The GnRH antagonist acyline prevented ovulation, but did not affect ovarian follicular development or gestational corpora lutea in the domestic cat.

Two experiments were conducted to investigate the effects of the GnRH antagonist acyline (330 microg/kg, given sc) on ovarian follicular development and ovulation, as well as on pregnancy maintenance in domestic cats. In the first experiment, seven queens in proestrus (total of 24 proestrus periods), were randomly assigned to treatment with either acyline (ACY; n=17) or a placebo (PLC; n=7). All queens were mated with a fertile tomcat. In the ACY and PLC groups, cessation of estrus occurred (mean+/-SEM) 7.0+/-1.3 and 7.0+/-1.7 d after treatment (P>0.1), ovulation occurred in 2 of 17 and all seven estrus periods (P<0.05), and pregnancy rates were 1 of 16 and 7 of 7 (P<0.05), respectively. In the ACY and PLC groups, intervals from treatment to the onset of the ensuing proestrus were 18.4+/-1.7 and 120+/-17.2 d. In the second experiment, 14 pregnant queens were randomly allocated, according to their mating date, to treatment with acyline in early pregnancy (from 20 to 25 d, n=3), mid pregnancy (from 26 to 45 d; n=4), late pregnancy (> 45 d; n=3), or injection of a placebo in early (n=1), mid (n=2), or late pregnancy (n=1). Ultrasonographic assessments of the uterus were done every second day for 2 wk post treatment, and serum progesterone (P(4)) concentrations were determined before treatment, and at 7 and 14 d after treatment. No pregnancies were prematurely terminated and post-treatment P(4) concentrations did not differ among treatment groups (P>0.1). In conclusion, in the domestic cat, GnRH withdrawal by acyline prevented ovulation when given in early follicular phase (proestrus), but did not significantly affect luteal function during pregnancy.

Comparison of two doses of the GnRH antagonist, acyline, for pregnancy termination in bitches.

Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P(4)) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 microg/kg; n = 6) or high (ACY-H; 330 microg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 +/- 1.9 and 6.4 +/- 1.3 days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P(4) serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P(4) diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P(4) reached basal concentrations. In PLACE animals, gestation progressed normally and P(4) did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P(4) serum concentrations.

Interruption of the canine estrous cycle with a low and a high dose of the GnRH antagonist, acyline.

To test the efficacy and clinical safety of a low and high dose of the GnRH antagonist, acyline, on estrous cycle interruption and anovulation in female dogs, 20 proestrous (<3d) bitches were randomly assigned to one of the following pharmacological protocols (given sc): acyline 110 microg/kg (ACY-L; n=6); acyline 330 microg/kg (ACY-H; n=8); or placebo (PLACE, n=6). The animals were monitored (clinical and vaginal cytology examinations) daily for 60d. Blood samples for serum progesterone serum concentrations were collected 14d after treatment to determine if ovulation had occurred. Appearance of side effects and days to the onset of the first spontaneous estrous cycle after treatment were also recorded. In both ACY groups, but not the PLACE group, estrous cycles were interrupted after treatment (P<0.05). The interval from treatment to estrus interruption in ACY-L and ACY-H groups was 3.0+/-0.6 and 3.2+/-0.2d, respectively (LSM+/-SEM; P>0.05). In the PLACE bitches, physical, behavioral and cytological proestrus slowly progressed to estrus and diestrus. Ovulation was absent in all ACY, but not in PLACE bitches (P<0.05). None of the females manifested side effects related to the treatments (P>0.05). Spontaneous return to a normal estrous cycle during the study period occurred in all ACY (ACY-L 19.5+/-2.7d vs ACY-H 24.8+/-2.0d; P>0.05), but in none of the PLACE bitches (P<0.05). In conclusion, acyline efficiently, safely and reversibly interrupted an early phase of the estrous cycle in bitches by preventing ovulation.

Effect of the GnRH antagonist, acyline, on canine testicular characteristics.

The primary objective was to assess the effects and clinical safety of a single high-dose of the third generation GnRH antagonist, acyline, on testicular characteristics in male dogs. Seven dogs were followed up weekly for six, 2-week periods (-2, -1, 1, 2, 3 and 4). At the end of the second period, they were given acyline (330 microg/kg sc). Responses to treatment varied among individual animals. Testicular consistency and scrotal diameter were slightly diminished (P>0.05) in Periods 1, 2, and 3. Libido and erection decreased during Periods 1 and 2 (P<0.05). Second and third fractions of the ejaculate volume, sperm count and motility varied throughout periods (P<0.01); there was a clear impairment of these parameters (< or =0.2 mL, < or =0.6 mL, < or =0.5 million/mL and < or =30%, respectively) around the second week of Period 1, followed by slow improvement (to the end of the study). Semen volumes and motility diminished during Period 1 (P<0.05). Sperm count decreased during Periods 1, 2, and 3, relative to Periods -2 and -1 (22.7+/-11.7, 62.8+/-19.9, and 51.0+/-25.4 versus 235.7+/-63.3 and 315.5+/-27.3, respectively; P<0.05; (L.S.M.+/-S.E.M.). Morphologically abnormal sperm increased during Periods 2 and 3 (up to 64.9+/-2.6%; P<0.05). Throughout the study, no dog had hematological, biochemical, local, or systemic side effects. In conclusion, a single high-dose acyline treatment severely decreased semen quality with no adverse effects.

Decrease of body temperature after aglepristone treatment in bitches.

Body temperature responses and the timing of abortions were evaluated in pregnant bitches with the anti-progestin aglepristone. Fifteen purebred and crossbred, 25-45 days pregnant, were included in this study and seven untreated bitches at the same stage of pregnancy served as controls. Treated bitches were administered two applications of aglepristone (10 mg/kg SC) 24 h apart for pregnancy termination. Pregnancy termination was confirmed by ultrasonographic assessment. Body temperature was rectally measured three times a day for 6 days beginning 24 h before treatment or pregnancy diagnosis in the treated and control bitches, respectively. Additionally, serum progesterone concentrations were assessed at time points during the study in the treated bitches. Pregnancy was terminated in 14 treated bitches in a mean+/-S.E.M. of 4.3+/-0.7 days after treatment. Control bitches remained pregnant. In the treated bitches, but not in the controls, body temperature significantly decreased 24 h after the beginning of the treatments (P < 0.01) and then gradually returned to pre-treatment values. Correlation between the day of mean minimum body temperature and the day of pregnancy termination was low (0.07; > 0.05). Progesterone did not show significant change throughout the study. Body temperature does not seem to be a suitable variable to clinically monitor the aborting effect of aglepristone. Decrease of body temperature after aglepristone treatment could represent further evidence of its hypothalamic effects.