Normal Canine Reproduction
Normal canine reproduction requires a healthy reproductive tract, ovulation of normal ova, insemination during the fertile window and the ability to maintain a pregnancy for 2 months.
After the first heat cycle, the bitch experiences puberty and achieves reproductive maturity. The typical age of onset of puberty is 10 to 12 months (range, 6 to 24 months). Breed differences and size can account for some of these variations. For example, large- and giant-breed dogs come into heat at an older age than small-breed dogs.
The ovaries contain the developing follicles. The follicles produce estradiol (E2) and contain the oocytes that are released at the time of ovulation. The subsequent corpus luteum will then produce progesterone (P4) and, unlike in other species, continue to produce P4 for the length of gestation regardless of pregnancy status.
The canine uterus is bicornate with long horns and a short uterine body. The cervix joins the uterus to the vagina. In the dog, the cervix is positioned perpendicular to the dog’s longitudinal axis.
The vagina, vestibule, vulva are not sterile environments. The vagina is very long in the dog and the vestibule contains the urethral opening. During artificial insemination, care should be taken not to accidentally catheterize the urinary bladder.
Sperm must undergo capacitation within the female tract before fertilization can occur. Fresh normal sperm can last up to 7 to 9 days in the tract, which is why under natural conditions when the bitch is receptive to the stud dog, the sperm have plenty of time to meet up with the mature oocyte for fertilization.
The copulatory lock “tie” is not necessary for conception. The purpose of the copulatory lock is to promote the forward movement of the spermatozoa; however, it is not an indicator of a successful mating.
When considering prevention of canine pregnancy, the most common choice is permanent sterilization by means of ovariohysterectomy (OHE) or ovariectomy (OE). Ovariohysterectomy is still the standard procedure performed but ovariectomies are becoming more popular and have the advantages of reduced surgery and anesthesia time, a smaller incision, and less abdominal trauma.
No difference in short or long-term complications between OE and OHE have been found.
When considering permanent sterilization, there is no consensus as to the optimal age. Factors that need to be considered for the best age to spay may differ for every patient. Questions that should be addressed when making this decision may include whether the dog has an owner. Early spays are conducted in shelters based on research showing that many who adopt animals neglect to get them spayed in a timely fashion, if at all.
Studies showing the benefits of hormone retention in dogs have provoked controversy over spay timing. Several studies showed beneficial effects of hormone influence in certain breeds of animals. Each patient and client should be considered individually to formulate a plan to best manage reproductive capacity in their animal.
Other options for preventing pregnancy being investigated are new forms of contraception, abortifacients and estrus suppression. The concerns for leaving dogs sexually intact include ovarian, uterine, and mammary neoplasia; ovarian cysts; and pyometra.
OHE is not without risk or postsurgical complications. Obesity, estrogen-responsive urinary incontinence, increased bone turnover, and loss of bone have been documented in spayed females. Regardless of which option for preventing pregnancy is chosen, the relative risks of death from diseases preventable by spaying must be weighed against those less likely to occur in sexually intact bitches of a specific breed and type.
There are nonsurgical options for contraception as well. Progestins can be used for postponing estrus.
Studies have found megestrol acetate (2.2 mg/kg for 8 days starting at the very beginning of proestrus) to be 92% effective at postponing estrus in female dogs. If not started early enough or if started at an insufficient dose, megestrol acetate is ineffective for this indication. In dogs, megestrol acetate postpones estrus for what is approximately an entire reproductive cycle, usually 4–6 months (range, 1–7 months). Complications of megestrol acetate use can include pyometra, mammary hyperplasia and cancer, diabetes mellitus, and adrenal gland suppression. Weight gain and lethargy as well as other behavioral changes are commonly reported. Typically, extended use is not recommended.
Mibolerone is an androgen that can be used to suppress the onset of estrus for up to 24 months. Androgens must be administered at least 1 month before the bitch is expected to go into heat. After discontinuing treatment, most bitches return to estrus in 2 to 3 months. Mibolerone is approved for use in dogs but not cats and is contraindicated for females that have impaired liver function or are lactating or pregnant because female fetuses may be masculinized.
Other nonsurgical options for contraception include GnRH analogues and immunosterilization.
Pregnancy Termination in Dogs
Indications for terminating pregnancy may include an animal that is too young or too old, has bred with an undesirable male, or that has other illness that a pregnancy may worsen.
No pregnancy termination protocols should be followed until pregnancy has been confirmed either by ultrasonography or serum relaxin assay. Often, mismating is reported soon after it was witnessed. Detection of sperm in the vaginal vault may confirm that a mating took place, but pregnancy confirmation is nonetheless needed approximately 30 days before initiating a termination protocol.
If future breeding is not wanted, OHE or OE can be performed at any time.
Estrogens (estradiol cypionate) are not recommended due to serious complications (estrogen-induced myelotoxicity, aplastic anemia, thrombocytopenia, leukopenia, pyometra) that can occur.
Prostaglandins and prolactin inhibitors are options for termination of pregnancy.
The mechanism of action of prostaglandins (PGF2a or PGF2a analogues) is to induce luteal regression. Either dinoprost (50 to 250 mcg/kg, SC, every 8–12 hours for 4 days or until pregnancy is terminated) or cloprostenol (2.5 mcg/kg, SC, every 48 hours for 3 doses) may be used.
High doses are needed during the first 25 days of pregnancy, so it is best to treat 30–40 days following pregnancy confirmation. There is no need to subject the dam to high doses of prostaglandins if not pregnant.
Adverse effects include abdominal pain, tachypnea, hypersalivation, vomiting, and diarrhea. The GI adverse effects may be minimized by concurrent administration of atropine (0.025 mg/kg, SC). Fetal loss should be confirmed by ultrasonography.
The mechanism of action prolactin inhibitors is to decrease function of corpus luteum (CL) and decrease progesterone.
Dopamine agonists like bromocriptine (15 to 30 mcg/kg, PO, every 12 hours after mid-gestation until pregnancy is terminated) or cabergoline (5 mcg/kg, PO, every 24 hours after mid-gestation until pregnancy is terminated. are ergot alkaloids, with strong D2 receptor agonist activity, and thus can reduce prolactin secretion and thereby suppressing progesterone concentrations.
Adverse effects with prolactin inhibitors are fewer than with prostaglandins, but anorexia and vomiting may still occur.
A prostaglandin may be combined with a prolactin inhibitor at the low end of the dose range.
No medical pregnancy termination protocol is reported to be 100% effective and none of these drugs are approved for pregnancy termination in bitches in the United States but can be used in an extralabel fashion.
The progesterone receptor antagonist aglepristone (10 mg/kg, SC, every 24 hours for 2 doses) has been reported to terminate pregnancy given at day 15, 30 or 34 of pregnancy. It is currently not available in the United States but marketed in a limited number of countries in Europe with an indication for termination of pregnancy any time after mating.
When terminating a pregnancy it is important to prepare the client for the adverse effects and what to expect. The consequences of when the pregnancy is terminated vary. When a pregnancy is terminated prior to 40 days of gestation, all evidence of the pregnancy will be gone. The later into gestation the termination takes place, the more developed the fetal tissue and therefore there will be more material passed via the vulva. After 55 days, puppies may be born alive and have to be euthanized. It is recommended to hospitalize the patient during pregnancy termination to provide supportive care to the bitch.
Canine Estrous Cycle
The bitch is a spontaneous ovulator (ie, ovulation occurs without any breeding stimulus). The bitch starts cycling with the influence of hormones released from the hypothalamus and pituitary glands. Gonadotropin-releasing hormone (GnRH), released from the hypothalamus, stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH has a primary responsibility for growth of follicles on the ovaries, whereas LH causes final maturation and ovulation of the follicles.
There are four stages of the canine estrous cycle that can be classified based on physical and behavioral characteristics, endocrinologic status, vaginal exfoliative cytologic evaluation, and physiologic changes: proestrus, estrus, diestrus, and anestrus.
The external physical changes seen during proestrus are the onset of vulvar swelling. The turgidity of the vulva reaches its maximum in late proestrus coincident with the E2 concentration peak. Proestral bleeding can also be seen and is a result of extravasation of erythrocytes by diapedesis from the hyperemic endometrium under E2 stimulation.
The internal physical changes include the endometrium becoming edematous and the endometrial glands undergoing hypertrophy. The uterus enlarges, almost doubling in length, and the cervix becomes palpable at approximately the level of the wings of the ileum, cranial to the pubic bone.
During proestrus the bitch will attract male dogs but is still not receptive to breeding. As proestrus continues, she will become more playful and passive.
The main hormonal changes during proestrus include concentrations of E2, P4, LH, and FSH. During proestrus, E2 concentration peaks midway and then decreases prior to estrus. P4 concentration is at baseline (< 1 ng/mL) and will begin to rise prior to estrus. LH concentration is low until the E2 concentration decreases and P4 concentration begins to increase, which is coincident with the LH surge. This occurs at the end of cytologic proestrus or in early cytologic estrus. FSH concentration peaks before the onset of proestrus and decreases during proestrus.
Estrus could be characterized physically by the period in which the bitch allows breeding to occur. The vulva is no longer as swollen or turgid as in proestrus, and the serosanguineous discharge is usually decreased and is more a straw color, if still present at all. Another physical feature seen during estrus is that perineal stimulation will induce a bitch to deflect the tail or “flag.”
The onset of estrous behavior results from the decrease in E2 concentration and the rise in P4 concentration (doubles the baseline). The LH surge is considered day zero (0) of estrus and lasts for approximately 24–48 hours.
As estrus subsides and the bitch enters diestrus, she is no longer receptive to breeding. The uterine horns become remarkably toned and torturous under the influence of P4. Mammary development in the nonpregnant bitch is subtle, but is noticeable by careful palpation approximately 30 days after the LH surge. In diestrus, both E2 and FSH concentrations are low. P4 concentration will peak during diestrus then decline back to basal concentration (< 1 ng/mL) and LH pulses increase in late diestrus.
The physical signs of anestrus are similar to diestrus but the vulva continues to decrease in size. Cytologically, noncornified intermediate and parabasal cells predominate, similar to a spayed bitch; however, the ovaries are active (follicles present), E2 concentration fluctuates, and LH and FSH concentrations are elevated in late anestrus.
Feline Estrous Cycle
In contrast to the bitch, which is a spontaneous ovulator, the queen is an induced ovulator but still experiences a diestrus period of progesterone secretion if mating does not occur after ovulation.
The estrous cycle of the cat consists of proestrus, estrus, postestrus, diestrus, and anestrus:
Proestrus is variable in length (from 0–2 days) and may not be observed in all queens.
Estrus lats from 2–19 days and is the behavioral stage of receptivity to mating. Duration of estrus has been found to not significantly differ between bred and not bred queens. During feline estrus, peak follicular activity occurs, and E2 concentrations may reach 70 pg/mL.
Estrous behavior in the cat includes restlessness, vocalization, crouching and lordosis, treading with hind legs, and tail deviation. Copulation may occur 20–36 times over the course of 36 hours. The magnitude of LH secretion increases with the number of copulations during the receptive period, and only about half of queens only bred once will secrete adequate LH to induce ovulation.
Unique to the queen, postestrus is the term for the interestrous period lasting from 8–10 days that follows one estrus and precedes the next in queens that have not been induced to ovulate.
During postestrus, plasma E2 concentration is < 20 pg/mL and no sexual behavior or receptivity is present.
The term metestrus used in the cow to describe the period following estrus is not appropriate for the queen in which ovulation does not occur since metestrus involves formation of a corpus hemorrhagicum and differentiation of granulosa and theca cells into large and small luteal cells.
Queens that do ovulate will experience a diestrus period during which the corpora lutea are functional and producing P4. Serum P4 concentration ranges from 1.5–20 ng/mL. Diestrus lasts about 40 days in the pseudopregnant queen and 60 days in the pregnant queen. There is no receptive behavior during diestrus.
The queen experiences a seasonal anestrus during the late fall months (October, November, December) when exposed to natural daylight in the northern hemisphere.