ergoline and Abortion--Veterinary

Cabergoline (CAB) is a potent dopamine agonist and an inhibitor of prolactin (PRL). In red foxes (Vulpes vulpes), a single oral dose of 100 microg kg(-1) CAB can cause abortions and postnatal cub mortality from at least Day 21 of the 52-day pregnancy. The abortifacient activity of CAB is owing to the suppression of PRL, which is essential for luteotrophic support in some eutherian species. Postnatal cub mortality probably results from a reduction in the development of the mammary ductile system, which is also partially dependant on PRL during pregnancy. This paper investigates the potential risks faced by non-target mammalian species that may consume CAB baits intended for fox control. Baiting with CAB is proposed from 1 August until 1 October each year, to correspond with the time that most vixens are pregnant in south-eastern Australia. Thirty-four endemic mammals in south-eastern Australia (9 eutherians and 25 marsupials) are considered to be potentially bait-consuming (PBC) species. The percentage overlap of pregnancy and birth periods for each PBC species was compared with the duration of the proposed CAB baiting period. Only Antechinus (3 species) and Sminthopsis leucopus have greater than 40% overlap, whereas overlap in endemic rodents ranges from 0% to 22%. Overall, most PBC rodent populations appear to face little risk from CAB baiting, as their period of pregnancy does not overlap significantly with the proposed CAB baiting period. The Antechinus species, Phascogale tapoatafa and Dasyurus maculatus, are the only PBC mammals that are seasonally mono-oestrous and are thus probably more susceptible to disruption of breeding compared with polyoestrous species that may breed many times a year. At a baiting density of 8 baits km(-2), theoretical bait availability for small dasyurids, rodents and peramelids is low. This suggests a low potential for affecting these populations if CAB was indiscriminate in affecting reproductive success in all mammal groups. Presently, studies in a limited range of marsupials suggest that, unlike eutherians, the marsupial corpus luteum is independent of pituitary control and thus suppression of PRL is not likely to cause abortions in marsupials. As yet, CAB has not been shown to be orally active in any PBC species other than rodents and carnivores. Oral doses of CAB given post partum have not been found to affect lactation in Sminthopsis crassicaudata, Trichosurus vulpecula, Macropus eugenii and Setonix brachyurus. Furth

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Animals; Australia; Cabergoline; Embryo Implantation; Ergolines; Female; Foxes; Lactation; Mammals; Population Control; Pregnancy; Prolactin; Reproduction

The aim of the present study was to compare the clinical and endocrinological effects of four different treatments for the induction of abortion in bitches. For this purpose, 28 pregnant bitches between days 25 and 35 of gestation, were randomly assigned to four groups. In group I (n = 7), only aglepristone (AGL, 10mg/kg bw, two injections 24 h apart, s.c.) was administered. In group II (n = 7), AGL (as in group I), cabergolin (CAB, 5 μg/kg, daily p.o., until completion of abortion) and misoprostol (MIS, 200 μg for bitches with ≤ 20 kg bw, 400 μg for bitches with > 20 kg bw, daily intravaginally, until completion of abortion) were administered. In group III (n = 7), AGL (as in group I) and MIS (as in group II) were administered. In group IV (n = 7) AGL, (as in group I) and cloprostenol (CLO, 1μg/kg bw, s.c., two injections 24 h apart with the AGL injections) were combined. In all groups, bitches were examined daily, clinically and ultrasonographically to monitor resorptions/abortions. To measure serum progesterone (P4) and total estrogen (TE) concentrations, blood samples were collected in all groups immediately after the first AGL administration and every other day until completion of abortion. No statistical differences were found between groups concerning the duration until completion of abortion following treatment (n.s.); however, in Group III, 6 d after the start of treatment all pregnancies were terminated whereas in Group I, II and IV, only 57.1% (4/7), 85.7 % (6/7) and 42.8 % (3/7) of pregnancies were terminated. In the latter groups, all pregnancies were terminated between days 8 and 10 after the start of treatment. In Group IV, P4 concentrations on days two and one before the beginning of abortion and the day the abortion started was significantly lower than in the other groups (P < 0.01). No statistical differences were found between groups for TE concentrations (P > 0.05). In Groups I, II and III, no severe side effects occurred. Severe vomiting after each treatment and until the end of abortion was observed in Group IV only. In conclusion, only when a combination of AGL and MIS was used abortion was completed within 6 d in all bitches whereas the additional use of CAB did not improve the treatment.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Animals; Cabergoline; Cloprostenol; Dogs; Ergolines; Estrenes; Estrogens; Female; Misoprostol; Pregnancy; Progesterone; Time Factors

The aim of the present study was to investigate the effects of two medications on two subsequent abortions and plasma hormone concentrations of dogs. For this purpose, two groups of bitches (n=5 each), received the antiprogesterone aglepristone (Alizine) at 10mg/kg body weight on two subsequent days around day 30 after mating. In group II, the antiprolactin cabergoline (Galastop) was additionally administered po at 5 microg/kg body weight until the start of abortion. The plasma concentrations of relaxin, progesterone (P4) and estradiol-17beta (E2) were measured before, during and after each abortion. During the next cycle after the abortion, the same bitches were mated again and in pregnant animals, induction of abortion was performed as before. During the third cycle, pregnant bitches were allowed to whelp. Termination of first pregnancy occurred significantly earlier after the combined treatment (6.8 versus 10.6 days, p<0.05). In both groups and during both abortions, relaxin varied between individuals; however, there was a continuous decrease after the abortions and no significant differences between groups (p>0.05). In one bitch with high relaxin concentrations before treatment (11.6 ng/ml), a cystic endometrial hyperplasia was diagnosed. In the aglepristone only group, P4 concentrations increased significantly after the first application (p<0.05), then decreased continuously until day 45 after the beginning of abortion. In the combined group, there was a continuous decrease until day 45 (p>0.05). At this time, P4 concentrations between 0.47 and 84.9 nmol/l were measured in both groups. The level of E2 over time was not influenced by any medication. We therefore note that the two medications mainly influenced plasma concentrations of P4 in different ways, probably due to specific treatment-hormone interactions. However, all measurements fell within the range considered normal.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Animals; Cabergoline; Dogs; Drug Combinations; Ergolines; Estradiol; Estrenes; Female; Pregnancy; Progesterone; Relaxin

Single oral doses of 100 microg kg(-1) cabergoline (CAB) were previously found to affect the reproductive success of silver fox (Vulpes vulpes) vixens from Day 28 post insemination (PI) onwards by causing abortions and postnatal mortality. The present trial investigated the effect of a single oral dose of 100 microg kg(-1) CAB given to farmed silver fox vixens at 7, 14, 21 or 28 days PI. Six vixens were dosed with CAB at each day PI and abortions, total post-partum litter loss and the combined effects of both were compared with a group of vixens that received a placebo and a control group of vixens that received no treatment. No significant difference existed between the placebo and control groups in the incidence of abortion, postnatal litter loss and litter size at 3 weeks post partum. Overall, a significantly higher frequency of abortions were detected in vixens dosed with CAB (6/24) compared with the combined placebo and control (0/41) groups (P<0.01). Cabergoline administration was significantly associated with complete litter loss (P<0.01) and the combined effects of abortion and litter loss (P<0.001). Oral CAB significantly reduced the reproductive success of vixens when given at Day 21 and Day 28 PI, but not at Day 7 and Day 14 PI.

Topics: Abortion, Induced; Abortion, Veterinary; Administration, Oral; Animals; Cabergoline; Dopamine Agonists; Ecosystem; Ergolines; Female; Fertility; Foxes; Litter Size; Male; Population Control; Pregnancy; Pregnancy, Animal

Cabergoline, a potent dopamine agonist and inhibitor of prolactin secretion, was investigated as a potential fertility control agent in the red fox ( Vulpes vulpes). Sixty silver fox vixens were selected randomly and artificially inseminated. Cabergoline was fed to groups of 12 vixens in a minced beef ration either as a single dose of 25, 50 or 100 microg kg(-1), or a dose of 50 microg kg(-1) that was repeated 2 days later (2 x 50 microg kg(-1)). Four foxes from each group of 12 were given cabergoline at day 28, day 35 or day 48 after artificial insemination, and a control group of four foxes was used as a comparison for each dose day. In a separate trial, two groups of five foxes were selected randomly from the farm population and fed 100 microg kg(-1) of either cabergoline or a placebo each day from day 42 to day 46 of pregnancy. Foxes that received single doses of cabergoline of 100 microg kg(-1) or 2 x 50 microg kg(-1) aborted at day 28, but the same doses did not result in abortions when administered on days 35 and 48. Although lactation was not terminated in groups that received a single or double dose of cabergoline, increased post-natal cub mortality was associated with cabergoline administration. Growth of cubs between 4 and 8 weeks of age was not inhibited in vixens that received cabergoline. Doses of 100 microg cabergoline kg(-1) administered each day from day 42 to day 46 resulted in abortions and terminated lactation. The capacity of single doses of cabergoline to cause abortions in the red fox during mid- rather than late pregnancy is contrary to reported observations for the domestic dog. This finding indicates that luteotrophic support of the corpus luteum by prolactin may be more important at mid-pregnancy in the red fox. The results of this study support previous field observations that cabergoline delivered in bait affects the reproductive success of vixens and may be a practical adjunct to the lethal control of wild red foxes in Australia.

Topics: Abortion, Induced; Abortion, Veterinary; Animals; Animals, Newborn; Cabergoline; Dose-Response Relationship, Drug; Ergolines; Female; Foxes; Gestational Age; Lactation; Litter Size; Placebos; Pregnancy; Time Factors

Red foxes (Vulpes vulpes) are a major pest species in Europe and Australia. Traditional methods of control such as hunting or poisoning are no longer sufficient or feasible. As with domestic dogs and cats, prolactin (PRL) in the vixen is an essential luteotropin during the second half of gestation. Hence, PRL inhibitors such as cabergoline have been used to induce abortions. Eighteen mated silver fox vixens (three groups of six foxes each) were treated orally with a placebo of paraffin oil (I), or with 15 microg/kg cabergoline in feed once (11) or twice (III), on day 30 (I and II) or days 30 and 32 (III) post-coitum. Blood samples were taken prior to and after treatments and concentrations of PRL and progesterone (P4) were determined. Normal parturitions were observed in five of six, five of six and two of six vixens in groups I, II and III, respectively. In group III plasma concentrations of PRL and P4 decreased significantly but only temporarily. This drop in hormone concentrations was more pronounced in the vixens that did not carry to term. In conclusion, doses in excess of 15 microg/kg of cabergoline are likely to prevent the development of fetuses to term in pregnant vixens.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Administration, Oral; Animals; Cabergoline; Dose-Response Relationship, Drug; Ergolines; Female; Foxes; Pregnancy; Progesterone; Prolactin

The aim of this study was to describe the changes in the resistance index (RI) and systolic/diastolic ratio (S/D) of the uterine arteries during mid-pregnancy abortion induction in the dog. Sixteen 30-35 day pregnant bitches were randomly assigned to either a pharmacological protocol to interrupt gestation (n = 8) or were used as untreated control group (n = 8). Doppler assessments of uterine arteries blood flow were carried out before the initiation of the protocol and then every other day up to abortion (treated group) or parturition (control group). All treated bitches aborted 6 +/- 1.2 days after initiation of the treatment (while none of the non-treated bitches aborted). Pre-treatment RI and S/D did not differ between groups (p > 0.2) while average post-treatment indexes were (mean +/- SD): 0.62 +/- 0.1 vs 0.53 +/- 0.1 (p < 0.01) and 2.96 +/- 0.9 vs 2.23 +/- 0.3 (p = 0.01), for the treated and non-treated group respectively. Correlations between days to abortion and RI or S/D were 0.75 (p < 0.01) and 0.79 (p < 0.01) and, -0.78 (p < 0.01) and -0.73 (p < 0.01) for the treated and non-treated groups respectively. In the treated group, correlations between serum progesterone (P(4)) concentrations and RI and S/D were -0.76 (p < 0.01) and -0.59 (p < 0.01) respectively. It is concluded that, during induction of abortion, RI and S/D of uterine arteries progressively increased while P(4) decreased.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Animals; Blood Pressure; Cabergoline; Cloprostenol; Dogs; Ergolines; Female; Pregnancy; Pregnancy Outcome; Pregnancy, Animal; Uterine Artery; Uterus

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(2alpha)-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.

Topics: Abortion, Induced; Abortion, Veterinary; Animals; Cabergoline; Cloprostenol; Dogs; Embryonic Development; Ergolines; Estrenes; Female; Pregnancy; Pregnancy, Animal; Progesterone; Prolactin; Relaxin

Topics: Abortifacient Agents; Abortion, Veterinary; Animals; Cabergoline; Dogs; Ergolines; Female; Legislation, Veterinary; Netherlands; Pregnancy; Pregnancy, Animal; Ultrasonography, Prenatal

The efficacy of cabergoline solely or combined with a PGF2alpha analogue in inducing abortion at different stages of pregnancy was investigated in 18 queens. The queens were assigned to two treatments: Group I ( n=10 )-cabergoline (15 microg/kg; daily, orally) and Group II ( n=8 )-cabergoline (15 microg/kg; daily, orally) combined with alfaprostol (10 microg/kg; every other day, subcutaneously). Each group was divided into two subgroups according to the duration of pregnancy when treatments started: Group IA ( n=8 ) included queens from Days 34 to 42 after mating. Group IB cats ( n=2 ) started treatments on Day 45 post-mating. Similarly, the combination of cabergoline and PGF2alpha analogue was first given to Group IIA ( n=6 ) from Days 25 to 40 of pregnancy and to Group IIB ( n=2 ) on Days 45 and 47, respectively. Termination of pregnancies was successful in all cats of Group IA, while treatments failed in both cats of Group IB, even though seven and eight treatments, respectively, were given. Mean (+/-S.D.) plasma progesterone concentrations before the start of treatments were 85.0+/-12.3 nmol/l and decreased within 3 days to 8 nmol/l and subsequently to basal values, when the queens aborted (Group IIA, n=6 ) or gave birth prematurely (Group IIB, n=2 ). When abortions failed (Group IB, n=2 ), progesterone concentrations remained elevated (16.9 and 9.8 nmol/l). Duration of combined therapy during late pregnancy in Group IIB ( n=2 ) lasted about 10 days. In both cases, premature birth occurred and the kittens died within 16 h after birth. Overall, treatments starting on Days 25-42 of pregnancy (Groups IA and IIA) had abortion rates of 100%. The average duration of treatments was 5.6+/-1.5 days (range, 3-8). Side effects seen were vomiting and occurred in 6 of the 109 (5.5%) treatments. In conclusion, pregnancies were successfully terminated in the second trimester of feline pregnancy by daily application of cabergoline solely or combined with the PGF2alpha analogue alfaprostol (given every other day). Cabergoline alone was ineffective in inducing abortion at later stages of pregnancy.

Topics: Abortion, Induced; Abortion, Veterinary; Animals; Cabergoline; Cats; Ergolines; Female; Pregnancy; Progesterone; Prostaglandins F; Time Factors

The combination of a dopamine agonist, cabergoline, and a synthetic analogue of prostaglandin F2 alpha, 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. Cabergoline was administered orally at 5 micrograms/kg daily and cloprostenol was injected subcutaneously at 1 microgram/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 corresponding period (from day 25 to day 50 after the estimated luteinising hormone surge). In the treated group, interoestrous intervals (98 +/- 41 days) were reduced, compared with previous cycles (194 +/- 9 days) or with those of the control animals (205 +/- 37 days). It is concluded that the combination treatment with the anti-prolactinic agent, cabergoline (5 micrograms/kg/day), and the synthetic prostaglandin F2 alpha, cloprostenol (1 microgram/kg/two days), is an easy, practical, reliable and safe method to terminate pregnancy near and before mid-gestation in dogs.

Topics: Abortion, Induced; Abortion, Veterinary; Administration, Oral; Animals; Cabergoline; Cloprostenol; Dogs; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Injections, Subcutaneous; Pregnancy; Pregnancy Outcome; Progesterone