ASSESSING THE EFFICACY OF DESLORELIN ACETATE IMPLANTS (SUPRELORIN) IN ALTERNATIVE PLACEMENT SITES.

Hormonal contraception is being increasingly used to manage captive animals in zoological collections. Many of the animals placed on contraception are of genetic importance within captive breeding programs; therefore, it is imperative that the application of contraceptive products minimize potential side effects and facilitate a return to fertility if required. Deslorelin acetate implants (Suprelorin®) are one example of a hormonal contraceptive that is frequently used in captivity as they are easy to use and effective in most species. It is hypothesized that removing implants may hasten reversal of contraception treatment; therefore, placement in a location where they can easily be recovered is advocated. In this report, the efficacy and safety of Suprelorin implants placed in their recommended site between the scapulae is compared with alternative placement sites where implants can more easily be located for removal. Using the European Association of Zoos and Aquariums (EAZA) Group on Zoo Animal Contraception (EGZAC) Contraception Database, rates of success, failure, and reversal in 561 records of Suprelorin use in European collections are compared. Of these, 357 have information relating to the location of implant placement. When correctly applied, rates of efficacy were high (>99%) irrespective of placement site. Rates of reversal were 33.3% higher in alternative placement sites, although in most cases it is unknown whether implants were removed or not. In conclusion, the placement of Suprelorin implants in alternative sites does not negatively affect the efficacy, facilitating at the same time implant removal, minimizing potential side effects, and reducing reversal time, allowing for effective use in captive conservation breeding programs.

COMPARISON OF TWO 4.7-MILLIGRAM TO ONE 9.4-MILLIGRAM DESLORELIN ACETATE IMPLANTS ON EGG PRODUCTION AND PLASMA PROGESTERONE CONCENTRATIONS IN JAPANESE QUAIL (COTURNIX COTURNIX JAPONICA).

Reproductive disease in captive avian species is common, and medical management is often chosen over surgical removal of the reproductive tract. In a previous study with Japanese quail, a single 4.7-mg deslorelin acetate implant reversibly decreased egg production in 6 out 10 birds for 70 days. The objective of the current study was to evaluate the effects of two 4.7-mg deslorelin acetate implants versus one 9.4-mg implant on egg production and plasma progesterone concentrations in Japanese quail ( Coturnix coturnix japonica). Following a 10-day period of consistent egg laying, 30 adult female Japanese quail were anesthetized and received two 4.7-mg deslorelin implants (n = 10), one 9.4-mg deslorelin implant (n = 10), or a single, identical placebo implant (n = 10) s.c. between the scapulae. Egg production was monitored daily, and plasma progesterone concentrations were measured on days 0, 14, 29, 120, 148, and 182 via enzyme-linked immunoassay. All birds were weighed periodically and euthanized at day 182, after which their reproductive tracts were evaluated at gross necropsy. Seven out of 10 birds treated with two 4.7-mg implants ceased egg laying 1 wk after implantation and remained nonovulatory for approximately 100 days. Cessation of egg laying for the 9.4-mg treatment group occurred in 7 out of 10 birds; onset was variable (weeks 5-12) and continued for the remainder of the study period. Plasma progesterone concentrations for deslorelin treatment groups were not significantly different compared to the placebo group at any time point. In conclusion, the two 4.7-mg and the one 9.4-mg implant treatments ceased egg laying in a similar number of birds, but the 9.4-mg implant had a slower onset of action and the effects on egg laying were inconsistent throughout the study period. Further studies evaluating use of deslorelin acetate in other avian species are needed.

Use of Deslorelin Acetate Implants to Mitigate Aggression in Two Adult Male Domestic Turkeys (Meleagris gallopavo) and Correlating Plasma Testosterone Concentrations.

Two adult, male domestic turkeys were treated with implants of deslorelin acetate, a gonadotropin-releasing hormone agonist, to reduce intermale aggression and aggression directed toward the animal care team at a zoologic institution. The turkeys were manually restrained and either two 4.7-mg or two 9.4-mg implants were placed within the pectoral musculature on 3 occasions over the course of approximately 1.5 years. Plasma testosterone concentrations were measured by radioimmunoassay every 2 weeks for the first month after a new implant placement and then monthly thereafter. Testosterone concentrations remained low and aggressive behavior was decreased for a period of several months after implant placement. At necropsy of both birds, no adverse gross or histologic lesions were noted at the implantation sites in the pectoral musculature or within the gonadal tissue. Deslorelin acetate implants are a treatment modality to consider for mitigation of aggression in male domestic turkeys.

Effect of a subcutaneous implant of deslorelin acetate on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises.

Deslorelin acetate is a gonadotropin-releasing hormone agonist formulated in a controlled-release subcutaneous implant and designed for reversible suppression of testosterone production in dogs. It has also been demonstrated to be effective in other animal species, but no data on its effectiveness in male land tortoises are available. This study aimed to evaluate the effect of a 4.7-mg deslorelin acetate implant on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises. Twenty adult male tortoises housed under the same environmental conditions were enrolled for the study and randomly assigned to a treatment (D, n = 10) or a control (C, n = 10) group. Starting in May, males from the D group were implanted with a 4.7-mg deslorelin acetate device, whereas males from the C group did not receive any treatment. Blood samples were collected once immediately before implant application (S0-May) and at 15 days (S1-June), 2 (S2-July), and 5 (S3-October) months after application. Serum testosterone at each sampling time was measured through a solid-phase, enzyme-labeled, competitive chemiluminescent immunoassay. Median serum testosterone concentrations were not significantly different between the two groups in all sampling times, and no interaction between treatment and sampling time was observed. The present study, therefore, suggests that a single treatment with a 4.7-mg deslorelin acetate implant has no effect on testosterone circulation in male Hermann's and Greek tortoises during the following 5 months.

Ovulatory response to GnRH agonist during early and late fall in mares.

This study aimed to assess the ovulatory response of deslorelin acetate during the fall and the response to PGF2α 8 d post-ovulation. One hundred estrous cycles from 22 mares kept in 40° latitude were evaluated. Mares were checked by transrectal ultrasonography until a preovulatory follicle was detected and ovulation induced with deslorelin acetate. Ovulation was confirmed by ultrasonography performed at 24, 36 h post-induction and then repeated at 2-h intervals post-induction. Serum progesterone concentrations and luteal tissue area were determined daily to assess CL function. A dose of PGF2α was administered 8 d post-ovulation and interval to the subsequent ovulation was observed; each mare completed up to five cycles. The effects of local climate on endpoints were analyzed. Cycles were grouped as early (Sept 13, 2020-Oct 31, 2020; n = 55; 22 mares) and late fall (Nov 1, 2020-Dec 31, 2020; n = 45; 20 mares) based on the date of induction. The overall number of cycles with ovulations between 24 and 48 h was 90%. The number of multiple ovulations were similar between early (n = 5) and late (n = 4) fall (P = 0.87). There were no differences in deemed spontaneous ovulations occurring before 24 h between early (n = 6) and late (n = 2) fall (P = 0.29). Two failures to respond to deslorelin by 48 h were recorded in early fall and none in the late fall. The interval from induction to ovulation was similar in early (40.6 ± 0.4 h) and late (41.2 ± 0.5 h) fall (P = 0.55). The percentage of mares ovulating between 36 and 48 h post-deslorelin did not vary between early and late fall (91 vs. 95%, P = 0.21), as did not for ovulation occurring between 38 h and 44 h (62 vs. 60%, P = 0.69). Edema scores varied with time relative to ovulation (P < 0.001) and were lower in late fall (P = 0.01). Progesterone concentrations varied with time (P < 0.001) but did not differ between early and late fall (P = 0.73) and correlated weakly with the luteal area (r = 0.13; P = 0.031). Follicles <35 mm at the PGF2α had a shorter interval to the next ovulation than follicles ≥ 35 mm (9.2 ± 0.5 d vs. 10.6 ± 1.2 d) (P = 0.03). Lower temperature was associated with a smaller follicle size at induction (P = 0.0021) and ovulation (P = 0.009) and lower relative humidity was associated with a larger follicle size at ovulation (P = 0.032). In conclusion, cycling mares displayed a highly efficacious response to deslorelin acetate and apparently normal luteal function during the fall, despite lower edema scores in late fall.

A Comparative Study of the Effects of Osaterone Acetate and Deslorelin Acetate on Sperm Kinematics and Morpho-Functional Parameters in Dogs.

Benign prostatic hyperplasia (BPH) is one of the most common problems in older male dogs that often has a huge impact on their health and welfare. This article presents a comparison between osaterone acetate (Ypozane®; Virbac®)(OA) and deslorelin acetate (Suprelorin®; Virbac®)(DA), medications that are the main therapeutic alternative to castration in dogs with BPH. Forty dogs were divided into four groups: I-negative control (five dogs without BPH); II-positive control (10 individuals diagnosed with BPH); III-15 dogs treated with DA, and IV-10 individuals treated with OA. Semen fractions were collected on days 0 (day of treatment), 7, 14, and 21, and weeks 8, 12, 16, and 20. Macroscopic, microscopic and CASA analyses were performed. Both DA and OA significantly affected the properties of the canine ejaculate. The DA lead to the lack of libido and had lesser effects to the sperm function before it caused azoospermia, whereas OA had no effect on libido and only temporary reduction in seminal plasma volume was observed, which resulted in temporary deterioration in the percentage of motile and progressive spermatozoa.

Use of GnRH Agonist in Dogs Affected with Leishmaniosis.

Sex-associated hormones such as testosterone have been demonstrated to modulate immune responses, which can result in different disease outcomes. The present study was aimed at evaluating the efficacy of a gonadotropin-releasing hormone GnRH agonist implant as deslorelin acetate in association with meglumine antimoniate plus allopurinol in dogs with canine leishmaniosis (CanL). Twenty-two dogs with CanL confirmed by clinical findings and laboratory tests were included in the study. Dogs were randomized into two groups. A control group (CTR, n = 12) was treated with meglumine antimoniate 50 mg/kg SC q 12 h for 28 days plus allopurinol at 10 mg/kg PO q 12 h for the whole study period (six months). An experimental group was treated with allopurinol and meglumine antimoniate, plus an implant of 4.7 mg deslorelin acetate (DES, n = 10). The animals were observed for three months, during which clinical evaluation, indirect fluorescent antibody test (IFAT) titre and testosterone assay were performed on time at day (D)0, 90 and 180. A significantly lower clinical score was recorded in DES than in CTR (p < 0.01) at D90 and D180 (p < 0.01). After 180 days of treatment (D180), a significant reduction of mean levels of IFAT was observed in the DES group (p = 0.03). A highly significant reduction of testosterone (p = 0.01) was observed in the DES group during the study. No statistical correlation between clinical scores, IFAT titres and testosterone within two groups was observed. Data suggested that the agonist of GnRH may be useful in the treatment of CanL.

Long-term effect of repeated deslorelin acetate treatment in bitches for reproduction control.

Long-acting gonadotropin-releasing hormone (GnRH) analogs, which are approved for male dogs and ferrets, have been used off-label to suppress estrus in bitches predisposed to the side effects of spaying. Health data from the past 12 years were evaluated from bitches without progestogen pretreatment that received deslorelin acetate (DA) to suppress estrus for the first time before the age of 4.5 years. The study population included 32 client-owned bitches repeatedly treated with either 4.7 mg or 9.4 mg DA implants for a period of 5.3 ± 3.4 years (range 0.5-11.3 years). Follow-up information concerning immediate side effects of DA occurring within five months after the first DA treatment (n = 23) as well as long-term side effects of sustained gonadal suppression occurring after five months up to three years (n = 2), three years up to five years (n = 2) or more than five years (n = 8) were assessed through a questionnaire. Treatment was considered successful if no major side effects requiring medical treatment occurred, which applied to 26 out of 32 (81 %) bitches. In the six remaining bitches, the following major side effects led to treatment discontinuation: persistent urinary incontinence (n = 1), reoccurring induced heat (n = 1), uterine disease (n = 3) and/or ovarian tumor (n = 3). The bitches recovered completely after surgical spaying and/or DA implant removal. Minor side effects that did not require therapy or affect animal welfare included body weight changes (n = 18), subtle behavioral changes (n = 13), induced heat (n = 12), coat changes (n = 11), pseudocyesis (n = 6), transient urinary incontinence (n = 4), and/or temporary thickening of the uterine wall with little anechogenic content (n = 2). To examine a possible causal relationship between adverse side effects and DA treatment, further studies should compare the frequency of pathologies between groups of GnRH-treated, intact and spayed bitches of similar breeds and ages. Nevertheless, DA application before the age of 4.5 years may be a means of postponing surgical spaying for several years in breeds at high risk for developing urinary incontinence. Before DA is used in bitches, owners should be fully informed regarding possible side effects.

Determination of Efficacy of Single and Double 4.7 mg Deslorelin Acetate Implant on the Reproductive Activity of Female Pond Sliders (Trachemys scripta).

The use of long-acting gonadotropin-releasing hormone (GnRH) agonists to suppress fertility has been poorly investigated in reptiles, and the few available studies show inconsistent results. The efficacy of single and double intramuscular 4.7 mg deslorelin acetate implants in captive pond sliders (Trachemys scripta) was investigated, with 20 animals divided into three groups: a single-implant group (6 animals), a double-implant group (6 animals), and a control group (no implant). During one reproductive season (March to October), plasmatic concentration of sexual hormones (estradiol, progesterone, and testosterone) and ovarian morphometric activity via computed tomography were monitored about every 30 days. A significative decrease in the number of phase II ovarian follicles was detected in the double-implant group compared with the control group, but no significant difference was noted in the number of phase III and phase IV follicles, egg production, and plasmatic concentration of sexual hormones. Results show that neither a single nor a double deslorelin acetate implant can successfully inhibit reproduction in female pond sliders during the ongoing season, but the lower number of phase II follicles in the double-implant group can possibly be associated with reduced fertility in the following seasons.

Comparison of Clinical Effectiveness of Deslorelin Acetate and Osaterone Acetate in Dogs with Benign Prostatic Hyperplasia.

This article presents the results of a randomized clinical trial, designed to compare the efficacy and therapeutic profiles of YpozaneTM (osaterone acetate-OA) or SuprelorinTM (deslorelin acetate-DA) in male dogs with clinical signs of benign prostate hyperplasia (BPH). Forty-five intact male dogs were used in the study. The Group I (negative control) included 10 healthy dogs, the Group II (positive control) included 10 dogs with confirmed BPH and no treatment, whereas Group III and IV consisted of dogs with BPH and treated either with DA (15 dogs) or OA (10 dogs). The clinical response, testosterone and estradiol levels, hematology, biochemistry, and adverse effects incidence were evaluated. Both OA and DA proved to be effective for BPH treatment in dogs, as they allowed for the clinical remission in all treated dogs. The complete alleviation of BPH symptoms was noticed sooner with the use of OA (in 80% of dogs from day 7) compared to DA (in 40% of dogs within the first 21 days). The recurrence of clinical signs related to BPH was observed from week 24 in dogs treated with OA, whereas no relapse was noticed in dogs treated with DA at the end of the 36 weeks of the observation period. In 5 dogs (33%) treated with DA, a flare-up effect (increase in the clinical signs associated with BPH) was noticed on day 7. Despite individual differences in the clinical action, both medications were effective and safe options for the treatment of symptoms related to BPH in dogs.

Influence of a Sustained Release Deslorelin Acetate Implant on Reproductive Physiology and Associated Traits in Laying Hens.

The aim of this study was to develop an animal model with non-laying hens which would allow for investigation of the relationship between egg production and common diseases in hens. A total of 40 Lohmann Selected Leghorn hens were kept for 20 weeks in a floor housing system in two groups: group "Adult" (21 weeks of age) and group "Juvenile" (14 weeks of age). In each group, 10 hens were administered a 4.7 mg sustained release deslorelin acetate implant subcutaneously; in group "Adult" after, in group "Juvenile" before the onset of lay. In both groups, the remaining hens served as control hens. An examination of each hen was performed weekly, including ultrasonography to check for ovarian follicles, analysis of estradiol-17ß plasma concentration, and assessment of comb size. Digital radiographs of the keel bone were taken in experimental weeks 7 and 15. No follicles were detected on the ovary of treated hens for a certain time period which varied between individuals (between 8 weeks and until the end of the experiment). Estradiol-17ß concentrations were significantly higher in control hens. The comb was significantly smaller in treated hens. A lower prevalence of keel bone damage (group "Adult") and foot pad dermatitis (FPD) (both groups) was found in treated compared to control hens. These results show that a model with laying and non-laying hens can be achieved by administering a deslorelin acetate implant. Furthermore, they indicate a relationship between egg production and keel bone damage as well as FPD.

Induction of ovulation in quarter horse mares through the use of deslorelin acetate and human chorionic gonadotrophin (hCG)

The aim this study was to compare two protocols of induction for ovulation by desloreline acetate and hCG in Quarter Horse mares. The choice of the animals was based on the observations by the estrus, by rectal palpation of the ovaries and by ultrassonography of the follicular dynamics. After estrus detection and follicle control, the measurement of the follicles and the classification of uterus were carried out. The animals that had dominant follicle (diameter more than 35 mm) and swollen uterus were used. In these conditions, the mares received hCG or desloreline acetate. Once ovulation occurred, the artificial insemination was carried. Two groups were performed: G1 (20 animals) received 1.5 mg desloreline acetate and G2 (20 animals) received 1700 IU of hCG. Following 6h intervals, the control follicular was performed by ultrasonography. The follicular average diameter was 42.6 cm for the groups and set up a score of 0 to 3 of uterine edema displayed by the device as well as the time of ovulation. In conclusion, the desloreline acetate showed better performance than hCG, because the ovulation was induced in less time (nine hours than hCG) (p<0.05).The pregnancy rate was 80 and 75 percent, respectively in G1 and G2.