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Termination of unwanted pregnancy in dogs. Mesalliance Estradiol bezonateEstradiol bezonate –after mating Progesterone receptor antagonist: Mifepristone(RU486),

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Presentation on theme: "Termination of unwanted pregnancy in dogs. Mesalliance Estradiol bezonateEstradiol bezonate –after mating Progesterone receptor antagonist: Mifepristone(RU486),"— Presentation transcript:

1 Termination of unwanted pregnancy in dogs

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4 Mesalliance Estradiol bezonateEstradiol bezonate –after mating Progesterone receptor antagonist: Mifepristone(RU486), AglepristoneProgesterone receptor antagonist: Mifepristone(RU486), Aglepristone –mid-gestation Glucocorticoid: DexamethasoneGlucocorticoid: Dexamethasone –mid- and late gestation

5 Mesalliance PGF 2  : Dinoprost, CloprostenolPGF 2  : Dinoprost, Cloprostenol –mid- and late gestation Dopamine agonist: Cabergoline, BromocryptineDopamine agonist: Cabergoline, Bromocryptine –mid- and late gestation

6 Administration of Estradiol bezonate Risk after administration of estrogenRisk after administration of estrogen –Pyometra –Metritis –Ovarian cysts –Aplastic anemia, bone marrow suppression –Alopecia Clinically, > 60% bitches after an unwanted mating are not pregnant Feldman et al. 1993Clinically, > 60% bitches after an unwanted mating are not pregnant Feldman et al. 1993

7 Administration of Estradiol bezonate Estrogen prolongs the ovicduct transport time and tightens the utero-tubular junction, resulting in implantation failure or embryonic death. Estrogen prolongs the ovicduct transport time and tightens the utero-tubular junction, resulting in implantation failure or embryonic death mg/kg im or sc0.01 mg/kg im or sc repeated injection at 3rd, 5th and 7th day after matingrepeated injection at 3rd, 5th and 7th day after mating mg/kg for one injection within 4 days of mating?0.1-3 mg/kg for one injection within 4 days of mating?

8 Progesterone receptor antagonist Concannon et al mg/kg mifepristone, sc, bid for 5 days 32 days → abortion(5/5) Sankai et al mg/kg mifepristone, single sc, ~ 56 days → abortion(8/8 mixed dogs) Fieni et al aglepristone → abortion(66/69) Galac et al mg/kg aglepristone, sc, for 2 days 30 days after ovulation → abortion(5/5 beagle bitches) within 4-7 days Interestrus interval 155 ± 10 d vs 199 ± 15 d

9 Plasma concentrations of prolactin( ● ) and progesterone ( ○ )in a beagle bitch, starting from the day of ovulation (Day 1) to the end of the luteal phase. On Day 30 & 31, the bitch was treated with aglepristone. Galac et al. (1999)

10 Progesterone receptor antagonist Aglepristone is a safe, reliable and effective abortifacient during mid-gestation.Aglepristone is a safe, reliable and effective abortifacient during mid-gestation. The only side-effect of treatment was some mucoid vaginal discharge in the 1st week.The only side-effect of treatment was some mucoid vaginal discharge in the 1st week. Aglepristone do not impair future fertility? (but only 1/6 bred later)Aglepristone do not impair future fertility? (but only 1/6 bred later)

11 Administration of Dexamethasone Wanke et al pregnant bitches (day 30-35) 6 pregnant bitches (day 45-50) 62 bitches mg/kg,po, bid for 2 days → decrease to 0.02 mg/kg for 5 days →5 bitches failed to abort 18 bitches 0.2 mg/kg,po, bid for 7 days → decrease to 0.02 mg/kg for 5 days → 100% abortion

12 Administration of Dexamethasone Side effects: polydipsia, polyuria, vaginal discharge, restlessness, anorexia or vomiting 20 bitches were mated and had normal pregnancies and normal litters. Wanke et al Wanke et al. 1997

13 Administration of PGF 2  - more resistant to the luteolytic effect of PGF 2  and susceptible to its deleterious side effects (→ atropine 50 ug/kg, im) - the narrow margin between a LD50(5 mg/kg, 2-12 hrs after inj.) and therapeutic one - side effects such as vomiting, diarrhea, pupil dilation, hyperpnoea, salivation, urination, anxiety and ataxia

14  Reports on experimental use of PGF2  to determinate pregnancy in bitches days of Dinoprost Days No. of Abortions side Pregnancy (ug/kg) treated Dogs effects , bid % , bid % , bid , bid % , sid % , bid , bid % , bid , bid % , sid % , sid % , sid % ++

15 Administration of PGF 2  The rapidly developing CL during the early luteal phase are more resistant to the luteolytic effects of PGF 2  than are fully developed CL after days.The rapidly developing CL during the early luteal phase are more resistant to the luteolytic effects of PGF 2  than are fully developed CL after days. Even with ug/kg, abortive efficacy is dependent on an injection frequency greater than sid.Even with ug/kg, abortive efficacy is dependent on an injection frequency greater than sid. - repeated administration with low to modest dose for 4-10 days

16 Efficacy of repeated administration of PGF 2  in 30 case of misalliance at University of Pretoria ( ) Days after administration No. of dogs efficacy% Mating of Dinoprost(sc, bid) ug/kg for 4-5 days ug/kg for 5-7 days ug/kg for 4-8 days ug/kg for 4-5 days ug/kg for 4 days ug/kg for 4 days ug/kg for 3-4 days 2 100

17 Efficacy of repeated administration of PGF 2  in 18 dogs of 14 breeds from Edward et al. (1993) Days after administration No. of dogs efficacy% Mating of Dinoprost (sc) I. 0.1 mg/kg, tid until abortion II mg/kg, bid until abortion III. 0.1 mg/kg, tid for 2 days, then 0.2 mg/kg, tid until abortion 6 100

18 Plasma progesterone concentration after initiating PGF 2  treatment. Day 0 represents the pretreatment concentration. Edward et al. (1993)

19 Administration of PGF 2  All dogs aborted all fetuses within 9 days of beginning treatment.All dogs aborted all fetuses within 9 days of beginning treatment. Plasma progesterone concentration  2.0 ng/ml would result in termination of pregnancy in bitches.Plasma progesterone concentration  2.0 ng/ml would result in termination of pregnancy in bitches. Hospitalization is recommended to allow observation of the bitch and to avoid having the owner witness the abortion process.Hospitalization is recommended to allow observation of the bitch and to avoid having the owner witness the abortion process.

20 Dopamine agonist Prolactin, interacting with lipoproteins to enhance P4 production in the luteal cells, is one of the important luteotropic hormones in pregnant dogs, especially in the 2nd half of pregnancy.Prolactin, interacting with lipoproteins to enhance P4 production in the luteal cells, is one of the important luteotropic hormones in pregnant dogs, especially in the 2nd half of pregnancy. Concannon et al Anti-prolactin agents, such as dopamine agonists, have been used to induce abortion, from days after LH surge. Concannon et al Anti-prolactin agents, such as dopamine agonists, have been used to induce abortion, from days after LH surge. Wichtel et al Wichtel et al. 1990

21 Concannon et al mg/kg im for 6 days 8-22 days, decreasing P4 for 4-6 days → no abortion 42 days, decreasing P4 → abortion Wichtel et al mg/kg, po, bid for 4 days 42 days → abortion 62.5 mg/kg, po, bid for 6 days days → 50% abortion Effects of bromocriptine on the pregnancy of the bitch

22 6 beagle Cabergoline 5 ug/kg, po for 28 days after mating → no abortion 4 bitches 3-6 weeks of gestation 5-15 ug/kg, po daily for 5 days → no abortion, Prolactin  , P4 > 1 ng/ml 8 bitches > 6 weeks of gestation 5 ug/kg, po daily for 5 days → 100% abortion 3-5 days after the treatment, P4 < 1 ng/ml Effects of cabergoline on the pregnancy of the bitch Post et al. 1988

23 Dopamine agonist The CL of the bitch are not sufficiently sensitive to the luteolytic effect of cabergoline or bromocriptine during the early to mid stage of gestation.The CL of the bitch are not sufficiently sensitive to the luteolytic effect of cabergoline or bromocriptine during the early to mid stage of gestation. The administration of cabergoline or bromocriptine has few side effects and may be preferable over the use of PGF 2 .The administration of cabergoline or bromocriptine has few side effects and may be preferable over the use of PGF 2 .

24 PGF 2  + Dopamine agonist Recently, a treatment combining reduced doses of PGF 2  (25 ug/kg → 2.5 or 1 ug/kg once daily) and a dopamine agonist which inhibits pituitary prolacin secretion was shown to terminate early pregnancy.Recently, a treatment combining reduced doses of PGF 2  (25 ug/kg → 2.5 or 1 ug/kg once daily) and a dopamine agonist which inhibits pituitary prolacin secretion was shown to terminate early pregnancy. Onclin & Verstegen 1996 Onclin & Verstegen 1996

25 PGF 2  + Dopamine agonist The regression of the CL is achieved directly by the PGF 2  and indirectly by the carbergoline by withdrawing its main luteotropic support, prolactin.The regression of the CL is achieved directly by the PGF 2  and indirectly by the carbergoline by withdrawing its main luteotropic support, prolactin. Okkens et al Okkens et al. 1990

26 Onclin et al Cabergoline Cabergoline Cabergoline Alphaprostol 20 Cloprostenol 2.5 Cloprostenol 1.0 n=5 n=5 n=5 Dose(ug/kg) Cabergoline Days of treatment 32nd 25th 25th Resorption/Expulsions 2/3 5/0 5/0 Side effects none Interestrus interval (days) pretreatment 182 ± ± ± 5 treated 134 ± ± ± 44 Control group 198 ± pregnant beagle administrated cabergoline together with selective dose of alphaprostol or cloprostenol daily for 5 days

27 Onclin & pregnant beagle 25 ± 4 days after 1st mating mean Verstegen ± SD Cabergoline (days) 5 ug/kg daily ± 1 Cloprostenol inj. No. (1 ug/kg/2 days) ± 1 Days to abortion ± 2 Vulvar discharge (days) ± 2 Mode of termination resorption of all fetuses Interestrus interval pretreatment (days) ± 9 treated ± 41 Control group 205 ± 37

28 Progesterone concentrations in the 5 control bitches Progesterone concentrations in the 5 beagles bitches treated with cabergoline (5 ug/kg daily) and cloprostenol (1 ug/kg/2 days). Arrow indicates start of treatment (25th day after LH surge)

29 PGF 2  + Dopamine agonist The start treatment in the early pregnancy: Day 25 after the 1st mating; a mean of 28 days after the LH surge.The start treatment in the early pregnancy: Day 25 after the 1st mating; a mean of 28 days after the LH surge. –close to the earlest time at which pregnancy can be diagnosed by palpation or by ultrasound –treatment at this time terminating pregnancy by resorption

30 Onclin & Verstegen Cabergoline oral for 10 days + Cloprostenol 2 Bromocryptine oral tid for 10 days + Cloprostenol 3 Cabergoline oral for 10 days + Cloprostenol 4 Bromocryptine oral tid for 10 days + Cloprostenol Dose(ug/kg)CabergolineCloprostenol Bromocryp- tine 5 beagles 5 beagles beagles 5 beagles beagles 5 beagles 5 1(28th, 32nd) 1(28th, 32nd) 5 beagles 5 beagles 1(28th, 32nd) Days of pregnancy -Start of treatment -Normal whelpings 28th day after LH peak th day after LH peak 0

31 1 Cabergoline oral for 10 days + Cloprostenol 2 Bromocryptine oral tid for 10 days + Cloprostenol 3 Cabergoline oral for 10 days + Cloprostenol 4 Bromocryptine oral tid for 10 days + Cloprostenol Side effect trembling, hyperpnoea, mild prostration, hypersalivation, vomiting, diarrhea none none 2/5 (mild hypersalivation, trembling, and vomiting after the 1st injection Interestrus interval(days) -Pretreatment -After treat- ment 209 ± 46 days vs control group 205 ± 37 days 209 ± 46 days vs control group 205 ± 37 days 150 ± ± ± ± ± ± ± ± 50

32 Mean plasma progesterone concentra- tions in 5 control untreated bitches and in groups of 5 bitches treated with bromocriptine. Mean plasma progesterone concentra- tions in 5 control untreated bitches and in groups of 5 bitches treated with cabergoline. One bitch, Dog 77, treated with cabergoline and 2 inj. of PG had higher P4 levels than the other dogs in this group.

33 PGF 2  + Dopamine agonist A reduced interestrus interval of treated dogs suggests that inhibiting circulating prolactin, combined with direct luteolysis by PGF 2 , may release the inhibitory mechanisms responsible for prolonging the obligatory anestrus phase of a dog’s estrus cycle.A reduced interestrus interval of treated dogs suggests that inhibiting circulating prolactin, combined with direct luteolysis by PGF 2 , may release the inhibitory mechanisms responsible for prolonging the obligatory anestrus phase of a dog’s estrus cycle.

34 Conclusions Advantage:Advantage: –safe for the bitch –terminating pregnancy by resorption rather than by abortion –effective as early as 25 days after the 1st mating All the treated bitches returned in heat and become pregnant and had normal litters. Thus, this treatment did not compromise the fertility of the treated animals.All the treated bitches returned in heat and become pregnant and had normal litters. Thus, this treatment did not compromise the fertility of the treated animals.

35 The bitch became Bromocryptine(30ug/kg), po, tid for 10 days and an injection of Cloprostenol(2.5 ug/kg) about days after mating. Five fetus were delivered 6 days after treatment. Chan et al. 2003

36 Thanks for your attention!


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