CARNIVORES

PRIMATES

Prosimians
New World Monkeys
Old World Monkeys
Lesser and Great Apes

UNGULATES

Perissodactyls
Artiodactyls

Bats and Rodents

MARINE MAMMALS

Pinnipeds
Cetaceans

Marsupials

HOW TO CHOOSE THE APPROPRIATE CONTRACEPTIVE METHOD

A variety of factors such as efficacy and safety of available methods, the animal’s age, behavioral and social ramifications, the practicality of different delivery systems, and the individual’s reproductive status must be considered when selecting an appropriate contraceptive method. It is unlikely that the same birth control method will be the most appropriate choice during all stages of an animal’s life. Permanent Sterilization or Participation in Contraceptive Studies is encouraged for Surplus Animals.

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MGA (melengestrol acetate) Implants

Manufacturer - ZooPharm division of Wildlife Pharmaceuticals, Colorado, USA.

Product Information - MGA implants are the most frequently used and consequently the contraceptive method for which we have the most information in the Wildlife Contraception Center database. Melengestrol acetate is a synthetic progestin. MGA implants contain 20% melengestrol acetate by weight in a silastic matrix. Because different species require different dosages, implants are not interchangeable. Although duration of MGA implant efficacy may vary by individual and species, the continued recommendation is to replace them at 2-year intervals.

Storage – Implants should be stored at refrigeration temperatures (4°C).

Sterilization – MGA implants should be inserted using sterile surgical technique. In addition, it is recommended that implants be gas-sterilized with ethylene oxide followed by de-gassing at room temperature for a minimum of 2 weeks prior to use. Because the implants are porous, they must be de-gassed longer than metal instruments. Inadequate de-gassing may result in residual gas that may evoke a tissue reaction. If ethylene oxide sterilization is not available, the implant may be rinsed with alcohol and dried with sterile gauze prior to placement. Sterilization with a cold-soak solution is not recommended, because the chemicals can be absorbed and/or MGA may be leached from the implant. Possible effects of hydrogen peroxide sterilization (STERRAD) on MGA implant release dynamics have not been tested, so it can not be recommended or advised against at this time. Because heat may change the structure of the MGA, implants should not be autoclaved.

Insertion - Implants should be inserted between the scapulae intra-muscularly if possible, but, if subcutaneous placement is necessary, place implant in a “tunnel” created by blunt dissection of fascia away from the incision. Migration may be controlled by suturing the implant in place at the time of insertion.

Implant loss can be reduced by properly sterilizing implants before insertion, using sterile insertion technique, and separating the animal from conspecifics during the period of healing. (NOTE: in some taxa such as the callitrichids and small prosimians, steel sutures have been successful in preventing over-grooming and implant removal by conspecifics, thereby avoiding the need to separate animals). The implant’s presence should be confirmed whenever the animal is handled.

Monitoring implant placement - Identification transponder microchips inserted in MGA implants can be used to confirm presence and location. Implants cannot be supplied with transponders already in place; however, chips can be inserted in implants that are longer than the chip. Using sterile procedure, puncture implant longitudinally with needle containing transponder chip (it comes sterile) and insert into implant as you would under the skin. Insert implant into animal using standard surgical technique as outlined above. Secondly, stainless steel suture or comparable material may be incorporated into the implant to make it visible on radiographs prior to sterilization.

Implant disposal – used implants received from ZooPharm or Ed Plotka should be disposed of in proper waste containers after use.

Latency to effectiveness - Although individuals vary, threshold levels of the hormone should be reached in the blood within 1 to 3 days following IM insertion and within 1 week after SQ insertion. However, pre-ovulatory follicles are difficult to suppress, so, if cycle stage is not known, extra time must be allowed. Therefore, separation or alternative contraception should be used for at least 1week (if IM) or 2 weeks (if SQ) following insertion.

Estrous cycles during treatment - MGA may effect contraception by blocking ovulation, causing thickening of cervical mucus, slowing ovum transport, and/or interfering with fertilization or implantation. However, follicle growth may continue and sometimes be accompanied by estrogen production sufficient to cause estrous behavior. Ovulation may occur even though pregnancy does not ensue. Higher progestin doses may be preferred, so that estrous behavior is prevented, but may not be effective in completely suppressing follicle growth and some estradiol production.

Duration of efficacy and reversibility - Implants are considered effective for at least 2 years and possibly much longer, depending on species and individual differences, but in some cases have been found to be effective for as much as 5 years when left in place. This means that implants should be replaced every 2 years to insure contraception, but should be removed when pregnancy is desired. Once the implant is removed, the circulating MGA clears very rapidly, so that ovulation and conception may occur within days, although actual latency is usually longer and will depend on the individual (see Reversibility Considerations).

Use during pregnancy - Synthetic progestins like MGA are not recommended in pregnant animals because of the possibility of prolonged gestation, stillbirth, abortion, etc. in some species, although the effect may depend on dose. Progestins in late pregnancy seem not to interfere with parturition in primates, but this may be a taxon-specific phenomenon.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Use in pre-pubertals or juveniles – Future reproduction was not affected in calves of domestic cows on MGA-treated feed, but no studies of pre-pubertal treatment with MGA or other progestins have been conducted with other species, so possible long-term effects on fertility are not known.

Precautions – MGA can cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season. However, in canids, treatment should begin more than two months before the time of anticipated estrus, because proestrus increases in estradiol can begin as much as two months before estrus, and it is known that this endogenous estradiol can exacerbate deleterious effects of progestins on the uterus and mammary glands. This synergy of estradiol and progestins may also occur in other carnivores, such as mustelids and ursids.

Reporting Requirements - All institutions must submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. The product will no longer be sold to any institution that fails to submit the annual survey.

Request for purchase – MGA implants may be purchased by prescription through ZooPharm. All prescriptions should be written using their protocol and MUST include an authorization number designated by the AZA Wildlife Contraception Center. MGA implants cost $25/gram plus shipping and handling. To request authorization for ordering MGA implants, please complete the Implant Request Form and submit to:

Sally Boutelle, Program Coordinator

AZA Wildlife Contraception Center

Saint Louis Zoo

1 Government Drive

St. Louis, MO 63110

314-781-0900 x 384; fax: 314-768-5454

Contraception@stlzoo.org

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MGA MILLED IN FEED

Manufacturer - Purina Mills LLC/Mazuri, St. Louis, USA.

Product Information - Mazuri ADF-16 Herbivore pellet with MGA (a synthetic progestin) provides an alternative contraceptive method particularly for ungulates housed and fed in mixed species/mixed sex herds. The product is considered suitable for bovids, giraffes, cervids, camelids and hippos, but is not effective in suids or equids.

The product is available only as part of an experimental trial coordinated by the AZA Wildlife Contraception Center in collaboration with Purina Mills LLC/Mazuri brand. The goal of the study is to obtain approval for use of MGA-treated feed as a contraceptive method for exotic hoofstock species. However, at this time the feed must be considered experimental and all participants must adhere to strict protocols for data collection and reporting as dictated by the Food and Drug Administration (FDA). The AZA Wildlife Contraception Center is responsible for maintaining data collected by study participants and, in conjunction with Purina Mills LLC, submits regular reports to the FDA. The FDA requires all medicated diets be manufactured under an INAD (Investigational New Animal Drugs, 21 CFR 511.1(a)). Purina Mills LLC was granted permission to manufacture MGA-treated herbivore pellet for use in this project under their existing INAD on file with the FDA. Therefore, all participating institutions must obtain the experimental MGA feed through the AZA Wildlife Contraception Center and Purina Mills LLC until such time as it is approved by the FDA for general manufacture and feeding. NOTE: Under the current INAD the product is only available for bovids, giraffes, cervids, camelids, and hippos, and its use in other species or without registering with the AZA Contraception Center is prohibited.

Safety to humans - When used as directed, this product poses no health risk to humans. Domestic cattle are 240 times more sensitive to MGA than are humans, i.e., a human would have to ingest a dose 240 times higher than that ingested by cattle to have the same effect. The doses being recommended for exotic ungulates are within the range used for cattle. Purina Mills, Inc. believes it is not hazardous material according to the OSHA Hazard Communications Standard, 29 CFR 1910.1200 or the EPA Community Right-to-Know regulations. Questions about the Purina Mills MSDS program should be directed to Mr. Paul Luther at 314-768-4630.

Safety to treated animals - MGA has been fed to domestic cattle for decades without untoward effects, which suggests that it should be generally safe for ruminants. However, exotic species have not been treated for more than 10 years, so possible longer term effects have not been recognized. Also, species differences may apply.

Recommended doses - Mazuri ADF-16 0.5MA, containing 0.5 mg MGA/lb, can be used either alone or in combination with standard Mazuri ADF-16 to achieve the recommended daily MGA dose/animal for your individual feeding program. The following daily MGA doses are recommended:

0.5 mg MGA/day/animal: for species with body size smaller than an adult, female banteng. (about 800 lb).
1.0 mg MGA/day/animal: for species with body size similar to or larger than an adult, female banteng but smaller than a giraffe.
3.0 mg MGA/day/animal: giraffes and hippos

The maximum safe dose is considered to be more than 3 times those recommended here. NOTE: If the full dose is not consumed every day, the female should be separated from males, since follicle growth and ovulation may occur.

Nutritional considerations - The amount of pellet used depends on the species, the body size and on your particular feeding program. The MGA herbivore pellet is intended to replace the regular herbivore pellet in the current diet. The pellet should still be fed in conjunction with hay in an amount that meets the recommended minimum daily MGA dose, while still meeting the nutritional needs of the animals.

In general, ruminant herbivores have a daily diet intake of 1.5 – 4.0% body mass (BM), with larger species consuming food at a smaller percentage of BM than medium or small species. The amount of herbivore pellet to feed is based largely on the quality of hay fed, and the pellet is intended to correct the nutrient imbalances or deficits that might occur on a diet of only hay. Regular analysis of the nutrient content of your hay is highly recommended. It may be necessary to make adjustments in your current feeding regimens in order to deliver the appropriate dose of MGA via the new herbivore products. Current recommendations from zoo nutritionists suggest that medium to large size ruminant herbivores should receive 30-40% of the diet (by weight, as fed basis) as a nutritionally complete herbivore pellet and 60-70% of the diet (by weight, as fed basis) as hay. The type of hay(s) used (e.g., legume or grass hay, species of hay) in the diet is dependent on the nutrient content of the hay, the species being fed and hay types available in your area.

If you would like assistance in determining an appropriate feeding plan, please contact Jan Dempsey, Nutritionist, at jdempsey@purina.com.

Latency to effectiveness - As with MGA implants, separation or alternative contraception should be used for 1-2 weeks after initiation of the feed.

Estrous cycles during contraceptive treatment - Synthetic progestins may affect contraception by blocking ovulation, causing thickening of cervical mucus, slowing ovum transport, and/or interfering with fertilization or implantation. However, follicle growth may continue and sometimes be accompanied by estrogen production sufficient to cause estrous behavior. Ovulation may occur even though pregnancy does not ensue. Higher progestin doses may be preferred so that estrous behavior is prevented, but may not be effective in completely suppressing follicle growth and all estradiol production.

Duration of efficacy and reversibility - Duration of efficacy may not be much more than one day, so the product must be administered daily. Following cessation of treatment, rapid clearance can result in ovulation within a few days, but actual latency to conception will vary by individual.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Use in pre-pubertals or juveniles Future reproduction was not affected in calves of domestic cows on MGA-treated feed, but no studies of pre-pubertal treatment with MGA or other progestins have been conducted with other species, so possible long-term effects on fertility are not known.

Precautions – Progestins likely cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season.

Reporting requirements - All institutions using MGA feed must submit a bi-annual MGA Feed Survey to the AZA Wildlife Contraception Center. Any adverse effects must be reported in writing to the AZA Wildlife Contraception Center. The product will no longer be sold to any institution that fails to submit the bi-annual survey.

Request for purchase - Before placing your first order with your Purina product dealer, or to add species to an existing order, you must register with the AZA Wildlife Contraception Center. The Center will then notify Purina Mills, Inc. that you are an approved buyer, so you will be able to make the purchase through your regular Purina product dealer. Please submit the MGA Feed Registration Form to:

Sally Boutelle, Program Coordinator

AZA Wildlife Contraception Center

Saint Louis Zoo

1 Government Drive

St. Louis, MO 63110

314-781-0900 x 384; fax: 314-768-5454

Contraception@stlzoo.org

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MGA LIQUID

Manufacturer - ZooPharm division of Wildlife Pharmaceuticals, Colorado, USA.

Product information - MGA, a synthetic progestin dissolved in a special propylene glycol formulation for orally delivered contraception, is considered suitable for species in which orally delivered MGA has been shown to be safe and effective

Safety to humans - When used as directed, this product poses no health risk to humans. ZooPharm believes this MGA formulation is not a hazardous material according to the OSHA Hazard Communications Standard, 29 CFR 1910.1200 or the EPA Community Right-to-Know regulations. Therefore no Material Safety Data Sheets (MSDS) have been produced. If you have questions, call Dr. Bill Lance at 970-484-6267.

Safety to treated animals - MGA has been administered orally to domestic cattle for decades without untoward effects, which suggests that it should be generally safe for ruminants. However, exotic ruminants have not been treated orally with MGA for more than 10 years, so possible longer term effects are unknown. Also, as with most drugs, species differences apply. In particular, MGA liquid is not recommended for carnivores, since synthetic progestins have been shown to be associated with deleterious effects in this group. It may not be appropriate for primates, as a higher concentration is necessary for efficacy. It may not be effective in suids or equids.

Recommended doses - The product comes as a solution of 1mg MGA/ml. The following daily MGA doses are recommended:

0.1 mg MGA/day/animal - for small mammals such as bats and rodents

0.5 mg MGA/day/animal - for ungulates up to about 800 lbs
1.0 mg MGA/day/animal - for ungulates larger than 800 lbs, except giraffe and hippopotamus.
2.0-3.0 mg MGA/day/animal- for giraffe and hippopotamus

NOTE: If the full dose is not consumed every day, the female should be separated from males, since follicle growth and ovulation may occur.

Administration - MGA liquid can be added to a treat and delivered to individual animals, can be delivered directly into the mouth of animals such as hippos, or can be added to the regular diet and fed individually or to groups. However, it is important to insure that each female ingests at least the minimum effective dose every day or ovulation and pregnancy can result. If a female refuses to consume the dose, she should be separated from males until she is has consumed the proper dose again for at least one week.

Although progestin contraception can often be effective even when ovulation is not blocked, to ensure efficacy we recommend that the dose be sufficiently high to suppress estrous behavior. Please report observations of estrous behavior in treated animals to Cheryl Asa or Sally Boutelle to discuss a higher dosage.

Latency to effectiveness - As with MGA implants and feed, separation or alternative contraception should be used for 1-2 weeks after initiation of the product.

Estrous cycles during contraceptive treatment - Synthetic progestins may effect contraception by blocking ovulation, causing thickening of cervical mucus, slowing ovum transport, and/or interfering with fertilization or implantation. However, follicle growth may continue and sometimes be accompanied by estrogen production sufficient to cause estrous behavior. Ovulation may occur even though pregnancy does not ensue. Higher progestin doses may be preferred, so that estrous behavior is prevented, but may not be effective in completely suppressing follicle growth and all estradiol production.

Duration of efficacy and reversibility - Duration of efficacy may not be much more than one day, so the product must be administered daily. Following cessation of treatment, rapid clearance can result in ovulation within a few days, but actual latency to conception will vary by individual.

Use during pregnancy - Progestins are not recommended in pregnant animals because of the possibility of prolonged gestation, stillbirth, abortion, etc. in some species, although the effect may depend on dose. Progestins in late pregnancy seem not to interfere with parturition in primates, but this is probably a taxon-specific phenomenon.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Use in pre-pubertals or juveniles - Future reproduction was not affected in calves of domestic cows on MGA-treated feed, but no studies of pre-pubertal treatment with MGA or other progestins have been conducted with other species, so possible long-term effects on fertility are not known.

Precautions – Progestins likely cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season.

Reporting requirements - All institutions using MGA liquid must submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. The product will no longer be sold to any institution that fails to submit the annual survey.

Request for purchase - Before placing your first order with Zoopharm, or to add species to an existing order, you must register with the AZA Wildlife Contraception Center. The Center will then notify ZooPharm that you are an approved buyer so you will be able to make the purchase through a valid prescription faxed to ZooPharm at 307-721-3801. The formulation is compounded to a 1mg/ml strength in a 30 ml vial, at a price of $25.00 plus shipping and handling. A more dilute strength can be provided on request for smaller mammals. Cost of special flavorings would be extra but should be minimal. Please submit the MGA Liquid Registration Form to:

Sally Boutelle, Program Coordinator

AZA Wildlife Contraception Center

Saint Louis Zoo

1 Government Drive

St. Louis, MO 63110

314-781-0900 x 384; fax: 314-768-5454

Contraception@stlzoo.org

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DEPO-PROVERA® (medroxyprogesterone acetate) INJECTIONS

Manufacturer - Pfizer

Product information - With the second most numerous records in the Wildlife Contraception Center database, Depo-Provera® has been used most often in reproductively seasonal species (e.g., prosimians, bears, pinnipeds), species in which anesthesia for implant insertion is problematic (e.g., giraffes, hippos), and as an immediately available interim contraceptive (e.g., if an implant is found missing or has not been ordered). Medroxyprogesterone acetate is a synthetic derivative of progesterone administered as an acetate salt with anti-estrogenic activity.

Dose - Dosage studies have not been conducted for most species. Recommended doses and injection intervals vary according to species and experience. Current reports have indicated that 2-5 mg/kg body weight every 2-3 months has been effective (the higher dose for smaller species and the lower dose for larger ones). However, New World monkeys require as much as 20mg/kg monthly. For especially large species for which body weights may not be available, such as hippos, see Taxon-Specific Recommendations.

Latency to effectiveness - IM injection is roughly equivalent to implant insertion, i.e., separation or alternative contraception should be used, conservatively, for 2 weeks, but at least for1 week.

Duration of efficacy and reversibility - Duration of efficacy, and thus latency to conception following last injection, can be extremely variable and has been seen to vary from 4 weeks to 2 years in some individuals. In general, the recommended dose (2.5-5 mg/kg BW) is effective for at least 2 months in most species. Hippos and giraffe have been treated at lower doses and appear to need re-treatment every 6 weeks. New World primates require higher doses at more frequent intervals.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season. This does not include however canids or other carnivores due to the potential for progestin side effects addressed in the corresponding taxonomic sections below.

Precautions – Progestins likely cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon. In the human literature, Depo-Provera® has been linked to mood changes. Because it binds readily to androgen receptors and is anti-estrogenic, females may experience male-like qualities (increased aggression, development of male secondary sex characteristics, etc.)

Reporting requirements - All institutions using Depo-Provera® are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development.

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OVABAN®/MEGACE® (megestrol acetate) PILLS

Manufacturer – Ovaban®: Schering Plough; Megace®: Bristol-Myers Squibb

Product information – Megestrol acetate is a synthetic derivative of progesterone with anti-estrogenic activity. Ovaban® is approved for use in domestic dogs for no more than 2 cycles. Megace® is approved for treatment of estrogen-sensitive tumors and for anorexia in humans because it increases appetite. Both have been used occasionally for contraception in carnivores. Ovaban® can be used temporarily during the initial stimulation phase of the GnRH agonist products. It is provided in 5- and 20-mg tablets. The domestic dog dose is 1mg/kg body weight, but must be extrapolated for other taxa.

Latency to effectiveness - As with implants and injections, separation or alternative contraception should be used for 1-2 weeks after initiation of treatment.

Duration of efficacy and reversibility - Duration of efficacy may not be much more than one day, so must be administered daily. Following cessation of treatment, rapid clearance can result in ovulation within a few days, but actual latency to conception will vary by individual.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season. This does not include however canids or other carnivorous species due to the potential for progestin side effects addressed in the corresponding taxonomic sections below.

Precautions – Progestins likely cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Reporting requirements - All institutions using Ovaban® or Megace® are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development.

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REGU-MATE® (altrenogest) Oral Solution

Manufacturer – Hoechst-Roussel

Product information – Regu-mate®, marketed for short-term estrus suppression in domestic horses, has been used for aggression control in male Pzrewalski horses and for contraception in suids and some marine mammals. Evidence suggests the standard horse does is ineffective in tapirs.

Safety to humans - Protective gloves should be worn during administration, since it is readily absorbed through skin and can cause disruption of menstrual cycles and prolongation of pregnancy in humans.

Latency to effectiveness - As with implants and injections, separation or alternative contraception should be used for 1-2 weeks post initiation of product.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season.

Precautions – Progestins likely cause weight gain in all species. Regu-mate® has caused endometritis in domestic horses and cystic follicles in suids at low doses. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Reporting requirements - All institutions using Regu-mate® are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development.

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PROGESTIN ONLY PILLS

· Ovrette® (norgestrel) pills – 0.075mg

· Jolivette® (norethindrone) pills – 0.35mg

· Micronor® (norethindrone) pills – 0.35mg

· Nora-Be® (norethindrone) pills – 0.35mg

· Nor-QD® (norethindrone) pills – 0.35mg

· Cerazette® (Desogestrel) pills – 0.075mg

There are no data in the WCC database regarding the use of this orally active progestin-only contraceptive.

Manufacturer – See brand details and the list of manufacturers: BC Pills

Product information – A progestin-only oral contraceptive pill consists of synthetic progesterone, either norgestrel or norethindrone.

Latency to effectiveness - As with implants and injections, separation or alternative contraception should be used for 1-2 weeks after initiation of product.

Use during lactation - Progestins are sometimes prescribed for lactating women and are considered generally safe for nursing infants.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season. This does not include however canids or other carnivorous species due to the potential for progestin side effects addressed in the corresponding taxonomic sections below.

Precautions – Progestins likely cause weight gain in all species. Possible deleterious effects on uterine and mammary tissues vary greatly by species; see cautions for each taxon.

Reporting requirements - All institutions using Progestin-only pills are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development.

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COMBINATION BIRTH-CONTROL PILLS (Synthetic progestin plus synthetic estrogen)

Brand and Manufacturer – Available List of Birth Control Pills

Product information – Human birth control pills are available in different dose formulations with various administration, from 21 days with 7 days of placebo to allow menstruation, to 90 days before the placebo week. Treatment can begin in any phase of the cycle, but may not be effective in the first month if treatment begins near the time of ovulation. Survey reports to the WCC database indicate that birth-control pills have only been used in apes and some felids, and that, typically, the human regimen was followed.

Latency to effectiveness - As with implants and injections, separation or alternative contraception should be used for 1-2 weeks post initiation of product. Efficacy may take one month if treatment begins near the time of ovulation.

Estrous cycles during contraceptive treatment - Signs of estrus can occur during the placebo week.

Duration of efficacy and reversibility - Duration of efficacy for combination pills is more than one day, because conception is blocked during the one week of placebo administration in humans. However, minimum dosages have not been established for other species. Daily administration outside the placebo week is probably necessary to ensure contraception. Latency to reversal may be slightly longer than for oral progestins, since the estrogen component more effectively suppresses follicle growth, increasing the time to ovulation.

Use during pregnancy – Degree of risk to the fetus is uncertain, and manufacturers recommend discontinuation during pregnancy.

Use during lactation – Combination birth control pills may interfere with milk production or affect developing infant, so are not recommended. Progestin-only pills are sometimes prescribed for lactating women and are considered generally safe for nursing infants

Use in pre-pubertals or juveniles - Lack of data on pre-pubertal treatment and potential long-term effects on fertility contraindicate recommending contraception before puberty. Fertility is less likely to be affected by treatment administered after puberty.

Consideration for seasonal breeders - Treatment should begin at least one month before the anticipated onset of the breeding season.

Precautions - Weight gain is less likely than with progestin-only treatment, but the estrogen component may cause fluid retention.

Reporting requirements - All institutions using Birth Control Pills are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development.

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PORCINE ZONA PELLUCIDA (PZP) VACCINE

Manufacturer – Dr. Jay Kirkpatrick, Montana, USA

Product information – Derived from porcine zona pellucida, the PZP vaccine causes antibodies that prevent the attachment of sperm to ova, and thus, blocks fertilization. The Wildlife Contraception Center recommends its use in ungulates, pinnipeds, elephants and bears for:

1) short-term use (up to 3-4 consecutive years).

2) longer-term use in animals not essential for breeding programs, because of the possibility of reversal failure following long-term use.

3) animals requiring remote delivery of a contraceptive rather than hands on. Remote delivery is possible because of the 1.0cc volume.

Adjuvant information - The only adjuvant used with PZP is Freund’s Modified adjuvant, which DOES NOT CAUSE TB+ TEST RESULTS, and injection site reactions are less than 0.05%. Following the initial treatments, boosters are required, using only Freund’s Incomplete adjuvant.

Latency to effectiveness – PZP is not effective until after at least 2 injections (typically given at 2-4 week intervals), depending upon species and adjuvant. There must be a minimum 2-week interval after the last injection before the male is placed with the female. The timing of booster inoculations is species-dependent and each institution will be advised regarding booster inoculation intervals (Dr. Jay Kirkpatrick or Kim Frank).

Estrous cycles during contraceptive treatment – PZP should not suppress estrous cycles and may extend the breeding season beyond what is considered typical, resulting in additional estrous cycles.

Duration of efficacy and reversibility – PZP becomes effective after initial inoculations, typically given at a 2-4 week interval, depending upon the species.

Use during pregnancy - Does not interrupt pregnancy or affect fetus.

Use during lactation - No known contraindications.

Use in pre-pubertals or juveniles - PZP-treated prepubertal white-tailed deer and feral horses were fertile as adults, but there are no data for other species.

Consideration for seasonal breeders - Because PZP is not effective until after at least 2, preferably 3, injections (typically given at 2-4 week intervals), depending upon species and adjuvant, treatment should be initiated at least 2 months before the anticipated onset of the breeding season.

Precautions - In rabbits and possibly canids, PZP can cause depletion of oocytes and, in some primates, it can cause temporary cessation of estrous cycles. There is little data for carnivores, aside from pinnipeds and bears, and recent research with felids indicates that the antibodies will not cross-react with the sperm receptors, thus its use in carnivores is recommended only for pinnipeds and bears. It should not be used in suids.

Reporting requirements - All institutions using PZP must submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. The Science and Conservation Center also has a separate form they need completed which can be obtained directly from Kim Frank.

Request for purchase: Kim Frank

Science and Conservation Center

Zoo Montana

2100 South Shiloh Road

Billings, MT 59106

406-652-9719; fax: 406-652-9733

zoolab@wtp.net

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SUPRELORIN® (deslorelin) IMPLANTS

Manufacturer – Peptech Animal Health, Australia

Product information – Suprelorin® (deslorelin), a GnRH agonist, effects contraception by temporarily suppressing the reproductive endocrine system, preventing production of pituitary (FSH and LH) and gonadal hormones (estradiol and progesterone in females and testosterone in males). The observed effects are similar to those following ovariectomy or castration, but are reversed after the hormone content of the implant is depleted. As an agonist, deslorelin first stimulates the reproductive system, which can result in estrus and ovulation in females or temporary enhancement of testosterone and semen production in males. Then, down-regulation follows the initial period of stimulation. Although deslorelin can also be an effective contraceptive in males, we recommend its use primarily in females, since monitoring efficacy in females by suppression of estrous behavior or gonadal steroids in feces is more straightforward than ensuring continued absence of sperm in males, since most institutions cannot perform regular semen collections. It can, however, be used for aggression control in males.

Deslorelin implants are available in two formulations: 4.7-mg for 6-month duration, and 9.4-mg for 12-month contraception. Deslorelin has been tested primarily in domestic dogs and cats, which makes it most suitable for carnivores, and it has successfully reduced aggression in male lion-tailed macaques. However, it appears not to be effective in male bovids or marsupials. It is currently in use in a number of carnivores, primates, and female hoofstock species.

Storage – Implants should be stored at refrigeration temperatures (4°C).

Insertion – The implant comes pre-loaded in an insertion device. The recommended site of implant placement is between the shoulder blades. The area should be clipped and cleaned using standard surgical prep techniques. A fold of skin should be lifted and held between the thumb and fingers as the obturator (sent with the implant) is inserted. To prevent breakage of the implant during insertion, the barrel of the obturator should be slowly withdrawn as the implant is expelled. The implant should be held steady as the obturator is removed to insure release of the implant so that it remains in place under the skin.

Latency to effectiveness - Because the initial effect is to stimulate the reproductive system, it is important to either separate treated animals from opposite sex individuals during the period of enhanced fertility or use another form of contraception. Females treated with deslorelin should be considered fertile for 3 weeks following insertion. Males may remain fertile for 2 or more months, until residual sperm either degenerate or are passed (as following vasectomy). Lessening of aggression in some male primates treated with deslorelin or other GnRH agonists was not seen for 6-12 months, but the delay may have been due to an inadequate dose.

Suppression of initial estrus/ovulation – The estrus and ovulation that can occur within 2 weeks following implant insertion can be suppressed with supplemental progestin treatment for 15 days (7 days prior- and 8 days post-implant insertion). Ovaban® tablets (Megestrol acetate) are the simplest form for short-term progestin administration, with the tablet can be offered as a treat to insure ingestion. Depo-Provera® should not be substituted for Ovaban®, because its sustained release can interfere with Suprelorin® efficacy. MGA implants can be left in place for 2-3 weeks following Suprelorin® implant insertion, but then should be removed to prevent interference with the down-regulation action. Leaving them in place longer may compromise Suprelorin® efficacy.

Estrous cycles during contraceptive treatment - Deslorelin first stimulates, then suppresses estrus in females. Species with induced ovulation (e.g., felids, some mustelids, bears) may ovulate and become pseudopregnant (also canids) when first treated. In males, initial stimulation may be accompanied by increased aggression or sexual interest.

Duration of efficacy and reversibility – A new 12-month formulation containing 9.4mg deslorelin should be effective for approximately twice as long as the smaller (4.7mg) implants that have been supplied in the past. However, the dose needed per-kg-body-weight with the new 9.4mg implants is about twice that of the existing 4.7mg implants. For animals effectively contracepted for 6 months with two 4.7mg implants, two 9.4mg implants will be necessary, but the period of efficacy will be double (12 months). For 6 months contraception, one 9.4mg implants will not substitute for two of the 4.7mg ones. These dose recommendations should only serve as general guidelines, because individual animals may respond differently. Stated durations of efficacy should be considered minimums. The smaller implants may actually be effective for more than 6 months, and the larger ones for more than 12 months, in some animals. Data from various species have shown, though, that individual responses tend to be consistent and if animals reverse earlier than expected they will consistently do so. If it is not possible to wait for signs of reversal to determine duration of efficacy for the animal, then for continuous contraception the small implants should be replaced at least every 6 months and larger ones at least every 12 months.

Use during pregnancy – GnRH agonists should not be used during pregnancy, as they may cause abortion.

Use during lactation - No known contraindications once lactation has been established; however, treatment during pregnancy may impede proper mammary development.

Use in pre-pubertals or juveniles - Deslorelin may prevent epiphyseal closure of the long bones, resulting in taller individuals. GnRH agonist use in prepubertal domestic cats was followed by reproductive cycles after treatment ceased. However, species differences may occur.

Consideration for seasonal breeders – In females, GnRH agonists can induce estrus and ovulation even during the non-breeding season in some taxa. In males, GnRH agonists can transiently stimulate testosterone production even during the non-breeding season. Treatment should begin more than two months prior to anticipated breeding season to prevent initiation of spermatogenesis, because it appears that suppression of sperm production is more easily accomplished before it has commenced.

Precautions - In general, the effects on weight should be similar to those from ovariectomy or castration. Preliminary data indicate that increased appetite will result in weight gain, especially in females, unless food is restricted. In males, muscle loss may result in overall weight loss if not replaced by fat. In sexually dimorphic species, males may become the size (weight) of females.

Reporting requirements - All institutions using deslorelin must submit a complete Deslorelin Survey to the AZA Wildlife Contraception Center. The product will no longer be sold to any institution that fails to submit the annual survey.

Request for purchase - Deslorelin implants are available through the AZA Wildlife Contraception Center as part of an agreement with Peptech Animal Health, Australia. Cost is $25 per 4.7-mg implant or $50 per 9.4-mg implant, to be paid to the Contraception Center as reimbursement, as the product is not for commercial sale. Please submit the Deslorelin Agreement Form to:

Sally Boutelle, Program Coordinator

AZA Wildlife Contraception Center

Saint Louis Zoo

1 Government Drive

St. Louis, MO 63110

314-781-0900 ext 384; fax: 314-768-5454

Contraception@stlzoo.org

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LEUPROLIDE (leuprolide acetate) INJECTABLE – Not Currently Available

LUPRON® (leuprolide acetate) DEPOT INJECTION

Manufacturer – TAP Pharmaceuticals

Product information – Lupron®, approved by FDA, a GnRH agonist approved for treatment of prostate cancer, is very expensive if purchased, but can sometimes be acquired through donation from the manufacturer. In captive animals it has been used primarily in males to suppress testosterone and sperm production. It is probably not effective in male bovids or marsupials.

Latency to effectiveness - Because the initial effect is to stimulate the reproductive system, it is important to either separate treated animals from opposite sex individuals during the period of enhanced fertility or use another form of contraception. Females treated with a GnRH agonist should be considered fertile for 3 weeks following insertion. Males may remain fertile for 2 or more months, until residual sperm either degenerate or are passed (as following vasectomy).

Suppression of initial estrus/ovulation – The estrus and ovulation that can occur within 2 weeks following implant insertion can be suppressed with supplemental progestin treatment for 15 days (7 days prior- and 8 days post-implant insertion). Ovaban® tablets (Megestrol acetate) are the simplest form for short-term progestin administration, as the tablet can be offered as a treat to insure ingestion. If the animal has an unexpired MGA implant in place (less than 2 years old), MGA removal could be delayed until 3 weeks post Lupron injection. Similarly, Lupron can be injected while the animal is being contracepted with Depo-Provera®.

Estrous cycles during contraceptive treatment - Lupron first stimulates, then suppresses estrus in females. Species with induced ovulation (e.g., felids, some mustelids, bears) may ovulate and become pseudopregnant (also canids) when first treated. In males, initial stimulation may be accompanied by increased aggression or sexual interest.

Duration of efficacy and reversibility – Lupron is available in various formulations lasting from 1 to 6 months, but because the release of hormone from the depot formulation varies by individual, actual duration of efficacy and time to reversal can vary considerably.

Use during pregnancy – GnRH agonists should not be used during pregnancy, as they may cause abortion.

Use during lactation – No information specifically for Lupron, but probably acts as other GnRH agonists.

Use in pre-pubertals or juveniles – Lupron may prevent epiphyseal closure of the long bones, resulting in taller individuals. GnRH agonist use in prepubertal domestic cats was followed by reproductive cycles after treatment ceased. However, species differences may occur.

Reporting requirements - All institutions using Lupron are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center.

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OVOCONTROL™ G 0.25% and OVOCONTROL™ P 0.5%

(nicarbazin) Ready to Use Bait

Manufacturer – Innolytics, LLC, Rancho Santa Fe, CA

Product Information – OvoControl G interferes with the hatchability of avian eggs. The active ingredient, nicarbazin, is registered both by the FDA and EPA. Originally used as a drug to control coccidiosis in chickens, the compound has been developed and registered for hatch control in pest birds such as Canada geese and feral pigeons. Further EPA registration applications in other avian species are pending.

OvoControl interferes with the development of the vitelline layer separating the egg white and yolk. This membrane is vital to the viability of the egg and without it the egg cannot develop or hatch. Nicarbazin has been tested in mallard ducks, Japanese quail, feral pigeons, Canada geese, domestic turkeys and chickens and Pekin ducks. While all avian species are considered sensitive, different doses may be required to achieve the optimal contraceptive effect.

At the recommended dose, the bird will continue to lay eggs, although the eggs will not hatch. At higher dose levels, the bird may actually stop laying eggs altogether.

OvoControl is considered a restricted use pesticide due to its potential to interfere with the hatchability of non-target avian eggs. Care should be taken to avoid administration to non-target birds and other animals. For a current copy of the EPA approved label, see the Innolytics website at www.hatchcontrol.com.

Dosage - The recommended contraceptive dose for a resident Canada goose (average body weight = 4.5kg) is 28mg of nicarbazin/kg body weight, or 50 grams of OvoControl G 0.25%/day. The recommended dose for feral pigeons (average body weight = 0.32kg) is 83.3 mg of nicarbazin/kg body weight or roughly 5 grams of OvoControl P 0.5%/day. In order to maintain a contraceptive blood level, OvoControl must be administered daily. The product is not toxic and has a wide range of safety. OvoControl must be consumed for several days to achieve blood levels that affect the hatchability of eggs that are forming. Nicarbazin is undetectable in the plasma of Canada geese, mallards, and chickens 4-6 days after consumption of the OvoControl bait has stopped. The levels of DNC in the blood are reduced by half within one day after bait consumption stops. Once the level of DNC falls by approximately one half its peak levels, the effect on egg being formed has almost disappeared. By two days after bait consumption has stopped, no effects on the egg being formed is seen.

Toxicity - The LD50 of nicarbazin is greater than 25,000 and 10,000mg/kg body weight in the mouse and rat, respectively. A recent study in pigeons (Avery, 2006) showed no adverse effects at a dose level of 206/mg/breeding pair (2.5 x the recommended dose) over 36 days. The recommended dose to achieve contraception in pigeons is 82.5mg/kg bw/day. Too much OvoControl does not harm the bird and overdoses will result in a reduction, eventually dropping egg production to near zero. No adverse effects, other than hatchability, have been noted at any of the dose levels or studies.

Side Effects - The main side effects of nicarbazin when used to control coccidiosis in chickens include reduced hatchability of eggs; reduced numbers of eggs laid, and reduced eggshell pigment in eggs that contain the brown pigment porphyrin. No side effects have been noted when used to control hatchability in other birds.

Teratology - There has been no reported teratology from the use of OvoControl or nicarbazin in any species. There appears to be a threshold level of DNC in the blood or egg below which the embryo forms normally and hatches normally to yield a healthy gosling and above which the embryo does not develop and does not hatch. Also, there have been no reports over the past 50 years of teratogenic effects in birds in the literature.

Secondary toxicity - Fortunately, the chemistry of the active ingredient assures that there is an extraordinarily low risk of any secondary effect on a raptor. A raptor would have to consume a treated goose daily, immediately following the ingestion of the bait and while it is still in the crop and unabsorbed—and this repeatedly, consistently and daily, and during the raptor’s own breeding season. Once OvoControl is digested and absorbed, it is no longer biologically available to a secondary species. While raptor exposure is theoretically possible, it is nearly impossible to have a secondary effect.

Aquatic toxicity - Nicarbazin as a complex has poor solubility in water. As nicarbazin goes into solution it dissociates into DNC and HDP. HDP facilitates the absorption of DNC in the gut. As nicarbazin is excreted as DNC and HDP, DNC excreted in the form of goose feces would not be well absorbed from the gastrointestinal tract and would pass through the animal with very minimal absorption.

Recommended Use - OvoControl baiting should begin 14 to 21 days before the onset of nesting or a minimum of 7 days prior to the laying of the first egg. It is difficult to administer exact doses of OvoControl under free-feeding conditions such as those that will exist using bait stations or broadcast feeding. However, OvoControl has been shown to have a wide margin of safety and efficacy.

It is possible that the geese may not eat enough bait over the period of a few days in a row to reach the target dose. In this case, the level of DNC in the blood would be too low to affect the egg being formed that day, and, therefore, that egg may hatch. If the same goose ate the target amount of nicarbazin bait the next day, then the egg formed with enough DNC in the blood could be affected and the egg would not hatch.

Efficacy - OvoControl has no effect on the adult or juvenile population of resident birds. Under ideal conditions, with all mating geese consuming the appropriate dose during the breeding season the expected outcome is no new goslings.

It is quite likely that each female Canada goose will still lay a clutch of eggs. If the OvoControl dose is high enough and the blood DNC levels are high enough, fewer eggs than normal may be laid. OvoControl mainly works to reduce hatching of the eggs that are laid. Recent studies in Pekin ducks (Barbato, et al., 2006) demonstrated that egg laying will actually cease at higher dosages.

Non-targets - OvoControl only has a contraceptive effect in birds. Studies of the effects of nicarbazin on animals other than birds that lay eggs have been limited to snakes. When brown tree snakes were treated with nicarbazin, reproduction was not affected. The number of eggs laid, the hatchability of the eggs, and the health of the offspring were not affected by treatment of the snake with nicarbazin.

Reporting requirements - All institutions using OvoControl are asked to submit a complete Contraception Center Survey to the AZA Wildlife Contraception Center. It is essential that accurate records of doses and intervals be maintained and results reported to the Wildlife Contraception Center Database to contribute to dosage development and to monitor any possible side effects.

Storage - Cool and dry storage conditions

Ordering Unit - OvoControl G (20-lb bags) and OvoControl P (30-lb bags) are available direct from Innolytics, LLC

Ordering Information- Email: Innolytics@cox.net

FAX: 858-923-2060

Phone: 858-759-8012

Website: www.hatchcontrol.com

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REVERSIBLE VASECTOMY

This technique has been used successfully in thousands of lab rodents and humans (90% success rate in more than 4,000 cases: Silber & Grotjan 2004), but has only been attempted in a few exotic species, so should be considered experimental. Reversals have been accomplished in bush dogs (DeMatteo et al. 2006) and initial vasectomies have been performed in chimpanzees but reversals not yet attempted. Thus, the procedure should not be used in males likely to be recommended for subsequent breeding until more experience is gained with a broader range of species.

To increase the chance of successful reversal, it is important that an "open-ended" vasectomy be performed, leaving the distal (testicular) end open to permit leakage, which allows a pressure-relieving granuloma to form, minimizing vas or epididymal damage (Silber 1977a). The proximal (abdominal) end can be cauterized, providing an effective seal which prevents spontaneous recanalization (Silber 1976, 1977a,b)

Reversal surgery is possible subsequent to other vasectomy procedures but requires a very difficult anastomosis of the vas to the epididymis to reverse. The “open-ended” vasectomy permits reversal via the much simpler vasovasostomy (Silber 1977a, 1978, Silber et al. 1977).

Open-Ended Vasectomy Procedure - The typical midline incision used in neutering results in difficulty freeing the proximal end of the vas deferens during the subsequent reversal procedure. Rather, the vas should be isolated from the cord via a small incision in the upper scrotum or at the external inguinal ring. Because the thickness of the scrotal skin may preclude the scrotal approach used for humans, a 1- to 1.5-cm incision should be made over the external inguinal ring. The vas deferens should be kept moist by pulsatile irrigation with heparinized saline (2500U heparin/500 ml NaCl) to avoid post-operative scarring. After the vas deferens is transected, the abdominal (proximal) cut end should be cauterized by inserting a needle electrode about 1 cm internally. If only the mucosa is cauterized, leaving the muscle is unharmed, a very tight seal will form to achieve blockage. The distal end should be left open for leakage to release pressure.

Vasovasostomy - Dr. Sherman Silber, the physician who pioneered the technique, has offered his services to the zoo community to perform reversals. If there is sufficient interest among zoo veterinarians, we can organize training session in the technique. Otherwise, Dr. Silber should be contacted to perform the surgery. In general, the procedure entails making an incision over the upper scrotum and external ring similar to the original incision for the vasectomy, exposing the vas deferens longitudinally by blunt dissection, facilitated by placing a small Penrose drain underneath the vas. The distal and proximal ends of the vasa are held with vasovasostomy clamps and the scarred ends of both sides are resected. Translucent fluid is aspirated from the distal cut end with 22 g medicut and 1-cc syringe to check for the presence of sperm. Absence of sperm in the fluid may indicate an epididymal blockage which makes successful vasovasostomy unlikely. However, if the original vasectomy was open-ended, this complication is very unlikely. The vasovasostomy is performed using 9-0 nylon interrupted mucosal sutures and 8-0 nylon interrupted muscularis sutures.

Latency to Effectiveness - Latency to disappearance of sperm following vasectomy will depend on the species and individual, perhaps as long as 2 months, until residual sperm either degenerate or are passed.

Precautions - Vasectomy is not recommended for species with induced ovulation because mating will result in female pseudopregnancies with prolonged periods of progesterone elevation, which can cause pathology of uterine and mammary tissue. Endogenous progesterone and progestin contraceptives cause similar disease.

Contact for More Information - Dr. Sherman Silber (DrSherm@aol.com)

References:

DeMatteo, K.D., Silber, S., Porton, I., Lenahan, K., Junge, R., Asa, C.S. 2006. Preliminary tests of a new reversible male contraceptive in bush dogs (Speothos venaticus): Open-ended vasectomy and microscopic reversal. J. Zoo Wildl. Med.

Silber S.J. 1976. Microscopic technique for reversal of vasectomy. Surg. Gynecol. Obstet. 143: 630.

Silber S.J. 1977a. Sperm granuloma and reversibility of vasectomy. Lancet 2:588-589.

Silber S.J. 1977b. Perfect anatomical reconstruction of vas deferens with a new microscopic surgical technique. Fertil. Steril. 28:72.

Silber S.J. 1978. Vasectomy and vasectomy reversal. Fertil. Steril. 29:125-140.

Silber S.J., Galle, J., and Friend, D. 1977. Microscopic vasovasostomy and spermatogeneis. J. Urol 117:299.

Silber S.J., and Grotjan, H.E. 2004. Microscopic vasectomy reversal 30 years later: a summary of 4010 cases by the same surgeon. J. Androl. 25:845-859.

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

CARNIVORES

CANIDS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) Ovariohysterectomy or Ovariectomy are safe methods and effective

methods for preventing pregnancy if permanent sterilization is an option

(but see Caution 1 for males).

Cautions

(1) Vasectomy or castration of males will not prevent potential adverse effects to females from prolonged, cyclic exposure to endogenous steroids associated with the obligate hormonal pseudo-pregnancy that follows ovulation in canids. Endogenous steroids and steroid contraceptives cause similar side effects.

(2) Progestin contraceptives are associated in canids with progressive uterine growth that can result in infertility, infections, and sometimes uterine cancer; mammary tissue stimulation also can result in cancer. Signs of diabetes mellitus have also been reported.

a) If a progestin is used, treatment should only be short term, because of the increased likelihood of side effects with prolonged exposure.

b) If a progestin is used, treatment should start well BEFORE any signs of proestrus, since the elevated endogenous estrogen can exacerbate side effects of the progestin. Proestrus can begin 2 or more months before estrus in some canid species.

c) Progestins should not be used in pregnant animals, since they may suppress uterine contractions necessary for normal parturition. Thus, progestins should only be administered to females CONFIRMED non-pregnant.

d) Progestins

· MGA Implant for 2 years, then remove for 1 pregnancy if possible; non-fertile ovulatory cycles do not substitute for pregnancy in reversing deleterious effects on the uterus; not recommended for more than a total of 4 years (F).

· Depo-Provera injection (5 mg/kg body wt. every 2 months) (F).

· ovaban for seasonal breeders, but for no more than 2 consecutive seasons (F).

(3) PZP vaccine efficacy and safety have only been demonstrated in pinnipeds and bears among the carnivores. In other carnivores, there is mounting evidence that anti-PZP antibodies do not cross-react with the sperm receptor on the ovum, or may cause depletion of ovarian oocytes. PZP is contraindicated in species in which pseudopregnancy is common.

(4) Mibolerone, a synthetic androgen, is sometimes used in female domestic dogs; however, because it can also increase aggression, it is not recommended for exotic canids.

Research Projects

(1) Continued surveillance for deleterious effects (Pathology and Database surveys).

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FELIDS

Recommendations

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) Ovariohysterectomy, Ovariectomy (F) or Castration (M) are safe

methods and effective methods for preventing pregnancy if permanent

sterilization is an option (but see Caution 1 for males).

Cautions

(1) Vasectomy of males will not prevent potential adverse effects to females from prolonged, cyclic exposure to endogenous steroids associated with the obligate hormonal pseudo-pregnancy that follows copulation-induced ovulation in felids. Endogenous steroids and steroid contraceptives cause similar side effects.

(2) Progestin contraceptives are associated in felids with progressive uterine growth that can result in infertility, infections, and sometimes uterine cancer; mammary tissue stimulation also can result in cancer. Signs of diabetes mellitus have also been reported.

a) If a progestin is used, treatment should only be short term, because of the increased likelihood of side effects with prolonged exposure.

b) If a progestin is used, treatment should start well BEFORE any signs of proestrus, since the elevated endogenous estrogen can exacerbate side effects of the progestin.

d) Progestins

· Depo-Provera injection (5 mg/kg body wt. every 2 months) (F).

· ovaban for seasonal breeders, but for no more than 2 consecutive seasons (F).

Research Project

(1) Continued surveillance for deleterious effects (Pathology and Database surveys).

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OTHER CARNIVORES

Recommendations

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) Ovariohysterectomy or Ovariectomy are safe methods and effective

methods for preventing pregnancy if permanent sterilization is an option but few data exist for carnivores other than canids and felids.

(see Caution 1 for males).

Cautions

(1) For species in with induced ovulation, Vasectomy of males will not prevent potential adverse effects to females from prolonged, cyclic exposure to endogenous steroids associated with copulation-induced ovulation resulting in pseudo-pregnancy. (Castration, which should eliminate copulation, would not result in female pseudo-pregnancies.) Endogenous steroids and steroid contraceptives cause similar side effects.

(2) Progestin contraceptives may be associated in carnivores with progressive uterine growth that can result in infertility, infections, and sometimes uterine cancer; mammary tissue stimulation also can result in cancer.

a) If a progestin is used, treatment should only be short term, because of the increased likelihood of side effects with prolonged exposure.

b) If a progestin is used, treatment should start well BEFORE any signs of proestrus, since the elevated endogenous estrogen can exacerbate side effects of the progestin.

d) Progestins

· Depo-Provera injection (5 mg/kg body wt. every 2 months) (F).

· Ovaban for seasonal breeders, but for no more than 2 consecutive seasons (F).

Research Project

(1) Continued surveillance for deleterious effects (Pathology and Database surveys).

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

Primates

PROSIMIANS

Recommendations

(1) MGA implant (F).

· insert 1 month before the breeding season and remove 1 month after end of breeding season (based on earliest and latest breeding dates; e.g., Eulemur macaco, E. fulvus, & Lemur catta: insert in early Sept., remove end of June; Varecia: insert Nov., remove May)

(2) Depo-Provera injection (5 mg/kg body wt. at 45-day intervals throughout breeding season) (F).

Cautions

(1) Depo-Provera is associated with weight gain and possible masculinization, e.g., in dichromatic species, female may take on aspects of male coloration.

Research Project

(1) Continued surveillance for deleterious effects (Pathology and Database Surveys)

NEW WORLD MONKEYS (GENERAL)

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) MGA implant (F)

· High endogenous steroid levels appear to require much higher exogenous steroid doses to effect contraception by negative feedback.

CALLITRICHIDS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(1) MGA implant (F)

(2) Depo-Provera injection

· Depo-Provera injection can be used to prevent the post-partum estrus (20mg/kg body wt, effective for approximately 1 month). (F)

Research

(1) Continued surveillance for deleterious effects (Pathology and Database Surveys)

CALLIMICO

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) Separation of reproductive individuals.

Caution

(1) MGA appears to cause excessive decidualization of the uterine endometrium in callimico, which may result in permanent damage; other progestins may induce the same effects.

Research Projects

(1) Evaluation of reversibility of uterine pathology

(2) Continued surveillance for deleterious effects (Pathology and Database Surveys)

CEBIDS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) MGA implant (F)

Research Project

(1) Continued surveillance for deleterious effects (Pathology and Database Surveys)

OLD WORLD MONKEYS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) MGA implant (F)

Cautions

(1) No deleterious effects noted, although caution is suggested with progestin use

Research Projects

(1) Chart sexual swelling in species for which it applies

(2) Continued surveillance for deleterious effects (Pathology and Database Surveys)

LESSER AND GREAT APES

GIBBONS

Recommendation

(1) MGA implant (F)

ORANGUTANS

Recommendations

(1) MGA implant (F)

(2) Permanent sterilization of hypbrids (as recommended by the Orangutan SSP)

Cautions

(1) Documented birth control pill failures are probably due to failure to swallow

Research Project

(1) Surveillance for deleterious effects (Pathology and Database Surveys)

CHIMPANZEE AND GORILLA

Recommendations

(1) MGA implant (F)

(2) Birth control pills (with females that reliably take medicated treats) (F)

(3) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

Cautions

(1) Chimpanzee sexual swelling: available data show that females exhibit partial to normal swellings on birth-control pills, and partial to no swellings on MGA, with differences likely due to relative doses or pill regimen that includes a placebo week.

Research Projects

(2) Surveillance for deleterious effects (Pathology and Database Surveys)

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

UNGULATES

PERISSODACTYLS

EQUIDS

Recommendation

(1) PZP vaccine (short term: 2-3 consecutive years) (F)

Cautions

(1) Progestins may cause endometritis, pyometra and hydrometra

(2) MGA efficacy has not been established in equids

(3) GnRH agonists previously tested were ineffective in males

(3) PZP may not be reversible after long-term use (>3 consecutive years)

Research Projects

(1) Deslorelin implants

(2) Surveillance for deleterious effects (Pathology and Database Surveys)

TAPIRS AND RHINOCEROS

Recommendations

(1) Depo-Provera (F)

· Tapirs: 5 mg/kg body weight every 3 months

(2) Regu-mate (F)

· Tapirs: estimate standard horse dose (0.044 mg/kg daily)

(3) PZP vaccine (short term: 2-3 consecutive years) (F)

Cautions

(1) Synthetic progestins may cause endometritis, pyometra and hydrometra

(2) PZP may not be reversible after long-term use (>3 consecutive years)

(3) Regu-mate not yet tested in tapirs

Research Projects

(1) Deslorelin implants

(2) Surveillance for deleterious effects (Pathology and Database Surveys)

ARTIODACTYLS

Recommendations

(1) MGA implant (F)

(2) MGA in feed (F)

(a) for bovids, cervids and camelids less than 800 lb: 0.5 mg/day/animal

(b) for bovids, cervids and camelids 800 lb or more: 1.0 mg/day/animal

(3) MGA liquid (daily doses as for MGA feed above) (F)

(4) PZP vaccine (short term: 2-3 consecutive years) (F)

(5) Depo-Provera injection (F)

· Giraffe dose: 450 mg every 6 weeks; if estrus occurs, increase by increments of 100 mg; Nile hippopotamus dose: 800 mg every 6 weeks

· Establishing a correct dosage is hampered by unavailability of body weight measures for individual giraffe and hippos

(6) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F)

· Lupron® Depot Injection (F)

Cautions

(1) Synthetic progestins may cause endometritis, pyometra and hydrometra

(2) PZP may not be reversible after long-term use (>3 consecutive years)

(3) Pregnant artiodactyls contracepted with progestins may be especially susceptible to suppression of uterine contractions; progestins should only be administered to animals CONFIRMED non-pregnant.

(4) Depo-Provera may be a particular problem in pregnant females, since length of efficacy is so variable (approximate range: 2-24 months)

(5) GnRH agonists are not effective in male bovids; effectiveness unknown for other artiodactyls.

(6) MGA feed and MGA liquid not recommended for suids; dose required for efficacy associated with side-effects

Research Projects

(1) PZP with Freund’s Incomplete Adjuvant, modified

(2) Surveillance for deleterious effects (Pathology and Database Surveys)

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

BATS AND RODENTS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) MGA implant (F)

(3) MGA liquid (F) (0.1mg/day)

(4) Depo-Provera injection for seasonal breeders (2-5 mg/kg body weight every 2-3 months) (F)

Caution

(1) Few data exist for these taxa

Research Project

(1) Surveillance for deleterious effects (Pathology and Database Surveys)

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

MARINE MAMMALS

PINNIPEDS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (F or M)

(2) Depo-Provera injection (2 mg/kg or 200 mg per animal, monthly) (F)

Cautions

(1) Few data exist for this taxon

(2) Progestins may cause endometritis, pyometra and hydrometra

(3) Lupron-depot injections may result in sterile abscesses

Research Projects

(1) Lupron-depot injection (1-mo.depot: 0.11-0.19 mg/kg monthly; 4-mo.depot: 0.9-1.1 mg/kg every 4 mo was successful for aggression reduction and may be contraceptive ) (M)

(2) PZP vaccine (F)

(3) Surveillance for deleterious effects (Pathology and Database Surveys)

CETACEANS

Recommendations

(1) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; males may require higher doses. Side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F or M)

· Lupron® Depot Injection (0.075 mg/kg) (F or M)

(2) Depo-Provera injection (2-5 mg/kg body weight every 2-3 months) (F)

(3) Regu-mate (0.044 mg/kg daily) (F)

Cautions

(1) Few data exist for this taxon

(2) Progestins may cause endometritis, pyometra and hydrometra

Research Projects

(1) Suprelorin treatment of dolphins (F)

(2) Surveillance for deleterious effects (Pathology and Database Surveys)

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THE USE OF ANY CONTRACEPTIVE IN NON-DOMESTIC ANIMALS IS CONSIDERED EXPERIMENTAL

(M=MALE-DIRECTED, F=FEMALE-DIRECTED METHOD)

MARSUPIALS

Recommendations

(1) MGA implant (F)

(2) Depo-Provera injection for seasonal breeders (2-5mg/kg body weight every 2-3 months) (F)

(3) GnRH Agonists - Gonadotropin Releasing Hormone Agonists are considered the safest reversible contraceptives, but dosages and duration of efficacy are not well established for all species; side effects are generally similar to those associated with gonadectomy, especially the potential for weight gain unless diet is controlled.

· Suprelorin® (deslorelin) Implants (F)

· Lupron® Depot Injection (F)

Cautions

(1) Few data exist for this taxon

(2) GnRH agonists have been shown to be ineffective in male marsupials

Research Project

(1) Surveillance for deleterious effects (Pathology and Database Surveys)

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ABOUT THE AZA WILDLIFE CONTRACEPTION CENTER RESEARCH PROGRAM AND DATABASE

Contraceptive methods currently used in captive or free-ranging wildlife must be considered experimental. For example, despite decades of MGA use, the U.S. Food and Drug Administration (FDA) still designates it as an Investigational New Animal Drug (INAD) when used in zoo animals. Because sufficient data on both efficacy and safety have not been generated for any of the contraceptives mentioned in these recommendations for any non-domestic species, they must be considered experimental. Therefore, the Wildlife Contraception Center maintains a database to monitor all contraceptives used in captive wildlife. Because the use of contraceptives that have not been commercially approved by FDA must be considered experimental, IACUC (Institutional Animal Care and Use Committee) approval is needed for compliance with the Animal Welfare Act. (The AZA Wildlife Contraception Center has obtained IACUC approval for MGA implants, MGA feed, and Suprelorin® implants for zoos participating in these programs). Commercially available products used in wildlife can be considered “extra label use” and do not require IACUC approval.

Contraception Database Survey

Because all contraceptives used in wildlife must be considered experimental, it is critical that records be kept on each method used, dose, date started, date ended, presence of opposite-sex in group, signs of estrous behavior, birth dates of any offspring born, abortions, date of death if an individual dies during treatment, and any other pertinent observations. Records must be included annually in the AZA Wildlife Contraception Center Survey. The resulting data will form the basis of the FDA reports and of Wildlife Contraception Center Recommendations. Failure to submit the Annual Survey will result in suspension from the trials. Each year a survey form is mailed to every institution requesting information from the previous year. Those for the MGA feed program will be mailed twice a year. Completed reports should be returned to:

Sally Boutelle, Program Coordinator

AZA Wildlife Contraception Center

Saint Louis Zoo

1 Government Drive

St. Louis, MO 63110 USA

314-781-0900 x 384; Fax: 314-768-5454;

Contraception@stlzoo.org

Pathology Database Survey

Dr. Linda Munson continues to conduct comprehensive pathologic examinations on reproductive tracts to detect deleterious effects associated with contraceptives. The results of these analyses become part of the AZA Wildlife Contraception Center Pathology Database and provide important information about contraceptive safety that is used to make informed decisions for our annual Recommendations. The data are also used for FDA reporting. Complete reproductive tracts are needed from BOTH CONTRACEPTED AND NON-CONTRACEPTED animals, so that we can determine if diseases are spontaneous in a species or caused by the contraceptive. We are requesting complete reproductive tracts and liver samples from CARNIVORES, MARSUPIALS, PRIMATES, MARINE MAMMALS, AND UNGULATES. Tissue collected by ovariohysterectomy or at necropsy are appropriate.

Tissue submission instructions – All reproductive tracts and other tissue samples must be prepared using the following instructions. A brief summary of the reproductive history of each animal should be included. Pathology evaluations will be conducted free of charge and a report will be sent to the contributing institution for the animal’s medical records and to Dr. Ed Plotka for inclusion in the FDA reports. For institutions with their own pathologist, please contact Dr. Munson concerning the sharing of tissues for this study. Please send tissues and reports accompanied by the Tissue Submission Form to:

Linda Munson, DVM, PhD

University of California

Dept VM‑PMI,1126 Haring Hall

1 Shields Ave

Davis, CA 95616

530- 754‑7567; Fax 530‑752‑3349

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REVERSIBILITY CONSIDERATIONS

Time to reversal varies for many reasons. The most basic measure of reversal is when the concentration of the contraceptive compound (or titer, in the case of vaccines) in the body drop below the level necessary for efficacy. However, it is often not possible to measure this event, so confirmation that reversibility has been successful must depend on documentation that ovulatory cycles have resumed (in cases where hormonal contraceptives have suppressed ovulation; the PZP vaccine may not interfere with ovulation), and/or diagnosis of pregnancy or birth of young. Many factors other than contraceptives affect ovulation and conception. These include reproductive history, age, health, body weight (very thin or obese animals may not ovulate or conceive) and, of course, fertility of the partner. The information of reversibility is found for each contraceptive listed in Currently Available Methods and their Administration. This information is based on what is known about clearance of the contraceptive from the body and does not take individual history or current condition into account.

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Directors and Staff

AZA Wildlife Contraception Center Director

Cheryl Asa, PhD, Saint Louis Zoo, 314-768-5488, Fax -5454; asa@stlzoo.org

AZA Wildlife Contraception Center Assistant Director

Ingrid Porton, MS, Saint Louis Zoo, 314-781-0900 x358, Fax -647-7969;

Program Coordinator

Sally Boutelle, MS, 314-781-0900 ext 384; Fax 314-768-5454; Contraception@stlzoo.org

www.stlzoo.org/contraception

Scientific Staff

Joan Bauman, PhD, Endocrinologist, jbauman@stlzoo.org

Jan Dempsey, MS, Nutritionist, Nestle Purina, jdempsey@purina.com

Linda Munson, DVM, PhD, Pathologist, University of California-Davis

Advisory Board

Medical Advisors

Paul Calle, VMD, Wildlife Conservation Society

Catherine Dean, MD, Women’s Health Partners

Lisa Harrenstien, DVM, Oregon Zoo

Nadine Lamberski, DVM, San Diego Zoo’s Wild Animal Park: nlamberski@sandiegozoo.org

Anneke Moresco, DVM, MS, University of California-Davis: amoresco@ucdavis.edu

Sherman Silber, MD, St. Luke’s Medical Center

Martha Weber, DVM, Saint Louis Zoo: weber@stlzoo.org

Reproductive Advisors

Wolfgang Jöchle, DVM, Consulting Theriogenologist: jochle@infionline.net

Jay Kirkpatrick, PhD, Science and Conservation Center at Zoo Montana: zoolab@wtp.net

Lynn Patton, MS, Endocrinology: mlp1@san.rr.com

Linda Penfold, PhD, Research Coordinator, White Oak Conservation Center: lindap@wogilman.com

Todd Robeck, Sea World San Antonio: Todd.Robeck@SeaWorld.com

Ed Plotka, PhD, MGA Implant Program – Retired, Plotkae@usa.net

Kim Bynum, PhD, Consulting Avian Physiologist kbynum@earthlink.net

Animal Managers

Bess Frank, PhD, Curator, Milwaukee County Zoo, retired: efrankwi@wi.rr.com

Dusty Lombardi, Curator, Columbus Zoo: Dusty.Lombardi@columbuszoo.org

Commercial Partners

Mark Griffin, Purina Mills, MGriffin@landolakes.com

William Lance, DVM, Wildlife Pharmaceuticals, WLance@WildPharm.com

Tim Trigg, PhD, Peptech Animal Health, trigg@peptech.com

Erick Wolf, Innolytics, innolytics@cox.net

Kim Frank, Science and Conservation Center at Zoo Montana: zoolab@wtp.net

Spanish Translator

Anneke Moresco, DVM, MS, University of California-Davis: amoresco@ucdavis.edu

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