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Changing dose of progesterone results in sudden changes in frequency of luteinizing hormone pulses and secretion of 17 beta-estradiol in bovine females.

The aim of the present study was to elucidate the time course according to which changes in circulating concentrations of progesterone influence pulsatile secretion of LH and secretion of 17 beta-estradiol. Our working hypothesis was that changing the dose of progesterone would result in changes in frequency of LH pulses and secretion of 17 beta-estradiol within 72 h. Five days after behavioral estrus, thirty-three cows were randomly assigned to one of five groups: 1) control, no treatment (CONT, n = 5); 2) treatment with two progesterone-releasing intravaginal devices (PRIDs) for 11 days (2PRID, 5-6 ng/ml plasma progesterone, n = 7); 3) treatment with a 0.5 PRID for 11 days (0.5PRID, 1-2 ng/ml plasma progesterone, n = 7); 4) treatment with 2 PRIDs for 8 days followed by treatment with a 0.5 PRID for 3 days (2-0.5PRID, n = 7); and 5) treatment with a 0.5 PRID for 8 days followed by treatment with 2 PRIDs for 3 days (0.5-2PRID, n = 7). Cows subject to PRID treatments received injections of prostaglandin F2 alpha on Days 1 and 2 (Day 0 = day of initiation of PRID treatments, fifth day of the estrous cycle in CONT cows) to lyse the existing corpus luteum. Cows were bled for 12 h at 15-min intervals on Day 7.5 of the treatment period (twelfth day of the estrous cycle in CONT cows). The dose of progesterone was changed on Day 8 in cows that were assigned to the 2-0.5PRID and 0.5-2PRID groups, and blood collections continued an additional 72 h to characterize profiles of circulating concentrations of LH and 17 beta-estradiol. Cows treated with a 0.5 PRID had a greater (p < 0.05) number of LH pulses and higher (p < 0.05) concentrations of 17 beta-estradiol throughout the entire blood collection period than cows in the 2PRID and CONT groups. An increase in the number of LH pulses was detected within 6 h after the change from the high to the low dose of progesterone (2-0.5PRID), and frequency of LH pulses was similar to that of cows in the 0.5PRID group for the remainder of the period of blood collection. LH pulse frequency declined within 6 h after the shift from the low to the high dose of progesterone (0.5-2PRID) and was similar to that of cows in the 2PRID group by 12 h after the dose was changed. Within 6 h after the dose of progesterone was changed, circulating concentrations of 17 beta-estradiol increased (p < 0.05) in cows shifted from the high to low dose (2-0.5PRID) and declined (p < 0.05) after the dose of progesterone was changed from low to high (0.5-2PRID). We conclude that changing the circulating concentrations of progesterone concurrently affects frequency of pulsatile LH release and secretion of 17 beta-estradiol within 6-24 h.

Administration, Intravaginal↗

Induced and synchronized estrus in cattle: dose titration of estradiol benzoate in peripubertal heifers and postpartum cows after treatment with an intravaginal progesterone-releasing insert and prostaglandin F2alpha.

Peripubertal beef heifers (n = 57) and postpartum multiparous cows (n = 52) were used to determine the optimal dose of estradiol benzoate (EB) to induce and synchronize estrus after treatment with intravaginal progesterone inserts (IVP4, EAZI-BREED CIDR). All females received an IVP4 for 7 d (d 0 = insertion day) with a 25-mg injection of PGF2alpha (Lutalyse) on d 6. At 24 to 30 h after IVP4 removal, females were randomly assigned to be injected subcutaneously with EB at the following doses: heifers 0, .2, .38, or .75 mg and cows 0, .25, .5, or 1 mg. Furthermore, seven heifers and seven cows from each dose group were bled every 4 h for 76 h starting at EB injection. Serum was collected and assayed for LH and estradiol-17beta (E2). Observations for signs of estrus were made twice daily for 21 d after removal of IVP4, and females were artificially inseminated 8 to 20 h after detection of estrus. The percentage of females showing estrous behavior was increased by EB (P < .04); the greatest response was at .38 mg in heifers (86%) and 1 mg in cows (100%). Dose x time interaction affected (P < .01) E2 concentrations in heifers and cows; the animals that received the higher doses of EB had greater E2 concentrations in a shorter time than those that received the smaller doses. The percentage of cows and heifers with an acute preovulatory LH release (peak LH) was affected by dose, with a linear (P < .01) and a quadratic (P < .01) response. Highest concentrations of LH during peak LH were affected by dose with a linear (P < .01) response in heifers and linear (P < .01) and quadratic (P < .08) responses in cows. Heifers receiving .38 mg and cows receiving .5 and 1 mg of EB had the highest peak LH. Time to LH peak had a linear (P < .03) response in heifers and had linear (P < .04) and quadratic (P < .05) responses in cows. Pregnancy rate was affected (P < .02) in heifers by whether or not they were anestrous before IVP4 treatment (those with estrous cycles = 52% vs those that were anestrous = 22%) and in cows by dose of EB (P < .01; 8, 23, 21, and 67% for 0, .25, .5, and 1 mg, respectively). In conclusion, in females treated with IVP4 and PGF2alpha to induce and synchronize estrus, an injection of EB increased concentrations of E2 and LH and increased number of animals showing estrus. Also, EB increased pregnancy rates in cows. Optimal responses were at .38 mg EB for heifers and at 1 mg EB for cows.

Administration, Intravaginal↗

Reproduction in dairy cows following progesterone insert presynchronization and resynchronization protocols.

The objectives of this study were to evaluate the effects of an intravaginal insert containing progesterone (CIDR, controlled internal drug releasing) administered in presynchronization and resynchronization protocols on cyclicity, detection of estrus, pregnancy rate, and pregnancy loss to first AI; reinsemination patterns; and pregnancy rates to second postpartum AI before and after the time of first-service pregnancy diagnosis in dairy cows. Holstein cows (n = 1,052) were blocked by parity and BCS at 3 +/- 3 d in milk (study d 0 = day of calving) and assigned randomly to 1 of 3 presynchronization treatments. During the presynchronization programs, all cows received 2 injections of PGF2alpha, on study d 35 and 49. Cows enrolled in the control presynchronization treatment received AI after detected estrus from study d 49 to 62. Cows enrolled in the CIDR estrus-detection (CED) presynchronization treatment received a CIDR insert from study d 42 to 49 and AI on detection of estrus from d 49 to 62. Cows enrolled in the CIDR timed AI (CTAI) presynchronization treatment received the same treatment as CED, but were subjected to timed AI on study d 72 after the Ovsynch (GnRH, 7 d PGF2alpha, 2 d GnRH, 24 h timed AI) protocol. The control and CED cows not inseminated by study d 62 were enrolled in the Ovsynch protocol on the same day and received timed AI on study d 72. After first AI, cows were assigned to no resynchronization (RCON) or resynchronization with a CIDR insert (RCIDR) between 14 and 21 d after AI. Blood samples collected on study d 35, 49, and 62 were analyzed for concentrations of progesterone and cows were classified as anestrous when progesterone was < 1.0 ng/mL in the first 2 samples. On study d 62, anestrous cows with progesterone > or = 1.0 ng/mL were classified as having resumed cyclicity. Pregnancy was diagnosed at 31 and 60 d after first AI and at 42 d after second AI. A greater proportion of anestrous cows in CED and CTAI became cyclic by d 62 postpartum than control cows. Resynchronization with the CIDR insert increased the pregnancy rate at 31 d after first AI in CED and CTAI, and at 60 d after AI in all cows because of reduced pregnancy loss. These results indicate that presynchronization with the CIDR insert increased induction of cyclicity in anestrous cows and that resynchronization with the CIDR insert did not affect the reinsemination rate but did reduce pregnancy loss and increased the pregnancy rate at 60 d after first AI.

Administration, Intravaginal↗

Effect of addition of a progesterone intravaginal insert to a timed insemination protocol using estradiol cypionate on ovulation rate, pregnancy rate, and late embryonic loss in lactating dairy cows.

The objectives of this study were to determine the effects of incorporating a progesterone intravaginal insert (CIDR) between the day of GnRH and PGF2alpha treatments of a timed AI protocol using estradiol cypionate (ECP) to synchronize ovulation on display of estrus, ovulation rate, pregnancy rate, and late embryonic loss in lactating cows. Holstein cows, 227 from Site 1 and 458 from Site 2, were presynchronized with two injections of PGF2alpha on study d 0 and 14, and subjected to a timed AI protocol (100 mixrog of GnRH on study d 28, 25 mg of PGF2alpha on study d 35, 1 mg of ECP on study d 36, and timed AI on study d 38) with or without a CIDR insert. Blood was collected on study d 14 and 28 for progesterone measurements to determine cyclicity. Ovaries were scanned on d 35, 37, and 42, and pregnancy diagnosed on d 65 and 79, which corresponded to 27 and 41 d after AI. Cows receiving a CIDR had similar rates of detected estrus (77.2 vs. 73.8%), ovulation (85.6 vs. 86.6%), and pregnancy at 27 (35.8 vs. 38.8%) and 41 d (29.3 vs. 32.3%) after AI, and late embryonic loss between 27 and 41 d after AI (18.3 vs. 16.8%) compared with control cows. The CIDR eliminated cows in estrus before the last PGF2alpha injection and decreased (P < 0.001) the proportion of cows bearing a corpus luteum (CL) at the last PGF2alpha injection because of less ovulation in response to the GnRH and greater spontaneous CL regression. Cyclic cows had greater (P = 0.03) pregnancy rates than anovulatory cows at 41 d after AI (33.8 vs. 20.4%) because of decreased (P = 0.06) late embryonic loss (16.0 vs. 30.3%). The ovulatory follicle was larger (P < 0.001) in cows in estrus, and a greater proportion of cows with follicles > or = 15 mm displayed estrus (P < 0.001) and ovulated (P = 0.05) compared with cows with follicles <15 mm. Pregnancy rates were greater (P < 0.001) for cows displaying estrus, which were related to the greater (P < 0.001) ovulation rate and decreased (P = 0.08) late embryonic loss for cows in estrus at AI. Cows that were cyclic and responded to the presynchronization protocol (high progesterone at GnRH and CL at PGF2alpha) had the highest pregnancy rates. Incorporation of a CIDR insert into a presynchronized timed AI protocol using ECP to induce estrus and ovulation did not improve pregnancy rates in lactating dairy cows. Improvements in pregnancy rates in cows treated with ECP to induce ovulation in a timed AI protocol are expected when more cows display estrus, thereby increasing ovulation rate.

Abortion, Veterinary↗

Effectiveness of intravaginal progesterone inserts and FSH for inducing synchronized estrus and increasing lambing rate in anestrous ewes.

The objectives of this study were to determine whether a new progesterone (P4)-releasing intravaginal insert would induce fertile estrus and whether FSH combined with the insert would increase prolificacy in anestrous ewes introduced to rams. Ewes of mixed breeding on six farms were assigned to four randomized treatments: control (C), n = 73; 12 d P4 (polycapralactone [PCL] insert with 0.82 g P4), (P12), n = 73; 12 d P4 plus i.m. FSH (Folltropin, 55 mg NIH-FSH-P1 equivalent) in propylene glycol, 24 h before insert removal, (P12F), n = 71; and 5 d P4 plus FSH (P5F), n = 77. Growth and ovulation of follicles were observed ultrasonographically in 20 ewes at four farms (five/treatment) at insert removal and 36, 48, 72, and 96 h later. Intact rams (1:15 ewes in multiple-sire groups) were joined at insert removal, and raddle marks were observed every 12 h for 5 d. On d 26 to 30, rams were removed; ewes were examined for pregnancy then and 20 d later. Percentage of ewes marked by rams was greater in P4-treated (66 to 79%) than in C (12%; P < 0.01) ewes and in P5F (79%) than in P12F (66%; P < 0.05). Diameters of largest follicles at insert removal were greater (P < 0.05) in P4-treated (5.5 +/- 0.2) than in C ewes (4.8 +/- 0.2). Progesterone increased numbers of follicles > 3 mm (P < 0.01) or ovulated (P < 0.05; 2.6 +/- 0.6 vs 1.3 +/- 0.6 in C ewes) and FSH increased number of follicles > 3 mm (P < 0.05). In FSH-treated ewes, ovulation rate tended to be greater after treatment with P4 for 5 than for 12 d (P = 0.09, 3.3 +/- 0.6 and 2.2 +/- 0.4, respectively). More P4-treated than C ewes lambed (P < 0.01) to the first (38 to 45 vs 0%) or both (63 to 66 vs 41%) service periods. Prolificacy (first service) did not differ between FSH-treated ewes (P12F + P5F; 1.8 +/- 0.1) and ewes treated with P4 only (P12; 1.6 +/- 0.1). However, FSH increased prolificacy to first service (1.8 +/- 0.1) over prolificacy to second service (C ewes 1.5 +/- 0.1; P < 0.05, and all ewes 1.4 +/- 0.1; P < 0.01). Pregnancy retention did not differ among treatments but was greater (P < 0.01) in ewes that conceived at the first (90.9 +/- 3.7) than at the second (72.5 +/- 3.3) service period. In conclusion, a PCL insert in combination with ram introduction at insert removal was more effective than ram introduction alone to induce synchronized estrus and ovulation and to yield pregnancy after one or two service periods. Treatment with P4 for 5 d was as effective as for 12 d to induce fertile estrus in FSH-treated anestrous ewes.

Administration, Intravaginal↗

A comparative study of the effect of 2 hormonal treatment protocols on the reproductive performance of previously anoestrous dairy cows.

The objective of this study was to compare the reproductive performance of anoestrous dairy cows treated just prior to the mating start date (MSD) with a Controlled Internal Drug Releasing Device (CIDR) which was placed intravaginaly for either 6 or 8 days, and a combination of oestradiol benzoate. Lactating dairy cows (n = 926) that had been diagnosed with anovulatory anoestrus were divided into two sub-groups. A hormonal treatment protocol that involved the use of a CIDR device containing 1.9 g of progesterone was inserted into the vagina of each cow and left intravaginally for either 6 (6-day group, n = 441) or 8 days (8-day group, n = 485). Every cow in the trial was inseminated after being detected in oestrus from Day -2 onwards (where Day 0, was a herd's MSD), using an appropriate detection aid according to the herds' preference. Cows that had been seen in oestrus and were inseminated by Day 2 were selected for re-synchrony. The standardised re-synchrony involved the re-insertion of a previously used CIDR device into the vagina of each cow on Day 14, together with an injection of 1.0 mg oestradiolbenzoate i.m. This CIDR device was removed on Day 22 and each of these cows injected with 1.0 mg oestradiol benzoate i.m. on Day 23. Each re-synchronised cow that was detected in oestrus was re-inseminated. Treatment with an 8-day CIDR increased the proportion of cows submitted for insemination within the first 3 days of the MSD, compared with the 6-day group (83.7 % vs 71.2%, respectively, P < 0.001), as well as the proportion of cows conceiving within the first 3 days of MSD (36.2% vs 27.7%, P = 0.02), but reduced both the interval from MSD to the first service (4.5 +/- 0.5 vs 6.8 +/- 0.7, P = 0.01), and the interval from MSD to conception (28.1 +/- 1.5 vs 34.0 +/- 1.8, P = 0.009). A greater percentage of the cows in the 6-day group that were not pregnant to the first insemination were submitted for a second insemination by Day 28 compared with the 8-day group (81.1% vs 68.3%, P < 0.001). Conception rates for cows submitted for this second insemination by Day 28 of the MSD were also higher in the 6-day than in the 8-day group (48.4% vs 33.9%, P = 0.009). The percentage of cows pregnant at the end of a herd's AI period of 6 weeks did not differ (57.1% vs 54.8% for 8-day and 6-day groups, respectively, P = 0.42); neither did the proportion of cows pregnant at the end of the a herd's combined AI and natural mating period of 21 weeks (81.4% vs 79.2%, for 8-day and 6-day groups respectively P = 0.36). Treatment of anovulatory anoestrous dairy cows with a combination of an 8-day CIDR and oestradiol benzoate before the MSD improved their reproductive performance by increasing the portion of cows submitted for insemination within the first 3-days of the MSD by reducing the interval from MSD to first service and by increasing the conception rate to the first insemination to collectively reduce the average interval from MSD to conception.

Administration, Intravaginal↗

Restoring ovulation in beef donor cows with ovarian cysts by progesterone-releasing intravaginal silastic devices.

The objective of this study was to determine the efficacy of a progesterone-releasing intravaginal silastic device (Controlled Internal Drug Release: CIDR) for inducing ovulation in beef cows with persistent ovarian cysts. Fifteen cows with cysts and abnormal cycles for over 40 days were randomly assigned to receive either a single CIDR (CIDR group, n=9), or a CIDR containing no progesterone (blank CIDR) (BLANK group, n=6) for about 14 days. Determination of plasma progesterone levels at the beginning of CIDR treatment indicated 4 of 6 BLANK cows with non-luteinized cysts and 5 of 9 CIDR cows with non-luteinized cysts. In 5 of 6 BLANK cows, one follicular wave appeared and newly emerged dominant follicles increased in size up to 20 mm in diameter and persisted during the experiment, while one cow experienced estrus with spontaneous ovulation. In contrast, during CIDR treatment, 2 or 3 waves, in which dominant follicles were from 7 to 15 mm in diameter, appeared approximately at 7-day intervals. Within 3 days after CIDR removal, estrous behavior was detected followed by ovulation of the dominant follicle in the last wave. All CIDR cows resumed normal cyclicity with 2 follicular waves for over 2 months. Insertion of a CIDR caused a rapid increase of about 2 ng/mL in plasma progesterone. The levels were greater than 1.3 ng/mL until removal of a CIDR, then dropped under 0.3 ng/mL. Concentrations of plasma estradiol in BLANK cows increased during growth of the cystic follicles, with high levels greater than 10 pg/mL for over 10 days. In 4 of 5 cows with non-luteinized cysts, with high plasma estradiol on the day of CIDR insertion, CIDR treatment resulted in rapid decline of estradiol levels. During placement of the CIDR, estradiol levels showed no increase in the growth phase of a newly appeared dominant follicle. After CIDR removal, however, estradiol significantly increased associated with the growth of ovulatory follicles in all 9 cows. A transient increase in plasma FSH levels preceded detection of each follicular or cyst wave in both BLANK and CIDR cows. Pulse frequency and mean concentration of LH in cows with non-luteinized cysts showed values corresponding to those in normal follicular phase. However, throughout CIDR treatment, these parameters reduced to levels found in the normal luteal phase. In cows with luteinized cysts, parameters of LH secretion were as low as in the normal luteal phase before and during CIDR treatment, then increased significantly after CIDR removal. Present results indicate that treatment with CIDR proved effective in restoring ovulation and reestablishing normal cyclicity in beef donor cows with cysts persistent for a long period. The CIDR reduced and maintained LH secretion at normal luteal levels, thereby, inducing atresia of estrogen-active cysts and preventing formation of cysts from the newly emerged follicles.

Administration, Intravaginal↗

Effect of oestrous synchronization with estradiol 17beta and progesterone on follicular wave dynamics in dairy heifers.

An experiment was designed to evaluate the effects of estradiol-17beta (E17beta) on follicular wave dynamics and ovulatory response in Holstein heifers receiving either a progestogen ear-implant (Crestar; Intervet International b.v. Boxmeer, The Netherlands) or an intravaginal progesterone-releasing device [controlled internal drug release-bovine device (Eazibreed, CIDR-B; Bodinco BV, Alkmaar, The Netherlands)]. For comparison, another group of heifers was also synchronized using Crestar plus an injection of estradiol valerate (EV) and norgestomet as recommended by the pharmaceutical company. Twenty 20-22-month-old cycling Holstein heifers were allocated to one of the following treatment groups at random stages of the oestrous cycle: (I) simultaneous insertion of Crestar and intramuscular injection of 3 mg norgestomet and 5 mg EV (Crestar 9 + EV 9); (II) simultaneous insertion of Crestar and intramuscular injection of 5 mg E17beta (Crestar 9 + E17beta 9); (III) insertion of Crestar followed 2 days later by intramuscular injection of 5 mg E17beta (Crestar 9 + E17beta 7); or (IV) insertion of CIDR-B device followed 2 days later by intramuscular injection of 5 mg E17beta (CIDR 9 + E17beta 7). The CIDR-B or Crestar implants were removed after 9 days and all heifers received 500 microg Cloprostenol (Estrumate, Pitman-Moore Nederland BV, Houten. The Netherlands). Ovarian ultrasonographic examinations were performed once daily during the synchronization period using a B-mode scanner equipped with a 7.5 MHz linear-array transrectal transducer. In addition, heifers were scanned every 12 h after implant/device withdrawal until 3 days after ovulation in order to monitor follicular activity, detect ovulation and subsequent early luteal formation. Detection of oestrus was performed every 6 h for 4 days after device/implant removal. Oestrus was observed 24-32 h before ovulation in all heifers. The mean hours interval from treatment withdrawal to ovulation was not significantly different (84.0 +/- 16.5, 77.6 +/- 4.1, 73.6 +/- 4.1 and 64.0 +/- 4.4 h for treatments I, II, III and IV, respectively, p > 0.1). However, the variance for heifers treated with EV + norgestomet was significantly larger (Levene's Test; p < 0.01) than those treated with E17beta. All E17beta treatments resulted in dominant follicle suppression and a new wave emerged 4.1 days after treatment compared with 6.6 days for the EV + norgestomet treatment (p < 0.05). The time from emergence of the new ovulatory wave to ovulation was longer for the new wave that emerged after E17beta treatment (9.2 +/- 0.3 days) than after EV + norgestomet treatment (6.9 +/- 0.4 days; p < 0.05). The results of this study suggest that the four treatments used were effective in inducing synchronous behavioural oestrus and ovulation. However, a higher degree of oestrus and ovulation synchrony was observed in heifers treated with E17beta than in heifers treated with EV + norgestomet. Synchronization treatments with exogenous E17beta or EV + norgestomet at the time of progestin device insertion (Crestar or CIDR-B) or 2 days later in heifers can regulate a different emergence pattern of ovarian follicular development in randomly cyclic heifers. The E17beta was effective in inducing follicular suppression and resulted in the consistent emergence of a new follicular wave.

Administration, Intravaginal↗

Oestradiol potentiates a prolonged progesterone-induced suppression of LH release in ovariectomised cows.

Our working hypothesis was that the negative feedback effect of progesterone on LH secretion in ovariectomised cows is greatly enhanced by oestradiol when both hormones are administered intravaginally. Each of eight ovariectomised cows had a progesterone releasing device ('CIDR-1'; Eazi-breed CIDR-B. InterAg, Hamilton, New Zealand) inserted into the vagina for 3 days, followed by an injection of 1 mg oestradiol benzoate (ODB) in peanut oil 24 h after device removal. The timing of this injection was designated as Day 0. The CIDR-1 was reinserted concurrently with an injection of 0.4 mg ODB on Day 5. An additional device ('CIDR-2') was inserted 4 days later (Day 9). In four of the cows, an ODB capsule (CIDIROL), Douglas Pharmaceuticals. Auckland, New Zealand) was placed into a groove on the surface of CIDR-2 preceding insertion. CIDR-2 was withdrawn after 5 days (Day 14) and CIDR-1 was withdrawn 2 days later (Day 16). The treatment regimen was repeated in a cross-over design where each cow received CIDR-2 with or without an ODB capsule. Blood samples were collected at intervals of 15 min for a period of 16 h beginning 8 h before insertion of CIDR-2 to determine changes in LH secretion pattern, and then at intervals of 8 h until 48 h after removal of CIDR-1 to determine mean LH and steroid concentrations. Concentrations of progesterone in plasma reflected the effects of inserting and removing each CIDR device. The insertion of CIDR-2 elevated progesterone from 2.0 +/- 0.1 ng ml-1 to 4.9 +/- 0.1 ng ml-1 within 30 min (P < 0.01) and maintained levels > 3 ng ml-1. Withdrawal of CIDR-2 produced a new baseline level of 1.8 +/- 0.1 ng ml-1 within 4 h (P < 0.01). Concentrations of oestradiol-17 beta in plasma increased from a baseline of < 1 pg ml-1 to-a-maximum of 12.6 +/- 2.2 pg ml-1 at 22 h after insertion of an ODB capsule. Initial pulse frequency of LH (1.2 +/- 0.05 pulses h-1) and mean concentration of LH (1.6 +/- 0.1 ng ml-1) declined (P < 0.05) to 0.2 +/- 0.1 pulses h-1 and 0.5 +/- 0.1 ng ml-1 during the period from 2 to 8 h following insertion of CIDR-2. Mean concentrations recovered to pre-treatment levels (> 1 ng ml-1) within 48 h if CIDR-2 was inserted without an ODB capsule. In contrast, LH levels remained less than 0.7 ng ml-1 for 5 days following this form of ODB treatment. A subsequent increase in mean LH of 1.4 +/- 0.2 ng ml-1 (P < 0.05) was inversely synchronised with the precipitous decline in progesterone of 1.2 +/- 0.1 ng ml-1, following removal of CIDR-2. The inclusion of an ODB capsule with insertion of CIDR-2 reduced concentrations of FSH from 166 +/- 17 ng ml-1 to a new baseline of 105 +/- 16 ng ml-1 within 24 h (P < 0.05). In conclusion, an acute increase in progesterone induced a transient suppression of LH lasting less than 48 h. This suppression was prolonged to 5 days by the concurrent insertion of a capsule containing 10 mg ODB. The subsequent recovery of LH was coincident with the decline in progesterone following removal of CIDR-2.

Administration, Intravaginal↗

Frequency of luteinizing hormone pulses in cattle influences duration of persistence of dominant ovarian follicles, follicular fluid concentrations of steroids, and activity of insulin-like growth factor binding proteins.

The objectives of the present study were to determine how varying frequency of LH pulses as controlled by varying treatments with progesterone (P4) in cattle would affect: (1) concentration of steroid hormones and activity of insulin-like growth factor binding proteins (IGFBPs) in the ovarian follicular fluid and blood plasma, and (2) duration of persistence of largest ovarian follicles. There were four treatment groups (n=7 per group) and a control group (n=5) of mature, non-lactating beef cows. Treatments were: (1) two progesterone releasing intravaginal devices (PRIDs) for 16 days (2PRID); (2) a half PRID for 16 days (0.5PRID); (3) two PRIDs for 8 days, then a half PRID for 8 days (2-0.5PRID); or (4) a half PRID for 8 days, then two PRIDs for 8 days (0.5-2PRID). Treatment was initiated on the fifth day of the estrous cycle, which was designated as Day 0, and continued for 16 days. All P4-treated females were administered prostaglandin F2alpha on Day 0 and 1 to regress their corpora lutea. Frequency of LH pulses was greater during treatment with the smaller dose of P4 compared with treatment with the larger dose of P4 and the control group. Ovarian follicles were classified into five categories based on ultrasonographic observations: growing (G); atretic (A); growing dominant (GD); growing persistent (GP); or atretic persistent (AP). At ovariectomy on Day 16, the largest and second largest follicles collected were re-classified into five categories based on follicular concentration of steroids. Classification of the largest follicle collected on Day 16 was influenced by treatment (P<0.005), with the 2PRID group having A follicles, the 2-0.5PRID group GP follicles, the 0.5-2PRID group AP follicles, and the 0.5PRID group GD and GP follicles. Concentrations of 17beta-estradiol (E2) were greatest in GD and GP follicles (P<0.05). There was less (P<0.05) activity of IGFBP-2 in GD follicles and less (P<0.05) activity of IGFBP-3 in GD and GP follicles than other follicles. Activity of IGFBP-4 and -5 was greater (P<0.05) in A and AP follicles than G, GD, and GP follicles. Maintenance of a frequent release of LH pulses over a 16-day period did not result in maintenance of persistent follicles throughout this period indicating that duration of dominance of these follicles is finite even when there is frequent release of LH pulses. Follicular atresia is associated with greater activity of IGFBP-2, -4, -5, and greater concentrations of P4 in follicles, whereas growing dominant and persistent follicles contained greater concentrations of E2, androstenedione (A4), and less IGFBP-2 activity than follicles of other classes. Follicle classifications based on ultrasonography or follicular concentration of steroids did differ (P<0.05) for the largest follicles from the 2PRID group. Two follicles in this group appeared as GD follicles by ultrasonography, but these were atretic based on follicular steroid contents. Objective 1 of the present study yielded the conclusion that concentrations of steroid hormones in follicular fluid and blood plasma could be predictably controlled by regulating the frequency of LH pulses with varying doses of P4. Objective 2 yielded the conclusion that maintain frequent release of LH pulses over a 16-day period could not maintain persistent follicles throughout this period, indicating that duration of dominance of these follicles is finite even when there is frequent release of LH pulses. Follicular atresia in the present study was associated with increased follicular fluid activity of IGFBP-2, -4, -5, and P4, whereas growing dominant and persistent follicles contained greater concentrations of E2, A4, and less IGFBP-2 activity than follicles of other classes.

Administration, Intravaginal↗

Mifepristone (RU 486): current knowledge and future prospects.

Mifepristone (RU 486) has received recent attention for its effects as an abortifacient. Mifepristone has not yet been approved for use in the United States. The Food and Drug Administration issued an "approvable letter" in September 1996, but mifepristone will not be available in the United States until a new manufacturer is found. Experience with mifepristone is extensive in Europe, and there have been retrospective studies and large, controlled clinical trials of its efficacy. It is most efficacious when administered to women who are less than 8 weeks pregnant, in a single 600-mg oral dose followed 48 hours later by administration of intravaginal misoprostol. This regimen has a success rate of 98%, as do most surgical abortive procedures. The most frequent adverse effect is painful contractions, which occur in up to 93% of women, with oral analgesia required in as many as half the cases. Large-scale surveys of women who elected medical abortion reported high patient satisfaction. Mifepristone is likely to have additional clinical uses. Researchers are exploring mifepristone's potential uses in cervical ripening and labor induction; contraception; delivery after intrauterine demise; treatment of breast cancer, unresectable meningioma, and prostate cancer; amelioration of endometriosis; and management of Cushing syndrome.

Abortifacient Agents, Steroidal↗

Fluorescence spectroscopy of the cervix: influence of acetic acid, cervical mucus, and vaginal medications.

BACKGROUND AND OBJECTIVE: Fluorescence spectroscopy has been shown to provide information useful in the detection of cervical dysplasia. The goal of this study was to determine if substances found on the cervix such as acetic acid, mucus, and vaginal medications can influence the fluorescence in the spectral region useful for discriminating normal cervical tissue from abnormal tissue. STUDY DESIGN/MATERIALS AND METHODS: Fluorescence spectra were collected at 337 nm excitation from the cervix in vivo both before and after application of acetic acid; the data were analyzed to identify the effects of the acetic acid on the spectra. Cervical mucus was acquired from patients referred for colposcopy and frozen until measurements were taken. Fluorescence excitation-emission matrices (EEMs) were measured for the mucus samples. Additionally, the transmission spectra of mucus were measured to determine if its absorption could influence the fluorescence signal measured from the tissue. EEMs were measured for samples of commonly prescribed vaginal medications. All EEMs were compared to those of cervical biopsies. RESULTS: Acetic acid introduces changes in both the lineshape and intensity of the spectra. On average, the changes are more significant in spectra of abnormal tissue. Cervical mucus was found to have no significant absorption bands, but the measured fluorescence was approximately the same order of magnitude as that measured from the cervix in vitro. Most medications exhibited significant fluorescence in the spectral region of diagnostic interest for the cervix. CONCLUSIONS: Acetic acid appears to increase the differences in fluorescence emission spectra of normal and pre-cancerous cervical tissues; thus, its use is beneficial. The presence of cervical mucus can possibly interfere with the collection of fluorescence spectra for tissue classification. Patients should not use vaginal preparations during the 48 hours prior to tissue fluorescence measurements.

Acetic Acid↗

Can group B streptococci cause symptomatic vaginitis?

BACKGROUND: Maternal cervicovaginal colonization with Lancefield group B streptococci (GBS) is an important risk factor for neonatal morbidity and mortality. About 15% of women are carriers of GBS. Usually, they are asymptomatic. CASES: We describe two patients with symptomatic vaginitis for which no apparent cause was found. Both patients were heavily colonized with GBS. After antibiotic treatment, both became asymptomatic and culture negative, but after recolonization with GBS, symptoms resumed. This phenomenon was repeatedly observed. After emergence of resistance to antibiotics, local application of chlorhexidine appeared to be the only useful treatment. CONCLUSION: We hypothesize that GBS-vaginitis may be a possible disease entity. Although at present it is not clear why some patients become symptomatic, we speculate that the immunologic response is somehow selectively hampered in such patients.

Administration, Intravaginal↗

Serial changes in the biophysical profile in patients undergoing cervical ripening with a controlled release PGE2 vaginal pessary.

OBJECTIVE: The purpose of this study was to evaluate the effects of exogenous administration of PGE2 upon the components of the biophysical profile. METHODS: The study group included 17 nulliparas at > or = 38 weeks gestation, with a Bishop score of < or = 4, requiring induction of labor. A controlled release vaginal pessary containing 10 mg of PGE2, designed to release hormones at approximately 0.8 mg per hour in vitro, was used for 12 hours of cervical ripening. The BPP was performed by the same sonographer at three intervals: prior to pessary insertion, at 6 hours, and 12 hours. RESULTS: None of these patients had membrane rupture or went into spontaneous labor during the ripening process. All patients subsequently required amniotomy and oxytocin. The proportion of patients scoring 2 points for fetal breathing movements decreased from 59% at baseline to 0% at 12 hours, P < 0.0005, and the proportion of patients with fetal body movements decreased from 100% at baseline to 25% at 12 hours, P < 0.0005. However, the other components of the biophysical profile were not affected. The mean maternal plasma PGE2 metabolite concentrations were 235 pg/ml, 475 pg/ml, and 466 pg/ml at 0, 6 and 12 hours, respectively, P < 0.005. CONCLUSIONS: In term patients, vaginal administration of the PGE2 pessary was associated with improved Bishop score over 12 hours and significant increases in maternal plasma PGEM levels at 6 hours and 12 hours. These changes were inversely related to fetal breathing and body movements.

Administration, Intravaginal↗

Vaginal misoprostol vs. concentrated oxytocin plus low-dose prostaglandin E2 for second trimester pregnancy termination.

OBJECTIVE: To examine the efficacy of vaginal misoprostol for mid-trimester pregnancy termination. METHODS: This randomized trial compared misoprostol, 200 microg per vaginum q 12 h to a protocol of concentrated oxytocin plus low-dose vaginal prostaglandin E2 suppositories (10 mg q 6 h). Success was defined as an induction-to-delivery interval < or =24 h. RESULTS: Interim analysis of the first 30 (15-misoprostol, 15-concentrated oxytocin) women demonstrated that the 2 groups were similar with regard to indication for delivery, gestational age, and demographic characteristics. Misoprostol was associated with a lower success rate (67 vs. 87%, P = .2), a longer induction-delivery interval (22 h vs. 18 h, P = .09), a higher rate of retained placenta requiring curettage (27 vs. 13%, P = .65), and a higher live birth rate (50 vs. 0%, P = .006). CONCLUSIONS: Compared to a regimen of concentrated oxytocin plus low-dose prostaglandin E2, misoprostol administered as vaginal tablets in a dose of 200 microg q 12 h is not satisfactory for mid-trimester pregnancy termination in an unselected population.

Abortion, Induced↗

Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection.

BACKGROUND: Early-onset group B beta-hemolytic streptococcus (GBS) infection accounts for approximately 30% of neonatal infections, has a high mortality rate and is acquired through vertical transmission from colonized mothers. Several trials have demonstrated the efficacy of intrapartum chemoprophylaxis (IPC) for preventing early-onset disease (EOD). Vaginal disinfection with chlorhexidine during labour has been proposed as another strategy for preventing GBS EOD in the preterm and term neonate. Chlorhexidine has been found to have no impact on antibiotic resistance, is inexpensive, and applicable to poorly equipped delivery sites. OBJECTIVES: To determine the effectiveness of vaginal disinfection with chlorhexidine during labour for preventing early-onset GBS infection in preterm and term neonates. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth trials register (October 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to March 2003), CINAHL (1982 to March 2003) and LILACS (1982 to September 2003). SELECTION CRITERIA: Randomized and quasi-randomized trials comparing vaginal disinfection with chlorhexidine to placebo, or no treatment. DATA COLLECTION AND ANALYSIS: We extracted information from the results sections of the included studies. We reported relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes. We calculated the number needed to treat (NNT) with 95% CIs when a statistically significant RD was found. We used a chi square test (chi2) and the I2 analysis to test for heterogeneity, and applied a fixed or random effects model accordingly. MAIN RESULTS: Five studies, including approximately 2190 term and preterm infants, met the inclusion criteria and reported on at least one of the outcomes of interest for this systematic review. When all studies were combined there was a statistically significant (p = 0.005) reduction in colonisation (RR 0.72, 95% CI 0.56 to 0.91); RD -0.16 (95% CI -0.26 to -0.05); NNT 6 (95% CI 4 to 20). There was no statistically significant between-study heterogeneity. There was no statistically significant between-study heterogeneity both for RR (chi(2) = 3.21 [p = 0.2], I(2) = 37.8%) and for RD (chi(2) = 1.66 [p = 0.44], I(2) = 0%). There was no statistically significant reduction in EOD including GBS infection, GBS pneumonia, GBS meningitis or mortality. REVIEWERS' CONCLUSIONS: Vaginal chlorhexidine resulted in a statistically significant reduction in GBS colonisation of neonates, but was not associated with reductions in other outcomes. The review currently does not support the use of vaginal disinfection with chlorhexidine in labour for preventing EOD. Results should be interpreted with caution as the methodological quality of the studies was poor.

Administration, Intravaginal↗