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Advances in reproductive control technology

Graeme Brown

INTRODUCTION managing small accessible populations. Its main advan- tage over the newer developments is that the sterility Population control of both domesticated and wild, free- obtained is permanent. Its main disadvantages are that it roaming animals is a major problem in remote and is costly, time consuming, there are infection risks and it indigenous communities. In fact, overpopulation of free- is impractical for large populations. roaming animals is a problem worldwide. This overpopu- lation has led to social problems, degradation of the Non-surgical methods ecosystem and increased risks of zoonotic disease. The six non-surgical mechanisms suggested for blocking It is clear that an inexpensive and non-surgical method of reproduction in the female are: permanent contraception would be of enormous benefit · suppression of anterior pituitary secretion of in reducing these populations. Reproductive control is gonadotrophins, considered a more sensible, humane and ethical manage- · prevention of follicle development and ment approach than allowing young to be born and then maturation, later spending valuable resources to capture and · blocking the passage of ova in the oviduct, euthanase them. However, the ethics of using a particular · prevention of fertilisation, method of population control will depend on its humane- · prevention of implantation, ness, its safety and its effectiveness compared to other · interference with gestation. available methods. These factors have to be weighed against euthanasia or just doing nothing. In males there are three suggested mechanisms: The objects of this paper are firstly to review current dog · suppression or interference with secretion of and cat reproductive control methods, and secondly to gonadotrophins, discuss advances in this field and how these advances · inhibition of spermatogenesis, might apply to animals in remote and indigenous · interference during transport and storage of communities. sperm. Chemosterilants are chemicals that cause permanent or REPRODUCTIVE CONTROL AT A temporary sterility in either sex, reducing the number of POPULATION LEVEL offspring or altering the fertility of offspring produced. Most methods of fertility control have examined effects Immunocontraception is the technique of raising on reproduction only, without looking at the effects any antibodies against sperm, eggs or reproductive hor- control mechanism might have on population dynamics. mones, and so inhibit reproduction. Such information is essential for estimating the value of any population control technique. Numbers and compo- Immunosterilisation involves the ability to produce an sition of populations are forever changing and these immune response that leads to the animal’s sterilisation. changes are the result of many factors, only one of Currently, the following antibodies have been produced which is reproduction. against: With polygamous matings at a population level (eg. free- · Releasing (GnRH), roaming and feral dogs and cats), the effect of · gametes (Zona Pellucida antigens and sperm), sterilisation of males will have no impact at all on · implantation and gestation (HCG). population size. A very high level of female sterilisation Currently available methods (mainly producing is needed in these populations to achieve a decrease in numbers. Modelling suggests that between 80-90% of temporary sterility) females need to be sterilised to obtain zero population 1. Synthetic progestins - growth. - MGA ( ) implants - MPA ( acetate) injections The effectiveness of any fertility control program will - Covinan () injections depend on the balance between survival rates and the - Norplant ( acetate) implants productivity of the remaining fertile animals. For example, - Ovarid ( acetate) tablets the reduced production of young caused by sterilisation - Tardak ( acetate) injections is compensated for by an increased survival rate of juveniles and the remaining adults. - Implanon () implants - acetate injections METHODS OF FERTILITY CONTROL 2. antagonists There are 3 main methods of manipulating fertility in - RU486 () tablets mammals: surgical and the non-surgical methods of 3. Prolactin inhibitors chemosterilisation and immunocontraception. - Bromohexal,Parlodel (bromocriptine) tablets Surgical sterilisation is considered the ‘gold standard’ - Dostinex (cabergoline) tablets of fertility control and is still the method of choice for

Urban Animal Management Conference Proceedings 2003 - Text copyright © AVA Ltd - Refer to Disclaimer 108 Graeme Brown 4. would be given in a single delivery, be inexpensive, and - Cheque () drops be safe to both targeted animals and to humans inadvert- - implants ently exposed. 5. Vaccine There are still many questions that remain regarding the - Porcine Zona Pellucida vaccine (PZP) development of effective, affordable, long lasting and injections safe immunocontraceptive vaccines in female dogs and 6. Gonadotropin Releasing Hormone (GnRH) cats. This is disappointing, as immunocontraception agonists using porcine zona pellucida as an antigen is already a - Lupron (leuprolide acetate) injections reality for wildlife population control. SpayVac™, a 7. Chemical Methods commercially available porcine derived ZP did not induce - Neutrosol (intra-testicular injection of contraception in cats. Some studies using PZP have sclerosing agent) demonstrated significant side-effects such as cystic - Biotumer (copper IUD) ovaries in dogs. ADVANCES IN NON-SURGICAL The main disadvantage of PZP vaccines is that treated TECHNIQUES FOR FERTILITY CONTROL females tend to have recurring and sometimes prolonged oestrous cycles. However, a hybrid antigen consisting of Because of a need for newer non-surgical techniques to ZP3 and a universal T-cell epitope, creates a substantial produce either temporary or permanent sterility, some enough reaction in canine ovaries to eventually destroy advances in reproductive control technology have been the integrity of the ovary. This results in made in the past few years. (There have been advances immunosterilisation, and at the moment, looks to be a in anaesthetic agents that have led to improvements in promising approach for nonsurgical sterilisation, though the surgical approach to fertility control, but these are several injections 3 to 4 months apart have to be beyond the scope of this paper). The need for new administered. strategies has arisen as a result of the side-effects from the long-term use of progestins and the unreliability and In , a contraceptive vaccine is being developed undesirable reactions from many of the contraceptive by a group from the CRC for Vaccine Technology in vaccines. Brisbane, the University of Melbourne and CSL. Their contraceptive vaccine is designed to render a dog or It is important to remember that in remote and indigenous bitch infertile for at least six months. It works by generat- communities, the use of any product that prevents ing antibodies to luteinising hormone-releasing hormone pregnancy without preventing oestrous cycles would be (LHRH) and therefore suppresses the production of the a poor alternative to surgically sterilising dogs and cats. sex . Products being developed but not yet available commercially. It is worth noting that when a vaccine for reproductive 1. Prolactin Inhibitors control is used, animals with a poor immune response are - Melatonin implants affected less than animals with a good immune response, 2. Vaccine so immunosterilisation could, therefore, select for - CSL’s Luteinising hormone-releasing hormone immunocompromised animals that are more susceptible (LHRH) to disease. - GnRH conjugate (gonexPets) An Australian Biotechnology company Peptech Animal

- Sperm antigens e.g. LDH-C4 Health has developed a GnRH analogue implant to 3. Gonadotropin Releasing Hormone (GnRH) produce reversible long-term suppression of reproduc- Agonists tive function in male and female dogs and cats. - Deslorelin / Suprelorin (PepTech) It has been demonstrated that the slow release pellet 4. Chemical containing the GnRH analogue deslorelin, which is - Novel peptides targeting primordial follicles placed under the skin in the neck of the dog, acts as a producing permanent sterility reversible anti-fertility agent in dogs for periods exceed- REPRODUCTIVE CONTROL TECHNOLOGY ing one year. In females, postponement of oestrus for periods up to 27 months has been observed. Deslorelin RESEARCH - CURRENT SITUATION has recently been registered in as A variety of the above methods of reproductive control Suprelorin®. Its approval for registration in Australia is technology have been explored, but to date, none have anticipated within the next six months. shown sufficient efficacy to be widely deployed. In fact, There are two new non-surgical methods that have been it was summarised at the 2002 International Symposium developed to permanently sterilise male dogs. Of interest on Nonsurgical Methods for Pet Population Control, is Neutersol™, which is a and l-arginine based that a commercial product – an alternative to surgical compound injected into each of the testicles of pups, castration or ovario-hysterectomy for either dogs or cats causing permanent sterility. At the moment, its use is – might still be 10 years away. Despite scientists approved in USA for male pups between three and ten investigating methods for the control of reproduction for months. over 30 years, there are still no commercially successful products being marketed. Ideally, the perfect non- There is another method being developed in USA in surgical sterilisation method would cause permanent loss which a hand-held, high intensity focused ultrasound is of fertility, permanent loss of sexual behaviour and be used on the epididymides of anaesthetised dogs to effective in dogs and cats – both males and females. It induce thermal coagulative necrosis and subsequent epididymal occlusion. It is claimed to provide a rapid non-invasive alternative to vasectomy.

Urban Animal Management Conference Proceedings 2003 - Text copyright © AVA Ltd - Refer to Disclaimer Advances in reproductive control technology 109 CONCLUSION REFERENCES Although non-surgical methods for permanent Alliance for Contraception in Cats and Dogs (2002). sterilisation for dogs and cats have been explored for Proceedings of the 2002 International Symposium on quite some time, we appear to be only a little closer to Nonsurgical Methods for Pet Population Control. Held achieving that goal. We are battling the biology of at Callaway Gardens, Pine Mountain, Georgia USA April reproduction that has enabled dogs and cats to survive 19-21, 2002 for many thousand of years. Barber MT et al (2000). Possible mechanisms of mamma- lian immunocontraception. 46:103-124 ABOUT THE AUTHOR Barlow ND et al (1997). Modelling the relative efficacy of culling and sterilisation for controlling populations. Graeme Brown Wildlife Research 24: 129-141 Discipline of Biological Sciences University of Newcastle Bomford M (1990). A role for Fertility Control in Callaghan NSW 2308 Wildlife Management? (Bureau of Rural Resources Bulletin No 7). Australian Government Publishing Graeme Brown BVSc, graduated from the University of Service: Canberra. Sydney and spent fiveyears working for NSW Agriculture and various mixed veterinary practices in Delves PJ et al (2002). Antifertility vaccines. Trends in Australia and UK. In 1972, he established Merewether Immunology 23: 213-219 Veterinary Hospital and has developed a strong interest Fayrer-Hosken RA et al (2000). Immunocontrol in dogs. in wildlife diseases and population biology. Animal Reproduction Science 60-61: 365-373 Graeme is currently enrolled as a post-graduate student McCallum H (1996) Immunocontraception for wildlife at the University of Newcastle studying the ‘Population population control. Trends in Ecology and Evolution dynamics of free-roaming dogs in Aboriginal (TREE) 11: 491-493 communities’. Trigg TE et al (2001) Use of a GnRH analogue to produce reversible long-term suppression of reproduc- tive function of male and female domestic dogs. Journal of Reproduction and Fertility Supplement 57: 255-261 Tuyttens FAM et al (1998). Fertility control: An option for non-lethal control of wild carnivores? Animal Welfare 7: 339-364

Urban Animal Management Conference Proceedings 2003 - Text copyright © AVA Ltd - Refer to Disclaimer