by C. Scott Bailey, DVM, DACT
Despite much of discussion on the subject, there is still
a great disparity in treatment protocols for mismated companion animals in the
USA and elsewhere. Numerous treatment protocols are available.
Ovariohysterectomy has the advantage of permanently removing the risk of an
unwanted pregnancy. Medical treatments have varying side effects depending on
the protocol selected, and depend on owner vigilance to prevent future
pregnancies. Medical treatment is most often performed in early gestation or
mid gestation. Pregnancy termination after fetal ossification (45 days) results
in abortion of non-viable or poorly viable fetuses.
Treatment
choices should be guided by an animal’s actual risk of pregnancy. In dogs, a
vaginal swab and cytologic evaluation provide 2 key pieces of information: 1)
Detection of sperm heads on cytology can confirm exposure to a male, and 2)
determination of estrus stage at the time or presentation. In a study involving
16 females with known breeding histories, Whitacre and coworkers demonstrated
that sperm could be seen microscopically in 100% of cases within 24 hours of
breeding and in 75% of cases within 48 hours of breeding, using a modified
sampling technique. Determination of estrus stage is also a key component of
determining the risk of pregnancy. Bitches with known or suspected exposure to
a male during proestrus are at much lower risk of pregnancy than those exposed
during estrus. Cytologic diagnosis of proestrus can be further confirmed with
serum progesterone concentrations of <2ng/mL. As cats are induced ovulators,
serum progesterone will likely be low in unexposed cats (<2ng/mL) and would
rise after coitus in exposed cats.
Prior to any treatment, it is important to carefully
consider options for treatment. Animals that are not intended to be breeding
animals, do not have high risk-factors for spay-associated disease and which
are not in show, should undergo ovariohysterectomy in early diestrus/pregnancy.
This will prevent future unwanted pregnancies and may decrease the animals’
risk of several diseases, including pyometra, mammary and ovarian neoplasia.
Animals which cannot be spayed may be treated medically with a variety of
protocols.
Early pregnancy termination
Several
protocols have been proposed to medically treat bitches as soon as a mismating
occurs. This approach is attractive, but may pose a greater risk to the animal
and have lower success rates than other protocols. As a result, most reviewers
have recommended against these treatment regimens.
Estrogens
have been widely used for this purpose in the past, but potentially severe
side-effects should raise concerns. Several reports indicate significant health
risks associated with estrogen treatment in dogs and cats, including an
increased risk of pyometra, infertility and toxicity.
Pregnancy termination in mid-gestation
In the
dog, pregnancy can be readily diagnosed by palpation approximately 30 days
after mating, whereas ultrasonographic examination can confirm pregnancy as
early as 15-18 days after the LH surge (~10-20 days after mating). Embryos are
easily detectable between day 22 and 25 after LH surge. In the queen,
ultrasonographic pregnancy diagnosis can be achieved as soon as 11 days after
mating and the embryo becomes visible by 14 or 15 days after mating.
At this
stage, embryonic fluids and tissues are resorbed by the uterus and few clinical
signs are expected in response to medical intervention. A bloody discharge may
be seen in bitches and queens after approximately 30 days. Abortion (fetal
expulsion) occurs after 40-45 days, when fetal ossification is underway.
Prostaglandins
Natural prostaglandins can be used to terminate
pregnancy beginning 5 days after ovulation, however prior to 25 days, higher
doses are required than later in gestation. Hospitalization and careful
monitoring of animals are recommended to control side-effects, which tend to be
more severe early and diminish during the course of treatment. Side effects may
be minimized by using low doses of prostaglandin, or by starting with a lower dose and gradually
increasing it. It should be noted that low doses may not induce permanent
luteolysis, resulting in loss of only some pups or fetal death followed by
mummification. The synthetic prostaglandin cloprostenol has also resulted in
effective pregnancy termination, with few side effects.
Dopamine
Agonists
In both
the bitch and queen, prolactin plays a necessary luteotrophic role in pregnancy
maintenance. Progesterone can be reduced or eliminated during late pregnancy by
administering a dopamine agonist, which inhibits endogenous prolactin secretion.32 However, treatment success for pregnancy termination
has been inconsistent in both dogs and cats and dopamine agonists alone are
rarely used in companion animals.
Combined
Prostaglandin/Dopamine Agonist Regimen
Extensive
work by Verstegen and coworkers, demonstrated that a dual approach to pregnancy
termination results in reliable efficacy in mid gestation. Low doses of either
natural or synthetic prostaglandins result in luteolysis, while dopamine
agonists inhibit prolactin release. In a series of studies, administration of
cabergoline and cloprostenol resulted in fetal resorption with minimal
discharge or unwanted drug-effects in both dogs and cats. Treatment was
continued until ultrasonographic confirmation of fetal demise. The above
protocol has several distinct advantages over other protocols described: Both
prostaglandins and dopamine agonists are readily available in the USA. The
combined luteolytic and antiluteotrophic mechanisms decrease dosages of each
drug, substantially reducing side effects. The protocols can be instituted
around day 25 and result in resorption prior to fetal ossification, when most
animals would abort formed fetuses. The use of orally administered dopamine
agonists and long-acting, synthetic prostaglandins eliminates the need for
frequent examination and hospitalization.
Conclusions
In conclusion, risk for pregnancy should be determined
at the time of mismating and ideally pregnancy should be confirmed prior to
treatment in order to avoid unnecessary and potentially harmful medical side
effects. Treatment choices should be based on the animal’s stage of gestation
and availability and should be tailored to minimize side effects as much as
possible. A treatment onset between 25 and 30 days and combination of two
drugs, including a prostaglandin and dopamine agonist minimize drug dosage and
side effects while inducing fetal resorption rather than abortion.