Current and future options in fertility control of dogs and cats

Weedon, G. R., & Fischer, A. 2015. Surgery Not Required: Current and Future Options in Fertility Control of Dogs and Cats.
There is a long road from demonstrating that a certain contraceptive approach can suppress fertility in a dog or a cat, and achieving regulatory approval for a product that can be marketed. Although some approaches can be shown to be safe and effective, the time and technical expertise required for developing a manufacturing process that can be scaled up and result in a stable, reproducible product is often the main obstacle to regulatory approval. Regardless, the need exists for products to help with animal population control worldwide. As new tools are developed to prevent animal reproduction, countless lives will be spared in shelters and on the street. 

Defining priorities for dog population management through mathematical modeling

Baquero, O. S., Akamine, L. A., Amaku, M., & Ferreira, F. (2015). Defining priorities for dog population management through mathematical modeling. Preventive veterinary medicine.

We simulated dog population dynamics for a thirty-years period using a logistic growth model. Through sensitivity analyses, we determined the influence of the parameters used in the model. Carrying capacity was the most influential parameter in all simulations. In the owned-dog population, the influence of immigration, abandonment and births was 19%, 16% and 6% of the influence of the carrying capacity, respectively. In the sterilized owned-dog population, the influence of abandonment, female and male sterilization was 37%, 30% and 27% of the influence of the carrying capacity. In the stray population, the influence of abandonment, carrying capacity of the owned-dog population and adoption was 10%, 9% and 6% of the influence of the carrying capacity. In the sterilized stray population, the influence of births, female sterilization and male sterilization was 45%, 15% and 13% of the influence of the carrying capacity. Other parameters had lower influence values. Modification of the carrying capacity requires different interventions for the owned- and stray-dog populations. Dog trade control is a way to reduce immigration. The evaluation of sterilization effects must focus on the variations in the infertile population fraction. Adoption may improve the effects of the reduction in carrying capacity on the stray-dog population.

Identifying cats treated with non-surgical fertility control

Benka, V. A. (2015). Ear tips to ear tags. Marking and identifying cats treated with non-surgical fertility control. Journal of feline medicine and surgery, 17(9), 808-815.

Current approaches: Trap–neuter– return (TNR) introduced a humane means of managing free-roaming and feral (‘community’) cats; it also necessitated a method of marking and identifying these cats as sterilized. Although multiple identification methods have been studied or attempted in the field, ear tipping (or, less commonly, ear notching) has proven to be the best option and is used internationally. However, ear tipping must be performed under general anesthesia, and it conveys only binary information: yes, a cat has gone through a TNR program (and is sterilized); or, no, a cat has not gone through a TNR program (and may or may not be sterilized).
Future requirements: Future non-surgical feline fertility control options will require an alternative to ear tipping for identifying community cats, one that does not require anesthesia in order to mark the animal as treated. Long-term contraceptives (vs permanent sterilants) will also require a marker that can denote the time when a cat was last treated.
Objectives and progress: To address this need, the Alliance for Contraception in Cats & Dogs is working with an interdisciplinary team from Cornell University, USA, to develop an effective, humane marking method. Their focus is a new generation of ear tag. The prototype design uses different shapes and materials, and a different application process, than tags used to date. The objective is to minimize tag weight, application discomfort, and likelihood of blood loss and infection, while simultaneously allowing for coding of information, including treatment time period.

Contraception implant for cats

Fontaine, C. (2015). Long-term contraception in a small implant A review of Suprelorin (deslorelin) studies in cats. Journal of feline medicine and surgery, 17(9), 766-771.


Rationale: Deslorelin (Suprelorin®; Virbac) is a gonadotropin-releasing hormone (GnRH) agonist licensed in select countries for the long-term suppression of fertility in adult male dogs and male ferrets. This article summarizes studies investigating the use of deslorelin implants for the long-term suppression of fertility in male and female domestic cats.
Evidence base: Slow-release deslorelin implants have been shown to generate effective, safe and reversible long-term contraception in male and female cats. In pubertal cats, a 4.7 mg deslorelin implant suppressed steroid sex hormones for an average of approximately 20 months (range 15–25 months) in males and an average of approximately 24 months (range 16–37 months) in females. Reversibility has been demonstrated by fertile matings approximately 2 years post-treatment in both male and female adult cats. In prepubertal female cats of approximately 4 months of age, puberty was postponed to an average of approximately 10 months of age (range 6–15 months) by a 4.7 mg deslorelin implant.
Challenges: The large variability in the duration of suppression of gonadal activity makes the definition of the optimal time for reimplantation quite challenging. In addition, the temporary stimulation phase occurring in the weeks following deslorelin implantation can induce in adult female cats a fertile estrus that needs to be managed to avoid unwanted pregnancy. Longer duration and larger scale controlled field studies implementing blinding, a negative control group and a carefully controlled randomization to each group are needed. Furthermore, the effects of repeated treatment need to be investigated. Finally, the effect of treatment on growth and bone quality of prepubertal cats needs to be assessed. However, the ease of use, long-lasting effects and reversibility of deslorelin implants are strong positive points supporting their use for controlling feline reproduction.

Use of melatonin to suppress feline reproduction

Kutzler, M. A. (2015). Alternative methods for feline fertility control Use of melatonin to suppress reproduction. Journal of feline medicine and surgery, 17(9), 753-757.

Practical relevance: Reversible contraceptives are highly desired by purebred cat breeders for managing estrous cycles and by scientists managing assisted reproduction programs. A variety of alternative medicine approaches have been explored as methods to control feline fertility.
Scope: In the field of veterinary homeopathy, wild carrot seed and papaya have been used for centuries. Both appear to be safe, but their efficacy as feline contraceptives remains anecdotal. In contrast, the use of melatonin in cats has been investigated in a number of studies, findings from which are reviewed in this article.
Rationale: Cats are seasonally polyestrous (they cycle several times during their breeding season) and are described as long-day breeders because endogenous melatonin negatively regulates estrous cyclicity. Exogenous melatonin administered parenterally also suppresses ovarian activity in cats, and long-term oral or subcutaneous melatonin administration is safe.
Challenges: The therapeutic use of melatonin is limited by its short biological half-life (15–20 mins), its poor oral bioavailability and its central effects in reducing wakefulness. Research is required to determine whether higher doses, longer-release formulations, repeated administration or combination implants might overcome these limitations.

Progestins to control feline reproduction

Romagnoli, S. (2015). Progestins to control feline reproduction Historical abuse of high doses and potentially safe use of low doses. Journal of feline medicine and surgery, 17(9), 743-752.

Relevance: The high fertility rate of cats means that methods to control feline reproduction are a requirement for cat breeders and pet owners, as well as for those involved in the management of feral cat populations. Progestins continue to be used to prevent queens from cycling, and also as an adjunct or alternative to surgical sterilization within trap–neuter–return (TNR) programs.
Evidence base: A considerable body of information exists on megestrol acetate (MA) and medroxyprogesterone acetate (MPA), thanks to the many studies and case reports published in the scientific literature over the past 50 years documenting their clinical use in cats. Comparatively less is known about the use in cats of more recent progestins such as levonorgestrel, proligestone, delmadinone, chlormadinone and altrenogest.
Dosing, safety and efficacy: Based on a combination of dose, frequency and duration of treatment, MA can be categorized into low (0.625 mg/kg/week for up to 30 weeks), medium (0.625 mg/kg q24h for 1 week or q48h for up to 2 weeks) and high (0.625 mg/kg q24h or q48h for several weeks, or weekly for months or years) dosages. Studies suggest that low dosages can be used relatively safely in cats, while higher dosages increase the risk and severity of adverse reactions. Early work showing that an oral MPA dosage of 0.01 mg/kg administered q24h for 12 months suppresses oestrus in queens effectively and safely has not been considered, and much higher MPA dosages (>6.25 mg/kg q24h) have been used in cats over the past 40 years.
Recommendations: Progestins should always be used with caution. Using the lowest possible dosages, MA and MPA may, however, continue to be used safely in pet queens as well as (in conjunction with TNR programs) for the control of feral cat colonies. More recent progestins appear to be effective and safe, albeit their efficacy and safety need to be further investigated.

No surgery required: the future of feline sterilization

Johnston, S., & Rhodes, L. (2015). No surgery required: the future of feline sterilization. An overview of the Michelson Prize & Grants in Reproductive Biology. Journal of feline medicine and surgery, 17(9), 777-782.

Overview: For many years, researchers have been studying reproduction of cats and dogs, including approaches to non-surgical sterilization, but scant funding has been available for this work. Recognizing the need to fund research and to attract researchers from the biomedical community to apply their expertise to this area, the Michelson Prize & Grants (MPG) in Reproductive Biology program was founded. Since 2009, it has funded 34 research projects in seven countries toward discovery of a safe single-administration lifetime non-surgical sterilant in male and female cats and dogs.
Goal: The goal of the MPG program is the reduction or elimination of the approximately 2.7 million deaths of healthy shelter cats and dogs in the US every year. The successful product is expected to be a single-dose injectable product approved by the US Food and Drug Administration as a veterinary prescription item. The most optimistic prediction is that such a product will reach the hands of practicing veterinarians within the next decade.
Areas of research: Active research is in progress using approaches such as immunocontraception with a single-administration vaccine against gonadotropin releasing hormone (GnRH). Long-term therapy with GnRH agonists such as deslorelin administered in controlled-release devices is also being studied. Other scientists are targeting cells in the brain or gonads with cytotoxins, such as are used in cancer chemotherapy. Gene therapy expressing proteins that suppress reproduction and gene silencing of peptides essential to reproduction are further avenues of research. Findings are available at www.michelsonprizeandgrants.org/michelson-grants/research-findings

Attitudes towards fertility control methods in cats

Murray, J. K., Mosteller, J. R., Loberg, J. M., Andersson, M., & Benka, V. A. (2015). Methods of fertility control in cats: Owner, breeder and veterinarian behavior and attitudes. Journal of feline medicine and surgery, 17(9), 790-799.

Overview: Fertility control is important for population management of owned and unowned cats, provides health benefits at the individual level and can reduce unwanted sexually dimorphic behaviors such as roaming, aggression, spraying and calling. This article reviews the available evidence regarding European and American veterinarian, owner and pedigree cat breeder attitudes toward both surgical sterilization and non-surgical fertility control. It additionally presents new data on veterinarians’ and pedigree cat breeders’ use of, and attitudes toward, alternative modalities of fertility control.
Proportion of cats that are neutered: Within the United States and Europe, the proportion of cats reported to be sterilized varies widely. Published estimates range from 27–93% for owned cats and 2–5% for cats trapped as part of a trap–neuter–return (TNR) program. In some regions and populations of cats, non-surgical fertility control is also used. Social context, cultural norms, individual preferences, economic considerations, legislation and professional organizations may all influence fertility control decisions for cats.
Non-surgical methods of fertility control: Particularly in Europe, a limited number of non-surgical temporary contraceptives are available for cats; these include products with regulatory approval for cats as well as some used ‘off label’. Non-surgical methods remove the risk of complications related to surgery and offer potential to treat more animals in less time and at lower cost; they may also appeal to pedigree cat breeders seeking temporary contraception. However, concerns over efficacy, delivery methods, target species safety, duration and side effects exist with current non-surgical options. Research is under way to develop new methods to control fertility in cats without surgery. US and European veterinarians place high value on three perceived benefits of surgical sterilization: permanence, behavioral benefits and health benefits. Non-surgical options will likely need to share these benefits to be widely accepted by the veterinary community.

Modeling to improve TNR

Boone, J. D. (2015). Better trap–neuter–return for free-roaming cats Using models and monitoring to improve population management. Journal of feline medicine and surgery, 17(9), 800-807.

Overview: Trap–neuter–return (TNR) for cat management is transitioning from an enterprise driven mainly by an urge to ‘help’ into an enterprise that draws useful guidance and precedent from the fields of population biology and wildlife management. This transition is in its infancy, however. At the present time many TNR programs do not produce substantial and persistent reductions in cat populations, and those that do often fail to effectively document this achievement or to publicize their success.
Challenges: As a result, TNR has become increasingly controversial, with TNR advocates and wildlife conservationists often staking out fundamentally incompatible positions. This may ultimately prove to be an unproductive debate, since public opinion in developed countries is unlikely to support a total abandonment of TNR in favor of widespread cat management using lethal methods, and since wildlife advocates are unlikely to support TNR as it is typically practiced.
Advancements: In contrast, improving the effectiveness of TNR as a population management tool can benefit both cats and wildlife, potentially on a broad scale. Making these advancements requires the diligent promotion, dissemination and adoption of tools like population modeling, population monitoring and adaptive management. By virtue of their training and exposure to the scientific method, veterinarians are uniquely well positioned to translate the more technical aspects of these approaches to TNR practitioners, and to facilitate their wider use.
Aim: The purpose of this review is to describe for a veterinary audience how to facilitate more effective sterilization-based management of outdoor cats, using a combination of theoretical knowledge derived from population modeling and empirical knowledge derived from population monitoring. Using both of these information sources synergistically can offer a viable pathway to better management outcomes.

Non-surgical fertility control: current and future options for cat health and welfare

Briggs, J. (2015). Non-surgical fertility control: current and future options for cat health and welfare. Journal of feline medicine and surgery, 17(9), 740-741.

...
The 10 articles in this issue are authored by experts in the field and are, for the most part, review articles. Five cover specific contraceptives used to date for cats, or the limited array of sterilants and contraceptives being researched or used off-label in cats in the past decade. The emergence in 2008 of a USD$25 million prize and up to $50 million in grant funds has spurred more research than ever before, and in a number of novel areas. A glimpse into that new work is shared by the Director of Scientific Research for the Found Animals Foundation, the parent organization for this initiative: the Michelson Prize & Grants in Reproductive Biology.
...

Potential biological control of cats in Australia

Moodie, E. (1995). The potential for biological control of feral cats in Australia. New South Wales National Parks and Wildlife Service.


There is a need to clarify the impacts of feral cats on wildlife populations and thus set clear objectives for their control.

No method of biological control is available for immediate use. Fertility control using a contraceptive vaccine is the option with the most promise. This approach and two other broad strategies (a mortality approach usint lethal disease and environmental manipulation) are discussed in detail.

Although Feline Parvovirus has been used in attempts to control feral cats elsewhere, animal welfare concerns and probable immunity are likely to prevent its use in mainland Australia. No other feline diseases would cause rapid death in a relatively humane manner to a large enough proportion of a cat population to be useful for biological control.

The diseases and ecology (including population dynamics, reproduction and behaviour) of cats, and community attitudes to their control are discussed in depth. Relatively little information was available on feral cats. Most is derived from studies of domestic cats. Research currently underway is described. More information is needed on the ecology and epidemiology of diseases in feral cat populations in order to develop predictive models for specific biological control agents. Serological surveys for viral diseases in feral populations are given nights priority.

A fertility control approach using an immunocontraceptive vaccine probably has a reasonable chance of success in relation to public acceptability if the technical hurdles can be overcome. These include ensuring that the vaccine is cat specific, that it induces sterility without affecting social behaviour and that it's effects last long enough to be worthwhile. No effective chemical sterilants are available.

Results of research programs on immunocontraception of rabbits and foxes should indicate whether it is a feasible option for vertebrate pest control. Non-transmissible agents are more likely to be publicly acceptable because of concerns over the safety or other species and pet cats.

Attributes of successful pest control programs (for cats and other vertebrate pest species) are discussed. Refinement and combined use of conventional control methods will be essential for future cat control whether of not biological control is used.

Suppression of Fertility in Pre‐pubertal Dogs and Cats.

Schäfer‐Somi, S., Kaya, D., Gültiken, N., & Aslan, S. (2014). Suppression of Fertility in Pre‐pubertal Dogs and Cats. Reproduction in Domestic Animals, 49(s2), 21-27.

Pre-pubertal gonadectomy in dogs and cats is still controversially discussed because some consequences cause health problems. Nevertheless, postponement of puberty, that is, prevention of an increase in sexual hormones and thereby prevention of their manifold effects, is of major importance, not only in controlling overpopulation but also to preserve the genetic base for future breeding stock and pets. Therefore, alternatives for surgical suppression of fertility in pre-pubertal animals were critically reviewed. As a promising alternative, the slow-release GnRH agonist deslorelin and other GnRH analogues have been investigated. In female dogs and cats, puberty could be significantly postponed without initial flare-up effect and without disturbance of body development. First trials to delay puberty in female and male cats by application of a 4.7-mg deslorelin implant 24 h after birth so far are promising. In female dogs, a previous investigation showed that when the implant was inserted at the age of 4 months, the initial flare-up effect was prevented. Body development was normal in the studies reviewed here, and with the 9.4-mg implant, puberty was significantly delayed until the age of 21 months or older. In one study, bitches either received a 4.7- or a 9.4-mg implant at the age of 4 months and the epiphyses were mostly closed before the time of first oestrus. Using a 4.7-mg deslorelin implant in pre-pubertal male dogs significantly postponed puberty, and age at puberty was >2 years when a 9.4-mg implant was used. However, further investigations are required, especially concerning the effect of different GnRH agonist dosages and resorption rates on the duration of postponement of puberty as well as long-term effects in both dogs and cats.

Suppression of Fertility in Adult Cats

Goericke‐Pesch, S., Wehrend, A., & Georgiev, P. (2014). Suppression of Fertility in Adult Cats. Reproduction in Domestic Animals, 49(s2), 33-40.

Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific and clinical options are available for the suppression of fertility in adult cats and the decision as to which should be chosen – independent of the legal registration of any state – depends on different facts: (i) feral or privately owned animal? (ii) temporary or permanent suppression of fertility wanted/needed? (iii) sex of the animal? New effective and available methods for hormonal contraception include melatonin implants for short-term post ponement of oestrus in adult queens and slow-release GnRH-agonist implants containing deslorelin (Suprelorin^®) for short- and long-term contraception in male and female companion and breeding cats.

Virus-vectored immunocontraception to control feral cats

Courchamp, F. & S.J. Cornell. 2000. Virus-vectored immunocontraception to control feral
cats on islands: a mathematical model. Journal of Applied Ecology, 37: 903-913.

1.  Feral cats Felis catus introduced onto oceanic islands pose a major ecological threat to endemic vertebrates, but their control is difficult. Immunocontraception has not been considered previously as a method for their control or eradication, and therefore we used a modelling approach to assess whether virus-vectored immunocontraception (VVIC) might be effective.

2.  We compared the relative efficiency of cat control/eradication using immunocontraception and three different disseminating techniques, i.e. baits, genetically modified viral vectors, or both. We accounted for several forms of dynamic compensation likely to arise in a population with artificially reduced fertility.

3.  We conclude that, under the assumptions of our model, immunocontraception can control or eradicate feral cats on oceanic islands. VVIC was found to be a more efficient dissemination technique than baits, but an integrated method involving viral-infected baits was the most likely to lead to eradication.

4.  We advocate field trials of this VVIC technique, when available, under island conditions where any risks to non-target fauna would be minimal.

Nonsurgical fertility control for managing free-roaming dog

Massei, G., & Miller, L. A. (2013). Nonsurgical fertility control for managing free-roaming dog populations: A review of products and criteria for field applications.Theriogenology.

About 75% of dogs worldwide are free to roam and reproduce, thus creating locally overabundant populations. Problems caused by roaming dogs include diseases transmitted to livestock and humans, predation on livestock, attacks on humans, road traffic accidents, and nuisance behavior. Nonsurgical fertility control is increasingly advocated as more cost-effective than surgical sterilization to manage dog populations and their impact. The aims of this review were to 1) analyze trends in numbers of scientific publications on nonsurgical fertility control for dogs; 2) illustrate the spectrum of fertility inhibitors available for dogs; 3) examine how differences between confined and free-roaming dogs might affect the choice of fertility inhibitors to be used in dog population management; and 4) provide a framework of criteria to guide decisions regarding the use of nonsurgical fertility control for dog population management. The results showed that the 117 articles published between 1982 and 2011 focussed on long-term hormonal contraceptives, such as gonadotropin-releasing hormone agonists, immunocontraceptives, and male chemical sterilants. The number of articles published biennially increased from one to five papers produced in the early 1980s to 10 to 20 in the past decade. Differences between confined dogs and free-roaming dogs include reproduction and survival as well as social expectations regarding the duration of infertility, the costs of sterilization, and the responsibilities for meeting these costs. These differences are likely to dictate which fertility inhibitors will be used for confined or free-roaming dogs. The criteria regarding the use of fertility control for dog population management, presented as a decision tree, covered social acceptance, animal welfare, effectiveness, legal compliance, feasibility, and sustainability. The review concluded that the main challenges for the future are evaluating the feasibility, effectiveness, sustainability, and effects of mass nonsurgical sterilization campaigns on dog population size and impact as well as integrating nonsurgical fertility control with disease vaccination and public education programs.

TNR for feral cat: demography, ecology and potential pathogens

Nutter, F. B. (2006). Evaluation of a Trap-Neuter-Return Management Program for Feral Cat Colonies: Population Dynamics, Home Ranges, and Potentially Zoonotic Diseases. PhD
Management of feral cats is controversial, and alternatives to lethal control methods are gaining popularity. To evaluate the effectiveness of sterilization programs, nine feral cat colonies were divided into groups of three, managed either by spaying females and castrating males, spaying females and vasectomizing males, or leaving all cats intact. Colonies were followed intensively for four years, and intermittently for three additional years. Most cats were trapped in fewer than ten trap nights each. Breeding females produced a mean of 1.4 litters/year and 3 kittens/litter. Kitten mortality was 75% by 6 months of age. Feral and pet domestic cats had similar baseline health status and prevalences of FIV, FeLV, Cryptosporidium, Giardia, and Toxocara cati, but feral cats had higher prevalences of Bartonalla henselae and Toxoplasma gondii. Castrated male and spayed female cats survived longer than intact male and female cats. Survival times of vasectomized males were equivalent to those of intact males. Control colonies decreased in size and remained stable in composition, while intact colonies increased in size and had high turnover. One neutered colony went extinct and several others had fewer than five cats at the end of the project. Home ranges of both intact and neutered cats were small, usually less than 1 ha. Vasectomized males had larger home ranges than either intact or castrated males, probably because they were searching for intact females. Community-level stakeholder meetings were successful in building consensus among groups, and a basic decision tree for feral cat management was developed. Computer simulation modeling using VORTEX software suggested that harvesting breeding colonies every one or two years at 50% to 100% can keep colonies small, but will not lead to long-term reductions in cat numbers. Models of neutered colonies suggested that 75% to 80% sterilization is necessary to cause population decrease and eventual extinction. The mean estimated time to extinction of 12.8 years fits well with ongoing observations of steady decline in sterilized colonies.