Abortion in bitches and queens

Abortion means the spontaneous or induced interruption of a pregnancy with expulsion of the products of conception. A pregnancy can be interrupted at various points in its evolution and can be followed by embryonic reabsorption or expulsion of foetuses at different stages of development, dead, with or without lysis, maceration or mummification, or in some cases alive but incapable of ex utero survival.

SPONTANEOUS ABORTION

The very numerous causes of spontaneous abortion in bitches and queens (which cannot be dealt with in detail here) can be divided into the following main categories:

• Genetic and chromosomal causes
• Immunological causes
• Severe malformations
• Placental abnormalities
• Chronic systemic disorders (diabetes, heart disease, etc.)·Genital disorders (uterine cancer, endometrial cystic hyperplasia/pyometra, etc.)
• Bacterial infections (brucella, mycoplasma, ureoplasma, non-specific bacteria) and viral infections (distemper virus, canine parvovirus, canine herpes virus, feline panleukopenia virus, feline herpes virus, feline leukemia virus, feline immunodeficiency virus, etc.)
• Protozoan infections (toxoplasma, neospora, etc.)
• Endocrine causes (luteal failure, hypothyroidism, etc.)
• Malnutrition
• Traumatic causes or stress
• Iatrogenic causes (cortisones, antiprolactin drugs, chemotherapy, prostaglandins, oestrogens, etc.).

The signs many not be obvious if the pregnancy is interrupted in the early stages and if the cause of the abortion is not accompanied by systemic signs in the pregnant animal. In other cases the abortion may be associated with vulvar discharges of various types (mucosal, purulent, haemorrhagic) or expulsion of foetuses at different stages of development and states of conservation.

INDUCED ABORTION

A request for a voluntary termination of pregnancy is common in veterinary medicine and may be made for reasons of management (unwanted litters) or medical causes; these latter include:

• inappropriate pregnancies (females that are too old or too young, mating with an undesired male, disproportion in size between the male and female, poor general condition of the female and systemic disorders such as diabetes and heart disease);
• pathological progression of the pregnancy (endometrial cystic hyperplasia/pyometra, hypocalcaemia, and/or eclampsia, toxaemia, uterine torsion, rupture of the uterus, etc.).

INDUCED ABORTION IN THE BITCH

Depending on whether the owner wants to maintain the animal’s reproductive potential, the gestational age, the general condition of the patient and the state of the genital apparatus, a pregnancy in a bitch can be terminated in various ways, although these can essentially be divided into surgical or pharmacological methods. The diagnosis of a pregnancy can be made from the third week after mating, depending on the method used; however, owners often ask for a termination of pregnancy before the pregnancy has actually been confirmed, based simply on a presumed or real misalliance. The interruption of a potential pregnancy before its definite diagnosis is a controversial subject; while, on the one hand, early treatment can be considered ethically more appropriate (and, in some cases, also more efficient), on the other hand, there is a probability (of about 50%) of carrying out useless treatments in non-pregnant females. There is no method able to ascertain the existence of a pregnancy immediately after mating; colposcopy with cytological studies can only define the phase of the oestrous cycle at the time of mating more precisely and prove, in the case of finding sperm, that mating has indeed taken place. It should be noted that the lack of finding of spermatozoa on a vaginal smear is not definitive proof that mating has not taken place.

A more precisely targeted abortion management is based on pharmacological   or surgical treatment only after the pregnancy has been confirmed, which can be done early at 20 days after the peak of  the luteinising hormone (LH) (Fig. 1). When a termination of pregnancy is performed in mid-gestation or late in the pregnancy it is always appropriate to hospitalize the patient and it should be appreciated that an abortion carried out after 40-45 days of gestation can be followed by a period of lactation.

Surgical methods
Abortion is achieved surgically through an ovariohysterectomy or, when possible, an ovariectomy. Surgery is an excellent choice for subjects not destined to reproduction, providing contemporaneous termination of the unwanted pregnancy and definitive elimination of reproductive capacity. In contrast to widely held belief, ovariohysterectomy can be carried out at any time during gestation (Figs.  2 and 3) and, if the animal’s owner decides to resolve the problem of a possible undesired pregnancy immediately after a suspected or known mating, even in females still in oestrus. It should be noted that an intervention during oestrus requires greater surgical care because of the increased vascularisation of the genital apparatus as the result of the predominant action of oestrogens. An ovariohysterectomy carried out in late gestation also requires some special anaesthesiological and surgical precautions because of particular physiological conditions of bitches at the end of gestation.

Pharmacological methods
It is worth pointing out that none of the currently available pharmacological treatments for the termination of pregnancy in the bitch is “ideal”, as none fulfils all the following requisites:

• effective at any period of gestation
• absolute efficacy (100%)
• lack of side effects
• no effect on fertility
• easy to administer
• short duration of treatment
• no vulvar discharge or expulsion of foetuses
• inexpensive

The main, currently available options for the pharmacological interruption of pregnancy in the bitch are described below.

Oestrogens prevent implantation of blastocysts, delaying their descent into the uterus, causing congestion and oedema of the salpinges and closure of the uterine-tubal junction, but are associated with various adverse events such as the development of uterine pathologies and blood dyscrasias, which may be severe. For this reason some authors believe that the use of these hormones can be considered “professional negligence”. The most common side effect resulting from the use of oestrogens for pregnancy termination in bitches is the increased risk of development of endometrial cystic hyperplasia/pyometra, which has been recorded in between 7.3 and 15% of cases. Oestrogen-related bone marrow toxicity is characterized by haematological abnormalities, including thrombocytopenia, anaemia and leucocytosis or leucopenia, and often has a poor prognosis. The most widely used protocols describe the administration of oestradiol benzoate at a dose of 0.01 mg/kg on days 3, 5 and (only occasionally) on day 7 after the undesired mating (efficacy almost 95%) or of a single dose of 0.2 mg/kg 2 days after mating, with the same efficacy. The use of oestradiol cypionate has been associated with the development of pyometra in 25% of treated subjects.

Natural prostaglandins F2α (PGF2α) or their synthetic analogues have been used in very varied protocols with the purpose of  inducing luteolysis or at least a functional block of the corpora lutea and myometrial contractions, although they do not always ensure opening of the cervix. Unlike in other animals in which a single administration of PGF2α is able to induce luteolysis, multiple administrations are necessary in the bitch.

According to one of the most widely used protocols, cloprostenol, a synthetic PGF2α analogue, is administered, under the control of a veterinarian, at a dose of 1-2.5 mg/kg s.c. on alternate days (or daily) for 3-5 days until the levels of progesterone in the blood remain below the concentration of 2 ng/ml for at least 24 hours. The efficacy of this protocol was 100% after 4-7 days of treatment.

The natural PGF2α are used at doses between 20 and 250 μg/kg/8-12 hours for 4-7 days or at doses increasing from 25 μg/kg/8-12 hours for the first 2 days of treatment followed by 50 μg/kg/8-12 hours on the third and fourth days and 100 μg/kg/8-12 hours from the fifth day onwards.

The abortion is usually obtained within the ninth day of starting treatment, but in some cases may be only partial, compelling continuation of the treatment until there is ultrasonographic demonstration of an empty uterus. The efficacy of PGF2α is greater if these hormones are used in mid-gestation rather than at the beginning of a pregnancy (within 25 days). The patient must be admitted to hospital in order to monitor the possible development of side effects of PGF2α, which occur above all in the 30 minutes following the first dose and tend to decrease with subsequent administrations. Common side effects are restlessness, salivation, rapid breathing, vomiting, diarrhoea, colicky pain and muscle tremors, due to non-specific stimulation of smooth muscle. The duration and severity of side effects can be limited by the administration of atropine or chlorpromazine. Treatment with PGF2α leads to an early return of oestrus (within 1-3 months of the abortion) because the hormone interferes with the phase of dioestrus.

Aglepristone is a synthetic steroid that antagonises the effects of progesterone through receptor competition at the level of target organs, including the uterus, because of its greater affinity (three-fold greater) than progesterone for receptor binding. Aglepristone is able to induce abortion or embryonic reabsorption, depending on the period of gestation, within 7 days of treatment. The abortive treatment consists of two subcutaneous doses of aglepristone 10 mg/kg at a 24-hour interval and produces a peak blood concentration within 2.5 days; the steroid remains in the circulation for about 6 days. Its excretion is predominantly faecal and very slow, such that 10 days after administration, only about 60% has been excreted.

The use of aglepristone in the early stage of pregnancy must be preceded by colposcopy and cytological determination of the state of dioestrus. In fact, since the steroid acts within 7 days of administration, if the bitch has mated before ovulation and is treated with a single dose of aglepristone, the treatment could be ineffective. Despite this, aglepristone is the most effective drug with the fewest side effects used for the termination of pregnancy, particularly in the early phase of gestation; nevertheless, for large dogs the financial cost of “blind” treatment could justify waiting to have a definite diagnosis of a pregnancy.

The double treatment, separated by 24 hours and carried out within 21 days of the start of the pregnancy has been found to be effective in 99.6% of cases. The efficacy of aglepristone in mid-gestation (22-40 days) is good (94-96%), but lower than that in the early period and leads to a brownish, mucosal, vulvar discharge, slight sensorial depression, transient loss of appetite and swelling of the mammary glands about 24 hours before expulsion of the foetuses. It is, therefore, good practice to perform an ultrasound to confirm that the abortion has been complete ( Fig. 4).

In the case of partial abortion and incomplete emptying of the uterus, a second treatment with aglepristone in combination with PGF2α can be considered. Possible protocols include:

• Aglepristone 10 mg/kg s.c. + two administrations of natural PGF2α (dinoprost) at a dose of 50 μg/kg/12 hours s.c. separated by 24 hours until complete abortion;
• Aglepristone 10 mg/kg s.c.+ two administrations of cloprostenol at a dose of 1.5 μg/kg/die s.c. separated by 24 hours until complete abortion
• Aglepristone 10 mg/kg s.c. + two administrations of cloprostenol at a dose of 1 μg/kg 10 times a day separated by 24 hours for 2 days + metoclopromamide 0.5 mg/kg/12 hours i.v.

A recent study demonstrated that abortion times could be significantly reduced by intravaginal application of misoprostol (a synthetic analogue of PGE1), at a daily dose of 200 mg in bitches weighing ≤20 kg and 400 mg in bitches weighing >20 kg, in association with aglepristone (10 mg/kg for 2 consecutive days) between days 25 and 35 of pregnancy.

The administration of dopamine-agonists, used with the purpose of indirectly inducing luteolysis through an antiprolactin effect (eliminating the luteotrophic action of prolactin in the second half of pregnancy), must be limited to the second half of gestation (>40 days). Of the various antiprolactins, cabergoline is used at a dose of 5 mg/kg/die per os for 7-10 days and metergoline at a dose of 0.4-0.6 mg/kg/12 hours for 5 days also orally. Bromocriptine can also be given, but the high doses required (100-200 mg/kg for 6 days) frequently induce adverse events including vomiting, diarrhoea and lethargy.

Another protocol describes the combined use of dopaminergics and cloprostenol for the termination of pregnancies in their middle or terminal phase. These protocols are intended to reduce side effects and shorten the treatment times typical of PGF2α and increase the efficacy of the abortive treatment. Various different regimens, reported below, can be used:

• cabergoline 5 μg/kg/die per os for 9 days starting from 25 days after the LH peak + cloprostenol 1 μg/kg s.c. on alternate days (for up to a maximum of 9 days);
• cabergoline 5 μg/kg/die per os for 10 days (starting from 28 days after the LH peak) + cloprostenol 1 μg/kg s.c. on days 1 and 5 of treatment;
• cabergoline 5 μg/kg/die per os for 10 days + cloprostenol 2.5 μg/kg s.c. on day 1 of treatment;
• bromocriptine 30 μg/kg/8 hours per os for 10 days + cloprostenol 2.5 μg/kg s.c. on day 1 of treatment;
•  bromocriptine 30 μg/kg/8 hours per os for 10 days + cloprostenol 1 μg/kg s.c. on days 1 and 5 of treatment;
• cabergoline 5 μg/kg/die per os for 7 days not before 35-45 days after the mating + cloprostenol 1 μg/kg s.c. on days 1 and 3 of treatment.

Although numerous other protocols for the pharmacological termination of pregnancy in the bitch have been published, these protocols are not presented here given their experimental nature or the high risk of side effects associated with the drugs involved.

INDUCED ABORTION IN THE QUEEN

The pregnancy of a queen can be terminated by ovariohysterectomy, which can be carried out in any stage of gestation, but also by ovariectomy alone up to the fourth week of gestation. Pharmacologically induced termination can be achieved using the same drugs as those employed in bitches.

Aglepristone can be given at a dose of 15 mg/kg repeated after 24 hours, starting from the day of mating until 45 days later, while eoestradiol benzoate can be given in the first 10 days after mating at the dose of  0.1 mg/kg two or three times on alternate days.

Natural PGF2α or their synthetic analogues can be administered after 40 days of pregnancy: dinoprost at a dose of 500-1000 μg/kg/die s.c. repeated after 24 hours and cloprostenol at a dose of 2.5-5 μg/kg s.c for 5-7 days. The side effects, which develop 10-20 minutes after starting the treatment and last for about 1-3 hours, include nausea, vomiting, diarrhoea and exhaustion. Treatment with cabergoline has given conflicting results: some studies documented an only transitory decrease in progesterone levels in the blood not followed by complete abortion, while in other studies the administration of cabergoline 5-15 μg/kg/die per os for 5 days starting from 25-48 days after mating produced the desired abortion.

The protocol for the cabergoline + cloprostenol combination, used after the diagnosis of pregnancy, consists of cabergoline per os (5 μg/kg/die) and cloprostenol s.c. at a dose of 5 μg/kg/die for 7-14 days or 2.5 μg/kg s.c. on days 1, 3 and 5. This regimen does not appear to have side effects and has been followed by normal pregnancies.

Suggested readings

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10. Wanke MM, Romagnoli S, Verstegen J, et al. Pharmacological approaches to pregnancy termination in dogs and cats including the use of prostaglandins, dopamine agonists, and dexamethasone. In: Concannon PW, England G, Verstegen J, et al., eds. Recent Advances in Small Animal Reproduction. Ithaca NY: International Veterinary Information Service (www.ivis.org [5]), 2002:A1223.0802.2