 alpha-analogue at 10-15 days of pregnancy, pregnancy was maintained in 3 of 5 bitches that had received the treatment at day 10, while in the remaining two, all embryos died after implantation. In those that had received the same treatment at day 15, only 2 of 7 maintained pregnancy. Pregnancy was interrupted in eight bitches treated with doses of 100-200 micrograms at days 25-45. In four bitches treated with doses of 100-200 micrograms at day 55, premature birth was induced after 30-44 hr. In conclusion, regression of the corpus luteum, abortion, and premature birth were induced in bitches treated with 100-200 micrograms at each stage, except the beginning of the luteal phase and of the pregnancy.     

Synchronisation of oestrus and fertility in buffaloes using a prostaglandin analogue

Cloprostenol, a prostaglandin analogue, was administered intramuscularly to a total of 35 cycling buffalo cows and heifers in two doses, each of 0.5 mg, given 11 days apart. Out of five cows and 12 heifers subjected to observations after the second injection of cloprostenol (day 0), all except one heifer responded. Signs of oestrus were most marked on days 3 or 4. Eighteen treated heifers were kept with buffalo bulls for four days after the second injection while a control group of nine heifers was kept with bulls for 21 days. The first-service conception rate, diagnosed by rectal palpation at 60 days, was 33 1/3 per cent in both groups. Twelve treated heifers were artificially inseminated at 72 and 96 hours after the second injection of cloprostenol, using fresh semen diluted in egg yolk--citrate extender. The first service conception rate at 60 days was 30 per cent.     

Use of prostaglandins and bromocriptine mesylate for pregnancy termination in bitches

OBJECTIVE: To assess the efficacy and safety of 2 protocols using bromocriptine mesylate and prostaglandins to terminate unwanted pregnancy in bitches. DESIGN: Prospective randomized single-blind controlled study. ANIMALS: 34 crossbred and purebred bitches referred for possible pregnancy termination. Seven additional pregnant bitches were used as controls. PROCEDURE: Pregnancy was assessed by ultrasonographic examination from day 25 after mating in all bitches. Of the 34 bitches, 25 were pregnant and were randomly allocated to a treatment group. Group-1 dogs (n = 12) received a combination of increasing amounts of bromocriptine mesylate (15 to 30 microg/kg [6.8 to 13.6 microg/lb], p.o., q 12 h) and dinoprost tromethamine (0.1 to 0.2 mg/kg [0.045 to 0.09 mg/lb], s.c., q 24 h). Group-2 dogs (n =13) received a combination of increasing amounts of bromocriptine mesylate (the same schedule as group-1 dogs) and cloprostenol sodium (1 microg/kg [0.45 microg/lb], s.c., q 48 h). Both groups were treated until pregnancy termination. Results-Treatment success was 100% in both groups. Days of treatment required for pregnancy termination did not significantly differ between groups (5.0 +/- 0.6 vs 3.7 +/- 0.6 days, group-1 and group-2 dogs, respectively) although adverse effects only developed in group-1 dogs. At the end of the protocols, pseudopregnancy was observed in 3 of 12 and 6 of 13 group-1 and group-2 dogs, respectively. Pregnancy termination was followed by a mucoid sanguineous vulvar discharge for 3 to 10 days. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicate that protocols that combine the use of bromocriptine mesylate and prostaglandins for the termination of unwanted pregnancy in bitches are efficient and safe. The use of bromocriptine mesylate and cloprostenol had the best results and could be easily used on an outpatient basis.     

TERMINATION OF EARLY PREGNANCY IN EWES BY USE OF A PROSTAGLANDIN ANALOGUE AND SUBSEQUENT FERTILITY

SUMMARY Of 87 Dorset ewes injected at 20 to 60 days of pregnancy with either 125 μg or 250 μg of the prostaglandin F^2α analogue, cloprostenol, 72 (83%) were detected in oestrus by teaser rams within 7 days. A total of 60 ewes mated with fertile rams 14 to 28 days after treatment and 36 of these (60%) subsequently lambed. Thirty-eight ewes mated with fertile rams 29 to 56 days after treatment and 30 of these (79%) subsequently lambed. The difference in fertility between the 2 periods was not significant.
Six additional ewes which did not respond to the cloprostenol lambed normally within 6 weeks. They were more than 100 days pregnant when treated.
In ewes which first exhibited oestrus by 7 days of treatment, plasma progesterone concentrations fell from near 4 ng/ml to 0.6 ng/ml within 48 h of treatment. In ewes not detected in oestrus progesterone concentrations did not decrease to similar low levels (1.4 ng/ml; t-test p < 0.005). Concentrations in the 6 ewes treated near 100 days of pregnancy dropped from 7.4 to 4.4 ng/ml over 48 h. Overall, the progesterone concentrations indicated that 92% of ewes treated at 20 to 60 days of pregnancy experienced rapid luteolysis in response to the cloprostenol.
There were no differences between the 2 doses of cloprostenol in the responses or subsequent fertility of the ewes.     

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.     

Induced abortion with two Prostaglandin F2α analogues in mares: Plasma progesterone changes

Three experiments were conducted to test the abortifacient effects of PGF2α analogues on mares during midgestation (average gestation length 141.5 days). The progesterone concentration was measured by radioimmunoassay. In experiment I, five mares recieved an injection of PGF2α analogue (fluprostenol: 500 μg intramuscularly) and a second injection either at 24, 48, of 72 h. Although the progesterone concentration decreased (P < 0.05) an average of 44 per cent in 24 h, none of the pregnancies were terminated. In experiment 2, beginning at least 10 days after experiment I, the same five mares were given PGF2α analogue as follows: 250 μg intravaginally and 500 μg intramuscularly. The treatment was repeated 48 h later. Progesterone concentrations had not increased since experiment 1 and dit not decrease during the 48 h following either injection. In experiment 3, six mares (average gestation length 162 days) were treated every 6 or 12 h with PGF2α analogue (cloprostenol: 375 μg) until expulsion of the fetus occurred at 47 ± 25 h after the initial injection; the mares received an average of 5 treatments. The progesterone concentration averaged 22 ± 7 ng/ml before the initial PGF2α treatment, decreased (P<0.05) to 8.4 ±2.7 ng/ml by 12 h before expulsion and 1–8 ±0.4 ng/ml 12 h after fetal expulsion. The progesterone concentration remained below 1.0 ng/ml for the next 4 days. However, only one of six mares exhibited estrual behavior after induced abortion.     

Vaginal cytology and cervicovaginal mucus arborisation in the breeding management of bitches

Fifty bitches were mated on the basis of results of vaginal cytological and cervicovaginal mucus arborisation examination. When these were compared with a control group of 50 bitches mated on days 10 and 12 after the onset of proestrus there was a significant increase in pregnancy rate from 78 to 92 per cent. The litter size and bitch productivity was also increased, although this was not statistically significant. Forty-two per cent of bitches had two peaks of anuclear epithelial cells in the vaginal smear, separated by a mean of 3–6 ± 1–5 (SD) days. For these bitches, the maximum percentage of anuclear cells at the second peak was between 57 and 98 per cent, and the mean interval between the calculated day of the surge in plasma luteinising hormone (LH) and the second peak of anuclear cells was 4-4 ± 2-0 days. In bitches with one peak of anuclear epithelial cells, the maximum percentage of anuclear cells was between 43 and 94 per cent and the mean interval between the calculated day of the LH surge and the peak of anuclear cells was 1–9 ± 2-1 days. Arborisation of mucus collected from the anterior vagina was noted in all bitches; the mean interval between the calculated day of the LH surge and the peak of ferning was 2–3 ± 2-1 days. The collection of exfoliative cells by aspiration from the cranial vagina and the assessment of the anuclear cell index, may allow the identification of the fertile period after the surge of plasma LH. The anuclear cell index offers advantages over other methods of classification of exfoliative vaginal cells. When used in combination with examination of arborisation of cervicovaginal mucus this method can improve the breeding management of bitches.     

A Review of Canine Pseudocyesis

The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non‐pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non‐pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side‐effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [ bromocriptine (10–100 μg/kg per day for 10–14 days], cabergoline (5 μg/kg per day during 5–10 days), metergoline (0.2 mg/kg per day during 8–10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side‐effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.     

Fertility in buffaloes after oestrus synchronisation with cloprostenol and fixed time insemination.

Fifty-seven cycling buffalo cows of the river type were treated with two doses of 0.5 mg cloprostenol intramuscularly given 11 days apart. Each animal was inseminated twice at 72 and 96 hours after the second injection of cloprostenol. The first service conception rate diagnosed by rectal palpation at 90 days was 38.6 per cent. At the time of insemination the cervix was easily penetrable on both days in only 39 (68.4 per cent) of the animals. They were inseminated at or beyond the internal cervical os, while the others were inseminated in the cervical canal. There was a marked difference in conception rate between those receiving deep inseminations (48.7 per cent) and the others (16.7 per cent). In relation to the interval from calving to insemination the conception rates for those which had calved 60 to 90, 90 to 120 and 120 to 150 days earlier were 16.6, 36.4 and 55.5 per cent respectively. The use of cloprostenol treatment and fixed-time insemination is a useful method of overcoming the problem of oestrus detection in buffaloes. Acceptable levels of fertility can be obtained in those animals which have a sufficiently relaxed cervix to permit semen deposition at the internal os, provided the interval from calving to insemination is more than 90 days.     

Oestrus control in bitches with chlormadinone acetate

A clinical study of oestrus control in bitches with chlormadinone acetate (CMA) is reported. The commercial 1-0 per cent crystalline suspension of CMA was injected subcutaneously at a dose of 3 mg/kg, or somewhat lower for the largest animals. Treatment was initiated always in anoestrus and was repeated twice annually for as long as requested. The longest, 9-year, period of anoestrus was achieved by twenty repeated treatments. A total of 2,471 treatments were given to 568 bitches (an average of 4-4 treatments per bitch) during a period of over 10 years, with an efficacy of 98 per cent. The incidence of false pregnancy, uterine inflammatory disorders and mammary nodules in the treated group were compared to those of an age-related control group of 487 bitches that did not receive hormonal treatment. A lower incidence of false pregnancy and the two clinical entities was observed in the group of treated animals. It is concluded that CMA can be used safely and reliably for oestrus control in bitches and is therefore, an appropriate alternative for ovariohysterectomy.     

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.