4 Mesalliance Estradiol bezonate after matingProgesterone receptor antagonist: Mifepristone(RU486), Aglepristonemid-gestationGlucocorticoid: Dexamethasonemid- and late gestation
5 Mesalliance PGF2: Dinoprost, Cloprostenol mid- and late gestationDopamine agonist: Cabergoline, Bromocryptine
6 Administration of Estradiol bezonate Risk after administration of estrogenPyometraMetritisOvarian cystsAplastic anemia, bone marrow suppressionAlopeciaClinically, > 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.0.01 mg/kg im or screpeated injection at 3rd, 5th and 7th day after mating0.1-3 mg/kg for one injection within 4 days of mating?
8 Progesterone receptor antagonist Concannon et al. 19902.5 mg/kg mifepristone, sc, bid for 5 days32 days → abortion(5/5)Sankai et al. 1991mg/kg mifepristone, single sc,~ 56 days → abortion(8/8 mixed dogs)Fieni et al. 1996aglepristone → abortion(66/69)Galac et al. 199910 mg/kg aglepristone, sc, for 2 days30 days after ovulation → abortion(5/5 beagle bitches) within 4-7 daysInterestrus 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.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)
11 Administration of Dexamethasone Wanke et al. 199774 pregnant bitches (day 30-35)6 pregnant bitches (day 45-50)62 bitchesmg/kg ,po, bid for 2 days→ decrease to 0.02 mg/kg for 5 days→5 bitches failed to abort18 bitches0.2 mg/kg ,po, bid for 7 days→ 100% abortion
12 Administration of Dexamethasone Side effects: polydipsia, polyuria, vaginal discharge, restlessness, anorexia or vomiting20 bitches were mated and had normal pregnancies and normal litters.Wanke et al. 1997
13 Administration of PGF2 - more resistant to the luteolytic effect of PGF2 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 Pregnancy (ug/kg) treated Dogs effects Reports on experimental use of PGF2 to determinate pregnancy in bitchesdays of Dinoprost Days No. of Abortions sidePregnancy (ug/kg) treated Dogs effects, bid %, bid %, bid, bid %, sid %, bid, bid %, bid, bid %, sid %, sid %, sid %
15 Administration of PGF2 The rapidly developing CL during the early luteal phase are more resistant to the luteolytic effects of PGF2 than are fully developed CL after days.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 Mating of Dinoprost(sc, bid) Efficacy of repeated administration of PGF2 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 days30ug/kg for 5-7 daysug/kg for 4-8 days150ug/kg for 4-5 days30ug/kg for 4 daysug/kg for 4 days50ug/kg for 3-4 days
17 Mating of Dinoprost (sc) Efficacy of repeated administration of PGF2 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, tiduntil abortionII mg/kg, bidIII. 0.1 mg/kg, tid for 2 days,then 0.2 mg/kg, tiduntil abortion
18 Plasma progesterone concentration after initiating PGF2 treatment Plasma progesterone concentration after initiating PGF2 treatment. Day 0 represents the pretreatment concentration. Edward et al. (1993)
19 Administration of PGF2 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.Hospitalization is recommended to allow observation of the bitch and to avoid having the owner witness the abortion process.
20 Dopamine agonistProlactin, 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.Wichtel et al
21 Concannon et al. 19870.1 mg/kg im for 6 days8-22 days, decreasing P4 for 4-6 days → no abortion42 days, decreasing P4 → abortionWichtel et al. 199020-30 mg/kg, po, bid for 4 days42 days → abortion62.5 mg/kg, po, bid for 6 days42-45 days → 50% abortionEffects of bromocriptine on the pregnancy of the bitch
22 Effects of cabergoline on the pregnancy of the bitch 6 beagle Cabergoline 5 ug/kg, po for 28 days after mating→ no abortion4 bitches3-6 weeks of gestation5-15 ug/kg, po daily for 5 days→ no abortion, Prolactin , P4 > 1 ng/ml8 bitches> 6 weeks of gestation5 ug/kg, po daily for 5 days→ 100% abortion 3-5 days after the treatment, P4 < 1 ng/mlPost et al. 1988
23 Dopamine agonistThe 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 PGF2.
24 PGF2 + Dopamine agonist Recently, a treatment combining reduced doses of PGF2 (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
25 PGF2 + Dopamine agonist The regression of the CL is achieved directly by the PGF2 and indirectly by the carbergoline by withdrawing its main luteotropic support, prolactin.Okkens et al. 1990
26 15 pregnant beagle administrated cabergoline together with selective dose of alphaprostol or cloprostenol daily for 5 daysOnclin et alCabergoline Cabergoline CabergolineAlphaprostol 20 Cloprostenol 2.5 Cloprostenol 1.0n= n= n=5Dose(ug/kg)CabergolineDays of treatment nd th thResorption/Expulsions / / /0Side effects noneInterestrus interval (days)pretreatment ± ± ± 5treated ± ± ± 44Control group ± 12
27 Onclin & pregnant beagle 25 ± 4 days after 1st mating mean Verstegen ± SDCabergoline (days)5 ug/kg daily ± 1Cloprostenol inj. No.(1 ug/kg/2 days) ± 1Days to abortion ± 2Vulvar discharge(days) ± 2Mode of termination resorption of all fetusesInterestrus intervalpretreatment (days) ± 9treated ± 41Control group ± 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 PGF2 + Dopamine agonist 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 ultrasoundtreatment at this time terminating pregnancy by resorption
30 Onclin & Verstegen 19991Cabergoline oral for 10 days + Cloprostenol2Bromocryptine oral tid for 10 days + Cloprostenol34Dose(ug/kg)CabergolineCloprostenolBromocryp-tine5 beagles52.5301(28th, 32nd)Days of pregnancy-Start of treatment-Normal whelpings28th day after LH peak
31 1Cabergoline oral for 10 days + Cloprostenol2Bromocryptine oral tid for 10 days + Cloprostenol34Side effecttrembling, hyperpnoea, mild prostration, hypersalivation, vomiting, diarrheanone2/5 (mild hypersalivation, trembling, and vomiting after the 1st injectionInterestrus interval(days)-Pretreatment-After treat-ment209 ± 46 days vs control group 205 ± 37 days150 ± ± ± ± 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 PGF2 + Dopamine agonist A reduced interestrus interval of treated dogs suggests that inhibiting circulating prolactin, combined with direct luteolysis by PGF2 , may release the inhibitory mechanisms responsible for prolonging the obligatory anestrus phase of a dog’s estrus cycle.
34 Conclusions Advantage: safe for the bitchterminating pregnancy by resorption rather than by abortioneffective as early as 25 days after the 1st matingAll 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