Coyotes (Canis latrans) are predators of livestock. Current management programs, primarily lethal control, are ineffective for long-term management of predation. Controlling reproduction of coyotes may reduce depredations if territory fidelity is maintained by breeding pairs. Surgical sterilization is successful in altering predatory behaviors of coyotes but may provide a challenge for field implementation. An alternative approach is the development of a one-time non-transferable chemical contraceptive. This research is investigating the efficacy of a single high dose treatment of a sustained release gonadotropin-releasing hormone agonist, deslorelin, on coyotes as a long term contraceptive. Male coyotes were administered 47 mg deslorelin subcutaneously. Preliminary data show full suppression of the reproductive axis for over 12 mo as indicated by complete absence of sperm.

There are only two nonlethal approaches with which to manage wildlife populations: remove excess individuals or decrease reproductive rates. In the case of wild horse management, the latter has already been shown to be a more humane and less costly approach. Contraception has been known for many years to be effective in wild horses with regard to both fertility and population alteration. Field testing under real-world management situations is a critical aspect of wildlife contraception assessment. Field testing also requires documentation to justify eventual large-scale use of fertility control in population management. Furthermore, it is likely that full support by the managing agencies and acceptance of fertility control by the public will not occur until success has been demonstrated at the population level in the field. Because the transition from laboratory and captive animal trials to the real world of field research and testing of management potential in free-ranging wildlife is both essential and difficult, we identify considerations for optimizing success in the field, especially for controlling wild horse and white-tailed deer populations. This study identified the following categories for assessment: 1) field-specific logistics and tactics (including access to and identification of horses, censuses, pregnancy testing, and behavior monitoring), 2) training of field personnel and managers (including vaccine biology, preparation and delivery, and basic field methodology), 3) essential field considerations for enabling management (including population variables, environmental variables, and modeling), and 4) pitfalls of field contraception. In this assessment, we will highlight the capability for coincident pursuit of research and management and will explore field considerations applicable to many species where fertility control has potential as a management tool.

Reversible contraception that does not alter natural behavior is a critical need for managing zoo populations. In addition to reversible contraception, other fertility techniques perfected in humans may be useful, such as in vitro fertilization (IVF) or oocyte and embryo banking for endangered species like amphibians and Mexican wolves (Canis lupus baileyi). Furthermore, the genetics of human fertility can give a better understanding of fertility in more exotic species. Collaborations were established to apply human fertility techniques to the captive population. Reversible vasectomy might be one solution for reversible contraception that does not alter behavior. Reversible approaches to vasectomy, avoiding secondary epididymal disruption, were attempted in South American bush dogs (Speothos venaticus), chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), Przewalski's horse (Equus przewalski poliakov), and Sika deer (Cervus nippon) in a variety of zoos around the world. These techniques were first perfected in > 4,000 humans before attempting them in zoo animals. In vitro fertilization with gestational surrogacy was used to attempt to break the vicious cycle of hand rearing of purebred orangutans, and egg and ovary vitrification in humans have led to successful gamete banking for Mexican wolves and disappearing amphibians. The study of the human Y chromosome has even explained a mechanism of extinction related to global climate change. The best results with vasectomy reversal (normal sperm counts, pregnancy, and live offspring) were obtained when the original vasectomy was performed “open-ended,” so as to avoid pressure-induced epididymal disruption. The attempt at gestational surrogacy for orangutans failed because of severe male infertility and the lack of success with human ovarian hyperstimulation protocols. Vitrification of oocytes is already being employed for the Amphibian Ark Project and for Mexican wolves. Vasectomy can be a reversible contraception option in zoo animals, even in endangered species. Ongoing use of gamete and embryo freezing may salvage vanishing species.

Prior to 2010, the introduced population of American bison (Bison bison) on Santa Catalina Island, California, was managed through the shipment of surplus bison to private ranches, Native American reservations, and livestock auctions on the mainland. In response to escalating costs, transport-induced stress to the animals, and ecologic impacts associated with high bison numbers on-island between shipments, the use of the immunocontraceptive vaccine porcine zona pellucida (PZP) as a fertility control option for managing the population was investigated. Between 2009 and 2012, a total of 64 bison cows (≥1 yr old) received primer inoculations of 100 μg PZP emulsified with 0.5 ml Freund's modified adjuvant (FMA) delivered through a combination of intramuscular injections by hand (50 bison cows) during roundups and via field darting (14 bison cows). Pre-rut booster inoculations of 100 μg PZP emulsified with 0.5 ml Freund's incomplete adjuvant (FIA) were administered exclusively via field darting in 2010, 2011, and 2012 to 45, 48, and 61 bison cows (≥1 yr old), respectively. During the present study, 38 adult cows (marked and unmarked) received one or more PZP inoculations during their first, second, or third trimesters of pregnancy, and of these individuals, 35 successfully produced calves. Low pregnancy values detected in the remaining three cows have been attributed to residual progesterone associated with unsuccessful fertilization. The 2010 pretreatment calving rate (calves born per cow) determined via direct observation was 67.4% (29 calves from 43 cows). Through the use of PZP, the calving rate was reduced to 10.4% by 2011 and to 3.3% by 2012. Considering the annual mortality rate of 2–5% documented during this study, the results demonstrate the potential of PZP use as an effective nonlethal tool for controlling population growth in free-ranging bison.

In a joint program, Innolytics and the U.S. Department of Agriculture/Animal and Plant Health Inspection Service National Wildlife Research Center collaborated in the development of nicarbazin as an avian contraceptive, initially for resident Canada geese and subsequently for feral pigeons. Unfortunately, the introduction of the original goose product in 2005 was a commercial failure. Political and social barriers effectively thwarted attempts to establish the new technology with any meaningful market success. Although the market adoption of the pigeon contraceptive has been less difficult, the product still encounters significant social and political obstacles and opposition. Given the focus on instant results and gratification, the introduction of contraceptive technology for birds has been challenging and broad market acceptance remains elusive. Nevertheless, especially for short-lived and rapidly reproducing species, customers continue to replace outdated or ineffective techniques with the safer and more effective contraceptive tool.

Contraception offers potential as a tool for managing certain diseases in wildlife, most notably venereally transmitted diseases or diseases transmitted at parturition. Brucellosis is an excellent example of an infectious disease present in wild populations that could potentially be managed through immunocontraception. Previous studies in bison (Bison bison) suggest that a single injection of GonaCon™ (National Wildlife Research Center, U.S. Department of Agriculture/Animal and Plant Health Inspection Service/Wildlife Services, Fort Collins, Colorado 80521, USA) results in 3 or more yr of infertility. Ongoing studies will determine if the use of GonaCon in bison decreases shedding of Brucella abortus from infected animals and will better define the duration of infertility following a single injection

The development of sophisticated delivery equipment, as well as safer and more effective drugs, has made remote delivery of animal drugs a standard and readily available tool for wildlife professionals, veterinarians, ranchers, and animal control officers. In the 1980s, researchers began treating a wide variety of wildlife with injectable porcine zona pellucida immunocontraceptive vaccines. Remote delivery of immunocontraceptives has been proven effective at the individual and population level for wild horses and urban deer. However, it took only a short time at each study site to understand that each time an animal was treated with remotely delivered darts, it became more difficult to re-treat; researchers were required to adjust to the increased wariness of their targets. Multiyear vaccines will not reduce the need for researchers who can adapt to the many challenges of applying these nonlethal methods of population control in the field. Training, experience, and persistence are required for field personnel to adapt and develop new techniques for continued retreatment of previously treated free-ranging animals.

Several small, enclosed reserves in southern Africa are experiencing significant elephant population growth, which has resulted in associated environmental damage and changes in biodiversity. Although several techniques exist to control elephant populations, e.g., culling, relocation, and immunocontraception, the technique of laparoscopic vasectomy of free-ranging bull elephants was investigated. Bilateral vasectomies were performed in 45 elephants. Of these elephants, one died within 24 hr of recovery and two had complications during surgery but recovered uneventfully. Histologic examination confirmed the resected tissue as ductus deferens in all the bulls. Most animals recovered uneventfully and showed no abnormal behavior after surgery. Complications recorded included incisional dehiscence, 1 full-thickness and 2 partial-thickness lacerations of the large intestine, and initial sling-associated complications, for example, deep radial nerve paresis. One bull was found dead 6 weeks after surgery without showing any prior abnormal signs. Vasectomy in free-ranging African bull elephants may be effectively performed in their normal environment. The surgical procedure can be used as a realistic population management tool in free-ranging elephants without major anesthetic, surgical, or postoperative complications.

Native porcine zona pellucida (PZP) immunocontraception has been used to inhibit fertility in more than 80 species of ungulates, although the duration of contraception efficacy varies among species in both Perissodactyla and Artiodactyla. This study examined anti-PZP antibody titers in Dall sheep and domestic goats at the Milwaukee County Zoo, and also Himalayan tahr and Armenian Mouflon sheep at the San Diego Zoo Safari Park, and, for comparison, Altai wapiti, lowland wisent, Javan banteng, and southern pudu at the San Diego Zoo Safari Park, all were given a primer dose and booster dose of PZP. Of the San Diego Zoo Safari Park animals, the 4 comparison species demonstrated the typical 1-yr pattern of anti-PZP antibodies, whereas the Armenian sheep and Himalayan tahr showed prolonged (2–3 yr) antibody responses after a single primer and booster dose. The Dall sheep and domestic goats had significantly longer durations of antibody titers (3 yr) from a single year's treatment (primer plus booster). Analysis of the data indicates that Armenian sheep, Himalayan tahr, Dall sheep, and domestic goats have prolonged responses, and are more sensitive to PZP in that they produce a protracted antibody response.

For over 25 years, the Reproductive Health Surveillance Program has collected, processed, evaluated, and archived reproductive tracts from nondomestic mammals submitted by zoos. The analysis of the data from this archive has been used to recognize lesions associated with exposure to certain contraceptives; but arguably more importantly, to also document naturally occurring lesions. The goals of this program are to enhance the reproductive management of captive and free-ranging species by providing information about the effects of various contraceptives and to provide basic information regarding the natural reproductive histories and naturally occurring lesions in male and female zoo animals.

In recent years, the Bureau of Land Management's (BLM) Wild Horse and Burro Management program costs have increased dramatically due to a rise in the number of animals removed from public lands coupled with significantly decreased adoption rates. To assist with development and implementation of effective, cost-containing management programs, a robust economic model to project the costs and optimize outcomes of various management scenarios was created. For example, preliminary demonstration model runs show that by gradually replacing “removal-only” programs with contraception-and-removal programs on one hypothetical Herd Management Area (HMA), the BLM could save about US$8 million over 12 years while maintaining an area target population of 874 horses. Because the BLM estimates that more than 38,000 wild horses roam on 179 HMAs in the United States, the use of this economic model could result in a cost-savings of tens of millions of dollars if applied broadly across all HMAs.

Biologists have been testing wildlife contraceptives in the field for nearly a half century. Although effective new contraceptive agents have been identified, new delivery technologies developed, and some success with population management demonstrated, progress in this area should be further along. Why is it taking so long? First, the task is complex. Most drugs and vaccines fail in development. The technical leaps from in vitro to in vivo, from controlled studies to field studies, from effectiveness in individuals to management of populations, are all formidable and frequent failures are inevitable. Testing the long-acting contraceptives required for successful population management demands experiments that take 3–5 yr to complete. Development of wildlife contraceptives has been further hampered by the lack of large-scale investment and the complex and shifting regulatory landscape that often greets novel enterprises. But there has also been focused resistance to the implementation of wildlife contraceptive studies and to the dissemination of results such studies have produced. This phenomenon, which sociologists label “socially constructed ignorance,” has taken a variety of forms including denial of research permits, omission from research reports and management documents, and repetition of misleading or false information in public forums and the media. The persistence and effectiveness of this social resistance suggest that the ethical foundation of wildlife contraception is incomplete. As the institutional affiliations of participants of the 7th International Conference on Fertility Control for Wildlife confirmed, wildlife contraception has its ethical roots in the animal welfare and integrated pest-management communities. Absent from the discussion are the conservation community and the values they represent. To secure societal acceptance of wildlife contraception as a management technique, researchers and advocates for wildlife contraception must address conservation issues and build an ethical foundation that balances concern for individual animals and human needs with concern for the health of biologic communities.

Several fertility control agents have recently been registered with the U.S. Environmental Protection Agency for management of wildlife or other free-ranging animals. The registration of GonaCon™ Immunocontraceptive Vaccine for use in white-tailed deer (Odocoileus virginianus) and OvoControl for use in Canada geese (Branta canadensis) and pigeons (Columba livia) has caused state wildlife and land management agencies to review their regulatory authority over the use of contraceptives in wildlife. As a result, many states are taking steps to ensure legislation or policies are current with emerging technologies. This article examines the various approaches states are taking to regulate the use of contraceptives. Regardless of the final regulatory approach, biological, social, economic, and political implications must all be discussed as this new tool is introduced into the field of wildlife management. Thoughtful consideration of all aspects of wildlife contraceptive use will lead to the development of sound, best management practices for current and future products.

Opinions are divided as to whether human intervention to control elephant (Loxodonta africana) population growth is desirable, partly because of elephant welfare concerns. Female contraception through immunization with porcine zona pellucida (PZP) proteins is viable. The effects of sustained use and application of the PZP vaccine on elephant behavioral and spatial responses were examined by evaluating herd ranging, fission–fusion dynamics, association patterns, and reproductive and sexual behaviors. Minimal change was anticipated as a result of long calf dependence on and association with cows, a reduced but not indefinite 0% growth rate and the known mechanism of action of PZP vaccines, and minimal expected change in resource requirements necessitating behavioral or spatial use adaptations. Although behavioral effects identified in previous hormonal contraceptive trials were evident, it was demonstrated that immunocontraception caused no prolonged behavioral, social, or spatial changes over the 11-yr study period. Individually identified elephants were monitored from 1999 to 2011. Minimal, short-term social disruption, with temporary changes to the herds' core ranges, was observed during the annual treatment events, particularly in the first three treatment years, when vaccinations were conducted exclusively from the ground. Thereafter, when vaccinations were conducted aerially, minor disruptions were confined to the morning of administration only. Despite sustained treatments resulting in demographic changes of fewer calves being born, treatments did not alter spatial range use, and no adverse interherd–intraherd relations were observed. Similarly, resource requirements did not change as calving still occurred, although in fewer numbers. It was concluded that PZP immunocontraception has no detectable behavioral or social consequences in elephants over the course of 11 yr, providing a convincing argument for the use of sustained immunocontraception in the medium to long term as an important tool for elephant management. Behavioral consequences of alternative management approaches should all receive similar scrutiny to enable managers to make informed decisions when weighing management interventions.

Previous reports have demonstrated gradual reductions of white-tailed deer (Odocoileus virginianus) populations through immunocontraception, with stabilization occurring after 2–4 yr of treatment, and subsequent reductions of 6–10% annually. These studies employed porcine zona pellucida (PZP) vaccines that required two initial treatments and annual retreatments. From 2005 to 2010, 258 adult and yearling female deer on Fripp Island, South Carolina, were treated with one of several PZP preparations designed to produce 2 yr of effective contraception with a single treatment. These included several preparations of SpayVac® and of native PZP-adjuvant emulsion plus PZP and QA-21 in timed-release pellets. Deer were chemically immobilized, ear-tagged, and administered initial treatments by hand in February–March. Some treated deer were boosted remotely with PZP-adjuvant emulsion 1.5–4.5 yr after initial treatments. Ground-based distance sampling was used to estimate deer population density at Fripp Island, a resort community, and at a relatively undeveloped neighboring control site, Hunting Island. Most vaccine preparations tested reduced fawning rates by 75% to 95% for at least 1 yr. From 2005 to 2011, deer density on Fripp Island declined by 50%, from 72 deer/km² to 36 deer/km², an average annual reduction of 11%. In contrast, population density on the Hunting Island control site fluctuated between 2005 and 2011, averaging 23 deer/km² (range, 19–28 deer/km²). Population declines on Fripp Island were associated with an increase in the proportion of treated females and with a progressive decrease in winter fawn:doe ratios, from 1.21 fawns/doe in 2005 to 0.19 fawns/doe in 2010. Winter fawn:doe ratios averaged 1.36 fawns/doe (range, 0.84–1.62 fawns/doe) at the Hunting Island control site. Annual survivorship averaged approximately 79% among ear-tagged females. The rate at which deer populations diminished in association with PZP treatments on Fripp Island was higher than that seen at other study sites, although the reasons for the more rapid decline on Fripp Island are not well understood.

The National Wildlife Research Center (NWRC) began immunocontraception vaccine research by testing porcine zona pellucida (PZP) on white-tailed deer (Odocoileus virginianus). Early PZP research demonstrated that PZP induced infertility; however, increased length of the rut was observed in PZP-treated deer. An alternative vaccine using a keyhole limpet hemocyanin-gonadotropin-releasing hormone (KLH-GnRH) conjugate formulated with modified Freund's adjuvant was developed at NWRC. Suppression of GnRH has reduced reproduction in both sexes but is most effective in females. This vaccine was effective in preventing contraception in female deer for several years after a prime and boost. Due to adverse side effects of Freund's adjuvant, NWRC developed a new adjuvant called AdjuVac, a mineral oil/surfactant adjuvant with the addition of Mycobacterium avium as an immunostimulant. The price of KLH prompted a search for a more economical hemocyanin carrier protein for the GnRH peptide. Blue protein, derived from the mollusk Concholepas concholepas, proved to be a successful option. Formulation improvements resulted in a vaccine that can be effective as a single injection for multiple years, now called GonaCon. GonaCon is registered with the Environmental Protection Agency (EPA) for use in white-tailed deer in urban/suburban areas and for wild horses (Equus caballus) and burros (Equus asinus). Future GonaCon applications may include reducing reproduction to manage populations of other wildlife species, such as prairie dogs (Cynomys ludovicianus) in urban areas and suppressing reproduction to reduce the spread of venereal diseases such as brucellosis. Research is being conducted to develop a GnRH vaccine used in combination with the rabies vaccine to control population growth in free-roaming dogs, with the secondary effect of managing the spread of rabies. The EPA would regulate all these uses. Research is also ongoing on a GnRH vaccine to delay the onset of adrenocortical disease in pet ferrets (Mustela putorius), a use regulated by the United States Department of Agriculture.

Rodent pests cause major damage to the world's agricultural crops and food stores. Rodenticides used since World War II did not lead to sustained reduction of rodent populations, and so fertility control is becoming attractive because rats reproduce with great efficiency. Chemical acceleration of ovarian failure via oral dosing also would improve management of rat pest populations. The chemical 4-vinylcyclohexene diepoxide (VCD) is orally efficacious, causing depletion of nonregenerating primordial ovarian follicles of Sprague-Dawley rats. However, to cause rapid reduction in pups in the first breeding cycle after dosing, all stages of ovarian follicle development must be targeted. To achieve this goal, the Chinese herb triptolide was tested because it can precipitate apoptosis and deplete growing follicles. The impact of triptolide was tested in cultured postnatal day 4 Sprague-Dawley rat pup ovaries. Triptolide at 5 nM caused 100% primordial, primary, and secondary follicle depletion after 8 days of culture, compared to 38% follicle depletion caused by VCD at 30 μM. Next, a palatable rat bait was developed, containing 1% VCD with increasing concentrations of triptolide at 25, 50, and 100 μg/kg body weight. Rats ate an average 3–6% of their body weight/day over 15 feeding days. Two days after the end of baiting, rats were euthanized to conduct necropsies and collect ovaries to count all follicular stages and corpora lutea. At 50 μg triptolide/kg body weight, there was significant reduction of all follicular stages; primordial follicles were 50% lower, secondary follicles were 64% lower, antral follicles were 80% lower, and there were no corpora lutea. These results suggest that combining VCD and triptolide in an oral bait leads to significantly compromised rat ovarian function and reduced ovulations, and is likely to reduce pup production.

Gonadotropin-releasing hormone (GnRH) agonists are routinely used to suppress the reproductive axis of many mammals, especially in zoos. Current treatments are reversible. There is a need to develop nonreversible agents, and this study investigates the effects of high-dose and long-duration exposure to the GnRH agonist, deslorelin, in the rat model. Studies indicate that the follicle-stimulating hormone (FSH) gonadotropin is predominantly affected, and following high-dose exposure to deslorelin for a long duration, the ability of gonadotropes to synthesize FSH may be compromised, perhaps permanently. Understanding the mechanisms by which such persistent suppression of FSH occurs may facilitate the development of novel next-generation contraceptives. It is hypothesized that direct testicular effects of GnRH agonists may play a critical role in the efficacy of GnRH agonists in male contraception.