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. 

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.

Non-surgical contraceptives for use in cats and dogs

Rhodes, L. 2015. Getting non-surgical contraceptives approved for use in cats and dogs. Journal of Feline Medicine and Surgery, 17 (9): 783-789

Relevance: Non-surgical contraceptives or sterilants need regulatory approval to be sold for that use. This approval process gives veterinarians the information required to assess the benefits and risks of each product, and to provide comprehensive information on the required dose, method and duration of use, safety and effectiveness.
Aim: This article reviews the information that must be developed and provided to regulatory agencies worldwide, with a focus on the European Union and the United States, in order to achieve regulatory approval.
Processes: The main components of developing a drug include developing extensive information on the safety and effectiveness of the product, and also the safety to the environment and to humans handling and administering the drug. Most importantly, a robust method of manufacturing both the drug itself and the formulated drug product (pill, liquid implant or injection) must be developed to assure quality and consistency in each batch. This information is then compiled and submitted to regulatory agencies; in the United States, this includes the Food and Drug Administration, the United States Department of Agriculture and the Environmental Protection Agency, and, in Europe, the European Medicines Agency.
Challenges: Because of the unique nature of non-surgical contraceptives for use in cats and dogs, particularly the desire to have these products last over multiple years, there are special challenges to their regulatory approval that are discussed in this review.

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.

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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.
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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.

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.

Gonadotropin releasing hormone vaccine to control of female feral cats

Friary, J. (2006). Evaluation of a Gonadotropin releasing hormone vaccine for the humane control of female feral cats. (Doctoral dissertation, University of Florida).

The unwanted cat population in the United States numbers in the tens of millions and current control measures have only had limited success in reducing it. Immunocontraception has the potential to humanely reduce this population. The purpose of this study was to investigate the effectiveness of a GnRH-based vaccine for immunocontraception of female cats. It was expected that the treated cats would produce antibodies against GnRH and there would be a positive correlation between high titer and contraception. Adult female cats were divided into a sham group (n = 5) and a treatment group (n = 15) that was immunized once with 200 µg of synthetic GnRH coupled to keyhole limpet hemocyanin and combined with a mycobacterial adjuvant. GnRH antibody titer and serum concentrations of progesterone and estradiol-17β were determined monthly. For the duration of the study the daily photoperiod was manipulated in an attempt to induce estrus. A male breeding cat was housed with the females during the long-day periods, and continuous videography was used to monitor for signs of estrus and breeding. GnRH antibodies were detected in all treated cats by 150 days after immunization, but when the titer in four cats fell below 16,000, they became pregnant and were classified as nonresponders. The titers of the remaining 11 cats (responders) never decreased below 16,000. These cats displayed no signs of behavioral estrus and did not become pregnant by the end of the study 24 months after immunization. All five sham cats became pregnant within one month of the introduction of the male cat. From 60 days after immunization until the end of the study, progesterone concentrations in all responders remained at basal levels, and increased two months before parturition in all cats that became pregnant. The responder cats gained more weight than the nonresponders during the 14 months after immunization (P = 0.004), which is the same response observed in surgically sterilized cats. A single dose of GnRH vaccine resulted in contraception in 73% of the cats for at least 24 months.