Gonadotropin-Releasing Hormone (GnRH) Agonist Implants for Male Dog Fertility Suppression: A Review of Mode of Action, Efficacy, Safety, and Uses.

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.

Effectiveness of GonaCon as an immunocontraceptive in colony-housed cats.

Objectives Non-surgical contraceptive management of free-roaming cat populations is a global goal for public health and humane reasons. The objectives of this study were to measure the duration of contraception following a single intramuscular injection of a gonadotropin-releasing hormone-based vaccine (GonaCon) and to confirm its safe use in female cats living in colony conditions. Methods GonaCon (0.5 ml/cat) was administered intramuscularly to 20 intact female cats (queens), and saline was administered to 10 queens serving as sham-treated controls. Beginning in late February, 4 months after injection, all cats were housed with fertile male cats in a simulated colony environment. Time to pregnancy, fetal counts and vaccine-elicited injection-site reactions were evaluated. Results All control cats (n = 10/10) and 60% (n = 12/20) of vaccinated cats became pregnant within 4 months of the introduction of males. Two additional vaccinates became pregnant (70%; n = 14/20) within 1 year of treatment. Average fetal counts were significantly lower in vaccinated cats than in control cats. Vaccinates had a significantly longer ( P = 0.0120) median time to conception (212 days) compared with controls (127.5 days). Injection-site reactions ranging from swelling to transient granulomatous masses were observed in 45% (n = 9/20) of vaccinated cats. Conclusions and relevance A single dose of GonaCon provided contraception lasting for a minimum of 1 year in 30% (n = 6/20) of treated cats. The level of contraception induced by this GonaCon dose and vaccine lot was not sufficiently effective to be recommended for use in free-roaming cats.

Follicle-stimulating hormone receptors in oocytes?

The regulatory mechanisms of oocyte maturation remain poorly understood. Although gonadotropins play a major role in these processes, they have generally been considered to act on somatic supportive cells, but not directly on germ cells. We have raised high affinity monoclonal antibodies against LH and FSH receptors. When using the latter to study receptor distribution in human and pig ovaries we have observed the presence of FSH (but not LH) receptors in the oocytes. FSH receptors appeared in the oocytes of primary follicles during follicular development and persisted up to the preovulatory stage. In denuded human preovulatory oocytes, FSH receptor mRNA was detected at a concentration per cell exceeding by about 20-fold that present in granulosa cells. Saturable binding of [(125)I]FSH to the membrane of oocytes was demonstrated by autoradiography. When incubated with FSH, denuded oocytes responded by a mobilization of Ca(2+). These observations concur to demonstrate the presence of functional FSH receptors in oocytes and raise the possibility of direct control of oocyte development by FSH.