Reproductive Disorders Treatment effectiveness

Reproductive Disorders Treatment efficacy in animals should be undertaken to achieve efficiency of growth. The increasing demands for production efficiency, along with changing environments (eg, housing and management systems) and, in many instances, the successful eradication of specific infections (eg, brucellosis, tuberculosis, campylobacteriosis), have caused a shift in therapeutic strategies in several domestic species. Especially for food animals, and to some extent for horses, the therapeutic approach of choice often is a combination of pharmacologic agents and correction of management problems. Prevention through vaccination and treatments on a herd basis also have become more important, especially in light of the need for cost effectiveness, eg, the increased use of pharmacologic agents in reproductive management such as synchronization of estrus, superovulation, induction of parturition, and treatment of anestrus and subestrus. Other therapeutic trends in food animals are the result of an increasing awareness of the possible hazards of antimicrobial and hormone residues in tissues and milk; alternatives to antibiotic therapy warrant increased attention. In small animals, therapeutic strategy has not changed as much as in large animals. The individual animal is still the focus of therapeutic efforts, and the environment of these species has not undergone the same changes as that of large animals. However, diagnostic techniques and treatments have become more sophisticated. More effective therapy may actually propagate hereditary predisposition for lowered fertility by curing diseases that previously were selected against naturally; this should be considered when dealing with fertility problems.

Pharmacologic Control of Reproduction:

Control of the estrous cycle—most commonly synchronization of estrus—usually is based on agents that act directly on the ovaries (eg, FSH, LH, or preparations with similar effect, such as equine chorionic gonadotropin [eCG] or human chorionic gonadotropin [HCG], and prostaglandins) or on agents that act mainly at the pituitary-hypothalamic level (GnRH, progesterone, progestins). Superovulation, which has become an essential part of embryo transfer, usually is achieved by hormonal treatment during a certain stage of the cycle with FSH or agents with FSH effect (eg, eCG) combined with a product with LH effect (eg, HCG). In ruminants, PGF2α or its analogs are used to lyse the CL and control estrus after FSH stimulation of multiple follicle development.

Pathologic conditions of the ovaries (eg, cystic ovaries, delayed ovulation) are often treated with preparations with LH effect (eg, HCG) or GnRH. For persistent CL, as in cases of bovine pyometra, prostaglandins have become the treatment of choice. Postpartum ovarian inactivity (postpartum anestrus) has been experimentally treated with pulses of FSH or GnRH repeated over time. However, practical delivery systems for these products are currently unavailable, and conditions such as lactation anestrus remain difficult to treat. Delayed puberty in some species (eg, pigs) may respond to treatment with a product that has follicle-stimulating effect (FSH, eCG, or a combination of eCG and HCG).

Other areas in which exogenous hormones can play a role in the control of reproduction are pregnancy and parturition. Estrogens are used as abortifacients in some species (eg, bovine), but prostaglandins are usually more effective. Estrogens have been used for prevention of pregnancy after undesired mating (eg, canine). Progesterone or various progestogens can be used for suppression of estrus to prevent mating in all species. Induction of parturition has become an important management tool in some species (eg, horses, pigs, and cattle). Corticosteroid treatment or PGF2α, or a combination thereof, is used in cattle. Dams with a dead fetus usually do not respond well to corticosteroids. In pigs, it appears that either PGF2α or a combination of PGF2α and oxytocin is best. In mares, oxytocin is most effective. It is important in all species that the animal is prepared for parturition. The less prepared the reproductive tract (ie, cervix, fetoplacental unit, and mammary glands), the higher the risk of complications.

For conditions such as prolonged gestation, the same agents are used as for induction of parturition in normal animals. In uterine disorders ( pyometra, retained placenta, and endometritis), the best nonantibiotic agents are those that can cause myometrial contractions, increase uterine blood flow, and mobilize defense mechanisms to the uterus. This can be achieved with estrogens and oxytocin. Prostaglandins have a strong stimulus on myometrial contractions in dogs but not in postpartum cows. Pyometra in cows is best treated with PGF2α because the condition is defined as including presence of a functional CL.

Antimicrobial Treatment:

Antimicrobial agents, most commonly antibiotics, are used for treatment of infections of the reproductive tract in all species. Drug selection should be based, if feasible, on microbiologic culture and sensitivity tests. The dosage, route of administration, and interval between treatments vary among species and with microbiologic status, blood and tissue distribution, etc. Systemically administered antibiotics penetrate the reproductive tract tissues better than those administered locally by intrauterine infusion.

Nonantibiotic Alternatives:

Unsatisfactory results with antibiotics and increased concern about bacterial resistance and tissue residues (for food animals) emphasize the need for nonantibiotic alternatives for treatment of reproductive infections. In general, there are 2 desirable effects of nonantibiotics on the reproductive tract: the contractile effect that causes the evacuation of the tubular tract and the positive effect on the cellular and humoral local defense. Drugs of primary interest for evacuation of the uterus are oxytocin, ergonovine, estrogens, and in some species (eg, dogs), PGF2α . Of these drugs, estrogens and PGF2αmay have a dual beneficial effect, stimulating both the contractions of the uterus (eg, in cases of retained lochia or placenta, or postpartum metritis) and the local cellular defense. 

In addition to its contractile effect on the myometrium, PGF2α causes regression of the CL in several species. This allows estrus to occur, which reinforces the effect on the myometrium and produces endogenous estrogen. In pyometra, these effects may work synergistically. Drugs that stimulate either contractions of the tubular tract or local defense mechanisms are used in combination with antibiotics or as the only treatment in cases of retained placenta, metritis, delayed uterine involution, retention of lochia, metrorrhagia, uterine prolapse, pyometra, etc. Oxytocin is commonly used to stimulate milk ejection in mastitis in some species (cattle, horses, dogs, and pigs). In the past, use of disinfectant douches (eg, Lugol’s solution, chlorhexidine, hydrogen peroxide, various iodophors, etc) was common for certain infections. They are still used for that purpose, especially in large animals; however, some of these substances are irritating, and there are indications that the local use of disinfectants may disturb the local immune defense (eg, the phagocytic ability of the WBC). A major reason for the interest in disinfectants and other alternatives to antibiotics is to avoid the problem of antibiotic residues in milk; however, any substance infused into the uterus is likely to also be passed into the milk. Because the beneficial effects have not been confirmed, this type of treatment is now less frequently recommended. It might still have a place among possible treatments for certain purposes such as inducing premature estrus in cows during a certain stage of the cycle. However, the beneficial effect in such cases is associated more with the induction of endogenous PGF2α and estrogen production than with the antimicrobial effect of the drug.