Medical termination of pregnancy in canines: A review

Introduction

Intentional interruption of gestation is termed as Medical Termination of Pregnancy (MTP) (Concannon, 2011) [1] . The most common cause for termination is unwanted mating, occurring with an inappropriate mate or at an inappropriate age (Kustritz, 2010) [2] ; other indications include pre-existing medical conditions such as pregnancy-associated diabetes mellitus (Concannon, 2011) [1] , non-viable pregnancies (England et al., 1992) [3] , shelter overpopulation and hereditary-disease prevention (Kutzler, 2005) [4] , and owner-related constraints (Kustritz, 2010) [2] . Historically, only surgical removal of the uterus and ovaries was available; pharmacological interventions are now widely used. Pregnancy must always be confirmed before termination, since administration of these compounds to a nonpregnant animal can cause serious adverse effects. Ultrasonography is the modality of choice, allowing assessment of fetal viability and biometry; radiography is useful only after fetal skeletal calcification, and hormonal assays (progesterone metabolites, relaxin) may also assist (Eilts, 2002) [5] . Canine pregnancy is divided into an early stage (fertilization to implantation, Day 20-22 from the LH peak), a mid stage (implantation to ossification, Day 22-42), and a late stage (ossification to parturition, Day 42-65); estrogens and estrogenic compounds are typically used before implantation, while prostaglandins, dopamine agonists, progesterone receptor antagonists, and corticosteroids are used after implantation (Thangamani et al., 2018) [6] . This review is based on a narrative synthesis of peer-reviewed literature identified through PubMed, ScienceDirect, Google Scholar, and CAB Abstracts (1987-2024), using terms including "pregnancy termination," "mismating," "abortifacient," and "canine," together with individual drug names. Studies reporting original experimental or clinical data on pregnancy prevention or termination in the domestic dog were included; studies addressing these agents for unrelated indications were excluded unless directly relevant to termination pharmacology.

Pharmacological methods for termination of pregnancy

Estrogens

Estradiol cypionate (ECP), estradiol benzoate (EDB), and diethylstilbestrol (DES) have been used for prevention of pregnancy (Wiebe et al., 2009) [7] , with ECP considered the most efficacious (Eilts, 2002) [5] . Estrogens tighten the uterotubal junction, altering oocyte transport and causing implantation failure (Pettersson et al., 2009) [8] ; ECP at 44 μg/kg during estrus prevents pregnancy, but causes pyometra and bone marrow aplasia if given in diestrus (Bowen et al., 1988) [9] . Owing to this toxicity, estrogens are no longer recommended. Tsutsui et al. (2006) [10] showed a single postovulatory EDB injection (0.20 mg/kg) completely and dose-dependently prevented pregnancy.

Estrogenic compounds -Tamoxifen

Tamoxifen citrate, an antiestrogen in women, exhibits estrogenic activity in dogs at 1 mg/kg PO BID for 10 days. Given during proestrus, estrus, or early diestrus it completely prevents conception; on day 15 of diestrus it causes partial resorption/abortion, and on day 30 some pregnancies are carried to term (Bowen et al., 1988) [9] . Prolonged use causes vulvar edema, purulent discharge, retinitis, and pyometra (Tavares et al., 2010) [11] , so despite its efficacy it is not recommended clinically.

Prostaglandins

Prostaglandins are luteolytic, uterotonic prostanoids typically given after day 30 of gestation (0.1 mg/kg SC q8h × 2 days, then 0.2 mg/kg q8h until complete), causing vasoconstriction/degeneration of the corpora lutea and conduct myometrial contraction (Lein et al., 1989; Feldman et al., 1993) [13,12] . Fieni et al. (1997) [14] achieved complete termination in 67 bitches using cloprostenol (2.5 μg/kg SC × 3, 48 h apart, from day 30); Hubler et al. (1993) [15] described a gradual "25-50-100" μg/kg protocol over 7 days. Comparing agents, Wichtel et al. (1990) [16] found PGF 2 α achieved 100% abortion versus 50% for bromocriptine, with side effects of panting and emesis. [18,19] .

Progesterone receptor antagonists (Antiprogestins)

Antiprogestins bind the progesterone receptor, blocking endogenous progesterone and disrupting pregnancy maintenance (Galac et al., 2000) [20] . Aglepristone is licensed in dogs; given before day 25 it prevents pregnancy, and between days 26-45 it terminates pregnancy within 7 days (10 mg/kg SC, repeated once after 24 h) with 95-100% success and mild, transient side effects (Galac et al., 2000; Pettersson et al., 2009) [20,8] . Mifepristone, not licensed for veterinary use but used off-label, achieves complete termination within 3-5 days at 2.5 mg/kg PO BID × 4-5 days with no adverse effects reported (Concannon et al., 1990) [21] .

Corticosteroids

Dexamethasone, given orally in mid gestation, is an inexpensive termination option. Wanke et al. (1997) [22] terminated 58/62 pregnancies using a tapering BID protocol (200 to 10-20 μg/kg over 7.5-9.5 days). Its mechanism is not fully understood -progesterone decline may be a direct effect or a consequence of abortion and it causes transient adrenal suppression, polyuria, polydipsia, and milk secretion (Wanke et al., 2002) [17] . Zone et al. (1995) [23] confirmed termination in all 20 treated bitches (0.1-0.2 mg/kg BID/TID, tapered), with mild transient side effects.

Progesterone synthesis inhibitors

Epostane inhibits 3β-hydroxysteroid dehydrogenase delta 6-5 isomerase, reducing progesterone synthesis by the corpus luteum (Kowalewski et al., 2009) [24] . Given at 50 mg/kg/day PO for 7 days from the onset of diestrus, it offers a single-agent oral protocol, though with an increased chance of diestral disorders like mucometra (Thangamani et al., 2018) [6] .

GnRH antagonists

GnRH antagonists rapidly inhibit the gonadal axis (Hull et al., 1987) [25] . Valiente et al. (2009) [26] evaluated the third generation antagonist acyline in two different doses (low dose 110 μg/kg or and high dose 300 μg/kg, single SC dose, mid gestation) in 21 bitches at 25-35 days; all treated dogs aborted within 2-12 days, correlating with a marked progesterone decline, with no clinical or haematological side effects and only mild, transient discharge.

Combination therapies

Clinical considerations

Confirmation of complete termination is essential, since incomplete uterine evacuation predisposes to retained tissue, metritis, and pyometra; serial ultrasonography every 2-3 days is recommended until resorption/expulsion is confirmed, and owners should be advised to seek attention if discharge becomes purulent or systemic illness develops. Ovariohysterectomy remains the traditional alternative, offering single-procedure permanent sterilization but requiring anesthesia, surgery, and hospitalization while preventing future breeding; pharmacological termination preserves fertility and avoids surgery but requires accurate staging and repeated monitoring. The choice between the two should be individualized based on future breeding intent, owner's comfort, cost, and local availability of the agents discussed above.

Survey on MTP practices among Indian canine practitioners

A web-based survey of canine practitioners across states of India, circulated via Google Form, assessed case frequency, common reasons for termination, diagnostic preferences, drug choice, and protocol outcomes. Aglepristone emerged as the most preferred individual drug, and cloprostenol with cabergoline as the preferred combination; mifepristone with misoprostol is an increasingly used combination.

For initiating MTP, the most common indication recorded among various practitioners was "unwanted mating" (90.7%) and the preferred timing was "mid stage of gestation" (43.9%). Out of all diagnostic modalities, 82% of the practitioners preferred "ultrasonography". The effectiveness of the above mentioned protocols was rated as "very high" by the practitioners in their practice with 43.5% of complications and 29.7% systemic side effects.

Conclusion

Safe termination of pregnancy in bitches depends on accurate pregnancy diagnosis, appropriate drug selection, and close monitoring. The antiprogestin aglepristone was the most consistently effective agent, with high reported success rates and minimal side effects, and mifepristone alone is also effective. Combinations of an antiprogestin (mifepristone) or a prostaglandin (cloprostenol) with the dopamine agonist cabergoline may achieve successful termination with minimal side effects. Continued clinical and field-level research is warranted to identify a protocol effective at any stage of gestation while being free of side effects, preserving future fertility, and remaining affordable and widely accessible.

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