Termination of unwanted pregnancy in dogs

1. Termination of unwanted pregnancy in dogs

4. Mesalliance • Estradiol bezonate • after mating • Progesterone receptor antagonist: Mifepristone(RU486), Aglepristone • mid-gestation • Glucocorticoid: Dexamethasone • mid- and late gestation

5. Mesalliance • PGF2: Dinoprost, Cloprostenol • mid- and late gestation • Dopamine agonist: Cabergoline, Bromocryptine • mid- and late gestation

6. Administration of Estradiol bezonate • Risk 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. 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 sc • repeated injection at 3rd, 5th and 7th day after mating • 0.1-3 mg/kg for one injection within 4 days of mating?

8. Progesterone receptor antagonist

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

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. 1997

13. Administration of PGF2 - more resistant to the luteolytic effect ofPGF2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 30-58 30, bid 3 7 60% + 26-55 50, bid 4-10 6 83% + 6 60, bid 3 1 0 + 40 30, bid 3 1 100% + 27 250, sid 6 1 100% + 56 250, bid 4 1 0 ++ 13 250, bid 4 15 80% ++ 10 250, bid 5 5 0 ++ 35 250, bid 5 5 100% ++ 5-17 400-1000, sid1-2 8 25% + 25-51 400-1000, sid 1-5 7 14% ++ 55-58 200-500, sid1-2 9 88% ++

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 25-30 days. • Even with 250-400 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 PGF2 in 30 case of misalliance at University of Pretoria (1982-1987) Days after administration No. of dogs efficacy% Mating of Dinoprost(sc, bid) 21-27 150-250ug/kg for 4-5 days 8 100 30ug/kg for 5-7 days 2 100 28-34 250ug/kg for 4-8 days 6 100 150ug/kg for 4-5 days 4 100 30ug/kg for 4 days 2 50 35-55 250ug/kg for 4 days 2 100 50ug/kg for 3-4 days 2 100

17. 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) 30-35 I. 0.1 mg/kg, tid 6 100 until abortion II. 0.25 mg/kg, bid 6 100 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 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 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. Concannon et al. 1987 Anti-prolactin agents, such as dopamine agonists, have been used to induce abortion, from 30-40 days after LH surge. Wichtel et al. 1990

21. Effects of bromocriptine on the pregnancy of the bitch

22. 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 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 days Onclin et al. 1 2 3 1994 Cabergoline Cabergoline Cabergoline + + + Alphaprostol 20 Cloprostenol 2.5 Cloprostenol 1.0 n=5 n=5 n=5 Dose(ug/kg) Cabergoline 1.65 1.65 1.65 Days of treatment 32nd 25th 25th Resorption/Expulsions 2/3 5/0 5/0 Side effects +++ ++ none Interestrus interval (days) pretreatment 182 ± 11 186 ± 20 173 ± 5 treated 134 ± 18 125 ± 21 126 ± 44 Control group 198 ± 12

27. Onclin & pregnant beagle 25 ± 4 days after 1st mating mean Verstegen1996 1 2 3 4 5 ± SD Cabergoline (days) 5 ug/kg daily 9 9 9 11 9 9 ± 1 Cloprostenol inj. No. (1 ug/kg/2 days) 3 3 3 4 3 3 ± 1 Days to abortion 6 6 6 10 6 7 ± 2 Vulvar discharge (days) 15 13 17 18 18 16 ± 2 Mode of termination resorption of all fetuses Interestrus interval pretreatment (days) 187 198 183 198 206 194 ± 9 treated 122 144 113 57 52 98 ± 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. 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 ultrasound • treatment at this time terminating pregnancy by resorption

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 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.

35. The bitch became Bromocryptine(30ug/kg), po, tid for 10 days and an injection of Cloprostenol(2.5 ug/kg) about 33-35 days after mating. Five fetus were delivered 6 days after treatment. Chan et al. 2003

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