Effects of resynchronization programs on pregnancy per artificial insemination, progesterone, and pregnancy-associated glycoproteins in plasma of lactating dairy cows

Objectives were to develop a timed artificial insemination (TAI) resynchronization program to improve pregnancy per AI and to evaluate responses of circulating progesterone and pregnancy-associated glycoproteins in lactating cows. Cows (n = 1,578) were presynchronized with 2 injections of PGF_2α, given 14 d apart starting on d 45 ± 3 postpartum, followed by Ovsynch [2 injections of GnRH 7 d before and 56 h after injection of PGF_2α, TAI 16 h after second injection (d 0)]. The Resynch-treated cows received an intravaginal progesterone insert from d 18 to 25, GnRH on d 25, and pregnancy diagnosis on d 32, and nonpregnant cows received PGF_2α., GnRH 56 h later, and TAI 16 h later (d 35). The control cows were diagnosed for pregnancy on d 32 and nonpregnant cows received GnRH, PGF_2α 39 d after TAI, GnRH 56 h later, and TAI 16 h later (d 42). Pregnancy was reconfirmed on d 60 after AI. Ovarian structures were examined in a subset of cows at the time of GnRH and PGF_2α injections. Blood samples for analyses of progesterone and pregnancy-associated glycoproteins were collected every 2 d from d 18 to 30 in 100 cows, and collection continued weekly to d 60 for pregnant cows (n = 43). Preenrollment pregnancies per AI on d 32 did not differ for cows subsequently treated as Resynch (45.8%, n = 814) and control (45.9%, n = 764), and pregnancy losses on d 60 were 6.7 and 4.0%, respectively. Resynchronized service pregnancy per AI (36%, n = 441; 39.5%, n = 412) and pregnancy losses (6.3 and 6.7%) did not differ for Resynch and control treatments, respectively. Days open for pregnant cows after 2 TAI were less for the Resynch treatment than for the control treatment (96.2 ± 0.82 vs. 99.5 ± 0.83 d). Cows in the Resynch treatment had more large follicles at the time of GnRH. The number of corpora lutea did not differ between treatments at the time of PGF_2α. Plasma progesterone for pregnant cows was greater for Resynch cows than for control cows (18-60 d; 6.6 vs. 5.3 ng/mL), and plasma concentrations of progesterone on d 18 were greater for pregnant cows than for nonpregnant cows (5.3 vs. 4.3 ng/mL). Plasma pregnancy-associated glycoproteins during pregnancy were lower for cows in the Resynch treatment compared with control cows on d 39 (2.8 vs. 4.1 ng/mL) and 46 (1.3 vs. 3.0 ng/mL). Cows pregnant on d 32 that lost pregnancy by d 60 (n = 7) had lower plasma concentrations of pregnancy-associated glycoproteins on d 30 than cows that maintained pregnancy (n = 36; 2.9 vs. 5.0 ng/mL). Pregnancy-associated glycoproteins on d 30 (>0.33 ng/mL) were predictive of a positive d 32 pregnancy diagnosis (sensitivity = 100%; specificity = 90.6%). In conclusion, Resynch and control protocols had comparable pregnancy per AI for first and second TAI services, but pregnancy occurred 3.2 d earlier in the Resynch group because inseminations in the Resynch treatment began 7 d before those in the control treatment. Administration of an intravaginal progesterone insert, or GnRH, or both increased progesterone during pregnancy. Dynamics of pregnancy-associated glycoproteins were indicative of pregnancy status and pregnancy loss.     

Resynchronization strategies to improve fertility in lactating dairy cows utilizing a presynchronization injection of GnRH or supplemental progesterone: I. Pregnancy rates and ovarian responses

Objectives were to evaluate 3 resynchronization protocols for lactating dairy cows. At 32 ± 3 d after pre-enrollment artificial insemination (AI; study d −7), 1 wk before pregnancy diagnosis, cows from 2 farms were enrolled and randomly assigned to 1 of 3 resynchronization protocols after balancing for parity, days in milk, and number of previous AI. All cows were examined for pregnancy at 39 ± 3 d after pre-enrollment AI (study d 0). Cows enrolled as controls (n = 386) diagnosed not pregnant were submitted to a resynchronization protocol (d 0-GnRH, d 7-PGF_2α, and d 10-GnRH and AI) on the same day. Cows enrolled in the GGPG (GnRH-GnRH-PGF_2α-GnRH) treatment (n = 357) received a GnRH injection at enrollment (d −7) and if diagnosed not pregnant were submitted to the resynchronization protocol for control cows on d 0. Cows enrolled in CIDR treatment (n = 316) diagnosed not pregnant received the resynchronization protocol described for control cows with addition of a controlled internal drug release (CIDR) insert containing progesterone (P₄) from d 0 to 7. In a subgroup of cows, ovaries were scanned and blood was sampled for P₄ concentration on d 0 and 7. After resynchronized AI, cows were diagnosed for pregnancy at 39 ± 3 and 67 ± 3 d (California herds) or 120 ± 3 d (Arizona herds). Cows in the GGPG treatment had more corpora lutea than CIDR and control cows on d 0 (1.30 ± 0.11, 1.05 ± 0.11, and 1.05 ± 0.11, respectively) and d 7 (1.41 ± 0.14, 0.97 ± 0.13, and 1.03 ± 0.14, respectively). A greater percentage of GGPG cows ovulated to GnRH given on d 0 compared with CIDR and control cows (48.4, 29.6, and 36.6%, respectively), but CIDR and control did not differ. At 39 ± 3 d after resynchronized AI, pregnancy per AI (P/AI) was increased in GGPG (33.6%) and CIDR (31.3%) cows compared with control (24.6%) cows. At 67 or 120 ± 3 d after resynchronized AI, P/AI of GGPG and CIDR cows was increased compared with control cows (31.2, 29.5, and 22.1%, respectively). Presynchronizing the estrous cycle of lactating dairy cows with a GnRH 7 d before the start of the resynchronization protocol or use of a CIDR insert within the resynchronization protocol resulted in greater P/AI after resynchronized AI compared with control cows.     

Resynchronizing estrus with progesterone or progesterone plus estrogen in cows of unknown pregnancy status

Two experiments were conducted to test 2 progesterone (P4)-based treatments that were applied to lactating dairy cattle of unknown pregnancy status to resynchronize estrus of nonpregnant cows. In experiment 1, cows were assigned randomly before a timed AI (TAI) to 1) treatment with a CIDR (controlled internal drug-releasing intravaginal insert containing P4) for 7 d starting on d 13 after TAI (CIDR; n = 300) or 2) no P4 treatment (control; n = 330). Compared with controls, P4 increased the synchrony of those detected in estrus, but failed to increase the overall return rates of non-pregnant cows during the 6 d after CIDR removal (27% vs. 31%; d 20 to 26 after TAI) and did not alter synchronized conception rates (32% vs. 20%) of those inseminated. Use of P4 did not compromise pregnancies resulting from TAI compared with controls (38% vs. 42%), but increased embryo survival between d 29 and 57 after TAI (65.5% vs. 44.3%). In experiment 2, on d 13 after TAI, 196 cows were treated with a CIDR insert for 7 d. Controls received no further treatment. Remaining cows were treated with 1 of 3 estrogen regimens: 1 mg of estradiol benzoate (EB), 0.5 mg of estradiol cypionate (ECP), or 1 mg of ECP on both d 13 and 21. Only 60% of nonpregnant, estrogen-treated cows were detected in estrus between d 20 and 26, and rates of return and conception did not differ among treatments. Estrogen on d 13 did not consistently turn over the dominant follicle when given at CIDR insertion but did increase concentrations of estradiol and reduced luteal function when administered on d 13 and 21 (24 h after CIDR removal). Treatments had no negative effects on milk yield, dry matter intake, or established pregnancies. Use of P4 alone had little effect on overall rates of return to estrus or conception at the first eligible estrus in experiment 1. Combining estrogen with P4 in experiment 2 had no detrimental effects on established pregnancies or subsequent conception and failed to improve return rates beyond P4 alone.     

Fertility of dairy cows after resynchronization of ovulation at three intervals following first timed insemination

Lactating Holstein cows (n = 711) on a commercial dairy farm in Wisconsin received a hormonal synchronization protocol to initiate first timed artificial insemination (TAI) on the following postpartum schedule: two injections of 25 mg PGF2alpha at 32 +/- 3 d and 46 +/- 3 d (Presynch); 100 microg GnRH at 60 +/- 3 d; 25 mg PGF2alpha at 67 +/- 3 d; and 100 microg GnRH + TAI at 69 +/- 3 d (Ovsynch). At first TAI, cows were randomly assigned to initiate the first GnRH injection of a hormonal protocol for resynchronization of ovulation (Resynch; 100 microg GnRH, d 0, 25 mg PGF2alpha, d 7, 100 microg GnRH + TAI, d 9) at 19 (D19), 26 (D26), or 33 d (D33) after first TAI to set up a second TAI service for cows failing to conceive to Ovsynch. Overall pregnancy rate per artificial insemination (PR/AI) to Ovsynch assessed 68 d after TAI was 31% and did not differ among treatment groups. For Resynch, PR/AI was assessed 26 d after TAI for D19 and D26 cows and 33 d after TAI for D33 cows. Overall PR/AI to Resynch was 32%. However, the PR/AI for D26 (34%) and D33 (38%) cows to Resynch was greater than for D19 cows (23%). Cows with a CL at the PGF2alpha injection (D19 cows) or at the first GnRH injection (D26 + D33 cows) of Resynch exhibited greater PR/AI to Resynch compared with cows without a CL. Survival analysis (failure time) of cows in the D26 and D33 treatment groups across the first three TAI services did not differ statistically. Although administration of GnRH to pregnant cows 19 d after first TAI service did not appear to induce iatrogenic embryonic loss, initiation of Resynch 19 d after first TAI service resulted in a lower PR/AI compared with initiation of Resynch 26 or 33 d after first TAI service.     

航天器时间触发系统时钟同步算法的仿真分析

时间触发技术已经逐步应用于航天器导航制导与控制(GNC)系统的信息体系结构设计中,由于时间触发技术使用了经典的Welch-Lynch分布式时钟同步算法[1]因此在工程应用中存在固有的系统级时钟定向漂移问题[2].针对上述问题,提出了一种使用单一精确时钟对全系统进行整体时钟校时的方案,根据分布式系统工作时序的特点,使用同步误差的算法解决了单一节点无法修正整个分布式系统参数的问题,使系统可以在有限偏差范围内不断调整时钟相位,避免了系统级的时间误差累计.使用形式化方法对算法进行了有界性和收敛性证明,并在Matlab/Simulink平台中对基于时间触发体系结构的GNC系统进行了数学建模和仿真,仿真结果表明GNC系统内所有节点的时钟偏差收敛且有界,满足实际使用需求.     

Short communication: Optimization of a timed artificial insemination program for reproductive management of heifers in Canadian dairy herds

Pregnancy per AI (P/AI) following the use of 1 of 2 timed AI (TAI) protocols and 2 different intervals between TAI and resynchronization were compared in heifers that were inseminated with either conventional or sex-sorted semen. Holstein heifers (n = 317; 527 inseminations) were submitted to a 5-d Cosynch protocol with (+) or without (–) GnRH at the time of controlled internal drug release (CIDR) insertion on d 0, CIDR removal and a single PGF_2α treatment on d 5, and TAI plus GnRH on d 8 (72 h later). Visual estrus detection (ED) was conducted on d 6 in the afternoon and d 7 in the morning and heifers observed in estrus were artificially inseminated on d 7 in the afternoon. Heifers were alternately assigned conventional or sex-sorted semen. Pregnancy was diagnosed by ultrasound 27 and 42 d after AI, and heifers diagnosed as nonpregnant were resynchronized, up to 3 times, starting on d 27 or 34 to provide an interbreeding interval of 35 or 42 d. Overall, TAI protocol had no effect on P/AI at 27 or 42 d after artificial insemination or on pregnancy loss, but P/AI following the first service tended to be higher in the –GnRH TAI group (66.3 vs. 56.8%). Pregnancy per AI at 27 d (61.9 vs. 55.5%) tended to differ between conventional and sex-sorted semen. Heifers artificially inseminated based on ED tended to have a greater P/AI (67.6 vs. 58.2%) and had decreased pregnancy loss (0.0 vs. 4.1%) than those submitted to TAI. A greater number of heifers in the –GnRH TAI protocol were artificially inseminated on ED than the +GnRH TAI protocol (21.5 vs. 13.7%). No difference in P/AI was observed between the 35- and 42-d interbreeding intervals; however, more heifers in the 42-d group were artificially inseminated based on ED than in the 35-d group (22.7 vs. 7.8%). A 5-d Cosynch+CIDR TAI protocol without the initial GnRH and with a single PGF_2α at CIDR removal is an acceptable alternative to achieve high P/AI when either conventional or sex-sorted semen is used in Holstein heifers. Breeding heifers based on detected estrus increases labor, but has the potential to increase fertility.     

Resynchronization of ovulation protocols for dairy cows including or not including gonadotropin-releasing hormone to induce a new follicular wave: Effects on re-insemination pattern,ovarian responses,and pregnancy outcomes

Our objectives were to evaluate the pattern of re-insemination, ovarian responses, and pregnancy per artificial insemination (P/AI) of cows submitted to different resynchronization of ovulation protocols. The base protocol started at 25 ± 3 d after artificial insemination (AI) and was as follows: GnRH, 7 and 8 d later PGF_2α, GnRH 32 h after second PGF_2α, and fixed timed AI (TAI) 16 to 18 h after GnRH. At 18 ± 3 d after AI, cows were randomly assigned to the G25 (n = 1,100) or NoG25 (n = 1,098) treatments. The protocol for G25 and NoG25 was the same, except that cows in NoG25 did not receive GnRH 25 ± 3 d after AI. At nonpregnancy diagnosis (NPD), 32 ± 3 d after AI, cows from G25 and NoG25 with a corpus luteum (CL) ≥15 mm in diameter and a follicle ≥10 mm completed the protocol (G25 CL = 272, NoG25 CL = 194), whereas cows from both treatments that did not meet these criteria received a modified Ovsynch protocol with P4 supplementation [controlled internal drug release insert plus GnRH, controlled internal drug release insert removal, and PGF_2α 7 and 8 d later, GnRH 32 h after second PGF_2α, and TAI 16 to 18 h after GnRH (G25 NoCL = 53, NoG25 NoCL = 78)]. Serum concentrations of progesterone (P4) were determined and ovarian ultrasonography was performed thrice weekly from 18 ± 3 d after AI until 1 d after TAI (G25 = 46, NoG25 = 44 cows). A greater percentage of NoG25 cows were re-inseminated at detected estrus (NoG25 = 53.5%, G25 = 44.6%), whereas more cows had a CL at NPD in G25 than NoG25 (83.7 and 71.3%). At 32 d after AI, P/AI was similar for G25 and NoG25 for inseminations at detected estrus (38.4 and 42.9%), TAI services for cows with no CL (40.4 and 36.7%), and for all services combined (39.6 and 39.0%). However, P/AI were greater for cows with a CL in G25 than NoG25 (40.6 and 32.8%) that received TAI. More cows ovulated spontaneously or in response to GnRH for the G25 than the NoG25 treatment (70 and 36%) but a similar proportion had an active follicle at NPD (G25 = 91% and NoG25 = 96%). The largest follicle diameter at NPD (G25 = 15.0 ± 0.4 mm, NoG25 = 16.5 ± 0.6 mm) and days since it reached ≥10 mm (G25 = 4.0 ± 0.3 d, NoG25 = 5.8 ± 0.6 d) were greater for the NoG25 than G25 treatment. For cows with a CL at NPD, CL regression after NPD, ovulation after TAI, and ovulatory follicle diameter did not differ. In conclusion, removing the first GnRH of a modified Resynch-25 protocol for cows with a CL at NPD and a modified Ovsynch protocol with P4 supplementation for cows without a CL at NPD resulted in a greater percentage of cows re-inseminated at detected estrus and a similar proportion of cows pregnant in spite of reduced P/AI for cows with a CL at NPD.     

Effect of early or late resynchronization based on different methods of pregnancy diagnosis on reproductive performance of dairy cows

The aim of this study was to compare the reproductive performance of dairy cows subjected to early (ER) or late (LR) resynchronization programs after nonpregnancy diagnoses based on either pregnancy-associated glycoproteins (PAG) ELISA or transrectal palpation, respectively. In addition, the accuracy of the PAG ELISA for early pregnancy diagnosis was assessed. Lactating Holstein cows were subjected to a Presynch-Ovsynch protocol with timed artificial insemination (AI) performed between 61 and 74 DIM. On the day of the first postpartum AI, 1,093 cows were blocked by parity and assigned randomly to treatments; however, because of attrition, 452 ER and 520 LR cows were considered for the statistical analyses. After the first postpartum AI, cows were observed daily for signs of estrus and inseminated on the same day of detected estrus. Cows from ER that were not reinseminated in estrus received the first GnRH injection of the Ovsynch protocol for resynchronization 2 d before pregnancy diagnosis. On d 28 after the previous AI (d 27 to 34), pregnancy status was determined by PAG ELISA, and nonpregnant cows continued on the Ovsynch protocol for reinsemination. Pregnant cows had pregnancy status reconfirmed on d 46 after AI (d 35 to 52) by transrectal palpation, and those that lost the pregnancies were resynchronized. Cows assigned to LR had pregnancy diagnosed by transrectal palpation on d 46 after AI (d 35 to 52) and nonpregnant cows were resynchronized with the Ovsynch protocol. Blood was sampled on d 28 after AI (d 27 to 34) from cows in both treatments that had not been reinseminated on estrus and again on d 46 after AI (d 35 to 52) for assessment of PAG ELISA to determine the accuracy of the test. Cows were subjected to treatments for 72 d after the first insemination. Pregnancy per AI (P/AI) at first postpartum timed AI did not differ between treatments and averaged 28.9%. The proportion of nonpregnant cows that were resynchronized and received timed AI was greater for ER than for LR (30.0 vs. 7.6%). Cows in ER had a shorter interval between inseminations when inseminated following spontaneous estrus (21.7 ± 1.1 vs. 27.8 ± 0.8 d) or after timed AI (35.3 ± 1.2 vs. 55.2 ± 1.4 d). Nevertheless, the ER did not affect the rate of pregnancy (adjusted hazard ratio = 1.23; 95% confidence interval = 0.94 to 1.61) or the median days postpartum to pregnancy (ER = 132 vs. LR = 140). A total of 2,129 PAG ELISA were evaluated. Overall, sensitivity, specificity, and positive and negative predictive values averaged 95.1, 89.0, 90.1, and 94.5%, respectively, and the accuracy was 92.1%. In conclusion, PAG ELISA for early diagnosis of pregnancy had acceptable accuracy, but early resynchronization after nonpregnancy diagnosis with PAG ELISA did not improve the rate of pregnancy or reduce days open in dairy cows continuously observed for estrus.     

Intravaginal progesterone insert to synchronize return to estrus of previously inseminated dairy cows

An intravaginal progesterone insert (CIDR insert; 1.38 g of progesterone) was evaluated for synchronization of returns to estrus (SR), conception rate (CR), and pregnancy rate (PR) in dairy cows previously artificially inseminated (AI). Healthy, nonpregnant, lactating Holstein cows, > or = 40 and < or = 150 d postpartum at eight commercial farms were used. Cows detected in estrus and receiving AI 2, 3, or 4 d after one injection of PGF2alpha (25 mg) were assigned as either controls (n = 945), or to receive a CIDR insert (n = 948) for 7 d (14 to 21 +/- 1 d after AI). Cows were observed for returns to estrus from 18 to 26 +/- 1 d after initial AI (resynchrony period) and were reinseminated if in estrus. Vaginal mucus on CIDR inserts (97.3% retention) at removal was scored: 1 = no mucus; 2 = clear; 3 = cloudy; 4 = yellow; and 5 = red or brown. Percentage of cows in estrus (SR) during the 3 d after CIDR insert removal was contrasted to the highest 3-d cumulative percentage in estrus for controls. Cows conceiving to initial AI were omitted in calculations of SR, CR, and PR during resynchrony. Mucous scores of 3 or 4 (mild irritation) were observed in 65% of cows and a score of 5 (more severe irritation) was observed in 2%; otherwise, health was unaffected. The PR to initial AI was lower for cows subsequently receiving CIDR inserts than for controls (32.7 vs. 36.7%). The CIDR insert increased SR (34.1 vs. 19.3% in 3 d) and overall estrus detection (43% in 4 d vs. 36% in 9 d) compared with controls. For the 9-d resynchrony period, CR and PR for CIDR-treated (26.7, 12.2%) and control (30.9, 11.1%) cows did not differ significantly. The CIDR inserts improved synchrony of returns to estrus, slightly reduced PR to initial AI, but did not affect CR or PR to AI during the resynchrony period.