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At least 19 recordsLinked to original sources
PubMed1984

Intravaginal controlled administration of flurogestone acetate I: Development of a stability-indicating liquid chromatographic method and stability kinetics of flurogestone acetate.

Flurogestone acetate is a synthetic progestin useful for estrus synchronization in sheep. The estrus synchronization is achieved by inserting the drug-impregnated vaginal sponge in the sheep for up to 15 d, during which time flurogestone acetate is administered continuously by intravaginal absorption to suppress estrus and ovulation. The sponge is then withdrawn to regain estrus within 2-4 d. A review of the literature suggests that the analytical methods currently available are not specific, sensitive, and rapid enough. A stability-indicating high-performance liquid chromatographic method was developed, which is capable of characterizing the stability kinetics of flurogestone acetate under various environmental conditions and quantifying the release and absorption profiles of the drug from the vaginal sponges.

Animals↗
PubMed1984

Intravaginal controlled administration of flurogestone acetate II: Development of an in vitro system for studying the intravaginal release and permeation of flurogestone acetate.

A relatively simple and easily constructed in vitro system was developed for studying the mechanism of release and intravaginal absorption of flurogestone acetate from vaginal sponges. The stability-indicating high-performance liquid chromatographic method developed earlier was used to provide a rapid, reproducible, and sensitive assay. The in vitro intravaginal release/permeation system developed was capable of determining the rate of flurogestone acetate release from vaginal sponges and, simultaneously, the rate of absorption through the vaginal wall. The design, calibration, and applicability of the system, and the release and absorption profiles of the drug from vaginal sponges in this system are discussed.

Absorption↗
PubMed2005

Development of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of flurogestone acetate in ovine plasma.

Flurogestone (FGA) is a synthetic progesterone, with a progestational action higher than that of progesterone itself. It is intended for vaginal use in large animals to induce oestrus synchronization. A quantitative method for the analysis of flurogestone acetate (FGA) in ovine plasma by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed. After the incorporation of megestrol acetate (MGA) as internal standard (IS) and followed by a liquid-liquid extraction from plasma, FGA and MGA were chromatographed using a reverse-phase HPLC column and detected by tandem mass spectrometry with a TurboIonSpray source. Multiple reaction-monitoring (MRM) mode was used for the quantitative determination of FGA in ovine plasma. The precursor ions [M+H](+) at m/z 407.2 and 385.1 for FGA and MGA, respectively, produced product ions at m/z 267.1/285.1 for FGA and m/z 267.1/224.0 for MGA. The validated concentration range was 0.2-5.0 ng/ml based on 500 microl plasma aliquots. The lower limit of quantitation was 0.2 ng/ml. Fully validated selectivity, accuracy, precision and reproducibility criteria for routine use in pharmacokinetic studies were demonstrated.

Animals↗
PubMed1985

Lifespan of corpora lutea induced in estrous-synchronized cycling and anestrous ewes.

The effect of pretreatment with flurogestone acetate (FA) on the lifespan of corpora lutea induced with pregnant mare serum gonadotropin (PMS) was examined in cycling and anestrous ewes. Cycling ewes received one of three treatments: 750 IU PMS 2 d before expected estrus (P), FA-impregnated vaginal sponges for 16 d (F), and FA sponges for 16 d and 750 IU PMS 2 d before sponge removal (FP). A fourth group served as controls (C). When compared with d 12 means within treatment, plasma progesterone means were lower (P less than .05) on d 16 in control ewes, on d 15 in P and F ewes, and on d 14 in FP ewes. Only 44% of ewes receiving FA treatment alone exhibited estrus (P less than .05) compared with 100% of untreated ewes. The FP treatment increased ovulation rate compared with controls (P less than .01). The decrease in luteal lifespan observed in cycling ewes suggests a possibility of asynchrony between the uterus and embryo, which could result in failure of an embryo to prevent luteal regression, thus resulting in reduced fertility. None of the seasonally anestrous ewes that received PMS alone and only 55% of those treated with FA sponges for 8 d before PMS injection exhibited estrus. Ewes pretreated with FA exhibited higher plasma progesterone concentrations on d 10 through 16 after PMS injection. There were no differences in luteal lifespan as measured by peripheral plasma progesterone patterns. Although FA treatment did not alter luteal lifespan in anestrous ewes, the increased plasma progesterone concentrations observed with FA treatment suggest that progestogen pretreatment may be essential for optimal luteal function.

Anestrus↗
PubMed2000

Embryotoxic effects adjacent and opposite to the early regressing bovine corpus luteum.

Early luteal regression in cattle has an embryotoxic effect that is not overcome by replacement with progesterone, but is prevented by removal of the regressing CL. Two experiments were designed to test the null hypothesis that the luteal component of the embryotoxic effect is delivered by a systemic pathway. Beef heifers and cows (n = 39) received two good quality embryos, one placed into each uterine horn on Day 6 or 7 of the estrous cycle. Treated animals (n = 20) received 15 mg of PGF2alpha three times per day from Day 7 (n = 11; Experiment 1) or 5 (n = 9; Experiment 2) through 8; controls (n = 19) received saline. Progestogen replacement therapy (12 mg flurogestone acetate daily, s.c.) was provided from Day 6 (Experiment 1) or 4 (Experiment 2) until ultrasonographic diagnosis of embryo survival on Day 35 after estrus. The effects of treatment, location of the embryo and location by treatment interaction on embryo survival were tested by Chi square. In Experiment 1, there was no significant difference in embryo survival rate between PGF2alpha-treated and control recipients. In Experiment 2, only 6 of 18 embryos survived to Day 35 when transferred to animals treated with PGF2alpha compared to 12 of 18 in control animals (P< 0.05). The survival of embryos did not differ with location (adjacent or opposite to the regressing CL) or location by treatment interaction. Thus no evidence was obtained to support a local effect of the regressing CL. The embryo mortality associated with luteolytic doses of PGF2alpha in cows receiving replacement therapy with progestogen probably involves compounds that either act systemically or are transported via the uterine lumen to the uterine horn contralateral to the regressing CL.

Animals↗
PubMed1989

Some biological activities of cronolone and medroxyprogesterone acetate in the uterus of the sheep, mouse and rabbit.

Cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) is widely employed to regulate breeding activity in the ewe, but its biological activity in the uterus of this and most other species has not been studied. In this study several in vivo uterus-related activities of cronolone have been examined in the sheep, mouse and rabbit. In some experiments the corresponding activities of medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) were also examined. Cronolone maintained pregnancy in ovariectomized ewes but not in ovariectomized mice and rabbits; it terminated pregnancy in some mice and in all rabbits that were receiving daily progesterone treatment. Cronolone could not sensitize the mouse uterus for the induction of the decidual-cell reaction or block the induction of such sensitivity by progesterone, but did support limited growth of the oil-stimulated horn after sensitization with progesterone. Cronolone induced uteroglobin secretion by rabbit endometrium. It was concluded that, whereas MAP is a potent progestogen in the sheep, mouse and rabbit, cronolone is a progestogen in the sheep and rabbit only. In the mouse and especially the rabbit, cronolone has other, non-progestational activities, which block pregnancy.

Animals↗
PubMed1987

Reproductive performance of female goats given progestagen associated with PMSG and/or HMG in deep anestrus.

During deep anestrus and after a 21-day fluorogestone acetate (FGA) treatment, 200 pluriparous lactating Alpine goats were given randomly one of four treatments: (A) 500 IU of pregnant mare serum gonadotropin (PMSG) 48 h before sponge removal; (B) 500 IU of PMSG 48 h before sponge removal and an ampoule of human menopausal gonadotropin (HMG) at sponge removal; (C) two ampoules of HMG at sponge removal; (D) four ampoules of HMG at sponge removal. All the goats were mated naturally during estrus. The percentage of goats kidding (fertility rate) was 6, 34, 40 and 36% for groups A, B, C, and D, respectively; the number of kids/pregnant female (prolificacy) averaged between 1.33 and 1.72. The accuracy of pregnancy diagnosis on the basis of plasma progesterone concentration 20 to 22 days after mating was not particularly satisfactory, mainly because many pregnant goats, and especially group A goats, showed abnormally prolonged luteal activity. The determination of total estrone 60 days after mating gave almost 100% overall accuracy.

Anestrus↗
PubMed1991

Use of Chronogest implants and Folltropin for estrus synchronization and superovulation in goats.

Six Barbari goats each were assigned randomly to treatments 1,2 or 3, comprising im injections of FSH (folltropin) at 12, 14 or 16 mg dose level respectively. Estrus was synchronized with intravaginal sponge impregnated with flugestone acetate (30 mg; chronogest) inserted for 12 days and cloprostenol (125 micrograms) im at the insertion as well as at removal of sponge. FSH treatment started 48 hr before the sponge removal as 4-day declining dose scheme. Estrus could be effectively synchronized in all goats under the study, with significant difference (P less than 0.05) in the onset of estrus between the treatment groups. All goats were administered with 750 IU hCG i.v. at estrus. Recording of ovarian response and embryo recovery was done 45 hr after the onset of estrus. The prime aim of superovulation was effectively achieved in Barbari goats with the use of chronogest implants and folltropin. There was no difference (P greater than 0.05) between the treatment groups in recovery of transferable embryos, however, 14 mg folltropin appeared to be near optimal dose. There was no adverse effect on the quality of recovered embryos with high doses of folltropin.

Animals↗
PubMed1996

Characteristics of the plasma melatonin rhythm are not modified by steroids during the estrous cycle in IIe-de-France ewes.

Two experiments were designed to determine whether gonadal steroids during the estrous cycle may modify the characteristics of the plasma melatonin rhythm. In the first experiment, 12 ovariectomized estradiol-treated ewes were used and exposed to constant short days. The experimental design was a latin square to distinguish between steroid treatments and individual effects on melatonin secretion. Twenty four hours before the bleeding period (hourly during 20 hr) and with a 1 week interval, animals were treated with a) additional subcutaneous estradiol implants, b) progesterone devices, or c) control. In the second experiment, nine ewes received a treatment combining fluorogestone acetate devices and pregnant mare serum gonadotrophin to induce synchronous ovulations. Samples for melatonin determination were obtained hourly for 13 hr at three stages of estrous cycle: follicular phase, early luteal phase, and late luteal phase. Ovarian activity was monitored by taking daily samples for progesterone analysis and ovulation rate was determined by laparoscopy. Duration and mean melatonin plasma concentrations of the elevation were calculated for each ewe and each night and analysed by latin square test (experiment 1) or ANOVA (experiment 2). Melatonin concentrations of elevation and duration of elevation were not significantly affected by hormonal treatments or by phase of estrous cycle. A strong individual effect was detected (P < 0.01) for both parameters in both experiments. It was concluded that melatonin secretion is unaffected by steroid administration or by phase of estrous cycle. The existence of very high inter-individual variation suggest that both parameters are individual characteristics of each animal which may have a strong genetic basis.

Animals↗
PubMed1982

Synchronization of estrus and reproductive performance of ewes treated with synthetic progestogens administered by subcutaneous ear implant or by intravaginal sponge pessary.

Experiments were conducted to compare the efficacy of synthetic progestogens administered by subcutaneous ear implant or intravaginal sponge to induce a synchronized estrus in adult ewes and ewe lambs and to evaluate reproductive performance (fertility and litter size) to breeding at the synchronized estrus. Experimental animals were representative of three strains maintained in total confinement and exposed to a synthetic light regimen which alternated at intervals of 4 mo from 18 h day length to 10 h day length/24 h. Treatments were applied at different times of the year at the end of a low light cycle. Implants contained Norgestomet (3 mg) impregnated in a polymethacrylate polymer (Implant H) or impregnated in a silastic polymer containing 1.05 (Implant S1), 1.78 (Implant S2) or 2.60 mg (Implant S3) Norgestomet, respectively. Intravaginal sponges contained 40 mg Fluorogestone Acetate. Implants or sponges were left in situ for 12 d and 500 IU pregnant mares' serum gonadotropin was injected im at the time of removal. Following treatment with Implant H, 96% of ewes were judged to be in estrus at 48 h after implant removal. Fertility of adult ewes and ewe lambs (6 to 7 mo of age at time of breeding) at the synchronized estrus were similar after implant H or sponge treatment, but litter size was higher (P less than .05) for adult ewes treated with sponges. The percentages of adult ewes marked by rams within 60 h after removal of silastic implants or intravaginal sponges were similar. There was a tendency for ewe lambs to be marked later than adult ewes and for adult ewes treated with Implant S1 and Implant S2 to be marked earlier than ewes treated with Implant S3 or sponges. Higher percentages (P less than .05) of adult ewes and ewe lambs lambed to breeding at the synchronized estrus after treatment with Implant S2 or Implant S3, respectively, than after treatment with Implants S2 or sponges.

Animals↗
PubMed2001

The repeatability of superovulatory response and embryo recovery in sheep.

Over an 8-year period, a total of 328 Scottish Blackface donor ewes were involved in a MOET program. They were synchronized with fluorogestone acetate sponges and superovulated with ovine FSH. After the onset of estrus, ewes were hand-mated and laparoscopic artificial insemination was performed with fresh semen 44-46 h after sponge removal. Embryos were recovered semi-laparoscopically on either Day 5 or Day 6 after insemination. Of the 328 donor ewes used, 222 ewes were supervoulated only once, while the remaining ewes were superovulated either twice (73 ewes), 3 times (26 ewes) or 4 times (7 ewes) at yearly intervals to generate a maximum of 474 records for subsequent analysis. There was no significant change in either mean ovulation rate or the mean number of embryos recovered per donor ewe at successive treatments. However, significant (P < 0.05 at least) effects of both year and donor ewe age existed for superovulatory response and number of embryos recovered, though only the effect of year was significant (P < 0.001) for percentage embryo recovery. Repeatability was significant (P < 0.05 at least) for both superovulatory response (r = 0.55, s.e. 0.055) and number of embryos recovered (r = 0.38, SE 0.074), but not for percentage embryo recovery (r = 0.04, SE 0.102).

Age Factors↗
PubMed1997

Effect of service on duration of oestrus and ovulation in dairy goats.

In the autumn, Nubian goats (n = 24) were randomly divided into two equal groups after oestrus had been synchronized using fluorogestone acetate intravaginal pessaries (FGA, 30 mg) over a 20 day period. The onset of oestrus was detected at 8 h intervals using either of two vasectomized bucks fitted with an apron during the 5 days following pessary removal. A buck was permitted to mount and serve each doe only twice in 30 min within the first 8 h of oestrus initiation in the SER group. In the CON group, a buck was only permitted to mount. Ovulation was determined by laparoscopy at 8 h intervals starting 24 h after onset of oestrus. Duration of oestrus for SER and CON groups was (mean +/- SD) 26.7 +/- 7.1 and 36.0 +/- 8.0 h, respectively (P < 0.01). The first and last ovulations for SER and CON groups were 34.7 +/- 3.9 and 37.3 +/- 6.2 h, and 35.3 +/- 5.4 and 38.0 +/- 6.0 h from oestrus initiation, respectively (P > 0.05). No differences were found between right and left ovarian activity (P > 0.05). Ovulation rates did not differ (2.17 +/- 0.58 and 2.17 +/- 0.94). Ovulations occurred principally towards the end of oestrus in the CON group and after oestrus had ended in the SER group. Service reduced the duration of oestrus without affecting ovulation times or ovulation rates in Nubian dairy goats.

Animals↗
PubMed1981

Effects of prostaglandin F2 alpha and pregnant mares' serum gonadotropin (PMSG) on the reproductive performance of fluorogestone acetate PMSG-treated ewes.

Two experiments were conducted to examine the effect of prostaglandin F2 alpha (PGF2 alpha) and pregnant mares' serum gonadotropin (PMSG) on the reproductive performance (fertility, prolificacy and fecundity) of ewes previously treated with fluorogestone acetate (FGA) and PMSG. In the first experiment, 29 ewes were synchronized for estrus with FGA and PMSG but not bred at the postsynchronization estrus. On day 10 of the first post-synchronization estrous cycle, they were injected IM with 15 mg PGF2 alpha and 500 IU PMSG and exposed to experienced, fertile, raddled rams. Twenty-four of the 29 ewes (83%) had viable fetuses 9 weeks after the PGF2 alpha-PMSG treatment. In the second experiment, 64 ewes were treated with FGA-PMSG, and 33 were exposed to fertile, raddled rams at the synchronized estrus. A second group of 31 ewes was not bred at the synchronized estrus, but on day 12 of the postsynchronized estrous cycle, they were injected IM with 15 mg PGF2 alpha and 500 IU PMSG and exposed to fertile, raddled rams. Sixty-six percent of the 33 ewes lambed in the FGA-PMSG-treated group and 60% of the 31 ewes lambed in the PGF2 alpha-PMSG-treated group. Differences in reproductive performance between these two treatment groups were not statistically significant. The results suggest that the PGF2 alpha-PMSG treatment combination does not adversely affect reproductive performance of ewes.

Animals↗
PubMed1999

Response of Corriedale ewes to the "ram effect" after priming with medroxyprogesterone, fluorogestone, or progesterone in the non-breeding season.

One hundred eighty-nine Corriedale ewes were used during the non-breeding season to study the "ram effect" stimulus after priming with progestogens. Intravaginal sponges containing either medroxyprogesterone acetate (MAP group, n = 49), fluorogestone acetate (FGA group, n = 49), or progesterone devices (CIDR group, n = 46) were inserted on Day-6 (Day 0 = introduction of the rams). Forty-five ewes were untreated and kept as a control group. On Day 0 the sponges were removed and rams provided with marking harnesses for oestrous detection were placed with the ewes. Onset of estrus was monitored until Day 25, and conception was determined by transrectal ultrasonography. Ewes came into heat during 4 periods: Days 0-3, 5-7, 17-20, and 21-23. The overall number of oestrus ewes were 29%, 53%, 35%, and 50% for the control, MAP, FGA, and CIDR groups, respectively (MAP and CIDR > control, p < 0.05). Control ewes presented oestrus only on Days 17-20 and 21-23. Oestrus in the progestogen-primed ewes was concentrated during Days 0-3 and 17-20, and some ewes came into oestrus on Days 5-7. There were no differences between different primings neither in oestrous response nor in conception rate. The conception rate from matings occurring on Days 0-3 was higher than on those occurring on Days 17-20. We conclude that MAP, FGA, and CIDR is equally effective in improving the response to the ram effect, and the pattern of oestrus in primed ewes was different than previously reported.

Administration, Intravaginal↗
PubMed1989

In vitro binding of progesterone, cronolone and medroxyprogesterone acetate to uterine progesterone receptors of sheep, rabbit and mouse.

Various aspects of the binding of the synthetic progesteongens, cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) and medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) to uterine cytosol progesterone receptors of the sheep, rabbit and mouse were studied, in an attempt to explain interesting species differences in the biological activity of these steroids. For the sheep, data for binding-site concentration, relative binding affinity (RBA), dissociation constant (Kd) and rates of association and dissociation indicate specific binding of cronolone to the progesterone receptor and these would seem to explain in part the high progestational activity of cronolone in this species. By contrast, with the mouse, there was only a low level of specific binding of cronolone and this appears to explain its inability to maintain pregnancy in this species. Results for the binding activity of cronolone in rabbit uterus were similar to those for the sheep and thus inability of cronolone to maintain pregnancy in the rabbit is not explained by a failure to bind the progesterone receptor. Species differences in binding to the progesterone receptor were also seen with MAP where the RBA, with respect to progesterone, was high in the sheep and rabbit and lower in the mouse. The results, however, do not relate directly to the progestational activity of MAP in these species. Overall, the data indicate that species differences in the binding activity of steroid receptors constitute one factor that causes species-dependent variation in biological responses to progestogens.

Animals↗