Pregnancy Termination in Companion Animals

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.

 

Keeping up on the Science about Neutering

By C. Scott Bailey, DVM, MS, DACT

Keeping up with the discussion surrounding ovariohystorectomy can be difficult. In veterinary school, most of us were taught, as dogma, that dogs and cats should be neutered. Once in practice, however, other points of view and experiences make this decision less straightforward. We are faced with questions such as, “Should all animals be neutered? At what age should they be neutered? Are there contraindications or risk-factors associated with neutering beside the obvious surgical complications?” Often owners come with preformed opinions about these questions, and as veterinarians it is our job to give them balanced and scientifically accurate information so that their decision is based on more than blogs on the internet.

In the last 2 years, three well-written reviews of the veterinary literature have become available detailing benefits and potential complications (Root Kustritz MV - JAVMA 2007, Sanborn MS - Internet Source 2007, Reichler IM – Reprod Dom Anim 2009). Each discusses the potential population benefits in reducing the number of unwanted animals, many of which end up in shelters. In fact, the overall benefits of neutering animals for population control go largely unquestioned in all three reviews, despite a relative lack of epidemiologic studies to support the concept.

Perhaps of greater importance to the practitioner are the benefits to the individual animal and owner. Castration of male cats is often performed to avoid unwanted male sexual behaviors such as spraying and to control territorial behaviors. These behaviors can be so severe that intact males are considered undesirable by many owners. This incentive to neuter is often not present for owners of dogs or female cats; consequently the discussion can be much more heated.

In male dogs, the benefit to population control is likely the greatest, but the scientific evidence pointing to health benefits is the weakest. Intact male dogs have a low incidence of testicular neoplasms (0.9%), which rarely metastasize and have little impact on the dog’s wellbeing. Unlike men, the incidence of prostatic neoplasms is lower in intact animals (0.2-0.6%) than in castrated animals, which have roughly twice the risk of prostatic neoplasia and 2-5 x the risk of osteosarcoma and hemangiosarcoma (each 0.2% of animals, with significant breed variations). In addition, the risk of obesity is somewhat higher in neutered dogs of both gender, corresponding with a slightly increased risk of diabetes mellitus and rupture of the cranial cruciate ligament. That being said, the primary health benefit to a male dog is a dramatic decrease in the incidence of benign prostatic hyperplasia (BPH) and prostatitis, which can be seen in up to 80% of intact male dogs by 6 years of age. However, both these conditions are treatable (either medically or by castration) and BPH often is present in older intact animals without clinical signs and so only a small portion of those animals will be spared discomfort by preventive surgery.

With females, the situation is only slightly clearer. The primary benefit of neutering females lies solidly in the reduction of mammary gland tumors, which affect 2.5% (80% malignancy) of all queens and 3.4% (50% malignancy) of all bitches and which may cause significant morbidity and mortality. Furthermore, these neoplasms can be reduced by more than 90% if the animals are spayed before their first heat. In addition, the risk of pyometra is eliminated by ovariectomy or ovariohysterectomy. Pyometra affects up to 25% of dogs by the age of 10 years and may be associated with significant morbidity and mortality in some of these.
However, potential detriments of neutering include surgical complications (reported incidence of 2.6% in cats and 6.1% in dogs), obesity, and slightly increased risks of diabetes mellitus in both dogs and cats, as well as cranial cruciate rupture in dogs. With reported incidences of 5-20%, urinary incontinence is a common problem of spayed bitches. This has the potential to significantly impact the animal’s welfare, depending on the severity and the owner’s tolerance of this. In addition, spayed females are at increased risk of urinary tract infections, particularly those spayed at an early age and those animals spayed in the face of “puppy vaginitis”. These cases can result in chronic recurrent UTIs that may dramatically affect the animal’s welfare and result in large expenses to the owner.

As in males, neutered bitches also have a roughly 2-5x greater risk for osteosarcoma and hemangiosarcoma than intact animals. Overall the incidence of these neoplasms is low, affecting approximately 0.2% of all dogs. It should be noted, however, that significant breed variation is reported and that this may greatly influence the benefit-risk ratio of neutering a given animal. Dr. Root-Kustritz tabulated the relative risks for the population overall and also noted the breeds that were predisposed to a particular disease, but not the degree to which this would have an effect. Unfortunately, breeders/owners are often more aware of the diseases affecting their particular breed than their veterinarians. Consequently, they may question the traditional viewpoint presented to them. As an example, a study investigating 683 Rottweilers found an overall incidence of osteosarcoma of 12.6% (compared to 0.2% across all breeds), with the diagnosis twice as likely in neutered animals as in intact animals (Cooley DM - Cancer Epidemiology 2002). Furthermore, they demonstrated that Rottweilers neutered prior to one year of age had a significantly greater risk of osteosarcoma than other dogs, with diagnoses occurring in approximately 25% of animals. This example is one of several that highlights the need for breed- or animal-specific decision-making and owner consultation as opposed to a blanket approach to canine contraception.

A recent paper by the same group out of Purdue University further questions the policy of routine gonadectomy (Waters DJ – “accepted article”, Aging Cell 2009). An analysis of lifetime medical histories, age at death and cause of death for exceptionally long-lived Rottweiler dogs (>= 13 years, or >30% longer than the average life-expectancy) demonstrated that female dogs were more likely to achieve this age than male dogs and that gonadectomy before 4 years of age erased this advantage. “In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight and [genetics]”. This appears to fly the face of accepted tradition, which states that neutered animals live longer than their intact counterparts and may be interpreted as a reason to avoid gonadectomy by the larger community. However, the study focused only on exceptionally long-lived animals, not animals overall. In that larger population, it remains well-documented that neutered animals live longer than intact animals (Kraft W – Eur J Med Res 1998, Greer KA – Res Vet Sci 2007).

In conclusion, while many benefits of neutering the small animal patient remain important and valid, it is critical for veterinarians to remain aware of both benefits and contraindications to neutering in order to give owners a balanced, scientifically sound recommendation, individually tailored to the needs and benefits of our patients.