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PubMed1999

Estrus synchronization and artificial insemination of hair sheep ewes in the tropics.

Hair sheep ewes (St. Croix White and Barbados Blackbelly) were used to evaluate 3 methods of estrus synchronization for use with transcervical artificial insemination (TAI). To synchronize estrus, ewes (n = 18) were treated with PGF2alpha (15 mg, im) 10 d apart, with controlled internal drug release (CIDR) devices containing 300 mg progesterone for 12 d (n = 18), or with intravaginal sponges containing 500 mg progesterone for 12 d (n = 18). On the day of the second PGF2alpha injection or at CIDR or sponge removal, sterile rams were placed with the ewes. Jugular blood samples were collected from the ewes at 6-h intervals until the time of ovulation, and daily for 16 d after estrus (Day 0). Plasma was harvested and stored at -20 degrees C until LH, and progesterone concentrations were determined by RIA. There was no difference (P>0.10) in time to estrus among the CIDR-, PGF2alpha- or sponge-treated ewes. All of the ewes in the CIDR group and 94.4% of the sponge treated ewes exhibited estrus by 36 h after ram introduction, while only 72.2% of PGF2alpha-treated ewes showed signs of estrus by this time (P<0.06). The time from ram introduction to ovulation was not different (P>0.10) among the CIDR-, PGF2alpha- or sponge-treated ewes. The time to the preovulatory LH surge was similar (P>0.10) among CIDR, PGF2alpha and sponge treated ewes. Progesterone levels through Day 16 after the synchronized estrus were not different (P>0.10) among treatment groups. Hair sheep ewes (n = 23) were synchronized using PGF2alpha and bred by TAI using frozen-thawed semen 48 h after the second injection. The conception rate to TAI was 2/23 (8.7%) and produced 3 ram lambs. In a subsequent trial, 17 ewes were synchronized with CIDR devices and bred by TAI using frozen-thawed semen 48 h after CIDR removal, resulting in a conception rate of 52.9% (9/17). It is possible to synchronize estrus in hair sheep using either CIDRs, sponges or PGF2alpha. Even though there were no significant differences in the timing of ovulation or the LH surge among the treatment groups, a higher conception rate was achieved in ewes synchronized with CIDR devices during the second trial. This may reflect an increase in the skill level of the TAI technician.

Administration, Intravaginal↗

PubMedDate not supplied

The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha-treated anestrous goats.

The objective of this experiment was to determine the effect of a 5-day progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive performance of anestrous goats. Thirty-six Mountain Black goats were randomly assigned in a 2 x 2 factorial arrangement and were administered intravaginally on day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100 microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which the goats in the CGPE and GPE groups were administered 300 IU eCG injections and those in CGP and GP groups were administered the control solution. The goats were exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h intervals for 72 h. Blood samples were collected from all goats for progesterone analysis. Progesterone concentrations increased only in CGPE and CGP during the period of device insertion but remained low in GPE and GP groups (P < 0.001). Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/- 0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0 progesterone concentrations differed (P < 0.05) among groups and were significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE or between CGP and GP groups. The number of goats ovulating based upon elevated progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9) and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration on day 0 and none of the goats with basal progesterone levels became pregnant. Pregnancy and kidding rates, twinning percentage and the number of kids born per goat exposed were greater (P < 0.05) among goats treated with progesterone and eCG. In conclusion, progesterone priming and eCG are essential for producing higher rates of pregnancy and kidding in GnRH-PGF2alpha-treated anestrous goats.

Administration, Intravaginal↗

PubMed1999

Two dosing regimens for preinduction cervical priming with intravaginal dinoprostone pessary: a randomised clinical trial.

OBJECTIVE: To compare the efficacy within 24 hours of a three-times-a-day intensive dosing regimen with a standard once daily dosing regimen using dinoprostone vaginal pessary in preinduction cervical priming. DESIGN: Randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Singapore General Hospital. PARTICIPANTS: One hundred singleton term primigravidae with cephalic presentation with unfavourable cervical scores (Bishop score < or = 5) requiring induction of labour. METHODS: Eligible women were randomly assigned the standard regimen (3000 microg dinoprostone [Prostin, Upjohn, Crawley, UK] once daily) or an intensive regimen (3000 microg dinoprostone given sequentially three times daily four hours apart) for cervical priming until successful priming (Bishop score of > or = 6) or the onset of active labour occurred. MAIN OUTCOME MEASURES: Number of women whose cervices were ripened successfully or who entered active labour within 24 hours of starting cervical priming, priming to induction interval, and priming to delivery interval. RESULTS: Forty-nine women were assigned to the standard regimen and 51 to the intensive regimen. The median number (range) of dinoprostone pessaries used was two (one to seven) in the standard regimen and three (one to nine) in the intensive regimen. Forty-two women (82.4%) who underwent the intensive regimen achieved successful cervical ripening or active labour within 24 hours, compared with 21 assigned to standard regimen (OR 6.2, 95% CI 2.3-17.4). This difference was statistically significant. The median intervals from priming to induction, and from priming to delivery, were also statistically significantly shorter in women treated with the intensive regimen. Thirty-five women (68.63%) assigned the intensive regimen experienced pain, compared with 21 (42.86%) in the standard regimen (OR 2.92, 95% CI 1.19-7.21), with two and one women in the respective regimens requiring opiate analgesics. Five women with oligohydramnios had transient cardiotocographic abnormalities during priming with the intensive regimen, none of which required immediate intervention, and the babies were born in good condition. There were no cases of uterine hypertonus and the outcomes of labour were similar for women from both regimens. CONCLUSIONS: Preinduction cervical priming with the intensive dosing regimen improves the chances of successful ripening within 24 hours for primigravidae with unfavourable cervical scores at full term singleton pregnancies, and shortens the interval from priming to induction, and priming to delivery. This regimen may be more cost effective by shortening the period of hospital stay. The overall incidence of adverse reactions to the mother and fetus during priming was low. However, close fetal surveillance must be maintained, particularly in pregnancies complicated with oligohydramnios.

Administration, Intravaginal↗

PubMed2004

Ovarian follicular dynamics and hormonal profiles in heifer and mixed-parity Mediterranean Italian buffaloes (Bubalus bubalis) following an estrus synchronization protocol.

The primary objective was to elucidate ovarian follicular dynamics and hormonal profiles in nulliparous heifer (HE; n = 11 ) and mixed-parity (MP; n=10 ) Mediterranean Italian water buffaloes (Bubalus bubalis) following an estrus synchronization protocol. Both groups received a progesterone releasing intravaginal device (PRID) implant for 10 days; a luteolytic dose of synthetic prostaglandin was given 7 days after PRID insertion. Daily ultrasound monitoring and collection of blood to determine plasma concentrations estradiol and progesterone started 1 day after PRID removal and lasted for 55 and 65 days in HE and MP buffaloes, respectively. Data analysis was restricted to the first 5 days after PRID removal and to one estrus cycle following induced ovulation. The HE buffaloes were not inseminated and only one ovulated within 5 days after PRID removal; the remainder ovulated between 8 and 48 days after PRID removal (except one in which ovulation was never detected). All HP buffaloes were inseminated 72, 96 and 120 h after PRID removal; seven buffaloes ovulated within 5 days after PRID removal and two were pregnant. Mean diameter of the largest follicle was significantly smaller in HE than MP buffaloes the first 4 days after PRID removal. There was a parity by time interaction ( P=0.0047 ) for plasma progesterone concentrations; progesterone was higher in HE than MP buffaloes 1 day after PRID removal, but the converse was true 2 days after PRID removal. After induced ovulation, HE buffaloes exhibited a one-wave ( n=5; length of cycle, 8-12 days), two-wave ( n=4; range: 20-26 days) or three-wave cycle ( n=1; 25 days). In contrast, all non-pregnant MP buffaloes ( n=8 ) had a two-wave cycle (range: 19-25 days). For buffaloes with two-wave cycles, the growth rate and diameter of the largest follicle was significantly smaller in HE than MP buffaloes for both the first follicular wave (1.3mm versus 1.7 mm per day and 10.5 mm versus 13.3 mm, respectively) and the second follicular wave (1.0 mm versus 1.3 mm per day and 11.0 mm versus 13.8 mm). In conclusion, there were many significant morphological and endocrine differences between HE and MP buffaloes.

Administration, Intravaginal↗

PubMed1999

Comparison of oestrous synchronization regimens for lactating dairy cows.

The objective of this experiment was to evaluate various programmes for synchronization of oestrus. The focus of the study was to evaluate rates of detection of oestrus, synchrony of oestrus, pregnancy rate, and effect of ovarian status at initiation of the programmes on rates of detection of oestrus and pregnancy rate. Spring-calving, lactating dairy cows (n = 2009) were allocated at random to one of six treatments: (1) A (n = 335), progestogen (controlled intravaginal drug release; CIDR) inserted per vaginum 10 d before breeding season for 8 d, 10 microg of buserelin at CIDR insertion, PGF2alpha treatment on the day prior to CIDR removal, and AI of cows detected in oestrus within 6 d after CIDR withdrawal; (2) B (n = 330), as in A, plus 1 mg of oestradiol benzoate i.m. 10 h post CIDR withdrawal; (3) C (n = 347), as in A, except buserelin was replaced by 10 mg of oestradiol benzoate; (4) D (n = 335), as in A, plus PGF2alpha and oestradiol benzoate at CIDR insertion; (5) E (n = 332), CIDR containing a 10 mg oestradiol benzoate capsule inserted per vaginum for 12 d; or (6) F (n = 330), as in E, plus PGF2alpha on the day prior to CIDR withdrawal. The oestrous detection rate (number of cows detected in oestrus within 6 days of CIDR withdrawal as a proportion of the number of cows submitted for synchronization of oestrus) and oestrous synchrony (oestrous detection rate within 2 d of CIDR withdrawal), respectively, were greater (P<0.05) following B (95.7% of 330, 98.7% of 316) compared with any of the other programmes for synchronization of oestrus (A: 87.5 of 335, 79.4% of 293; C: 86.7% of 347, 80.0% of 301; D: 90.1% of 335, 89.8% of 302; E: 74.4% of 332, 70.4% of 247; F: 76.4% of 330, 78.5% of 252). The oestrous detection rate was reduced (P<0.05) among cows in metoestrus administered E (64.0% of 50) relative to similar cows administered F (82.8% of 64). Pregnancy rate was greater (P<0.05) following B (57.9% of 330) than A (48.9% of 335, P = 0.06), C (43.2% of 347), E (40.0% of 332), and F (35.1% of 330) but not D (59.3% of 302), when based on those cows presented for oestrous synchronization programmes. In conclusion, 1 mg of oestradiol benzoate administered 10 h post CIDR withdrawal (B) resulted in the best overall oestrous detection, oestrous synchrony, and pregnancy rates, which would be beneficial to a fixed-time AI program.

Administration, Intravaginal↗

PubMed1997

Delayed effect of progesterone on endometrial morphology in dairy cows.

Two experiments were conducted to investigate the effect of vaginal progesterone (P4) administered during the luteal phase, on endometrial morphology during the subsequent oestrous cycle. In experiment 1, lactating Holstein cows were allotted to three groups: (1) Control group in which cows remained untreated; (2) The CIDR group in which cows were treated with two P4-containing controlled intravaginal-drug releasing devices (CIDR) during days (d) 6-12 of the cycle; and (3) The PG + CIDR group of cows that received two prostaglandin F2 alpha (PGF2 alpha) injections on d 6 and 7 of the oestrous cycle, to regress the corpus luteum (CL), and were treated with CIDRs on d 6-12, like the CIDR group. All cows were slaughtered on d 3 of the subsequent oestrous cycle. In experiment 2, cows were allotted to three groups: (1) Control cows that remained untreated; (2) CIDR cows that were treated with two CIDRs from d 6 to 15; and (3) Early PG cows that received three i.m. injections of PGF2 alpha on d 3 and 4 of the oestrous cycle to reduce plasma P4. All cows were slaughtered on d 15 of the subsequent cycle. In both experiments, blood was collected during the treated and subsequent cycles to determine P4 and oestradiol (E2) concentrations, and tissue samples from the uterine horn ipsilateral to the CL were collected on the day of slaughter to evaluate endometrial morphology. In both experiments, plasma P4 differed between treatments during the treated cycle but no differences in P4 and E2 concentrations were recorded during the subsequent cycle. In experiment 1, the endometrial morphology of the cows from CIDR and PG + CIDR groups differed from that found in the control group: The surface epithelium was medium to high and the glands were round and tortuous, as compared with low epithelium and oblong glands in the control. In addition, the density of blood vessels and the level of edema was higher in the CIDR-treated cows than in the control cows. In experiment 2, the endometrial morphology of the CIDR-treated group differed from that of the control and early PG groups: Low surface epithelium and oblong glands in the former compared with high epithelium and tortuous glands in the latter. In summary, P4 supplementation during the luteal phase had delayed effect on endometrial morphology at different stages of the subsequent oestrous cycle.

Administration, Intravaginal↗

PubMed2001

Inclusion of an intravaginal progesterone insert plus GnRH and prostaglandin F2alpha for ovulation control in postpartum suckled beef cows.

Four experiment stations (IL, KS, MN, and MO) conducted experiments to determine effects of introducing a CIDR (controlled internal device release) into an ovulation control program for postpartum suckled beef cows. Five hundred sixty cows were assigned randomly to two treatments: 1) 100 microg of GnRH (i.m.) followed in 7 d with 25 mg of PGF2alpha, followed in 48 h by a second injection of GnRH and one fixed-time insemination (Cosynch; n = 287) or 2) Cosynch plus one CIDR during the 7 d between the first injection of GnRH and PGF2alpha (Cosynch+P; n = 273). Cows at three stations were inseminated at the time of the second GnRH injection (n = 462), whereas 98 cows at the fourth station were inseminated 16 to 18 h after that injection. Blood samples were collected at d -17, -7, 0, and 2 relative to PGF2alpha to determine concentrations of progesterone. Ultrasonography was used to monitor follicle diameter on d 2 and to determine the presence of an embryo at 30 to 35 d after insemination. Pregnancy rates were greater (P < 0.05) for Cosynch+P- (58%) than for Cosynch-treated (48%) cows. No station x treatment interaction occurred; however, cows at MO (62%) and KS (60%) had greater (P < 0.05) pregnancy rates than those at IL (47%) and MN (44%). Cows that had follicles > 12 mm on d 2 had greater (P < 0.01) pregnancy rates than those with follicles < or = 12 mm regardless of treatment. Pregnancy rates were similar between Cosynch and Cosynch+P treatments when cycling cows had elevated concentrations of progesterone at d 0, but pregnancy rates were greater (P < 0.05) in the Cosynch+P (79%) than in the Cosynch (43%) treatment when cycling cows had low concentrations of progesterone on d 0 (at PGF2alpha injection). Similarly, among noncycling cows, pregnancy rates were greater (P < 0.05) in the Cosynch+P (59%) treatment than in the Cosynch (39%) treatment. Cows in greater body condition at the onset of the breeding season experienced improved (P < 0.001) overall pregnancy rates. Pregnancy rates for cows that calved > 50 d before the onset of the breeding season were greater (P < 0.01) than those for cows that calved < or = 50 d. Thus, treatment of suckled cows with Cosynch yielded acceptable pregnancy rates, but addition of a CIDR improved pregnancy rates in noncycling cows. Body condition and days postpartum at initiation of the breeding season affected overall efficacy of the Cosynch and Cosynch+P protocols.

Administration, Intravaginal↗

PubMed2000

Comparison of different methods of diagnosis of cystic ovarian disease in cattle and an assessment of its treatment with a progesterone-releasing intravaginal device.

The aims of this study were to assess the accuracy of different common methods of differentiating between follicular and luteal ovarian cysts, and to monitor the response of the cysts to 12 days treatment with a progesterone-releasing intravaginal device (PRID). On the basis of agreement between the different methods, 25 of the 46 cases examined were diagnosed as follicular and 14 as luteal cysts; for the other seven cases the methods disagreed. The use of ultrasound was more accurate in diagnosing follicular cysts than luteal cysts, and combined with plasma progesterone concentrations gave the most accurate assessment of cyst type (92 per cent for follicular cysts and 82 per cent for luteal cysts). The mean (se) plasma progesterone concentration was lower in the cows with follicular cysts than in those with luteal cysts (0.29 [0.05] v 3.90 [0.63] ng/ml; P<0.05). Luteal cysts had thicker walls (5.3 [0.04] v 2.5 [0.2] mm; P<0.0001), and the wall thickness of all the cysts was positively correlated with plasma progesterone concentration (r=0.52, P<0.0004). Cows with luteal cysts had more additional follicles greater than 5 mm in diameter (P<0.01). In cows with follicular cysts and other follicles greater than 5 mm in diameter, the mean oestradiol concentration was 7.9 (1.8) pg/ml compared with 24.2 (3.1) pg/ml (P=0.002) in cows without other follicles greater than 5 mm in diameter on either ovary. At the time of PRID removal, plasma progesterone concentration had increased in the cows with follicular cysts to 1.59 (0.06) ng/ml (P<0.05) and decreased in the cows with luteal cysts to 0.87 (0.01) ng/ml (P<0.05), although there was no change in original cyst structure in 45 per cent of the cases. However, new ovarian structures were frequently observed during the treatment. The overall pregnancy rate for cows with both types of cyst after treatment was 50 per cent after three inseminations, but the first service pregnancy rate was only 18 per cent for cows with follicular cysts and 28 per cent for cows with luteal cysts. After treatment, the fertility of cows with follicular cysts was similar to that of paired herdmates, whereas cows with luteal cysts took 40 days longer to calve again than healthy herdmates. However, the culling rate was higher for cows with follicular cysts (41 v 11 per cent).

Administration, Intravaginal↗

PubMed2000

The strategic use of estradiol to enhance fertility and submission rates of progestin-based estrus synchronization programs in dairy herds.

Two experiments were performed to evaluate the efficacy of a progestin-based estrus synchronization program that incorporated the use of estradiol at the initiation of progestin treatment and at 48 h after progestin withdrawal (Exp. 2). In Exp. 1, cyclic, lactating dairy cows (n = 112) were assigned to receive either 1 (1mg) or 2 (2mg) mg of estradiol benzoate via an i.m. injection on d -9 (d 0 = initiation of the breeding season). All cows received an intravaginal progesterone-releasing insert (IPI; CIDR-B) on d -9. On d -2, the IPI was withdrawn and all cows were administered 500 microg of cloprostenol sodium. Beginning on d 0, cows were bred by AI upon detection of estrus. Estrus was observed in similar proportions of cows in each treatment during the first 6 d of AI (90% across treatments), but the interval to estrus was shorter (P < .05) in 1mg (1.26 +/- .18 d) than in 2mg (1.77 +/- .18 d). Conception and pregnancy rates did not vary among treatments; however, cows in estrus on d 0 tended to be less fertile (P = .11) than those in estrus on d 1. In Exp. 2, 408 cyclic cows from three herds were assigned to receive either no synchrony treatment (Control, n = 214) or the treatments described in Exp. 1 (1mg, n = 100; 2mg, n = 94). Anestrous cows from all herds received an IPI from d -9 to -2 (n = 143; Anestrus). All cows in the 1mg, 2mg, and Anestrus groups, with the exception of those detected in estrus between d -1 and 0, also received 1 mg of estradiol benzoate on d 0. Greater than 90% of cows that received an IPI were in estrus between d -1 and 3, and 92.1% of cows in the Control group were in estrus by d 21. Conception rate to first service in 2mg (61.7%) was similar to Control (57.0%), tended to be higher (P = .06) than 1mg (49.0%), and was greater (P < .05) than Anestrus (39.9%). The mean day of conception was earlier (P < .05) in the 2mg (d 13.1 +/- 2.0) than the Control (d 23.2 +/- 1.6) and Anestrus (d 22.4 +/- 1.9) groups. Conception occurred earlier in 1mg (d 17.4 +/- 2.1) than in Control. The proportion of cows that were pregnant at the end of the breeding season tended (P = .09) to be greater in the 2mg and Anestrus groups. This regimen of estrus synchronization improved reproductive competence in cyclic cows and resulted in similar reproductive performance in anestrous cows and untreated cyclic cows inseminated at a spontaneous estrus.

Administration, Intravaginal↗

PubMed2007

Ovarian, hormonal, and reproductive events associated with synchronization of ovulation and timed appointment breeding of Bos indicus-influenced cattle using intravaginal progesterone, gonadotropin-releasing hormone, and prostaglandin F2alpha.

The objectives of this study were to 1) compare cumulative pregnancy rates in a traditional management (TM) scheme with those using a synchronization of ovulation protocol (CO-Synch + CIDR) for timed AI (TAI) in Bos indicus-influenced cattle; 2) evaluate ovarian and hormonal events associated with CO-Synch + CIDR and CO-Synch without CIDR; and 3) determine estrual and ovulatory distributions in cattle synchronized with Select-Synch + CIDR. The CO-Synch + CIDR regimen included insertion of a controlled internal drug-releasing device (CIDR) and an injection of GnRH (GnRH-1) on d 0, removal of the CIDR and injection of PGF2alpha (PGF) on d 7, and injection of GnRH (GnRH-2) and TAI 48 h later. For Exp. 1, predominantly Brahman x Hereford (F1) and Brangus females (n = 335) were stratified by BCS, parity, and day postpartum (parous females) before random assignment to CO-Synch + CIDR or TM. To maximize the number of observations related to TAI conception rate (n = 266), an additional 96 females in which TM controls were not available for comparison also received CO-Synch + CIDR. Conception rates to TAI averaged 39 +/- 3% and were not affected by location, year, parity, AI sire, or AI technician. Cumulative pregnancy rates were greater (P < 0.05) at 30 and 60 d of the breeding season in CO-Synch + CIDR (74.1 and 95.9%) compared with TM (61.8 and 89.7%). In Exp. 2, postpartum Brahman x Hereford (F1) cows (n = 100) were stratified as in Exp. 1 and divided into 4 replicates of 25. Within each replicate, approximately one-half (12 to 13) received CO-Synch + CIDR, and the other half received CO-Synch only (no CIDR). No differences were observed between treatments, and the data were pooled. Percentages of cows ovulating to GnRH-1, developing a synchronized follicular wave, exhibiting luteal regression to PGF, and ovulating to GnRH-2 were 40 +/- 5, 60 +/- 5, 93 +/- 2, and 72 +/- 4%, respectively. In Exp. 3, primiparous Brahman x Hereford, (F1) heifers (n = 32) and pluriparous cows (n = 18) received the Select Synch + CIDR synchronization regimen (no GnRH-2 or TAI). Mean intervals from CIDR removal to estrus and ovulation, and from estrus to ovulation were 70 +/- 2.9, 99 +/- 2.8, and 29 +/- 2.2 h, respectively. These results indicate that the relatively low TAI conception rate observed with CO-Synch + CIDR in these studies was attributable primarily to failure of 40% of the cattle to develop a synchronized follicular wave after GnRH-1 and also to inappropriate timing of TAI/GnRH-2.

Administration, Intravaginal↗

PubMed2003

Resynchronization of estrus in cattle of unknown pregnancy status using estrogen, progesterone, or both.

Our objective was to develop treatments applied to cattle of unknown pregnancy status that would resynchronize the repeat estrus of nonpregnant females. In Exp. 1, previously inseminated dairy and beef heifers were assigned randomly to each of three treatments 13 d after AI: 1) no treatment (controls; n = 44); 2) 0.5 mg of estradiol cypionate (ECP) i.m. on d 13 and 20 at the time of insertion and removal of a used intravaginal progesterone (P4)-releasing insert (CIDR; P4 + ECP; n = 44); and 3) same as P4 + ECP without injections of ECP (P4; n = 42). The P4 + ECP (>90%) and P4 (>75%) protocols effectively synchronized repeat periods of estrus to 2 d and did not harm established pregnancies. In Exp. 2, treatments similar to those in Exp. 1 were applied to previously inseminated beef heifers (n = 439). Feeding 0.5 mg of melengestrol acetate (MGA) from d 13 to 19 after AI replaced the CIDR as a source of progestin. Of those heifers not pregnant (n = 65) after the initial AI, more than 86% were reinseminated, but conception was decreased (P < 0.05) by 28 to 39% compared with controls. In Exp. 3, previously inseminated lactating beef cows at four locations were assigned within herd to each of three treatments: 1) no treatment (control; n = 307); 2) same as in Exp. 1, but with P4 + 1 mg of estradiol benzoate on d 13 and 20 (P4 + EB; n = 153); and 3) same as in Exp. 1, P4 + ECP (n = 149). Treatments with P4 plus estrogen did not decrease conception rates in pregnant cows at any location, but increased (P < 0.05) the percentage of nonpregnant cows returning to estrus between 19 and 23 d after timed AI from 29% in controls to 86% in P4 + EB and 65% in P4 + ECP cows. Conception rates at the return estrus were not decreased when treatments occurred between d 13 and 20. In Exp. 4, lactating beef cows were assigned as in Exp. 3 to each of three treatments: 1) no treatment (controls; n = 51); 2) P4 + ECP (n = 47), as in Exp. 1; and 3) a single injection of ECP on d 13 (n = 48). Previously established pregnancies were not harmed (P = 0.70), and return rates of nonpregnant cows did not differ (P = 0.78) among treatments. In summary, in both heifers and lactating beef cows, the P4-based resynchronization treatments increased synchronized return rates when estrus detection rates were low, had no negative effects on established pregnancies, and decreased or tended to decrease conception rates at the resynchronized estrus.

Administration, Intravaginal↗

PubMed2000

A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women.

BACKGROUND: Although the male condom provides a reliable means of preventing HIV transmission, a broader choice of methods is required particularly in circumstances where the negotiation of condom use is difficult. Development of new products that may be effective as topical vaginal microbicides is the focus of a great deal of research activity currently. The novel agent PRO 2000, a naphthalene sulphonate derivative with in vitro activity against HIV and other sexually transmissible pathogens, is one such compound. We have studied the local and systemic safety and tolerance of a vaginal gel formulation of this agent at two concentrations (0.5% and 4%) over a 2 week period of daily exposure in two cohorts of healthy sexually abstinent women (one in London, UK, and the other in Antwerp, Belgium). METHODS: This was a randomised, placebo controlled, double blind, three arm clinical trial conducted on two sites. Macroscopic evidence of genital epithelial changes was sought using colposcopy and evidence of microscopic inflammation was acquired using high vaginal biopsy from predetermined sites (UK cohort only). Blood levels of PRO 2000 were measured and laboratory safety tests, including coagulation screens, were performed. The impact on vaginal ecology was also assessed. RESULTS: 73 women were enrolled across both sites (36 UK, 37 Belgium); 24, 24, 25 in the 4%, 0.5%, and placebo groups respectively. Of these, 70 completed 2 weeks' exposure to the study gel. Three (all in the 4% group) withdrew owing to adverse events which were possibly or probably gel related. Cervicovaginal abrasion was seen colposcopically in three subjects after 14 days of gel use (two in the 4% group and one in the placebo group). Genital ulceration was not seen during gel use in any of the subjects who completed the study. Histological evaluation of vaginal biopsy samples (36 women only) showed evidence of increased inflammatory signs in one participant of the 4.0% group. One volunteer in the placebo group had moderate inflammation at screening and at follow up. Severe inflammation was not seen among any of the subjects tested. Plasma levels of PRO 2000 and laboratory safety tests showed no evidence of systemic absorption. No impact was seen on normal vaginal ecology in the UK cohort where samples were taken 12 hours after the last gel application. CONCLUSION: In this phase I study PRO 2000 gel was found to be generally well tolerated with promising local and systemic safety profiles. The 0.5% gel was better tolerated than the 4% gel as fewer genital epithelial adverse events were seen in the former. Phase II studies are about to begin in sexually active women.

Administration, Intravaginal↗

PubMed2004

Ability of intravaginal progesterone inserts and melengestrol acetate to induce estrous cycles in postpartum beef cows.

Postpartum anestrous interval in beef cows is a major factor contributing to reproductive failure during a defined breeding season. Our objectives were to determine the ability of a controlled internal drug-releasing device (CIDR, 1.9 g of progesterone), a normal dose of melengestrol acetate (MGA, 0.5 mg x cow(-1) x d(-1)), or a high dose of MGA (4.0 mg x cow(-1) x d(-1)) to induce ovulation and to eliminate short estrous cycles. Multiparous beef cows (n = 100) were equally assigned to one of four treatments: CIDR, normal MGA, high MGA, or control by age, days postpartum, body condition, and body weight. All cows were fed carrier (0.9072 kg x cow(-1) x d(-1)) with (normal MGA, 0.55 mg/kg; high MGA, 4.41 mg/kg) or without MGA for 7 d (d -6 to 0). On d -6, CIDR were inserted and then removed on d 0. Estrous behavior was monitored continuously from d -6 until 29 using HeatWatch electronic mount detectors. Blood was collected on d -13, and three times weekly from d -6 to 29. Treatment influenced (P = 0.03) the percentage of cows that were detected in standing estrus. Beginning on d 2, more CIDR-treated cows had exhibited standing estrus compared with high MGA-treated or control cows, but CIDR- and normal MGA-treated cows did not differ. The percentage of CIDR-treated cows that had ovulated was greater (P < 0.05) than the percentage of normal MGA-treated, high MGA-treated, or control cows beginning on d 4. The percentage of cows that exhibited standing estrus before the first postpartum ovulation (CIDR = 65%, normal MGA = 57%, high MGA = 35%, control = 30%) did not differ (P = 0.09) among treatments. Luteal life span following the first ovulation postpartum and the percentage of cows with a normal luteal life span (i.e., progesterone > 1 ng/mL for > or = 10 d) was greater (P < 0.01) in CIDR-treated cows (14.0 +/- 0.8 d; 20/20, 100%) compared with normal MGA-treated (6.2 +/- 1.0 d; 3/13, 23%), high MGA-treated (9.6 +/- 1.0 d; 8/14, 57%), or control cows (6.1 +/- 0.9 d; 4/17, 24%), and greater (P < 0.03) in high MGA-treated cows than in normal MGA-treated or control cows. In the present study, treatment of early postpartum suckled beef cows with CIDR induced ovulation and initiated estrous cycles with a normal luteal life span in more cows than did treatment with MGA. Treatment with MGA (normal or high dose) did not induce ovulation earlier than in control cows, but a high dose of MGA increased the percentage of cows with normal luteal life spans following the first ovulation postpartum.

Administration, Intravaginal↗

PubMed2004

Ovarian follicular development in Holstein cows following synchronisation of oestrus with oestradiol benzoate and an intravaginal progesterone releasing insert for 5-9 days and duration of the oestrous cycle and concentrations of progesterone following ovulation.

The aim of this study was to determine if the duration of treatment with an intravaginal progesterone releasing insert (IVP(4)) after treatment with oestradiol benzoate (ODB) at the time of insertion and 24 h after removal would affect selected variables including: size of ovarian follicles at the time of removal of inserts, diameter of ovulatory follicles, plasma concentrations of progesterone following ovulation, and duration of the following oestrous cycle. Characteristics of oestrus at a synchronised and spontaneous oestrus were also monitored. Non-lactating Holstein cows were synchronised with an IVP(4) for 5 (n = 10), 7 (n = 10), 8 (n = 9) or 9 (n = 9) days together with injections of ODB at device insertion (2 mg) and 24 h after removal (1 mg). Ultrasonography showed no significant effect of treatment on the day of emergence of preovulatory follicles relative to the day of removal of inserts (overall mean = -4.22 +/- 0.58; P = 0.15) for cows that ovulated within 120 h insert removal (n = 36). Treatment with ODB and an IVP(4) for 5 days reduced the diameter of preovulatory follicles at the time of removal of inserts and for the following 2 days compared to cows treated for 7-9 days (mean difference 2.56 +/- 1.15 mm; P = 0.033) but did not reduce the diameter of the ovulatory follicle (P = 0.21). Day of emergence relative to removal of inserts was associated with the diameter of the ovulatory follicle (R2 = 0.69; P < 0.001). Concentrations of progesterone and the diameter of the corpus luteum following ovulation were not affected by treatment (P > 0.20), but were affected by the diameter of the ovulatory follicle (P < 0.01). Diameter of the ovulatory follicle did not affect interoestrous and interovulatory intervals (P > 0.40). We conclude that treatment with an IVP(4) for 5 compared to 7-9 days with ODB administered at device insertion, and 24 h after removal reduced the diameter of preovulatory follicles at the time of removal of the insert but did not reduce the diameter of the ovulatory follicle or concentrations of progesterone in plasma. Emergence of preovulatory follicles closer to the time of removal of inserts reduced the diameter of the ovulatory follicle when oestrus was induced with ODB. Ovulation of smaller follicles reduced concentrations of progesterone in plasma following ovulation but did not affect oestrous cycle duration.

Administration, Intravaginal↗

PubMed1999

Ovulation and estrus characteristics in crossbred Brahman heifers treated with an intravaginal progesterone-releasing insert in combination with prostaglandin F2alpha and estradiol benzoate.

Crossbred Brahman heifers (n = 60) were studied to determine the effect of a 7-d intravaginal progesterone-releasing insert (INSERT) in combination with PG (Lutalyse; 25 mg i.m.) and estradiol benzoate (EB; .5 mg i.m.) on time of ovulation and estrous behavior. In Phase I, heifers at unknown stages of the estrous cycle were assigned by BW and body condition score to one of the three treatments on d 0: 1) INSERT for 7 d and PG on d 7 (CONTROL; n = 10); 2) INSERT for 7 d, PG on d 7, and EB 24 h after INSERT removal (EB24; n = 10); or 3) INSERT for 7 d, PG on d 7, and EB 48 h after INSERT removal (EB48; n = 10). Blood samples were collected every 8 h after INSERT removal. Also, blood sampling and ultrasonography began 8 h after the onset of estrus, determined with HeatWatch devices, and every 4 h thereafter to detect ovulation. In Phase II, Phase-I treatments (n = 10/treatments) were replicated, but only behavioral estrus data were collected to minimize handling of heifers. Frequent handling of heifers did not influence (P > .1) the interval from INSERT removal to the onset of HeatWatch and visual estrus and duration of estrus, so behavioral estrus data were combined for Phases I and II. Interval from INSERT removal to HeatWatch estrus was decreased (P < .05) in EB24 (45.5 h) vs EB48 (55.9 h) and CONTROL (59.2 h). Interval from INSERT removal to ovulation differed (P < .04) between CONTROL, EB24, and EB48 (93.5, 74.5, and 78.9 h, respectively). Ovulatory follicle size was similar (P > .1) between CONTROL, EB24, and EB48 (14.4, 12.5, and 14.1 mm, respectively). Duration of estrus was similar for CONTROL, EB24, and EB48 (14.0, 15.1, and 17.6 h, respectively). No difference (P > . 1) was observed in number of mounts received between CONTROL, EB24, and EB48 (28.0, 25.7, and 39.4, respectively), but number of mounts received increased in Phase II vs Phase I (40.0 and 22.2, respectively; P < .05). In conclusion, EB hastened the interval from INSERT removal to ovulation without altering duration of estrus or number of mounts received. Frequent handling of heifers did not affect interval to first mount received after INSERT removal or duration of estrus, but it decreased the total number of mounts received.

Administration, Intravaginal↗

PubMed2001

Efficacy of an intravaginal progesterone insert and an injection of PGF2alpha for synchronizing estrus and shortening the interval to pregnancy in postpartum beef cows, peripubertal beef heifers, and dairy heifers.

The objective was to test the efficacy of an intravaginal progesterone insert and injection of PGF2alpha for synchronizing estrus and shortening the interval to pregnancy in cattle. Cattle were assigned to one of three treatments before a 31-d breeding period that employed artificial insemination. Control cattle were not treated, and treated cattle were administered PGF2alpha or an intravaginal progesterone-releasing insert (CIDR) for 7 d and treated with PGF2alpha on d 6. The treatments were applied in one of three experiments that involved postpartum beef cows (Exp. 1; n = 851; 56+/-0.6 d postpartum), beef heifers (Exp. 2; n = 724; 442.5+/-2.8 d of age), and dairy heifers (Exp. 3; n = 260; 443.2+/-4.5 d of age). Luteal activity before treatment was determined for individual cattle based on blood progesterone concentrations. In Exp. 1, there was a greater incidence of estrus during the first 3 d of the breeding period in CIDR+PGF2alpha-treated cows compared with PGF2alpha-treated or control cows (15, 33, and 59% for control, PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001). The improved estrous response led to an increase in pregnancy rate during the 3-d period (7, 22, and 36% for control, PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001) and tended to improve pregnancy rate for the 31-d breeding period for cows treated with CIDR+PGF2alpha, (50, 55, and 58% for control, PGF2alpha, and CIDR+PGF2alpha, respectively, P = 0.10). Improvements in rates of estrus and pregnancy after CIDR+PGF2alpha, were also observed in beef heifers. Presence of luteal activity before the treatment period affected synchronization and pregnancy rates because anestrous cows (Exp. 1) or prepubertal heifers (Exp. 2) had lesser synchronization rates and pregnancy rates during the first 3 d of the breeding period as well as during the entire 31-d breeding period. The PGF2alpha, and CIDR+PGF2alpha but not the control treatments were evaluated in dairy heifers (Exp. 3). The CIDR+PGF2alpha-treated heifers had a greater incidence of estrus (84%) during the first 3 d of the breeding period compared with the PGF2alpha-treated heifers (57%), but pregnancy rates during the first 3 d or during the 31-d breeding period were not improved for CIDR+PGF2alpha compared with PGF2alpha-treated heifers. In summary, the concurrent treatment of CIDR and PGF2alpha improved synchronization rates relative to PGF2alpha alone or control. Improved estrus synchrony led to greater pregnancy rates for beef cows and beef heifers but failed to improve pregnancy rates for dairy heifers.

Administration, Intravaginal↗

PubMed2002

Effect of treatment with progesterone and oestradiol benzoate on ovarian follicular turnover in postpartum anoestrous cows and cows which have resumed oestrous cycles.

Two experiments were carried out to determine the effect of a low dose of progesterone (P) with and without the addition of an injection of oestradiol benzoate (ODB) on ovarian follicle dynamics, oestradiol production and LH pulsatility in postpartum anoestrous cows, compared with cows which had resumed oestrous cycles (cycling cows). In the first experiment, anoestrous Jersey cows were treated with (AN+P, n=8) or without (AN-3, n=3) a previously used intravaginal progesterone releasing (CIDR) device for 10 days, commencing 3 or 4 days after emergence of a new dominant follicle (DF1) as determined by transrectal ultrasonography. Contemporary cycling cows (CYC+P, n=8) were similarly treated with used CIDR devices and injected with prostaglandin F(2alpha) (PGF) at the time of device insertion. Follicle turnover was monitored by daily ultrasonography and pulsatile release of LH was measured on the ninth day after device insertion. During the period of CIDR device insertion, a second dominant follicle emerged in 4/8 of the CYC+P group and 7/8 of the AN+P group (P=0.14). Maximum diameter of DF1 was greater in cows in the CYC+P compared with the AN+P group (P=0.02), but did not differ between cows in the AN+P and AN-P groups (P>0.1). Frequency of LH pulses was greater in cows in the CYC+P than AN+P group (P=0.06), and in cows in the AN+P than AN-P group (P=0.02). In the second experiment, anoestrous (n=20) and cycling (n=11) Friesian cows were treated with a new CIDR device for 6 days commencing 3 days after emergence of a new dominant follicle (DF1). Cycling cows were also injected with PGF on the day of device insertion. Half of the cows in each group were injected with 2mg ODB on the day of device insertion. Daily ultrasonography was used to monitor follicular dynamics throughout the experimental period. Follicular turnover was increased by ODB in cycling (5/5 versus 1/6; P<0.05), but not anoestrous cows (5/9 versus 4/11). Persistence of DF1 was reduced by ODB treatment in both cycling and anoestrous cows (P<0.001). Maximum diameter of DF1 was influenced by ODB treatment and reproductive status (P<0.05). In anoestrous cows in which a second dominant follicle did not emerge during the period of device insertion, the interval from emergence of DF1 to emergence of a second dominant follicle was significantly delayed by treatment with ODB (P=0.04). In conclusion, P treatment of anoestrous cows increased pulsatile release of LH, but did not induce the development of persistent follicles. Injection of ODB in association with P treatment reduced the persistence of dominant follicles in both cycling and anoestrous cows, but delayed subsequent follicular development in a proportion of anoestrous cows.

Administration, Intravaginal↗

PubMed2001

Effects of maturity of the potential ovulatory follicle on induction of oestrus and ovulation in cattle with oestradiol benzoate.

The effect of maturity of the dominant follicle (DF) on the capacity of oestradiol benzoate (ODB) to induce oestrus and ovulation was examined in cattle. In experiment 1, 31 prepubertal heifers each received an intravaginal progesterone insert (IPI) and 1mg ODB i.m./500kg BW (ODB1). Daily ovarian ultrasonography detected emergence of a new follicular wave 3.1+/-0.1 days after ODB1. The IPI was removed when newly emerged DF were "young" (1.3+/-0.1 days after emergence; YDF; n=15) or "mature" (4.2+/-0.1 days; MDF; n=16), and 24h later, heifers received 0.75mg ODB/500kg BW (ODB2; n=16) or no further treatment (NoODB2; n=15). Most of the heifers receiving ODB2 were observed in oestrus (15/16) and ovulated (12/16), as compared to 0/15 and 1/15 in the NoODB2 group, respectively (P<0.01). In experiment 2, 32 heifers received ODB1 on day 6 of the oestrous cycle, and new follicular wave emergence was detected 3.2+/-0.1 days later. Heifers received an injection of prostaglandin-F2alpha (PGF) when the DF was young (1.1+/-0.1 days after emergence; YDF; n=16) or mature (4 days; MDF; n=16), and then ODB2 24h later or no further treatment (NoODB2). The interval from PGF to oestrus was greater (P<0.01) in the YDF-NoODB2 (70+/-3.9h) as compared to MDF-NoODB2 group (57+/-1.8h). Inclusion of ODB2 reduced (P<0.01) this interval to 47.0+/-0.7h without regard to the maturity of the DF (maturityxODB2, P<0.05) and also reduced (P<0.05) the interval to ovulation. In experiment 3, 21 suckling anoestrous cows received an IPI and ODB1 at 29.3+/-1.7 days postpartum. The IPI were removed either 1 day (YDF; n=9) or 3.9+/-0.1 days (MDF; n=9) after emergence of a new follicular wave and every cow received ODB2. Oestrus was subsequently detected in all but one animal. Ovulation of the newly emerged DF was detected within 48h of ODB2 in nine of nine cows of the MDF group, and in four of nine of the YDF group (P<0.05). During the subsequent ovulatory cycle, luteal size and plasma concentrations of progesterone were greater (P<0.01) in the MDF group compared to the YDF group. We conclude that behavioural oestrus is readily induced by 0.75mg ODB i.m./500kg BW. Maturity of the DF appeared to have little influence on the ability of the DF to ovulate in heifers. In contrast, young DF in lactating anoestrous cows were less likely to respond to the ovulatory cue provided, and luteal development was compromised in those that did ovulate.

Administration, Intravaginal↗