p 257-270

• Breeding management is usually the number one problem associated with infertility. 
• Breeders will  'count days' and breed on days 11 and 13 when the bitch is not really in heat and wonder why breeding did not occur.  See estrous cycle graph. 
• Breeding will be left up to the male, so estrus detection and/or breeding may not occur. 
• It is essential that proper breeding management be used and that the breeding be timed properly and a fertile male used. Always manage one breeding before investigating any other infertility problems with too much vigor.
• Male infertility should be investigated. Has the male sired litters recently? A Breeding Soundness Examination of the male will ensure a relatively fertile male.

Functional breeding problems of the Vagina
 

Vaginal strictures

• Vaginal Strictures are a tight ring at vaginal-vestibular junction. They cause pain on intromission, so the bitch won't let the male breed. The client may present the bitch as 'not standing' in heat.
• Diagnosis is by either digital palpation or vaginoscopy. On insertion you cannot get in the vagina or the bitch shows pain on insertion.
• You can treat the condition using artificial insemination. A stricture may predispose to dystocia, but usually not.

Vaginal hyperplasia or hypertrophy or edema

233

• Vaginal hyperplasia (currently called vaginal edema...Root likes to call it vaginal prolapse!) usually occurs in younger, large breed dogs at estrus. It results from excess reaction to normal estrogen concentrations. It is actually edema of the tissue.
• You see a large red mass protruding from vulva. If the condition is chronic, the mass may be dried out. To make a definitive diagnosis examination of the mass will reveal a broad base, floor involved with the urethral orifice under the mass.
• Spontaneous regression will usually occur with conservative therapy. Ovariohysterectomy will prevent the occurrence in the future.
• Amputation is sometimes needed, and the condition will recur to some extent.
• You will probably have to perform artificial insemination if the bitch is to be bred.
• If it is not a breeding bitch you can administer OvaBan at a dose of 2.2 mg/kg for 7 days. Be sure to keep the mass moist while doing conservative therapy.

Vaginal Prolapse

• Vaginal prolapse, unlike vaginal hyperplasia, rarely occurs at estrus, but is most commonly seen post partum.
• The entire circumference of vagina involved and the hole you see is in the middle. The mass is usually partially reducible.
• The best treatment is amputation.

Vaginal Septae

228

• Most commonly seen are dorsoventral bands in the vagina.
• More often, the septae are a cause of dystocia than a breeding problem.
• These bitches may be presented for vaginitis or vaginal discharge.
• Diagnosis is via vaginoscopy, however a true endoscope allows a better view of the anterior vagina.
• Treatment is surgical removal.

Cervical Abnormalities

• Cervical problems in the bitch are very difficult to diagnose.
• A cervical problem may result in a fluid filled uterus.

Segmental aplasia of the paramesonephric ducts

• A partial aplasia may not cause infertility, because enough of the uterine horn is present to have normal fertility.
• In many cases it only involves one horn.

Oviduct problems and tubal occlusions

270

• Like cervical problems, oviductal problems are very difficult to diagnose in the bitch. Hysterosalpyngograpy or laparotomy may be attempted to diagnose a problem, but at this time we have no viable treatments anyway.

Neoplasia

239

• Neoplasia should be ruled out when looking at causes of breeding problems
• Transitional Venereal Tumors (TVT)
  • Complaint may be vaginal discharge.
  • Vaginal Cytolotogy
    • Prominant nucleoli
    • Mitotic figures

     

• Transitional bladder carcinomas
• Leiomyomas

Endometrial cyts

• A 'hot' topic these days

• Cysts in the endometrium seen as a process in Cystic Endometrial Hyperplasia (CEH)

• Are usually seen at surgery (for AI or as a diagnostic procedure)

• Can be seen with a great ultrasound machine (not the portables usually seen in practice)

• 'Associated' with infertility.......but

  • Infertile dogs have it diagnosed at surgery, then ruptured

  • Fertile dogs have not been examined to note their presence

• Many practitioners treat them by rupture, but the verdict is still out on the real success of this practice.

258

• Always make sure there is no chance that the bitch had a previous ovariohysterectomy.
  • You can try to palpate the uterus, look for a ventral midline scar
  • You may test for persistently high luteinizing hormone (LH) and  follicle stimulating hormone (FSH), which should occur after gonadectomy.
    • The Status LH kits work well for this
      • The test had excellent sensitivity (98%) but moderate specificity (78%) because of a high frequency of false-positive test results. This means that a single high serum LH concentration was not a reliable indicator of ovarian removal. However, a single low serum LH concentration was an excellent indicator that a bitch was sexually intact. The LH test results were positive within 10 days after ovarian removal and remained high in bitches from which ovaries had been removed > 5 years previously. (Evaluation of a commercially available luteinizing hormone test for its ability to distinguish between ovariectomized and sexually intact bitches. Lofstedt,R.M.; VanLeeuwen,J.A.J Amer Vet Med Assn 220:2002 pp 1331-1335)
  • Perform vaginal cytology weekly to try to detect estrus. 

Delayed puberty

• Delayed puberty is rarely a problem.
• Since dogs can normally take as long as 24 months to display the first heat, you should wait at least that long before considering delayed puberty or anestrus.

Chromosomal abnormalities

259

• Several syndromes have been described such as XXY, XO, XX/XY.
• A karyotype to check the chromosome numbers will quickly rule these out.

Molecular Cytogenetics Laboratory
Room 318 B
Bldg 1197
Department of Veterinary Integrative Biosciences
Texas A&M University
College Station, TX 77843-4458

Telephone: 979-458-0520
Fax: 979-845-9972

Please call in advance. Laboratory led by Dr. Bhanu Chowdhary

Also try:

University of Pennsylvania

 215-573-7545.

Call Ulana in the Cytogenetics lab for details.

Normal Chromosome Numbers

Species	#	Species	#
Cat	38	Domestic pig	38
Dog	78	Sheep	54
Donkey	62	Cow	60
Rabbit	44	Horse	64
Hare	46	Chicken	78

Sex reversal

193

• Sex reversal is when the genotypic sex disagrees with the phenotypic sex.
• This is an inherited disease in Cocker Spaniels. It is an autosomal recessive.

Male pseudohermaphrodites

193

• These are named after the Y chromosome they have, but they have female genitalia.
• Testicular feminization

Ovarian agenesis

• This is a rare condition which is sometimes seen in dogs that have not cycled.
• You may need to do a laparotomy to diagnose this condition.

Cushing's, Addison's, Hypothyroid

270

• These diseases usually do not cause embryonic death (EED) or infertility, rather the bitches just do not cycle.
• Bitches will usually show the classic clinical signs associated with the disease.
• Free T4 is best to diagnose hypothyroidism,. The LSU values are : 10.3-24.5 normal, 5.1-10.2 suspect, <5.1 low. TSH stimulation can also be used as diagnostic test.
• Most bitches respond well to therapy supplemental thyroid therapy and start to cycle in 4-6 weeks.
  • Hypothyroidism is known to be familial.
• Bitches with Cushing's and Addison's should be treated appropriately to start the bitch cycling again.

Exogenous Steroid Therapy

• This can cause a bitch to stop cycling.
• Has the bitch been on any estrus suppressing drugs? 

Clinical Management

• Do not attempt to induce estrus before the cause of the anestrus is ascertained.

• You can easily perform weekly vaginal cytology examinations to see if the bitch is truly cycling and the owner is just not observing a heat. 

• Most of our anestrus bitches are 'cured' this way.
  

Failure to Cycle With Previous Cycles

• Endocrine problems can be considered here also.
• Failure to observe estrus is a big problem. As with anestrus bitches, weekly vaginal cytology exams can 'cure' many of these.

Old Age

269

• As dogs get older they usually have longer interestrous intervals.
• Dogs must usually be greater than 8 - 10 years before they will actually stop cycling.

Premature Ovarian Failure

• Premature ovarian failure is similar to the 'menopause' (menopause is not a correct term in dogs because they have no menses, but everyone will know what I mean), but it occurs in young bitches.
• Rule out other problems first, before considering this.
• It may be diagnosed by the high follicle stimulating hormone (FSH), and luteinizing hormone (LH) concentrations and there is no gonadal feedback to keep these hormones at low concentrations. 
  • In reality, it is hard to find a lab that will run these tests and that knows what the values should really be. Maybe BET labs.

Luteal cysts

198

• These are abnormal luteal like structures that secrete progesterone, but do not undergo luteolysis as a normal corpus luteum would. This syndrome is common in cows, but may not be that common in dogs. It was reported in 9/400 dogs by Dow.

• Progesterone concentrations have not been reported, but are probably high.
• The prolonged high progesterone must not be confused with normal cycles.
• Ultrasound may be helpful, but it is not easy to routinely ultrasound a bitch's ovaries.
• Laparotomy and histology may be needed truly diagnose the condition.

• Prostaglandins are usually not successful. These structures may lack normal prostaglandin receptors. Whether this is true or not, I do not know, but it makes a good theory.

• A single 50 mcg GnRH dose may cause further luteinization and induce prostaglandin receptors.

• The structures may have to be removed or drained via a laparotomy. Ovariectomy (unilateral in a breeding bitch) may be an alternative.

Silent heat

• Silent heat may occur as Greyhounds commonly have a pseudogenetra (overt pseudopregnancy) without ever showing signs of heat.

Prolonged Estrus

• If estrus is prolonged more than about 10 days, fertility is usually low. This may be because the oocytes are aged when they ovulate, the follicles are anovulatory, or the follicles have become cystic.

Follicular cysts

195

• Many follicular cysts seen on laparotomy are nonfunctional ovarian cysts and are incidental findings only and the bitch has shown no problems.
• Estrogen producing cysts cause a prolonged heat (of elevated estrogen concentrations (greater than the normal 50 ng)
• Diagnosis is based on clinical signs, possibly on estrogen concentrations (although they are hard to run accurately and interpret), and histology after laparoscopy/laparotomy.
• Split heats in young dogs may confuse the diagnosis.
• Treatment
  • You can give Human Chorionic Gonadotrophin hCG at a dose of 500 IU SID for 3 days or

• GnRH - 50 mcg SID 3 days in an effort to luteinize the cyst and stop the estrous behavior.

Ovarian Tumors

200

• These are seen more in older nulliparous dogs.
• Granulosa cell tumors may have no estrogenic signs, even though they are granulosa cells.
• Cystadenoma
• Fibroma
• Diagnosis of tumors is best done via laparotomy.

Liver Disease

• Since the liver metabolizes steroids, any liver disorder may cause problems with the bitch's cycle.

Split Heats

• Split heats are when a bitch shows signs of heat for a few days (bleeding), then stops for 2-10 weeks, and then a normal cycle occurs.
• This is a fairly normal event in young bitches and should always be investigated before looking into other problems that prolong estrus.
• There is no infertility associated with this condition.

Short Interestrous (Anestrous) Intervals

• Since the bitch normally needs a 150 day interestrus (or 90 day anestrus) for endometrial repair to be complete, bitches that have shorter interestrous intervals are usually infertile.
• This could also be because of a failure to ovulate, hence there really was no luteal period. This can be diagnosed by checking progesterone concentrations.
• Split heats must also be ruled out.

• Mibolerone administration for 6 months is recommended by Feldman and Nelson and then breed at the next estrus. In our experience, this has resulted in poor fertility. It also may not be available in the United States at this time.

• Megestrol acetate (Ovaban)

• Although this is a theoretically poorer treatment (remember it is the progesterone that creates the need for endometrial repair and Ovaban is a progestatgen) the fertility results have clinically been better.
  • Treatment with 1 mg/lb during the first 3 days of a short interestrus interval delayed heat and resulted in conception in 10/10 that had been infertile due to short interestrus intervals. 

Ovulation Failure

270

• If the cycle appears normal, yet the bitch is not pregnant, she may not have ovulated.
• This can be definitively diagnosed by the bitch having low progesterone 30-45 days after the first day of diestrus.
• However, the bitch may fail to ovulate, yet the follicles luteinize, therefore resulting in high progesterone, yet not ovulation.

Hypoluteoidism

269

• Luteal insufficiency (lack of progesterone secretion by the corpora lutea) has been speculated to occur in the bitch and has recently been documented.

• Ovariectomy at any stage of pregnancy induces abortion within 48 hours. 

  • The blood progesterone concentration must be less than 2 ng/ml for greater than 24 hours to induce abortion using prostaglandin.

• Luteal insufficiency is suspected when a bitch has a history of being pregnant and then fails to whelp; however, at least four ruleouts for pregnancy loss should be investigated before luteal insufficiency can be seriously considered.

  •  First, an accurate pregnancy diagnosis must be assured. Ultrasound diagnosis of pregnancy gives both the clinician and the client an absolute assurance that the bitch is truly pregnant. If the bitch was pregnant and failed to whelp, identifying the gestational stage of the pregnancy loss will help determine subsequent treatments. Unless serial pregnancy determinations are performed, however, the clinician will rarely have this information on the bitch's first presentation. 

  • Brucella canis must also be considered a rule out in any pregnancy loss. 

  • Endometritis and cystic endometrial hyperplasia may also be suspected in cases of pregnancy loss. 

  • Finally, lethal congenital defects must be ruled out using test matings to another stud and/or necropsy of an aborted fetus. 

  • If all of these conditions are ruled out, then luteal insufficiency can be seriously considered.
    

• If a bitch is suspected of having luteal insufficiency, serial progesterone determinations can be performed starting approximately one week before the anticipated abortion. 

  • Since the bitch must maintain at least 2 ng/ml of progesterone in order to maintain pregnancy and since a decline below this value for greater than 24 hours will result in abortion, the timing of progesterone concentrations is important. 

  • If the time frame of the pregnancy loss is unknown, then progesterone concentrations should be determined immediately after the pregnancy is diagnosed.

  •  Radioimmunoassay determinations of progesterone are of little use when immediate progesterone values are needed.

  • If rapid quantitative progesterone values are available, they are the most accurate.

  •  An alternative progesterone test is the ELISA, which can be performed in a matter of minutes. 

    • The ELISA test has three possible results for the progesterone concentration, <1 ng/ml, 2-7 ng/ml, and > 7.5 ng/ml. 

    • If the initial ELISA sample shows the progesterone > 7.5 ng/ml, it may need to be analyzed by radioimmunoassay to determine the exact concentration. 

  • The frequency of the progesterone analysis should be based on the progesterone concentration. 

    • If the concentration is high (20-50 ng/ml) then the samples only need to be taken weekly; however, if the concentration is low (5-10 ng/ml) then the samples should be taken daily. 

    • If the progesterone is in the 2 ng/ml range, a diagnosis of luteal insufficiency definitely can be made. 

  • It may be safer to use 5 ng/ml as a diagnostic cutoff point for luteal insufficiency so that no bitches with borderline progesterone concentrations are left untreated. 

  • Total progesterone concentrations can be monitored while the bitch is being supplemented with exogenous progesterone to determine if supplementation is providing a concentration of at least 5 ng/ml. 

  • Endogenous progesterone can be monitored only if the bitch is supplemented with a progestogen that does not cross-react with the progesterone assay.

• Once a definitive diagnosis of luteal insufficiency has been made, treatment can begin. 

  • Pregnancy has been successfully maintained in bitches ovariectomized after 30 days of gestation with daily IM injections of 20-50 mg/dog (about 2-3 mg/kg) of progesterone in oil.

  • Daily IM injections of 3 mg/kg progesterone in sesame oil will maintain a progesterone concentration greater than 10 ng/ml in anestrus bitches. 

  • Since at least 2 to 5 ng/ml of progesterone are needed to maintain pregnancy, 3 mg/kg administered IM daily should provide enough exogenous progesterone to maintain pregnancy. 

  • In one report, however, a bitch diagnosed as having luteal insufficiency maintained pregnancy successfully after administration of 2 mg/kg of progesterone in oil IM every 48 hours along with monitoring plasma progesterone concentrations. 

  • This bitch, unlike the anestrus bitches in another study, did have some endogenous progesterone secretion; so it probably did not need the frequency of administration to keep the plasma concentration of progesterone above 5-6 ng/ml. 

  • Because injectable progesterone is difficult for an owner to administer, and because endogenous progesterone secretion cannot be monitored when natural progesterones are administered, an oral progestogen is an ideal alternative. 

    • An oral progestogen, ally-trenbolone, has been approved to maintain pregnancy in the mare. 

    • A dose of 0.088mg/kg ally-trenbolone (0.2cc/10 lbs) maintained pregnancy in 3/3 bitches ovariectomized in midgestation and 1/3 ovariectomized early in gestation. 

    • In contrast, the single control bitch (not supplemented) lost the pregnancy within 48 hours after ovariectomy. 

    • One bitch whelped on the expected due date but lost all the puppies because of fetal dystocia. 

    • The other two bitches whelped normal litters on the expected due date. 

    • The milk production was not optimal initially in these bitches, but after 2-3 days it was adequate to raise most of one litter and all of the other litter. 

      • Because the prolactin concentration rises dramatically before parturition (Concannon, 90), the lactation inhibition may be related to an ally-trenbolone mediated prolactin suppression near term. 

      • A client should be advised that milk supplementation of the puppies may be needed if the bitch is supplemented with ally-trenbolone. 

    • It is also imperative to calculate the whelping date accurately. 

      • The administration of exogenous progesterone for two days beyond the anticipated whelping date increases the chance of stillborn puppies.

      • Similarly, if the progesterone is discontinued too early, immature and/or stillborn puppies may result. 

      • Gestation length is consistent if measured from the LH surge or the first day of cytologic diestrus. 

        • If only breeding dates (or worse yet AI dates) are known, the accuracy of the estimated whelping date is compromised.

        • There may be a masculinization of female puppies after ally-trenbolone treatment. Experimentally it was not seen, but several cases have been reported by practitioners using the protocol. Administration of excess progesterone during gestation will also masculinize female pups, so the masculinization seen by practitioners may have been dose related (they supplemented bitches with already high progesterone).

• If a careful diagnosis of luteal insufficiency is made, pregnancy can be maintained successfully using either oral or injectable progestogens. The client must be advised about the problems of estimating gestation length, poor milk production, and potential masculinization of female puppies that may make the treatment undesirable.
  

Miscellaneous Causes of Infertility

270

• Male origin
• Sperm antibodies have been produced experimentally., but have not been isolated as yet clinically.
• Sperm inhibitors in mucus - same as sperm antibodies
• Inbreeding - Vicki Myers-Wollen at Cornell found that as the inbreeding coefficient rises in a kennel, fertility decreases, fecundity decreases and neonatal deaths increase.