Proceedings of the World Small Animal Veterinary Association Sydney, Australia 2007

Transcription

1 Proceedings of the World Small Animal Veterinary Association Sydney, Australia 2007 Hosted by: Australian Small Animal Veterinary Association (ASAVA) Australian Small Animal Veterinary Association (ASAVA) Australian Small Animal Veterinary Association (ASAVA) Next WSAVA Congress

2 APPROACH TO INFERTILITY IN THE BITCH AND IN THE DOG A. FONTBONNE DVM, MSc, Ass. Pr., Dipl. ECAR, Animal Reproduction - Alfort National Veterinary College (Paris), 7 avenue du Général de Gaulle, Maisons-Alfort Cedex, France afontbonne@vet-alfort.fr In comparison to the last 10 or 20 years, veterinarians are now frequently requested to solve fertility problems in the dog, mainly due to the increased popularity of purebred dogs as well as for sentimental or financial reasons. In fact, breeders may be concerned about different kinds of problems which include but are not limited to true infertility (their bitches produce no pups after mating or Artificial Insemination), anoestrus or a low prolificity rate. Many different problems can lead to infertility including hormonal problems, infectious diseases, congenital or acquired defects of the genital tract. We recommend that veterinarians follow a very strict progression, commencing with the most frequent cause to the most uncommon cause. In the bitch, things become even more difficult when we realize that apparent infertility can be due to very different situations which prove difficult to distinguish, such as lack of fertilization (no union between eggs and sperm) and early embryonic death. 1. In the bitch 1.1. Mistimed breeding or artificial insemination According to the vast majority of scientific publications, mistimed breeding represents by far the most common cause of infertility in the bitch. This is why a veterinarian willing to solve fertility problems in the bitch has first to be skilled in timing ovulation in the bitch. Apart from progesterone assays, ovarian ultrasonography is especially indicated in infertile bitches, as it represents the most accurate way to determine the precise date of ovulation Infertility with prolonged interoestrous intervals The apparent prolongation of interestrous intervals occurs in dogs with a silent heat, defined as ovarian activity in the absence of overt physical and behavioral changes characteristic of canine estrus. Among the hormonal causes of anoestrus we find hypothyroidism, hyperadrenocorticism, hyperprolactinemia, or bitches treated with hormonal compounds such as progestagens, androgens (racing dogs) or anabolic steroid compounds. Ovarian cysts that secrete progesterone may cause prolonged interestrous intervals. Bitches housed in very bad environmental conditions (including a high concentration of animals, low luminosity, low quality foood) may undergo prolonged interestrous intervals.

3 1.3. Infertility with shortened interoestrous intervals This type of infertility may be divided into two major causes: bitches suffering from ovarian hyperstimulation (mainly follicular cysts or Granulosa cells tumor), and/or bitches showing a premature decline in progesterone during diestrus Ovarian cysts or tumors. It is important to diagnose and remove these hormonally active cysts or tumors as quickly as possible for at least two reasons. First, it is necessary to cure them and try to restore fertility. Second, the secretion of high quantity of estrogens may act on the uterus as a potential factor towards the cystic endometrial hyperplasia pyometra complex, but also on the bone marrow in creating progressive non regenerative anemia. Follicular cysts may be single or multiple; if multiple cysts are present in one ovary, the cysts do not communicate. The ovarian cysts in the bitch may be present in only one or both ovaries. When possible, it is much more valuable to perform ovarian ultrasonography. Some authors recommend induction of luteinization of the cystic follicles, using GnRH or hcg. We personally do not recommend such protocols, as they increase the progesterone plasma level after a prolonged period of estrogen secretion. Based upon our clinical experience, this treatment very often leads to the occurrence of pyometra in the following weeks. Surgical removal of a cyst, or aspiration of a cyst with a fine sterile needle under laparotomy or ultrasonography may be new alternatives in therapy. Granulosa cells produce estrogens; and therefore, it is not surprising that GCTumours often lead to infertility with prolonged heat periods Premature decline in progesterone Split heats are defined as successive short proestrus signs, at intervals of 2 weeks to 2 months, associated with short interestrus intervals. This pattern is more often observed in young bitches and leads to no real infertility in the rest of the genital life of the bitch. Anovulatory cycles are not frequent in bitches. In such anovulatory cycles, serum progesterone level never increases above 3.5 to 6 ng/ml. This explains why the following heat period will often occur earlier than usual. Bitches may also suffer from hypoluteoidism, which is the lack of progesterone secretion during pregnancy which makes the pregnancy impossible to maintain. Some breeds are well known to express hypoluteoidism, like Rottweilers and German Shepherds. Progesterone supply can be given parentally (progesterone in oil: 2 mg/kg every 3 days; ally-trenbolone ). In France, veterinarians often use oral micronised progesterone which is currently given to women.

4 1.4. Infertility with normal or sub-normal interoestrous intervals Hormonal problems Hormonal defects may be suspected also in bitches with regular interestrous intervals, and veterinarians should control the hormonal status of the bitch during the heat period and also during pregnancy Infectious diseases Several viruses have been shown to play a potential role in canine infertility. Several elements suggest that Canine Herpes Virus (CHV) may well act on infertility in the bitch. Recently, some papers have pointed out the potential incidence of a parvovirus Minute Virus of Canines (CPV1) on resorption during the first half of pregnancy. The incidence of bacterial infections on canine infertility is better documented. Canine Brucellosis could generate early embryonic or fetal death through endometritis. Other specific bacterial diseases have been suspected to act on canine infertility. However, usual genital bacteria may play a real role on infertility. Canine Mycoplasms and Ureaplasms are commonly isolated in the genital tract of fertile and infertile bitches. But it has been shown that there is a higher incidence of these agents in the vagina of infertile bitches. Many bacteria are commonly isolated from the uterus and the vagina of normal fertile bitches. Several studies barely demonstrate any difference in the composition of the vaginal flora between fertile and infertile bitches. But it has been shown that in case of vaginitis, there are significant qualitative and quantitative variations. Strong evidence exists that bacteria causing vaginitis may lead to infertility. It may well have been underestimated due to lack of specific clinical signs and due to the difficulty of the clinical examination of the vagina of the bitch Drugs induced infertility In practice, many breeding bitches may be treated with drugs that may contribute to the decline of fertility. Steroid hormones and anti-fungic compounds may create hormonal defects in pre-puberal or adult bitches. Abortive drugs such as prostaglandins, antiprogestins and antiprolactinic substances have to be avoided during pregnancy Anatomical abnormalities of the genital tract Some bitches do not manage to mate because of congenital or acquired abnormalities of the posterior genital tract (vulva, vestibule or vagina). Acquired diseases or abnormalities of the posterior genital tact (scars after a bad parturition, episiotomy, violent mating ) may also lead to the lack of copulation.

5 Uterine pathology Endometritis is a common cause of infertility in mares. In bitches, however, it is hard to diagnose. Endometrial cytology, eventually performed after endoscopic canulation of the cervix, may be valuable. Bitches with cystic endometrial hyperplasia (CEH) are often infertile due to implantation failure after conception. Somehow, ultrasonography usually permits the visualization of the glandular endometrium Abnormal sexual behaviour Many psychological factors may influence sexual receptivity in bitches. Some authors think that psychology may influence factors like ovulation or early embryonic death in the bitch Miscellaneous causes Bitches with systemic diseases like diabetes mellitus, hyperadrenocorticism or renal insufficiency may likely be infertile. Finally, breeders stress nutrition when their breeding kennel suffers from decreased reproductive results. Little is known in this regard. 2. MALE INFERTILITY After mistimed breeding, male infertility may well be the most common cause of conception failure in bitches presented with infertility. Very little is known about male infertility in the dog. Regarding human male infertility, the cause remains unknown in 70% to 74 % of cases. In the area of human medicine, when the semen is of poor quality, most of the time assisted reproduction techniques are utilized such as in vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI). These techniques are not routinely available to the dog; therefore, the prognosis of infertility often remains very poor. However, some infertility causes can be partially or totally cured if the veterinarian is consulted early enough. But in only 10% of dogs presented with infertility may fertility be restored after diagnosis and appropriate treatment. Veterinarians willing to diagnose and attempt to cure male infertility must be completely knowledgeable about the investigation of the male reproductive function and especially the method of performing the sperm collection and analysis (spermogram) Prostatic problems A prostatic problem often plays a direct role in decreasing fertility. The prostate is the only accessory gland present in the dog, as no seminal vesicles exist. Chronic

6 prostatitis has been shown to be a rather common cause of infertility in dog. It is often suspected when a dog brought for semen collection for Artificial Insemination or freezing of the semen suffers from haematospermia, especially in the 3 rd fraction of the ejaculate. In case of haematospermia, when suspecting an infectious prostatitis, Lévy et al.(2006) showed that bacterial examination after an ultrasound-guided biopsy seems the only reliable diagnosis technique, much more than semen culture. When treating prostatic problems in the dog, the use of common anti-androgenic compounds may definitively alter the quality of semen and subsequent fertility. That is why many reports have been made about the use of 5 α reductase inhibitors (finasteride). Finasteride is a 4-azasteroid synthetic drug that inhibits 5αdihydroreductase, an enzyme that is responsible for the metabolism of testosterone to dihydrotestosterone in the prostate, liver and skin. Recently, some new anti-androgenic drugs (osaterone acetate) seemed to decrease the size of the canine prostate without altering spermatogenesis and may be potentially used in breeding dogs (Mimouni et al. 2006) Infectious diseases. Infectious diseases probably represent a major cause of infertility in male dogs living in breeding kennels. Germs can cause prostatitis, which may alter the biochemical composition of prostatic fluids and may induce a permanent or temporary blockage of the ducts as they enter the prostate. But infections often lead to an orchitis/epididymitis, with a subsequent alteration of the quality of the semen. Canine Brucellosis infection in males have been well described and any male dog suffering from infertility with a bad spermogram should be serologically tested for this disease. Recently also, the interest of leukocytes quantification in the ejaculate has been further studied (Martin 2005) Hormonal dysfunctions Central hormonal causes are not well documented. Testicular tumors which are responsible for excessive hormonal secretion (Sertoli cells tumors, Leydig cells tumors) may cause a decrease of spermatogenesis, even when these tumors are located only in one testicle and still quite small in size. Hypothyroidism is often stated as a potential cause of infertility. The link between hypothyroidism and low quality semen is still unclear and probably very much overestimated Retrograde ejaculation Retrograde ejaculation consists of a retrograde backflow of semen into the bladder when ejaculation occurs. This leads to either aspermia or oligospermia. In dogs, retrograde ejaculation is not well documented. This problem does not seem to be permanent. Treatment of retrograde ejaculation has been better documented recently (Romagnoli 2004, Beaufays et al 2004). Treatment may be attempted by collecting semen when the bladder is full (which makes the sphincter close more firmly). Sympathomimetic drugs like phenylpropanolamine (3 to 4 mg/kg per os twice daily)

7 or pseudoephedrine (4 to 5 mg/kg per os three times daily or 1 to 3 hours before semen collection or attempted breeding) may be tried.