Effect of pre-treatment with deslorelin on the ovarian response of ewes superovulated with FSH.

This study evaluated the use of the GnRH agonist hormone, deslorelin, to control the follicular population before initiating multiple ovulation and embryo transfer (MOET) treatment. Twenty-four cross-bred Santa Inês ewes, aged between 2 and 4 years, were randomly assigned to either a control group (n = 11) or a treated group (n = 13). All ewes received an intravaginal device containing 60 mg of medroxyprogesterone acetate on day 0, and a new device on day 7, which remained in place until day 14. Additionally, the ewes were administered 125 µg of cloprostenol on day 7. The superovulatory treatment involved administering 200 mg of pFSH, divided into eight decreasing doses at 12-h intervals starting on day 12. On day 14, 300 IU of eCG was administered. In the deslorelin group, three doses of 100 µg of deslorelin were administered starting on day 3 after the insertion of the vaginal device, with subsequent doses given at 72-h and 144-h intervals. Natural mating was performed 36 h after the removal of the progesterone implant using males with proven fertility. Embryo collection took place on the 6th day after mating, and the recovered structures were quantified and evaluated for quality and developmental stage. Transrectal ultrasonography was conducted on days 12, 16 and 21 to evaluate the ovaries, specifically to assess the ovarian follicular population and the presence of the corpus luteum. Ewes in the control group had higher embryo recovery rates (p < .01) compared to the treated group (5.2 ± 0.8 vs. 1.1 ± 0.8), with differences observed primarily in the number of morulae. The number of corpus luteum observed during the laparotomy on day 21 was significantly higher (p < .01) in the control group (10.44 vs. 4.5 corpus luteum per ewe). Yet, the treated group had a significantly higher number of follicles (p < .05) on the first day of pFSH application (5.5 vs. 3.0 follicles per ewe). In conclusion, although the inclusion of deslorelin in the superovulation protocol resulted in increased synchronization of oestrus and follicle number, it did not lead to an increase in the number of corpus luteum or harvested embryos.

Reproductive outcomes in Holstein heifers synchronized with timed-AI protocols that provide for a lengthened proestrus.

This study compared reproductive outcomes among two protocols for synchronization of ovulation that provide for a lengthened proestrus with the conventional oestradiol-based protocol currently used for timed-AI (TAI). Holstein heifers (13-15 months) at one location were assigned randomly to one of three TAI protocols. Heifers (n = 150) in the 7-day oestradiol benzoate (EB) group received a progesterone device (Cue-Mate) and 2 mg EB on Day 0; 500 µg of cloprostenol (PGF) and Cue-Mate removal on Day 7; 1 mg of EB on Day 8 and TAI on Day 9 (54 h after Cue-Mate removal). Heifers (n = 150) in the 5-day CO-Synch (CO) group received a Cue-Mate and 100 µg of gonadotropin-releasing hormone (GnRH) on Day 2; Cue-Mate removal and PGF (twice, 12 h apart) on Day 7; and GnRH along with TAI on Day 10 (72 h after Cue-Mate removal). Heifers (n = 150) in the J-Synch (JS) group received a Cue-Mate and 2 mg of EB on Day 1; PGF and Cue-Mate removal on Day 7; GnRH and TAI on Day 10 (72 h after Cue-Mate removal). Heifers were inseminated by one technician with frozen-thawed conventional semen from one of four commercially available sires. Plasma progesterone (P4) concentrations (ng/mL) were determined at Cue-Mate removal and TAI. Ovarian ultrasonography was done in a subset of 217 heifers at the initiation of protocols, at Cue-Mate removal; TAI; and 7 days after TAI. Approximately, 28 and 50 days after TAI pregnancy status was determined by ultrasonography. Mean (±SEM) plasma P4 concentration at Cue-Mate removal was greater (p < .01) in CO (6.02 ± 0.2) and JS (6.51 ± 0.2) compared to EB heifers (4.53 ± 0.2). Mean (±SEM) plasma P4 concentration at TAI was lowest in the JS (0.28 ± 0.05), intermediate in CO (0.46 ± 0.02), and greatest in EB heifers (0.66 ± 0.05, p < .01). The diameter of the ovulatory follicle (mean ± SEM) was the smallest in the JS group compared to that in the CO and EB groups (15.8 ± 0.5; 13.9 ± 0.5; and 12.7 ± 0.5 mm for EB, CO and JS, respectively). More (p < .01) heifers in the JS group had their oestrous cycle synchronized (50.0, 78.8 and 82.4% for EB, CO and JS groups), and were pregnant at 28 (40.3, 51.3 and 63.3% for EB, CO and JS groups) and 50 days after TAI (32.6, 46.0 and 60.0% for EB, CO and JS groups). In summary, heifers subjected to the J-Synch TAI protocol had lower P4 at TAI, and better overall response to hormonal treatments, which resulted in increased P/AI at 28 and 50 days after TAI compared to those heifers subjected to either a 7-day EB protocol or a 5-day CO-synch protocol.

The male effect associated with prostaglandins and reproductive outcomes in photo-stimulated Saanen goats during the non-breeding season.

The efficiency of combining oestrous induction via a light program (16 h of light and 8 h of darkness for 60 days, ending on Day 0 - D0) with cloprostenol administration, followed by the male effect or not, was tested in acyclic Saanen goats during the non-breeding season (June/2019 to January/2020). Initially, all animals (males and females) were submitted to the described light program; 60 days after its ending (D60), the females were divided into two groups, with (G1; n = 67) or without (G2; n = 61) a male effect from D60 to D75 after the light program. At D75, both groups received two cloprostenol doses (120 µg; intramuscular) 7.5 days apart (D75 and D82.5). Artificial insemination was performed at a specific time according to the oestrous onset (approximately 68.4 ± 1.2 h between the second cloprostenol dose and IA). Ultrasound scans were performed at different intervals to evaluate follicular dynamics and confirm pregnancy. At the first cloprostenol dose (D75), the proportion of does with at least a corpus luteum (CL), which indicates resumed cyclicity, was greater in G1 than in G2 (85.2% vs. 48.8%; p < .05), although no difference was found at the second dose (p > .05). The adjusted pregnancy rates (number of pregnant goats/oestrous goats) differed between G1 and G2 (21.7% vs. 42.0%; p < .05). G1 also showed a higher frequency of functional CL (based on blood flow and morphology) compared to G2 (96.9% vs. 66.7%; p < .05) at D116. A male effect using photo-stimulated bucks after the first cloprostenol dose increased the number of does presenting CL after buck removal, and no impairment in the pregnancy rates of multiparous does was found.

Effect of prostaglandin treatment on the estrus behaviour, follicular and luteal morphometry and serum hormone profile in sub-estrus buffaloes during non-breeding season.

Sub-estrus buffaloes do not exhibit estrus signs despite being cyclic contributing to extended service periods and inter-calving intervals causing significant economic loss. The present study described the effect of synthetic prostaglandin (PGF2α) on estrus behaviour, follicular and luteal morphometry, and serum estradiol (E2) and progesterone (P4) profile in sub-estrus buffaloes during the non-breeding season. The incidence of sub-estrus was 38.4% during the non-breeding season. The sub-estrus buffaloes (n = 33) were divided into two groups, viz., Control (n = 16) and PGF2α treatment (Inj. Cloprostenol 500 µg, i.m., n = 17). Estrus induction response was significantly greater in the treatment (100 vs. 18.75%, p < .001), and a relatively greater proportion of animals conceived in the treatment group (29.41 vs. 6.25%, p = .08). The time elapsed to induction of estrus and insemination following treatment was significantly lower in the treatment group than control. A significant increment in the follicle diameter (9.72 ± 0.45 vs. 13.00 ± 0.45 mm, P < .0001) and serum estradiol (E2) concentration (66.01 ± 11.92 vs. 104.9 ± 13.21 pg/mL, p = .003) observed at the post-treatment period in the PGF2α treatment group. At the same time, CL diameter was reduced significantly at a higher regression rate in the PGF2α treated buffaloes than those of control. Of the responded buffaloes, only 30% showed high-intensity estrus attributed to the expulsion of cervico-vaginal mucus (CVM), uterine tonicity, micturition, and mounting response by a teaser bull. From this study, it can be concluded that the administration of PGF2α could induce estrus in the sub-estrus buffaloes during the non-breeding season. Behavioural changes, along with sonographic observation of POF, regressing CL, and serum E2 and P4 concentration would be useful to determine the right time of insemination in sub-estrus buffaloes during non-breeding season.

Customized modified therapies for ovarian cyst and persistent follicle followed with TAI in early postpartum dairy cows.

Background: Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve reproductive performance in dairy cows has become a necessity. Aim: Improve reproductive performance and ovarian activity in postpartum cows with specific customized treatment for OC and PFs. Methods: The study included 48 cows at 14 days P.P, which received two dosages of 500 µg IM cloprostenol, 14 days apart as presynchronization protocol. Ultrasound ovarian scans 14 days after the last injection for 4 weeks. The cows were divided into three groups according to ovarian status: OC (n = 14), PF (n = 12), and NE (n = 22). In the OC group, received 500 µg IM cloprostenol and 100 µg IM cystoriline, a second dose of cloprostenol 14 days later and a second dose of cystoriline 36 hours later, and AI after 24 hours (GnRH+ PG/PG/GnRH). In the PF group, was fitted with progesterone-releasing intravaginal device (PRID) for 9 days; the same day, they received 100 µg cystoreline then 500 µg cloprostenol 7 days later, after PRID removal AI 56 hours later (PRID + GnRH/PG). In the NE group, artificial insemination was implemented until 28 days depending on estrus detection. Results: The ovarian activity was greatly affected by the customized treatments, leading to enhanced follicular and luteal activity, particularly after the PGF2α injection. The OC and PF groups showed substantial estrus responses of 71.43% and 75.02%, respectively, during AI time. While the NE group had an ovulation rate of 54.5% and a pregnancy rate of 31.8%, the treatment groups showed marked improvements in reproductive performance. The ovulation rates in the OC and PF groups were 71.43% and 75% and the pregnancy rates at the 1st artificial insemination were 64.28% and 66.7%. Conclusion: Improving reproductive performance and minimizing the time to first service are possible advantages of early case-specific treatment for postpartum cows with OC and PFs.

Early induction of luteolysis in a timed AI protocol increases reproductive performance in beef cows.

The aim of this study was to produce a longer proestrus by early administration of prostaglandin F2α (PGF) in a timed artificial insemination (TAI) protocol in non-suckling Bos taurus (Angus crossbreed) beef cows. On day 0, cows (n = 489) were treated with an intravaginal 1 g progesterone (P4) device and 2 mg of estradiol benzoate. On day 7, cows were randomized into two groups: PGF7(n = 244; 500 µg of sodium cloprostenol 24 h before P4 device removal) or PFG8 (n = 245; 500 µg of sodium cloprostenol at P4 device removal). On day 8, P4 device was removed and cows received 0.5 mg of estradiol cypionate. All cows were submitted to TAI on day 10 (48-50 hours after P4 device removal). Cows treated with PGF on day 7 had greater expression of estrus (91.3 vs 79.1 %; P = 0.0011), regardless of CL presence at beginning of the protocol. Cows from PGF7 group had lower circulating P4 concentrations on day 8 in comparison with PGF8 treated cows (1.86 vs 2.99 ng/mL; P < 0.001). However, preovulatory follicle diameter did not differ among treatments at TAI (11.9 vs 11.8 mm; P = 0.7881). Pregnancy per TAI (P/TAI) was greater for PGF7 (63.9 vs 50.6 %; P = 0.0114) than PGF8 treated cows. In cows with follicles <8.5 mm at TAI, expression of estrus (33.3 vs 26.6 %; P = 0.6427) and P/TAI (40 vs 26.6 %; P = 0.3657) were low in both PGF7 and PGF8 treated cows, respectively. In cows with medium follicle size (8.5 to 11.9 mm) PGF7 treated cows had greater expression of estrus (90.5 vs 80 %; P = 0.033) and P/TAI (62.2 vs 49 %; P = 0.053). In cows with follicles >12 mm, expression of estrus was greater for PGF7 than PGF8 treated cows (99.1 vs 93.3 %; P = 0.045), however P/TAI did not differ (68.2 vs 59 %; P = 0.149). In cows with P4 < 1.99 ng/mL on day 8, expression of estrus was similar between PGF7 and PGF8 treated cows (92.6 vs 90.4 %; P = 0.53), and P/TAI tended to be greater for PGF7 than PGF8 treated cows (63 vs 52.1 % P = 0.076). However, in cows with P4 > 2 ng/mL PGF7 cows had higher expression of estrus (89 vs 67.5 %; P = 0.0005) and P/TAI (64.8 vs 48.7 %; P = 0.021) than PGF8. Thus, increasing the proestrous period by inducing luteolysis 24 hours earlier than removing the P4 intravaginal device enhanced fertility in non-suckling cyclic beef cows by increasing expression of estrus and P/TAI.

Effect of prostaglandin alone and in combination with trace minerals on the follicular and luteal dynamics, estrus response and pregnancy in sub-estrus buffaloes (Bubalus bubalis).

Sub-estrus is a condition when buffaloes do not display behavioural estrus signs, despite being in estrus and causes a delay in conception and increases the service period. The present study describes the effect of synthetic prostaglandin (PGF2α) alone and in combination with trace minerals on the follicular and corpus luteum (CL) dynamics, serum estradiol (E2) and progesterone (P4) concentration correlating estrus response and pregnancy outcome in sub-estrus buffaloes during the breeding season. A total of 50 sub-estrus buffaloes, identified through ultrasonography (USG) examination, were randomly allocated into three groups, viz. T1 (Synthetic PGF2α, Inj. Cloprostenol 500 µg, i.m, n = 17), T2 (Synthetic PGF2α + Trace mineral supplementation, Inj. Stimvet 1 mL/100 kg body weight, i.m., n = 17) and control (untreated; n = 16). Following treatment, 100% of sub-estrus buffaloes were induced estrus in the T1 and T2 groups, while only 18.75% were induced in the control. The CL diameter and serum P4 concentration were significantly lower at post-treatment, whereas the pre-ovulatory follicle (POF) size and serum E2 concentration were significantly higher in the T1 and T2 groups as compared to the control (p < .05). The buffaloes of the T2 group had a greater proportion of moderate intensities estrus than those of T1. Moreover, the proportion of buffaloes conceived in the T1 and T2 were 41.2% and 52.95%, respectively. The larger POF diameter and higher serum E2 concentration were associated with intense intensity estrus and higher conception rate (66.7%) in sub-estrus buffaloes. Similarly, CL regression rate, POF size and serum E2 concentration were relatively higher in the buffaloes conceived as compared to those not conceived. It is concluded that synthetic PGF2α in combination with trace minerals induces moderate to intense intensities estrus in a greater proportion of sub-estrus buffaloes and increases the conception rate during the breeding season. Moreover, behavioural estrus attributes correlating follicle and luteal morphometry, serum E2 and P4 concentration could be used to optimise the breeding time for augmenting the conception rate in sub-estrus buffaloes.

Impact of presynchronization and Ovsynch on early postpartum ovarian activity and fertility of dairy cows in Libya.

Background: Reproductive efficiency affects dairy cow profitability. Ovarian function in postpartum (P.P.) has been better understood using ultrasound and hormonal assays. Optimizing ovulation synchronization and carefully timing artificial insemination (TAI) can greatly enhance reproductive rates in dairy cows. Aim: This experiment was designed to investigate the reproductive performance and ovarian activity in early postpartum lactating dairy cows using the Presynch-PGF2α, Ovsynch protocol, and TAI. Methods: Randomly the cows were assigned to a control group and a treatment group, based on the chronological order of their calving date. On day 14 P.P., both groups received two cloprostenol treatments, 14 days apart. Ultrasonographic inspections were conducted on day 14 to check ovarian activity and uterine contents. On day 11, after presynchronization, cows in the treatment group were given 100 µg IM. of cystorelin, followed by a luteolytic dose of 500 µg IM., cloprostenol on day 7, and a second dose of cystorelin on day 8 (36 hours later). After the second cystorelin injection by 16-20 hours, cows were inseminated, while the control group had all cows displaying spontaneous estrus between day 0 and day 28 were artificially inseminated. Results: Ovarian activity began to improve at 82.61% on day 19 P.P., with complete recovery between days 24 and 27 P.P. The second cloprostenol injection approached, causing follicular size to reach 8.41 ± 1.04 mm. After the second injection, ovarian activity switched from follicular to luteal, with corpus luteum rates of 23.91% and 26.1%. The presynchronized PGF2α regimen significantly enhanced ovarian activity from days 19-35 P.P. Ovulation and pregnancy rates in the Ovsynch group were 54.2% and 41.7% at the first timed artificial insemination (TAI), compared to 54.5% and 31.8% in the control group. There was no significant impact between them; it was just high in the presynchronized Ovsynch group. However, the P.P. period was minimized to 47-49 days till the first AI reached a 41.7% pregnancy rate and 20.8% at the second AI, for an overall 62.5%. Conclusion: The current study concludes that presynchronization during preservice in clinically normal P.P. dairy cows reduces P.P. duration, increases ovarian activity performance, and reduces ovarian dysfunctions from day 19 to day 35 P.P., as well as improves the pregnancy rate.

Cloprostenol effect with and without male stimulation on oestrus synchronization in Peru guinea pigs.

Cloprostenol, a synthetic derivative of prostaglandin F2α, effectively triggers functional and morphological regression of the corpus luteum (luteolysis). In rural Peru, the guinea pig (Cavia porcellus) holds significance within the local economy and serves as a valuable protein source. Enhancing reproductive efficiency is crucial to achieve uniformity in weight, age, and litter size across commercial systems. Thus, our study aimed to evaluate the effect of cloprostenol with and without male stimulation on the onset, duration, and intensity of oestrus in Peru guinea pigs. A total of 128 guinea pigs (120 females and eight males) between 8 and 12 months of age, weighing between 800 and 1200 g, were distributed in cages of 15 females per treatment. Cloprostenol sodium (0 [control], 0.20, 0.25, and 0.30 mg/animal) was IM administered to the groups with and without male stimulation. Four isolated males in individual cages, different from the one used for the treatment, were considered to detect oestrus. The oestrus intensity was assessed by observing sexual behaviour signs such as restlessness, moaning, attempts to mount, pelvic elevation, loin stretching, and vulvar inflammation. The oestrus was manifested 2 days after the administration of cloprostenol sodium. At a dose of 0.30 mg/animal and with male stimulation, the earliest oestrus was observed at 46.9 h. There was a reduction in the oestrus duration (p < .05) in guinea pigs that received the three doses of cloprostenol sodium compared to the control group. The highest percentages of frank oestrus intensity (66.7%) were strongly associated with the administered doses of cloprostenol sodium (p < .01). In conclusion, the cloprostenol sodium administration was proper for rapid oestrus induction in Peru guinea pigs.

A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study.

PURPOSE: To compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. METHODS: 691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. RESULTS: 661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia. CONCLUSION: The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.

The effectiveness of low-dose of eCG in timed AI Nelore (Bos indicus) heifers.

This study evaluated the efficacy of the administration of different doses of equine chorionic gonadotropin (eCG; 0 IU, 200 IU, or 300 IU) at the time of the progesterone device removal in 2-year-old Nelore (Bos indicus) heifers synchronized for fixed-timed artificial insemination (FTAI). On day 0 (D0), a total of 398 heifers received 2 mg of oestradiol benzoate i.m., 0.53 mg of cloprostenol i.m., and an eight-day previously used (second use) intravaginal device containing 1 g of progesterone (P4). Eight days later (D8), simultaneous with the P4 device removal, 0.5 mg of oestradiol cypionate i.m. and 0.53 mg of cloprostenol i.m. were administered. At the same time, heifers were randomly assigned to receive one of the following treatments: G-0 IU (n = 141; no eCG treatment), G-200 IU (n = 132; treated with 200 IU of eCG), and G-300 IU (n = 125; treated with 300 IU of eCG). FTAI was performed 48 h after the P4 device removal (D10). Ultrasonographic evaluations were performed at D0, D10, and D17. Heifers were scanned to measure the size of the largest follicle (LF), the presence, number, and size of the corpus luteum (CL), and the ovulation rate. Subsequently, at D40, the heifers underwent scanning to determine the pregnancy rate and identify any twin pregnancies. Additionally, at D70, scans were performed to assess pregnancy loss (PG). Data were analysed by orthogonal contrasts [C1 (eCG effect): control x (200 IU + 300 IU) and C2 (eCG dose effect): 200 IU × 300 IU]. On D0, CL presence was similar between the groups [G-0 IU = 65.2% (92/141), G-200 IU = 55.3% (73/132), and G-300 IU = 63.2% (79/125); p = .16]. No interactions between the presence of CL on D0 and eCG treatment were found for any of the variables (p > .05). The diameter of the LF at FTAI (D10) was not influenced by eCG treatment (p = .22) or eCG dose (p = .18). However, treatment with eCG increased the diameter of the CL at D17 (G-0 IU = 15.7 ± 0.3 mmb , G-200 IU = 16.6 ± 0.2 mma , and G-300 IU = 16.6 ± 0.3 mma ; p = .001), regardless of the dose used (p = .94). The ovulation rate was higher in heifers treated with eCG [G-0 IU = 79.4%b (112/141), G-200 IU = 90.2%a (119/132), and G-300 IU = 93.6%a (117/125); p = .002], but there was no effect of eCG dose (p = .36). Pregnancy per AI (P/AI) on D40 [G-0 IU = 32.6%b (46/141), G-200 IU = 42.4%a (56/132), and G-300 IU = 42.4%a (53/125); P = 0.05] and D70 [G-0 IU = 29.1%b (41/141), G-200 IU = 40.9%a (54/132), and G-300 IU = 40.8%a (51/125); p = .02] were higher on heifers that received eCG; however, no dose effect was observed for P/AI on D40 (p = .89) nor D70 (p = .98). Pregnancy loss between D40 and D70 tended to reduce (p = .07) in eCG-treated heifers without dose effect (p = .91). Heifers with CL at D0 presented a greater follicle diameter (LF) on D10 (With CL = 11.2 ± 0.2 mm and Without CL = 10.2 ± 0.2 mm; p = .05), CL diameter on D17 (With CL = 15.8 ± 0.03 mm and Without CL = 11.8 ± 0.6 mm; p = .01), and ovulation rate [With CL = 95.5% (233/244) and Without CL = 74.7% (115/154); p = .01]. However, no difference in pregnancy rate at D40 (p = .52) and D70 (p = .84) was found. In conclusion, eCG treatment increases ovulation and pregnancy rates of heifers submitted to a FTAI protocol. Furthermore, eCG treatment increases the diameter of the CL after FTAI and reduces pregnancy losses. No dose effect was observed, suggesting Nelore (Bos indicus) heifers respond to 200 IU of eCG treatment for FTAI.

Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells.

PURPOSE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. CONCLUSION: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.

Luteal tissue blood flow and side effects of horse-recommended luteolytic doses of dinoprost and cloprostenol in donkeys.

This study assessed luteolysis and side effects in jennies receiving standard horse-recommended doses of cloprostenol and dinoprost. Sixteen cycles of eight jennies were randomly assigned in a sequential crossover design to receive dinoprost (5 mg, i.m.) and cloprostenol (0.25 mg, i.m.) at 5-d post-ovulation. B-mode and Doppler ultrasonography were employed to assess luteal tissue size and blood flow before (-15 min and 0h) and after (0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, and 48h) administering PGF2α. Immunoreactive progesterone concentrations were assayed at similar timepoints via RIA. Side effects such as sweating, abdominal discomfort, and diarrhea were scored at 15-min-intervals for 1h after PGF2α. Data normality was assessed with the Shapiro-Wilk's test. Luteal tissue size and blood flow were analyzed using PROC-MIXED and post-hoc by Tukey. Non-parametric tests analyzed side effect variables. The luteal blood flow increased overtime by 27% at 45 min and peaked by 49% at 3 h for dinoprost, and conversely, it increased by 14% at 30 min and peaked at 39% at 5h for cloprostenol (P<0.05). Luteal blood flow was reduced by 50%, 25%, and 10% on both groups at 8, 12, and 24h (P<0.05). Immunoreactive progesterone concentrations decreased in 0.5h for dinoprost and 1h for cloprostenol and gradually decreased by 48h (P<0.05). Dinoprost induced greater sudoresis scores, while cloprostenol resulted in greater abdominal discomfort and diarrhea scores (P<0.05). In conclusion, dinoprost and cloprostenol effectively induced luteolysis with distinct side effects; this could guide practitioners' case selection to use one or another PGF2α.

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. METHODS: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. RESULTS: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. CONCLUSION: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Additional intracervical prostaglandin reduces induction to calving time in buffaloes affected with incomplete cervical dilatation post-uterine detorsion.

Conventional induction protocol (CIP) of calving in buffaloes employs the intramuscular (IM) administration of dexamethasone (40 mg) and cloprostenol sodium (500 µg). If there is no progression in terms of cervical dilatation, then a second dose of cloprostenol sodium (500 µg) is administered intramuscularly. This protocol possesses certain demerits: (1) a wide range of response time intervals, and (2) increased risk of fetal membrane retention. Considering the cervix as a caudal continuation of the myometrium with its own contractile potential, and the limitations of CIP, we developed intracervical (IC) drug administration route in buffaloes. The proposed technique was evaluated for its use in a total of 22 cases of incomplete cervical dilatation in uterine torsion-affected buffaloes (IC-14 and IM-8). In addition to CIP, the IC group received an intracervical injection of cloprostenol sodium (500 µg) at the start of the experiment whereas the IM group received an extra intramuscular dose of cloprostenol sodium (500 µg) either after 24 h or when no progression in cervical dilatation is noticed. Surprisingly, the average response time during the experiment in the IC group was 5.8 h shorter (p < 0.000) than in the IM group (IC-5.7 ± 0.17 h vs. IM-11.9 ± 0.74 h). The duration from calving to fetal membrane expulsion (IC-12.8 ± 0.60 h vs. IM-17.5 ± 1.40 h; p < 0.002) and incidence of retention of fetal membrane were also less in the IC group (57.1% vs. 87.5%). The proposed intracervical drug administration potentiates cervical dilatation and can be regarded as a safe, effective, and feasible technique for attaining reliable results.

Low progesterone concentration in early pregnancy is detrimental to conceptus development and pregnancy outcome in horses.

High progesterone concentrations in the early luteal phase support pregnancy, whereas subphysiological progesterone concentrations delay embryonic development at least until placentation. In this study, fetal growth and development of pregnancy was investigated in pregnancies with prostaglandin F2α-induced low progesterone concentrations (PGF) in the early luteal phase and control pregnancies (CON) in the same mares (n = 12). Mares were inseminated and in PGF pregnancies received the prostaglandin F2α analogue cloprostenol (62.5 µg) on days 0-3 after ovulation to induce subphysiological progesterone concentrations; CON pregnancies remained untreated. Mares were assigned to PGF or CON treatments in alternating order and received the opposite treatment in the following year. Blood was collected and conceptus size determined repeatedly by transrectal (≤day 101) and transabdominal (>day 101) ultrasonography. After birth, foals were weighed, measured and submitted to a clinical examination. Treatment PGF resulted in fewer pregnancies than CON treatment. All foals born from CON pregnancies were healthy and mature, whereas 4/7 PGF pregnancies were either lost (one embryonic death, one abortion) or resulted in the birth of compromised foals (P = 0.018). Size of the conceptus (e.g., diameter day 49: PGF 6.6 ± 0.7, CON 7.7 ± 0.7 cm, P = 0.006) and embryo proper (e.g., crown rump length day 54; PGF 4.4 ± 0.8, CON 5.8 ± 0.6 cm, P = 0.015) differed between treatments. These size differences decreased over time and at birth PGF foals did not differ significantly from CON foals. In conclusion, reduced progesterone concentration in the early luteal phase leads to delayed conceptus growth beyond placentation and increased pregnancy loss.

Intensity of estrus expression - valuable obvious determinant of fertility in Bos indicus cows.

This study aimed to characterize estrus response and to establish relationships between intensity of estrus, preovulatory follicle (POF) size and estradiol (E2) concentrations on day of AI, luteal profiles and pregnancy outcome in lactating Hariana breed of cows. 200 cyclic cows were subjected to Ovsynch (n = 54) and Pre-OV treatment (n = 146). Ovsynch: Buserelin acetate (BA; 10 µg), Cloprostenol (500 µg) and BA (10 µg) were injected i.m. on day 0, 7 and 9, respectively, irrespective of treatment. Pre-OV: BA (10 µg) and Cloprostenol (500 µg) was also injected i.m. simultaneously 7 days prior to initiate Ovsynch. On the basis of estrus behavior, the cows were classified into three groups: weak, moderate and intense. Artificial insemination performed at 18-24 hours after 2nd BA of Ovsynch in both treatments. The average duration of estrus did not differ (p > 0.05) between Ovsynch and Pre-OV treatment. A positive correlation was observed between estrus response and POF size, concentration of E2 on day of AI and luteal profiles on day 12 post-AI. First service conception rate was higher in cows exhibited intense (45.46%) and moderate (42.56%) estrus response than weak (28.57%) estrus response. In conclusion, intensity of estrus expression could be considered as important determinant for deciding pregnancy outcomes in Bos indicus cows.

Single Administration of Bimatoprost Implant: Effects on 24-Hour Intraocular Pressure and 1-Year Outcomes.

PURPOSE: To evaluate the effects of a single bimatoprost implant administration on 24-hour intraocular pressure (IOP) lowering at 8 weeks, and 1-year IOP-lowering efficacy and safety outcomes. DESIGN: Multicenter, open-label, 12-month, phase 3b study (NCT04285580). PARTICIPANTS: Adults with open-angle glaucoma or ocular hypertension. METHODS: Participants (n = 31) received 10-µg bimatoprost implant in the study eye on day 1; IOP (sitting and/or supine) was measured with pneumatonometry every 2 hours throughout a 24-hour period at baseline and week 8. IOP was measured by Goldmann applanation tonometry (GAT) at hour 0 (8 am ± 1 hour) at baseline, weeks 8 and 16, and months 6, 9, and 12. MAIN OUTCOME MEASURES: The primary endpoint was the week-8 hour-matched change from baseline in habitual position IOP over 24 hours assessed with pneumatonometry. Hour 0 IOP change from baseline measured with GAT in study eyes that received no additional (rescue) IOP-lowering treatment, treatment-emergent adverse events (TEAEs), and central corneal endothelial cell density (CECD) were evaluated through 12 months. RESULTS: The mean (standard deviation [SD]) baseline IOP at hour 0 was 24.2 (2.70) mmHg and 25.3 (7.15) mmHg by GAT and pneumatonometry, respectively. Pneumatonometer measurements of IOP taken over 24 hours at week 8 with the participant in habitual position (sitting from 8 am to 10 pm, supine from 12 am to 6 am) showed consistent IOP lowering through the day and night and reduced fluctuation in IOP. The range in IOP measurements over 24 hours was reduced from baseline by a mean (SD) of -1.6 (2.98) mmHg. All 31 bimatoprost implant-treated participants completed the 12-month study; 23 (74%) required no rescue IOP-lowering treatment. The mean (SD) IOP reduction from baseline at month 12 in nonrescued eyes was -4.3 (3.35) mmHg. The most common TEAE was conjunctival hyperemia (incidence 35.5%, 11/31). No implant-treated eye had a ≥ 15% loss in CECD from baseline. CONCLUSIONS: A single intracameral administration of the bimatoprost implant lowered IOP in the habitual position consistently throughout the day and night at week 8. The majority of participants continued to have reduced IOP for 1 year without additional therapy. The 1-year safety profile was favorable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intraocular Pressure and Eyedrop Usage Reduction with Intracameral Bimatoprost Implant.

Purpose: Sustained intraocular drug delivery devices are being developed to lower intraocular pressure (IOP) and improve adherence in patients with glaucoma. The purpose of this study was to assess the IOP and eyedrop usage reduction effects of intracameral bimatoprost implants. Methods: We retrospectively reviewed the records of 46 eyes from 38 patients who received an intracameral implant containing 10 µg of bimatoprost as a replacement or addition to their existing eyedrop regimen and investigated IOP, eyedrop usage, and adverse effects. Results: Patients were followed for an average of 274 ± 104 (mean ± standard deviation) days after implant. Mean reduction in IOP (mmHg) at 3 months ±30 days, 6 months ±60 days, and 12 months ±90 days postoperation compared to baseline was 1.26 ± 2.53 (P = 0.002), 0.93 ± 4.71 (P = 0.098), and 1.35 ± 5.24 (P = 0.053), respectively. Reduction in eyedrops at 3 months ±30 days, 6 months ±60 days, and 12 months ±90 days postoperation compared to baseline were 0.62 ± 0.49 (P < 0.001), 0.55 ± 0.73 (P < 0.001), and 0.51 ± 0.71 (P < 0.001), respectively. Fifteen eyes (32.6%) experienced implant failure, defined as either restarting IOP-lowering eyedrops or undergoing surgical intervention, at an average of 260 ± 122 days after implant. Conclusions: While some patients eventually experienced implant failure, intracameral bimatoprost implants may result in fewer adverse reactions and successfully lower IOP and eyedrop burden over a longer period than previously reported.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.