Publications

Silva ABR, Brito JLM, de Souza RLP, et al. Nanoparticle-mediated hyperthermia for male cat neutering: Disrupting fertility without surgery. Theriogenology. 2026;249:117635. https://doi.org/10.1016/j.theriogenology.2025.117635

Abstract

This study aimed to evaluate magnetic nanoparticle-mediated hyperthermia (MNH) as a potential method to induce infertility in male cats. The short- and long-term effects of the treatment on reproductive health parameters were assessed in 20 cats. Treatment consisted of a 150 μL intratesticular injection of a magnetic fluid composed of citrate-coated manganese ferrite (Ci-MnFe2O4) nanoparticles, followed by the application of an external magnetic field to raise and maintain testicular temperature at 45 °C for 15 min. Testicular MNH was found to be safe and well tolerated, with no signs of pain or clinical side-effects. Testicular volume increased significantly on Day 7 due to peritesticular inflammation, followed by a marked decrease on Day 180. Azoospermia was observed in 85 % of the treated animals, while 15 % were oligospermic. Histological analysis revealed substantial damage to seminiferous tubule architecture and epididymides. No hematological, biochemical or abdominal ultrasound abnormalities were observed in the treated animals. These findings demonstrated the strong potential of testicular magnetic hyperthermia mediated by Ci-MnFe2O4 nanoparticles as a non-surgical alternative method for male cat sterilization.

Florencia GM, Romina NF, Cecilia SM, et al. Reproduction control in a feral feline population using an anti-GnRH vaccine. Theriogenology. 2025;235:203-209. https://doi.org/10.1016/j.theriogenology.2025.01.017

Abstract

This study aimed to evaluate the use of the Improvac® vaccine to avoid heat and pregnancies in queens and fertility in males during the breeding season. Twenty-eight intact animals were divided into treated males (G1, n = 7), treated females (G2, n = 18), and untreated males (G3, n = 3) that were untamed and could not be captured for immunization. In cats from the G1 group, the testicular volume (337.35 ± 95.74 mm3) and testosterone concentration (1.31 ± 0.49 ng/mL) reached the lowest value 16 weeks after the first vaccination. At week 40, all queens exhibited both estrus cytology and estrus behavior, with serum estrogen (38.5 ± 1.93 pg/mL) and progesterone (0.5 ng/mL) concentrations within the physiological range for the phase. Eleven queens received a third dose of the vaccine at week 40, and none became pregnant by week 64. The remaining queens (n = 7) did not receive the third dose of the vaccine and became pregnant by week 44. In cats from the G1 and G2 groups, the hematologic parameters were within the physiological range for the species. The results of this study indicate that the Improvac® vaccine is safe and effective in the short to medium term in preventing cat reproduction.

Peña-Corona SI, Vaquera-Guerrero MA, Cerbón-Gutiérrez J, et al. Comprehensive Evaluation and Future Perspectives of Non-Surgical Contraceptive Methods in Female Cats and Dogs. Animals (Basel). 2025;15(10):1501. https://doi.org/10.3390/ani15101501

Abstract

The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and canine females. Immunocontraception via vaccination against gonadotropin-releasing hormone (GnRH), the luteinizing hormone receptor, zona pellucida proteins, and sperm, or use of viral-vectored delivery, is yet developing. Hormonal treatment (progestins, androgens, or GnRH) analogs act directly to block the reproductive axis. However, it produced essential side effects. Analogs of kisspeptin, non-steroid anti-inflammatory drugs such as firocoxib, and delivery of cytotoxins to the pituitary have shown non-conclusive results. Additional methods have also been tested, such as intraovarian injection of necrosing compounds or intravaginal and intrauterine devices. At present, neither of these methods offers permanent sterility that can replace surgical sterilization techniques. To our knowledge, none are currently authorized by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for contraceptive methods or sterilization of cats or dogs. Therefore, it is necessary to continue the development of a compound that warrants the sterility of cats and dogs.

Barnes J, Vansandt L. Estrous cycle manipulation in cats. Clinical Theriogenology. 2025;17:67-81. https://doi.org/10.58292/CT.v17.11649

Abstract

For decades, interest in reproductive physiology of the domestic cat has largely been driven by its importance as a model for wild felids and human biomedical research. As such, several assisted reproductive technologies have been established in cats. Despite the growing need for feline theriogenology, the application of these tools in clinical practice is extremely limited. We discuss: 1. reproductive physiology of the queen and her unique challenges; 2. estrus induction (photoperiod, social interaction, and pharmacologic [gonadotropins, GnRH agonists]); 3. natural cycle monitoring (blood hormones, fecal hormone metabolites, behavior, vaginal cytology, transabdominal ultrasonography) and ovulation induction (manual stimulation, pharmacologic [gonadotropins, GnRH agonists]); 4. estrus suppression (photoperiod, melatonin, GnRH agonists, progestins); and 5. permanent nonsurgical contraception (immunocontraception, gene therapy). This review will summarize published reports on estrous cycle manipulation in felids, both wild and domestic; notable differences between cats and dogs are highlighted and comments based on the authors’ personal experiences and preferences for application are included.

Ubilla MJ, Lopez-Bejar M, Siel D, Sáenz L. Reproductive control in dogs with emphasis on anti-GnRH immunocastration and its behavioral effects. Vet Sci. 2025;13(1):5. https://doi.org/10.3390/vetsci13010005

Abstract

Dog overpopulation poses serious challenges to public health, animal welfare, and environmental sustainability. While surgical castration remains the most commonly used method for controlling reproduction in dogs, it carries risks and limitations, including surgical complications and long-term behavioral or physiological side effects. This review examines the potential of immunocastration-vaccination targeting gonadotropin-releasing hormone (GnRH)-as an alternative approach. Immunocastration has been shown to suppress reproductive hormones, reduce gonadal function, and decrease behaviors such as roaming, aggression, and sexual mounting in dogs. The review also includes evidence from other species (e.g., pigs, cattle, and horses) to contextualize effectiveness and welfare implications. While behavioral effects are more variable and less frequently studied than physiological outcomes, recent findings suggest immunocastration may have fewer negative emotional side effects (e.g., anxiety and stress-related behaviors) than surgical sterilization. The review highlights the mechanisms, applications, and behavioral outcomes of immunocastration, including its reversibility, cost-effectiveness, and suitability for mass implementation. Overall, immunocastration offers a promising addition to dog population management strategies, particularly in regions with limited surgical infrastructure. Future research should focus on standardizing vaccine protocols and assessing long-term behavioral and welfare outcomes in diverse dog populations.

Amaral J, Briantais P, Fontaine C, Rigaut D. Efficacy and safety of 4.7 mg deslorelin acetate implants as a neutering option in male cats: a large-scale multicentre randomised controlled study. Animals (Basel). 2023;13(3):379. https://doi.org/10.3390/ani13030379

Abstract

This multicenter-controlled, double-masked randomized European study was conduc-ted to confirm both the efficacy and safety of a deslorelin implant in controlling fertility and sexual behavior in a large population of tom cats over a 12-month period. Among the 225 screened individuals, a total of 205 privately owned indoor intact male cats, aged 3 months of age or older, were randomly allocated to a deslorelin implant (n = 154) or to a negative control group (n = 51). After the screening visit performed between day (D)-14 and D-7, six additional visits were sche-duled on D0, D45, D93, D186, D279 and D372. Effects on testosterone, sexual behaviors, penile spines, testicular volume and intact male cat urine odor were assessed at every visit under masked conditions as regards to the treatment group. In addition, phone calls from the investigators to the owners were scheduled on D7 and then on a monthly basis whenever no visit was scheduled. Success was defined as an individual serum testosterone concentration below or equal to 0.10 ng/mL and was 77.9% at D45, 83.1% at D93, 84.4% at D186 and D279, and 61.7% at D372 in the deslorelin group, and 3.9% at D45, 5.9% at D93, 3.9% at D186, 7.8% at D279 and 3.9% at D372 in the negative control group. Testing for superiority was made stepwise from D45 to D372 upwards; the difference in success rates was significant from D45 to D372 (p < 0.001 for each time point). The mean testosterone concentration dropped from baseline in the deslorelin group, remaining below the set threshold of 0.1 ng/mL until D372. From D7 onwards, the mean sum score for sexual behaviors (including vocalization, urine marking, aggression and intact male cat urine odor) was significantly lower at each observation time point in the deslorelin group compared to the control group, where no decrease in scores was observed. The mean percent change to baseline of the testicular volume and the percentage of cats with a decreased visibility and adult appearance of penile spines were significantly lower in the deslorelin group as soon as D45. No relevant safety concerns were reported during the course of the study. The deslorelin implant Suprelorin® 4.7 mg (Virbac, Carros, France) is a safe and effective neutering option, inducing infertility over a 12-month period when administered to intact male cats aged between 3 months of age and 11 years of age. The implants also successfully reduced sexual behaviors (i.e., vocalization, urine marking, aggression), intact male cat urine odor, testicular volume and penile spine score for 1 year (372 ± 5 days).

Park CJ, Minabe S, Hess RA, et al. Single neonatal estrogen implant sterilizes female animals by decreasing hypothalamic KISS1 expression. Sci Rep. 2023;13(1):9627. https://doi.org/10.1038/s41598-023-36727-8

Abstract

Reproductive sterilization by surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive behaviors and diseases. This study explored the use of a single-injection method to induce sterility in female animals as an alternative to surgical ovariohysterectomy. The idea was based on our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin (KISS1), the neuropeptide that triggers and regulates pulsatile secretion of GnRH. Neonatal female rats were dosed with estradiol benzoate (EB) either by daily injections for 11 days or by subcutaneous implantation of an EB-containing silicone capsule designed to release EB over 2-3 weeks. Rats treated by either method did not exhibit estrous cyclicity, were anovulatory, and became infertile. The EB-treated rats had fewer hypothalamic Kisspeptin neurons, but the GnRH-LH axis remained responsive to Kisspeptin stimulation. Because it would be desirable to use a biodegradable carrier that is also easier to handle, an injectable EB carrier was developed from PLGA microspheres to provide pharmacokinetics comparable to the EB-containing silicone capsule. A single neonatal injection of EB-microspheres at an equivalent dosage resulted in sterility in the female rat. In neonatal female Beagle dogs, implantation of an EB-containing silicone capsule also reduced ovarian follicle development and significantly inhibited KISS1 expression in the hypothalamus. None of the treatments produced any concerning health effects, other than infertility. Therefore, further development of this technology for sterilization in domestic female animals, such as dogs and cats is worthy of investigation.

Alliance for Contraception in Cats & Dogs (ACC&D). Contraception and Fertility Control in Dogs and Cats. 2013. https://www.acc-d.org/resources/accd-e-book.

Preface

In 2002, Katherine Moldave, MBA and Linda Rhodes, VMD, PhD compiled and published Contraception and Fertility Control in Animals, believed to be the first effort to summarize the technologies and issues related to this topic in a comprehensive format that would be useful to scientists, academicians, the animal health and welfare industries, and interested laypeople alike. The authors subsequently donated the copyright to the Alliance for Contraception in Cats & Dogs (ACC&D). In the past decade, several contraceptive products for use in dogs have been approved in various markets, research in relevant traditional and emerging technologies has expanded greatly, interest in this area of animal health has increased, and, as a key component of our mission, ACC&D has worked to focus stakeholder attention on the opportunities and issues involved in non-surgical approaches to contraception and fertility control in “owned” and “unowned” cats and dogs. At the end of 2011, ACC&D decided that the time had come to update the portions of the report related to cats and dogs. The lead author for Contraception and Fertility Control in Cats and Dogs is one of the original authors of Contraception and Fertility Control in Animals (2002), Katherine Moldave. The regulatory chapter has been updated by its original author, Linda Rhodes. ACC&D commissioned this update with the support of a generous grant from PetSmart Charities®. Happily, this has been a more significant undertaking than originally anticipated since so much has occurred in the intervening years. ACC&D thanks Ms. Moldave for her many hours of work beyond what was contracted to update and expand the original text; her commitment to the project has truly gone above and beyond. Contraception and Fertility Control in Dogs and Cats is not a scholarly work or exhaustive review article. It is intended to provide a single source of information and foster collaboration among interested parties. We are counting on readers to help us identify information that may not have been included in this compilation but should be covered in future updates. We have tried to be as geographically inclusive as possible but acknowledge that some aspects of the compilation have a United States orientation. Therefore, we are particularly interested in updates, additional information, and perspectives from areas outside the US.

Please see the full Preface of the e-Book for the ACC&D scientific advisors, Board of Directors members, and field experts who provided information and/or review of this e-book.

Driancourt MA, Briggs JR. Gonadotropin-releasing hormone (GnRH) agonist implants for male dog fertility suppression: a review of mode of action, efficacy, safety, and uses. Front Vet Sci. 2020;7:483. https://doi.org/10.3389/fvets.2020.00483

Abstract

At present, only surgical sterilization is available for veterinarians and pet owners seeking suppression of fertility in male dogs, in most countries. An alternative contraceptive alternative approach is GnRH releasing implants that desensitize the pituitary to the stimulatory effects of GnRH and thereby block testicular function (testosterone and sperm production). Two GnRH agonists (deslorelin and azagly-nafarelin) have been researched in controlled release formulations for this purpose. A deslorelin-releasing biodegradable implant, marketed under the name Suprelorin®, has been available in Australia and New Zealand since 2007, the European Union (EU) since 2008, and received regulatory approval in China and Mexico in late 2019. Two versions of the implant are available, one labeled for a minimum of 6 months of fertility suppression in male dogs, and the other for a minimum of 12 months in male dogs. Another GnRH agonist (azagly-nafarelin) was also included in a solid implant (Gonazon®). Research results showed it delivered 6-months to 1 year of suppressed fertility; however, it is not commercialized. This review paper summarizes research on the mechanism of action for these technologies and compiles and interprets the research on efficacy and safety. New findings on usage of the deslorelin releasing implant in countries where veterinarians and pet owners have this option is shared. Research on off-label use of the product in male dogs is also reviewed. This review aims to aid in the evaluation of the deslorelin releasing implant as an adjunct or alternative for surgical sterilization of male dogs.