Prostaglandin Based Estrus Synchronization in Postpartum Dairy Cows: An Update

 

K. Murugavel^*

J. L. Yániz^†

P. Santolaria^†

M. López-Béjar^‡

F. López-Gatius^*

 

^*Dept. de Producción Animal, Universidad de Lleida, Spain.

^†Dept. de Producción Animal, Universidad de Zaragoza, Spain.

‡Dept. Anatomía y Embriología, Universidad Autónoma de Barcelona, Spain.

This study received financial support from the CTT of the University of Lleida (Grant C-0450 in collaboration with Schering Plough Animal Health, Spain).

 

KEY WORDS: prostaglandin, estrus synchronization, dairy cattle, update

ABSTRACT

Estrus synchronization programs used in dairy cattle mainly involve the use of the luteolytic agents prostaglandin or their analogues. Prostaglandin is able to synchronize estrus by inducing the regression of the corpus luteum. Because prostaglandin is only effective in diestrus cows, a double prostaglandin protocol applied 11 to 14 days apart seems to be capable of bringing most cows to estrus. The 14 day rather than 11 day interval gives rise to an improved conception rate, because most cows will be in the late luteal phase of the estrous cycle when they receive the second prostaglandin dose. The time of provoked estrus onset is affected by the estrous cycle stage at the time of prostaglandin treatment. Due to varying estrus-onset times, improved conception rates are obtained after AI at detected estrus rather than fixed-time AI in prostaglandin-treated cows. The administration of estradiol, hCG, or both after prostaglandin treatment improves the synchrony of estrus but does not enhance conception rate. Progesterone-based treatments for estrus synchronization are considered the most appropriate for noncyclic or anestrous postpartum dairy cows; prostaglandin alone is ineffective in these cows because of the absence of a mature corpus luteum. Improved estrus synchrony and fertility rate have been reported using short-term progesterone treatment regimes (7–9 days) with or without estradiol benzoate combined with the use of a luteolytic agent given 1 day before, or at the time of, progesterone withdrawal. The ovulation synchronization (Ovsynch) protocol, based on the use of GnRH and prostaglandin, was recently developed to coordinate follicular recruitment, CL regression, and the time of ovulation. This protocol allows fixed time insemination and has proven effective in improving reproductive management in postpartum dairy cows. However, it has not proven effective in heifers because of their inconsistent follicular wave pattern. The early luteal phase of the estrus cycle is considered optimal for initiation of the Ovsynch protocol in dairy cows. Presynchronization with prostaglandin to ensure the protocol is started in the early luteal phase has been found to improve pregnancy rates. To date, several prostaglandin-based, fixed-time insemination estrus synchronization protocols are available for use in early postpartum dairy cows with ovarian disorders. This report reviews the most recent developments in prostaglandin-based estrus synchronization programs for postpartum dairy cows and addresses the efficiency of controlled breeding protocols based on such developments for cows with an abnormal ovarian condition.

INTRODUCTION

Increased milk production demands have led to a decline in the reproductive performance of dairy cows due to a prolonged intercalving period.1 Several factors, such as a longer time period from parturition to first estrus, poor estrus expression or detection, improper timing of artificial insemination, and reduced conception rate at first AI, have contributed to a longer intercalving period. In doing so, they have compromised profitability in dairy farming.2-6 The situation is further aggravated by the fact that high yielding early postpartum dairy cows often suffer from one or another ovarian disorder.7-9

Treatments aimed at synchronizing estrus or inducing ovulation allow for the effective management of timed AI in lactating dairy cows, without the need for detecting estrus. Most estrus synchronization protocols are mainly based on the use of the luteolytic agents, prostaglandins or their synthetic analogues.

The use of prostaglandin as a drug for estrus synchronization10–17 or as a therapeutic agent18–25 has been extensively reviewed in both dairy and beef cows. Furthermore, several recent reports of protocols have been published in which prostaglandins are combined with other hormones for therapeutic estrus synchronization in early postpartum dairy cows with an ovarian disorder.26–29 We review these recent developments in prostaglandin-based protocols used to control the estrus cycle in dairy cattle, with special reference to lactating early postpartum dairy cows. Also discussed are prostaglandin-based controlled breeding protocols for cows showing an abnormal ovarian condition.

Prostaglandin treatment

The luteolytic effect of prostaglandin F2a (PGF2a) in cattle was described by several workers in the early 1970s.30–33 Subsequent research efforts thus attempted to improve the reproductive efficiency of dairy cattle by inducing estrus with PGF2a.34–42 Several studies demonstrated the capacity of PGF2a and its synthetic analogues, alfaprostol,43–47 cloprostenol,48,49 fenprostalene,50,51 and luprostiol52–54 to trigger the regression of mature corpus lutea in the ovary, thus provoking and synchronizing estrus.35,55–60 When PGF2a was administered to cows with a functionally mature corpus luteum, 85% to 95% reached estrus within 7 days of treatment;61–64 70% to 90% showed signs of estrus 3 to 5 days after treatment.65

For PGF2a treatment to achieve its luteolytic effects, the cows must be in the diestrus stage of the estrous cycle (day 7 to 17). Prostaglandin treatment in the early stage of estrous cycle (first 5 days) was found to be ineffective in causing a luteolytic response in cattle.49,66 Consequently, a double protocol in which  PGF2a was given at a 7, 11, or 14 day intervals was developed so that cows at a stage in the estrous cycle other than diestrus would have a functional corpus luteum when they received the second PGF2a dose.64,67–69 Kristula et al.69 reported that weekly doses of PGF2a allowed AI to be performed earlier, because cows not in the diestrus stage when subjected to the first PGF2a injection were found to have a functional corpus luteum when the second PGF2a injection was given 7 days later. However, several authors report the improved reproductive efficiency of cows detected to be in estrus after the second PGF2a dose using the double regime in which PGF2a doses are given 11 or 14 days apart.63,65,70

Lucy et al.71 showed that when randomly cyclic cows were subjected to the double 14 day prostaglandin protocol, at least 67% of the cows had a corpus luteum at the time of treatment onset on day 7 to day 20 of their estrous cycle, which underwent luteolysis either spontaneously (cows on cycle day 18 to 20) or in response to PGF2a treatment (cows on cycle day 7 to 17). These cows would be on day 9 to 14 of the estrous cycle when the second PGF2a was administered 14 days later. The remaining cows (33%) that had not responded to the first PGF2a dose (cows on cycle day 0 to day 6) would be on day 14 to 20 of the estrous cycle when given the second PGF2a dose. Furthermore, an enhanced estrous response and normal fertility were reported when PGF2a was given at the late, rather than early to middle, stage of the luteal phase in dairy cows72 and in heifers.73,74 Thus, the 14-day interval double prostaglandin regimen seems to show an improved response over the 11 day protocol, because two injections given 14 days apart ensures that most animals are in the late luteal stage (cycle day 11 to 14) when they receive the second PGF2a dose.63,64,75

Recently,16 the successful use of a new estrus synchronization protocol for lactating dairy cows has been described, in which three PGF2a doses are given. In this protocol, known as the Targeted Breeding Program, all the animals that were not detected to be at estrus following the first PGF2a injection were treated with a further two doses of PGF2a at 14-day intervals until artificial insemination at detected estrus or until timed artificial insemination was performed 72 to 80 hours after the third PGF2a dose.

There have been many reports of different intervals to estrus and ovulation following prostaglandin treatment.76–78 The time elapsed between PGF2a treatment and the onset of estrus depends on the stage of the estrous cycle at the time of PGF2a treatment61,73,79–83. The mean interval to estrus was 48 to 72 h when PGF2a was administered on estrous cycle Day 5 or Day 8 in dairy cows.73,74  Prostaglandin administration in mid-cycle (day 8 to day 11) or later in the luteal phase (day 12 to 15) resulted in a mean time to estrus of 70 and 62 hours, respectively.81,82 There are also reports of higher progesterone concentrations at the time of prostaglandin administration being associated with a delayed onset of estrus.12

The stage of follicular wave development at the time of PGF2a treatment appears to be the factor determining the time of estrus onset.65,84,85 Kastelic and Ginther86 reported that the time from PGF2a administration to ovulation was dependent on the maturity and size of the most emergent dominant follicle, because a small dominant follicle takes longer to grow into an ovulatory follicle. When the dominant follicle had reached the static phase, the time from treatment to ovulation was 3 days, and if a new dominant follicle had emerged at the time of luteolysis, this time period increased to 4.5 days. Smith et al.87 reported that the onset of estrus was significantly and inversely related to the size of the cavity of the smallest follicle over 5 mm in diameter.

Several researchers have noted normal or above normal fertility following synchronization of estrus with PGF2a in cows.56,88,89 Young and Henderson90 found no significant difference in conception rates among cows inseminated at the fixed time of 75 to 80 hours (46%), after a double 11 day interval treatment regimen using a prostaglandin analogue, cows inseminated twice at 72 and at 96 hours (47%) after the same treatment and control untreated cows (50%). However, improved conception rates have been noted after AI at detected estrus compared with timed AI after prostaglandin administration, due to variations in the time of ovulation.91–93 Reproductive performance in dairy cattle was also improved following double 14-day PGF2a treatment without assessing ovarian status when compared with a single dose based on detecting a corpus luteum by rectal palpation or by milk progesterone enzyme immunoassay.94 Tenhagen et al.95 noted that timed insemination after double 14-day prostaglandin treatment reduced the number of days open in lactating dairy cows when compared with AI performed at observed estrus. Finally, there have also been many reports of reduced fertility after double PGF2a treatment when artificial insemination was performed at detected estrus rather than normal estrus.72,88,96,97

There is considerable evidence that PGF2a is capable of improving the reproductive performance of dairy cows when given before the end of the voluntary waiting period.98,99 Administering PGF2a during the early postpartum period led to increased first service conception rates related to the associated benefits of enhancing uterine activity,100 thereby decreasing the interval between calving and conception.101–103 However, others suggest that the diminished intercalving period may be an effect of luteolysis and an increased number of estrus cycles.102,104,105 In a meta-analysis, Burton and Lean106 explored the effects of prostaglandin given in the early postpartum on the subsequent reproductive performance of dairy cattle. Their pooled data corresponded to 21 independent trails performed on 2,646 cows described in 10 papers. Meta-analysis of the effect of prostaglandin treatment during the early postpartum period revealed no increase in pregnancy rate to first artificial insemination in cows with a normal or abnormal puerperium, while the period from calving to first AI was significantly reduced, thus reducing the number of days open in the dairy farm. These results were, however, not considered conclusive by the authors.

Prostaglandin-based
combination treatments

Prostaglandin in
Progesterone-Based Treatments

One of the major limitations of the use of prostaglandins to synchronize estrus in dairy cows is the failure of the drug in anestrus or noncyclic cows.60 Progestogens have the advantage that, besides improving estrus synchronization, they also induce estrus and ovulation in an acceptable percentage of anestrus cows.107–110 Several works have shown that the estrous cycle in cows can be controlled by prolonging the luteal phase or establishing an artificial luteal phase by the administration of exogenous progesterone or synthetic progestogens10,12, because progesterone suppresses estrus and ovulation by inhibiting the release of luteinizing hormone, impeding the final maturation of follicles.111

Long-term progesterone treatment (14 to 16 days) leads to reduced fertility,112 probably due to development of persistent follicles and reduced oocyte competence.113,114 Lane et al.115 recommended prostaglandin administration when short-duration (7–9 days) progesterone treatments were started in the early or mid cycle, because the proportion of animals requiring exogenous luteolysis induction increases during this period. Indeed, short-term progesterone treatment using progesterone releasing intravaginal devices or subcutaneous ear implants combined with treatment with a luteolytic agent has proved successful in cattle.39,77,116–120

Pregnancy rates equal to or greater than control rates for cows in natural estrus were achieved when progesterone releasing devices were used in conjunction with prostaglandin F2a or one of its analogues.39,116,117,121–124 Several reports claim an improved response to estrus synchronization treatment when prostaglandin is administered 48 hours after intravaginal progesterone device removal in Bos taurus125–129 and Bos indicus cattle.130–131 Using a progesterone-releasing intravaginal device (PRID) prostaglandin procedure, the conception rate was reported to be higher when PRID was inserted in the early (day 1 to 10) rather than late (day 11 to 20) stage of the estrous cycle.132

When comparing the efficiency of prostaglandin treatment alone with that of combined progestin-prostaglandin treatment aimed at controlling estrus cycles in dairy cows, Chupin et al.133 found that combined treatment was more effective than prostaglandin alone in bringing more cows into estrus during the first 96 hours after the end of treatment. Similarly, Gyawu et al.126 observed that the progesterone/prostaglandin combination was more effective in synchronizing ovulation compared with prostaglandin alone. Several authors have also reported increased synchronization rates and fertility after progesterone plus prostaglandin treatment.77,125,134,135 Finally, Mialot et al.136 noted increased reproductive efficiency in cattle when prostaglandin instead of eCG was given 48 hours after PRID removal.

Ryan et al.114 reported that administering GnRH was more effective than giving estradiol benzoate at the start of a progesterone-prostaglandin regime in dairy cows. In contrast, Lane et al.115 reported that 0.75 mg of estradiol benzoate administered at the start of 8 days of progesterone treatment, with prostaglandin given one day before progesterone withdrawal, was more effective than GnRH for synchronizing estrus in heifers. Similarly, synchrony of estrus in dairy heifers sufficient for fixed time insemination was achieved using a protocol that involved the use of a progesterone controlled intravaginal drug releasing device (CIDR) for 10 days, a 10-mg estradiol benzoate capsule delivered at the time of device insertion, and prostaglandin administered 4 days before device removal.120,137,138 In a study undertaken during the AI breeding period in lactating dairy cows, pregnancy rates were higher among cows synchronized with GnRH and a progesterone CIDR followed 7 days later by PGF2a treatment, and device removal 1 day after or at the time of prostaglandin treatment, compared with control unsynchronized cows.139

Use of Estrogen and Human
Chorionic Gonadotrophin in Prostaglandin-Based Regimens

In the cow, estrogens are known to induce a preovulatory-like LH surge, ovulation,140 and luteolytic activity during the luteal phase.141 These effects could justify the inclusion of estradiol in the different synchronization regimens. Indeed, as noted previously, progestogen-estrogen combinations are widely used. Although synchronizing estrus using prostaglandins, several authors successfully synchronized ovulation by administering estradiol benzoate after prostaglandin treatment in cows142,143 and in heifers.144 A tighter synchrony of estrus with no effect on the conception rate was reported after treating dairy cows with 400 mg of estradiol benzoate 40 to 48 hours after prostaglandin treatment.145 An estrogen-prostaglandin combination protocol for synchronization of estrus was also found to increase the percentage of cows in estrus.146

The hormone hCG induces potent LH activity in ovarian cells, which can even lead to ovulation throughout the estrous cycle.147 The simultaneous administration of hCG and estradiol benzoate 12 hours after treatment with prostaglandins in dairy cows and heifers with mature CL has been reported to shorten the mean time to onset of estrus and increase the precision of synchrony in ovulation. Using this protocol, comparable pregnancy rates were achieved after fixed-time insemination to those recorded when cows were treated with prostaglandin alone148–149 or inseminated at natural estrus.150–151

GnRH-Prostaglandin Treatments

The random administration of GnRH during the estrous cycle results in LH release,152 causes ovulation or luteinization of large follicles present in the ovary, synchronizes the recruitment of a new follicular wave,119,153 and equalizes follicle development waves.84,119,153–155 Subsequent administration of PGF2a induces the regression of an original or GnRH-induced CL, and allows final maturation of the synchronized dominant follicle.156 Furthermore, there is no apparent detrimental effect of GnRH on the responsiveness of GnRH-induced CL or spontaneous CL to prostaglandin.85

Several reports84,153,157 have described a higher rate of estrus synchronization when GnRH is administered 6 or 7 days before PGF2a (80%) compared with prostaglandin alone (50% to 60%). However, LeBlanc et al.158 reported no advantage of adding GnRH on day 7 of a synchronization program based on double prostaglandin treatment given at a 14-day interval. Similarly, Stevenson et al.159 described a decreased conception rate (48.1%) when GnRH was administered between two PGF2a doses given 14 days apart compared with not including GnRH in the protocol (63.5%).

Pursley et al.160 observed a mean reduction of 27 days to first AI with a voluntary waiting period of 50 days after a GnRH-PGF2a regimen. The same regimen was found to fail to induce estrus in some cows due to incomplete luteolysis after prostaglandin treatment161 or because of differences in pituitary LH release at the time of treatment.162 De Rensis et al.162 compared the effects of intramuscularly administering 2000 IU of hCG 6 or 9 days before prostaglandin treatment and noted that the GnRH- and hCG-prostaglandin combinations led to similar estrus synchronization, treatment efficiency and conception rates in postpartum dairy cows.

To synchronize ovulation within a short time period and enable timed insemination in the GnRH-prostaglandin regime, an additional GnRH dose was included 24,163 48,160 54,85 and 60 hours164 after prostaglandin treatment. The effectiveness of the second dose of GnRH 48 hours after prostaglandin treatment in synchronizing the timing of ovulation has been established for dairy and beef cows.165,166 A second dose of GnRH given 48 hours after PGF2a injection improves the precision of ovulation over an 8-hour period from 24 to 32 hours after this second GnRH dose. The success of this addition to the standard combined GnRH-prostaglandin regime in dairy cattle gave rise to the recently developed Ovsynch or timed artificial insemination (TAI) protocol, which allows successful fixed-time AI without the need for estrus detection.160

In the Ovsynch program, 100 ag of GnRH are given at random during the estrous cycle, followed by 25 mg of PGF2a and a second dose of 100 ag GnRH.160 Ovulation is synchronized because the preovulatory follicles are at a similar stage in development and are responsive to LH at the time of the second GnRH treatment. This program coordinates follicular recruitment, CL regression, and time of ovulation and permits fixed time AI 16 hours after the second GnRH dose is administered. Thus by synchronizing ovulation, reproduction in lactating dairy cows can be effectively managed without the need for estrus detection.167 There have also been reports168 of fertile ovulation in anestrus cows after the Ovsynch program attributable to the incorporation of GnRH.169 Recently, the Ovsynch protocol has been slightly modified so that the second GnRH dose is given 36 instead of 48 hours after prostaglandin treatment.16,170 Pursley et al.171 concluded that AI performed close to 16 hours after the second dose of GnRH in the Ovsynch protocol seems to be optimal, though pregnancy rates per AI and calving rates are comparable to rates achieved after AI performed 0 to 24 hours after the second GnRH dose. Fricke et al.172 and Yamada et al.173 reported that the reproductive performance of dairy cattle is not affected when the GnRH dose is reduced to half (50 µg instead of 100 µg) in the Ovsynch protocol.

The success of the Ovsynch program has been proven to be influenced by the number of follicular waves or length of the follicular wave,170 as well as the stage of estrous cycle when the first GnRH dose is administered.174–176 Moreira et al.176 concluded that the early luteal stage of the estrous cycle (day 5 to 12) was the optimal period for initiating the Ovsynch program. Vasconcelos et al.174 also recorded a higher pregnancy rate when cows were started on the Ovsynch protocol in the early luteal phase compared with the first 3 days or after day 13 of the estrous cycle. These findings are inconsistent with those of Keister et al.,177 who noted similar reproductive performance in dairy cattle whether Ovsynch treatment was initiated at random or on day 7 of the estrous cycle.

Based on the reports that the luteal phase was the optimal time of Ovsynch protocol onset in terms of conception rates, Moreira et al.178 presynchronized cows using two prostaglandin doses given 14 days apart to initiate the Ovsynch protocol at the targeted early luteal phase. Presynchronization was found to increase the pregnancy rate in cyclic lactating dairy cows. Similarly, pregnancy rates in dairy cows were improved when Ovsynch was started on day 12179 or day 14180 after prostaglandin administration, because most cows would be in early diestrus before the beginning of the Ovsynch protocol. However, no beneficial effects were shown by presynchronization before Ovsynch in anestrous cows, given their lack of prostaglandin responsive CL.178

Although many workers168,181–184 have reported increased pregnancy rates in cows subjected to Ovsynch treatment, this increase has not been paralleled by conception rates because of the greater number of cows insemination after Ovsynch treatment.157,159. When Burke et al.181 compared the effectiveness of timed-AI versus AI at detected estrus after Ovsynch without administering the second GnRH dose in multiparous animals, they recorded higher conception rates in cows undergoing AI at detected estrus. However, pregnancy rates were similar in both groups. These authors also noticed a mean reduction to first AI in the timed AI program of 9.7 days, compared with AI at detected estrus and a 60-day voluntary waiting period. DeJarnette et al.185 suggested that pregnancy rates in the Ovsynch protocol can be maximized by improving estrus detection, because 20% of the cows display estrus outside the optimal time period for conception by TAI.

Timed AI following the Ovsynch protocol is advocated by authors such as Burke et al.181, Yamada et al.186 and Momcilovic et al.187 as an effective tool for improving reproductive management in dairy cows, since it avoids the need for estrus detection. In heifers, however, timed AI following Ovsynch seems to have no beneficial effects due to an inconsistent follicular wave pattern.170 Lactation stage has also been shown to affect pregnancy rates following Ovsynch in dairy cows, since cows started on the Ovsynch program 76 days after calving show improved pregnancy rates over those initiating Ovsynch between 60 and 75 days postpartum.170

Xu and Burton188 and Xu et al.189 suggested that the reproductive performance of cows undergoing Ovsynch treatment could be improved by administering progesterone during the period between GnRH and prostaglandin treatment. The rationale for this is that progesterone can prevent premature ovulation after spontaneous luteolysis during the treatment period in a small proportion of cows whose dominant follicles fail to respond to GnRH.84,174,190

Prostaglandin Based Estrus Synchronization Protocols for Cows With Ovarian Disorders

It has been recently possible to achieve estrus synchronization and acceptable pregnancy rates in dairy cows with different ovarian disorders detected during the early postpartum period, using various prostaglandin-based protocols in combination with progesterone and GnRH.

Progesterone was included in a GnRH-prostaglandin-GnRH protocol for the treatment of abnormal ovarian conditions in postpartum dairy cows. Following the treatment regime: progesterone for 9 days, GnRH on day 0, and PGF2a on D 7, it was possible to successfully synchronize dairy cows with ovarian cysts during the postpartum period.191 Using the Ovsynch protocol as a therapeutic strategy for ovarian cysts, Bartolome et al.26 recorded similar pregnancy rates in response to timed insemination in cows with and without cysts. Further, López-Gatius and López-Béjar29 successfully synchronized and time-inseminated lactating dairy cows with ovarian cysts using a protocol that combines GnRH and cloprostenol, starting treatment by simultaneously administering GnRH and cloprostenol. Pursley et al.28 observed that anovulatory cows fitted with an intravaginal progesterone device (CIRD) in the period between GnRH and PGF2a administration of the Ovsynch protocol showed higher pregnancy rates (55.2%) than anovulatory cows subjected to Ovsynch without a CIRD (34.7%). In another study, López-Gatius et al.27 were also able to successfully synchronize and time-inseminate lactating dairy cows with persistent follicles using a progesterone-GnRH-PGF2a treatment regimen.

CONCLUSIONS

In conclusion, prostaglandin and its analogues are the main components of different hormone combination protocols used to synchronize estrus or ovulation, giving rise to acceptable pregnancy rates in dairy cows. Prostaglandin alone or in combination with different hormones has proved to be efficient at synchronizing estrus in postpartum dairy cows, improving reproductive efficiency in dairy farms. Future investigations should be directed toward developing cost-effective prostaglandin-based timed-insemination protocols that lead to a high synchrony of ovulation and thus improve pregnancy rates, especially in early postpartum noncyclic or anovulatory dairy cows. Future developments will no doubt serve to improve reproductive performance in dairy farms by reducing the intercalving period to the minimum.

ACKNOWLEDGMENTS

The authors thank Ana Burton for assistance with the English translation.

REFERENCES

1. Butler WR, Smith RD: Interrelationships between energy balance and postpartum reproductive function in dairy cattle. J Dairy Sci 72:767–783, 1989.

2. Pelissier CL: Herd breeding problems and their consequences. J Dairy Sci 55:385–391, 1972.

3. Williamson NB, Morris RS, Blood DC, and Cannon CM: A study of oestrus behaviour and oestrus detection methods in a large commercial dairy herds. Vet Rec 91:58–62, 1972.

4. Foote RH: Estrus detection and estrus detection aids. J Dairy Sci 58:248–256, 1975.

5. Senger PL: The estrus detection problem: new concepts, technologies, and possibilities. J Dairy Sci 77:2745-2753, 1994.

6. Sturman H, Oltenacu EAB, Foote RH: Importance of inseminating only cows in estrus. Theriogenology 53:1657–1668, 2000.

7. Opsomer G, Gröhn YT, Hertl J, et al: Risk factors for post partum ovarian dysfunction in high producing dairy cows in Belgium: A field study. Theriogenology 53:841–857, 2000.

8. López-Gatius F, Santolaria P, Yániz J, et al: Risk factors for postpartum ovarian cysts and their spontaneous recovery or persistence in lactating dairy cows. Theriogenology 58:1623–1632, 2002.

9. Wiltbank MC, Gümen A, Sartori R: Physiological classification of anovulatory conditions in cattle. Theriogenology 57:21–52, 2002.

10. Odde KG: A review of synchronization of estrus in postpartum cattle. J Anim Sci 68:817–830, 1990.

11. Wenzel JGW: A review of prostaglandin F products and their use in dairy reproductive herd health programs. Vet Bull 61:433–447, 1991.

12. Larson LL, Ball PJH: Regulation of estrous cycles in dairy cattle: A review. Theriogenology 38:255–267, 1992.

13. Jochle W: Forty years of control of the oestrous cycle in ruminants: progress made, unresolved problems and the potential impact of sperm encapsulation technology. Reprod Fertil Dev 5:587–594, 1993.

14. Ryan DP, Snijders S, Yaakub H, O’Farrell KJ: An evaluation of estrus synchronization programs in reproductive management of dairy herds. J Anim Sci 73:3687–3695, 1995.

15. Gordon I: Controlled reproduction in cattle and buffaloes. Wallingford, UK: CAB International, 215–244, 1996.

16. Nebel RL, Jobst SM: Evaluation of systematic breeding programs for lactating dairy cows: A review. J Dairy Sci 81:1169–1174, 1998.

17. Thatcher WW, Moreira F, Santos JEP, et al: Effects of hormonal treatments on reproductive performance and embryo production. Theriogenology 55:75–89, 2001.

18. Oxender WD, Seguin BE: Some potential uses of prostaglandins in domestic animals. Bovine Pract 10:2–6, 1975.

19. Braun WF: A review of prostaglandin therapeutics in reproduction. Vet Med Small Anim Clin 75:649–656, 1980.

20. Seguin BE: Role of prostaglandins in bovine reproduction. J Am Vet Med Assoc 176:1178–1181, 1980.

21. Ott RS, Gustafsson BK: Therapeutic application of prostaglandins for postpartum infections. Acta Vet Scand Suppl 77:363–369, 1981.

22. Refsal KR, Morrow DA: Potential therapeutic uses for prostaglandin F2a in bovine practice. Bovine Pract 2:40–42, 1981.

23. Chauhan FS, Mgongo FOK, Kessy BM: Recent advances in hormonal therapy of bovine reproductive disorders: A review. Vet Bull 54, 991–1009, 1984.

24. Youngquist RS, Braun WF Jr: Management of infertility in the cow. J Am Vet Med Assoc 189:411–414, 1986.

25. Pankowski JW, Galton DM, Erb HN, et al: Use of prostaglandin F2a as a postpartum reproductive management tool for lactating dairy cows. J Dairy Sci 78:1477–1488, 1995.

26. Bartolome JA, Archbald LF, Morresey P, et al: Comparison of synchronization of ovulation and induction of estrus as therapeutic strategies for bovine ovarian cysts in the dairy cow. Theriogenology 53:815–825, 2000.

27. López-Gatius F, Santolaria P, Yániz J, et al: Persistent ovarian follicles in dairy cows: A therapeutic approach. Theriogenology 56:649–659, 2001.

28. Pursley JR, Fricke PM, Garverick HA, et al: Improved fertility in noncycling lactating dairy cows treated with exogenous progesterone during Ovsynch. Midwest Branch ADSA 2001 Meeting, Des Moines, IA, abstr 63, 2001.

29. López-Gatius F, López-Béjar M: Reproductive performance of dairy cows with ovarian cysts after different GnRH and cloprostenol treatments. Theriogenology 58:1337–1348, 2002.

30. Lauderdale JW: Effects of PGF2a on pregnancy and estrous cycle of cattle. J Anim Sci 35:246(abstr), 1972.

31. Liehr RA, Marion GB: Effects of prostaglandin on cattle estrous cycles. J Anim Sci 35:247(abstr), 1972.

32. Louis TM, Haf HD, Morrow DA: Estrus and ovulation after uterine PGF2a in cows. J Anim Sci 35:247–248, 1972.

33. Rowson LEA, Tervit R, Brand A: The use of prostaglandins for synchronization of oestrus in cattle (abstr). J Reprod Fert. 29:145, 1972.

34. Hafs HD, Louis TM, Noden PA, Oxender WD: Control of the estrous cycle with prostaglandin F2a in cattle and horses. J Anim Sci 38:(Suppl 1), 1974.

35. Lauderdale JW, Seguin BE, Stellflug JN, et ak: Fertility of cattle following PGF2a injection. J Anim Sci 38:964–967, 1974.

36. Louis TM, Hafs HD, Morrow DA: Intrauterine administration of prostaglandin F2a in cows: Progesterone, estrogen, LH, estrus and ovulation. J Anim Sci 38:347–353, 1974.

37. Lambert PW, Greene WM, Strickland JN, et al: PGF2a controlled estrus in beef cattle. J Anim Sci 42:1565 (Abstr), 1976.

38. Leaver JD, Mulvany PM, Glencross RG, Pope GS: Synchronization of oestrus in dairy cattle with a prostaglandin analogue (ICI 80996). Anim Prod 22:145–146, 1976.

39. Roche JF: Fertility in cows after treatment with a prostaglandin analogue with or without progesterone. J Reprod Fertil 46:341–345, 1976.

40. Macmillan KL: Oestrus synchronization with a prostaglandin analogue-III. Special aspects of synchronization. NZ Vet J 31:104–108, 1978.

41. Seguin BE, Gustafsson BK, Hurtgen JP, et al: Use of the prostaglandin F2a analog cloprostenol (ICI 80,996) in dairy cattle with unobserved estrus. Theriogenology 10:55–64, 1978.

42. Plunkett SS, Stevenson JS, Call EP: Prostaglandin F2a for lactating dairy cows with a palpable corpus luteum but unobserved estrus. J Dairy Sci 67:380–387, 1984.

43. Jochle W, Kuzmanov D, Vujosevic J: Estrous cycle synchronization in dairy heifers with the prostaglandin analog alfaprostol. Theriogenology 18:215–225, 1982.

44. Schams D, Karg H: Hormonal responses following treatment with different prostaglandin analogues for estrous cycle regulation in cattle. Theriogenology 17:499–513, 1982.

45. Randel RD, Del Vecchio RP, Neuendorff DA, Peterson LA: Effect of alfaprostol on postpartum reproductive efficiency in Brahman cows and heifers. Theriogenology 29:657–670, 1988.

46. Tolleson DR, Randel RD: Effects of alfaprostol and uterine palpation on postpartum interval and pregnancy rate to embryo transfer in Brahman influenced beef cows. Theriogenology 29:555–564, 1988.

47. Randel RD, Lammoglia MA, Lewis AW, et al: Exogenous PGF2a enhanced GnRH–induced LH release in postpartum cows. Theriogenology 45:643–654, 1996.

48. Cooper MJ: Control of oestrous cycles in heifers with a synthetic prostaglandin analogue. Vet Rec 95:200–203, 1974.

49. Cooper MJ, Rowson LEA: Control of the oestrous cycle in Friesian heifers with ICI 80, 996. Ann Biol Anim Biochem Biophys 15:427–436, 1975.

50. Martinez J, Thibier M: Fertility in anoestrous dairy cows following treatment with prostaglandin F2a or the synthetic analogue fenprostalene. Vet Rec 115:57–59, 1984.

51. Stotts J, Stumpf T, Day M, et al: Luteinizing hormone and progesterone concentrations in serum of heifers administered a short half-life prostaglandin (PFF2a) or long half-life prostaglandin analogue (fenprostalene) on days six or eleven  of the estrous cycle. Theriogenology 28:523–529, 1987.

52. Godfrey RW, Guthrie MJ, Neuendorff, DA, Randel RD: Evaluation of luteolysis and estrous synchronization by a prostaglandin analog (Luprostiol) in Brahman cows and heifers. J Anim Sci 67:2067–2074, 1989.

53. Plata NI, Spitzer JC, Henricks DM, et al: Endocrine, estrous and pregnancy responses to varying dosages of luprostiol in beef cows. Theriogenology 31:801–812, 1989.

54. Plata NI, Spitzer JC, Thompson CE, et al: Synchronization of estrus after treatment with luprostiol in beef cows and in beef and dairy heifers. Theriogenology 33:943–952, 1990.

55. Lee CN, Maurice E, Ax RL, et al: Efficacy of gonadotropin-releasing hormone administered at the time of artificial insemination of heifers and postpartum and repeat breeder dairy cows. Am J Vet Res 44:2160–2163, 1983.

56. Macmillan KL, Day AM: Prostaglandin F2a. A fertility drug in dairy cattle? Theriogenology 18:245–253, 1982.

57. Seguin BE, Tate DJ, Otterby DE: Use of cloprostenol in a reproductive management system for dairy cattle. J Am Vet Med Assoc 183:533–537, 1983.

58. Stevenson JS, Mee MO, Stewart RE: Conception rates and calving intervals after prostaglandin F2a or prebreeding progesterone in dairy cows. J Dairy Sci 72:208–217, 1989.

59. Sianangama PC, Rajamahendran R: Effect of human chorionic gonadotropin administered at specific times following breeding on milk progesterone and pregnancy in cows. Theriogenology 38:85–96, 1992.

60. Stevenson JS, Pursley JR: Use of milk progesterone and prostaglandin F2a in a scheduled artificial insemination program. J Dairy Sci 77:1755–1760, 1994.

61. Macmillan KL, Henderson NV: Analysis of the variation in the interval from an injection of prostaglandin F2a to oestrous as a method of studying patterns of follicle development during diestrus in dairy cows. Anim Reprod Sci 6:245–254, 1983.

62. Armstrong JD, O’Gorman J, Roche JF: Effects of prostaglandin on the reproductive performance of dairy cows. Vet Rec 125:597–600, 1989.

63. Folman Y, Kaim M, Herz Z, Rosenberg M: Comparison of methods for the synchronization of estrous cycles in dairy cows. Effects of progesterone and parity on conception. J Dairy Sci 73:2817–2825, 1990.

64. Rosenberg M, Kaim M, Herz Z, Folman Y: Comparison of methods for synchronization of estrous cycle in dairy cows. 1. Effects on plasma progesterone and manifestation of estrus. J Dairy Sci 73:2807–2816, 1990.

65. Ferguson JD, Galligan DT: Prostaglandin synchronization programs in dairy herds (part I). Compend Contin Educ Pract Vet 15:646–655, 1993.

66. Lauderdale JW: The use of prostaglandins in cattle. Ann Biol Anim Biochim Biophys 15:419–425, 1975.

67. Baishya N, Ball PJH, Leaver JD, Pope GS: Fertility of lactating dairy cows inseminated after treatment with cloprostenol. Br Vet J 136:227–239, 1980.

68. Selk GE, Fink MS, McPeake CA: Estrus synchronization of cattle using eleven day or fourteen day prostaglandin protocols. Anim Sci Res Ag Expt Sta, Oklahoma State Univ MP–125:34–37, 1988.

69. Kristula MR, Bartholomew R, Galligan D, Uhlinger C: Effects of a prostaglandin F2a synchronization program in lactating dairy cattle. J Dairy Sci 75:2713–1718, 1992.

70. Stevenson JS, Smith JF, Hawkins DE: Reproductive outcomes for dairy heifers treated with combinations of prostaglandin F2a, norgestomet, and gonadotropin-releasing hormone. J Dairy Sci. 83:2008–2015, 2000.

71. Lucy MC, Savio JD, Badinga L, De La Sota RL, Thatcher WW: Factors that affect ovarian follicular dynamics in cattle. J Anim Sci 70:3615–3626, 1992.

72. Xu ZZ, Burton LJ, Macmillan KL: Reproductive performance of lactating dairy cows following oestrus synchronization regimens with PGF2( and progesterone. Theriogenology 47:687–701, 1996.

73. Tanabe TY, Hann RC: Synchronized estrus and subsequent conception in dairy heifers treated with prostaglandin F2a. I. Influence of stage of cycle at treatment. J Anim Sci 58:805–811, 1984.

74. Watts TL, Fuquay JW: Response and fertility of dairy heifers following injection with prostaglandin F2a during early, middle or late diestrus. Theriogenology 23:655:661, 1985.

75. Young IM: Dinoprost 14-day oestrus synchronization schedule for dairy cows. Vet Rec 124:587588, 1989.

76. Johnson CT: Time of onset of oestrus after the injection of heifers with cloprostenol. Vet Rec 103:204–206, 1978.

77. Smith RD, Pomerantz AJ, Beal WE, et al: Insemination of Holstein heifers at a preset time after estrous cycle synchronization using progesterone and prostaglandin. J Anim Sci 58:792–800, 1984.

78. Voh AA Jr, Oyedipe EO, Buvanendran V, Kumi-Diaka J: Estrus response of indigenous Nigerian Zebu cows after prostaglandin F2 alpha analogue treatment under continuous observations for two seasons. Theriogenology 28:77–99, 1987.

79. Roche JF: Synchronization of oestrus and fertility following artificial insemination in heifers given prostaglandin F2a. J Reprod Fertil 37:135–138, 1974.

80. Jackson PS, Johnson CT, Furr BJ, Beattie JF: influence of stage of oestrous cycle on time of oestrus following cloprostenol treatment in the bovine. Theriogenology 12:153–154, 1979.

81. King ME, Kiracofe GH, Stevenson JS, Schalles RR: Effect of stage of estrous cycle on interval to estrus after PGF2a in beef cattle. Theriogenology 18:191– 200, 1982.

82. Stevenson JS, Schmidt MK, Call EP: Stage of estrous cycle, time of insemination, and seasonal effects on estrous and fertility of Holstein heifers after prostaglandin F2a. J Dairy Sci 67:1798–1805, 1984.

83. Voh AA Jr, Oyedipe EO, Pathiraja N, et al: Peripheral plasma levels of progesterone in Nigerian Zebu cows following synchronization of oestrus with prostaglandin F2 alpha analogue (Dinoprost Tromethamine). Br Vet J 143: 254–263, 1987.

84. Twagiramungu H, Guilbault LA, Proulx JG, et al: Influence of an agonist of gonadotropin-releasing hormone (buserelin) on estrus synchronization and fertility in beef cows. J Anim Sci 70:1904–1910, 1992.

85. Twagiramungu H, Guilbault LA, Dufour JJ: Synchronization of ovarian follicular waves with a gonadotropin-releasing hormone agonist to increase the precision of estrus in cattle: A review. J Anim Sci 73:3141–3151, 1995.

86. Kastelic JP, Ginther OJ: Factors affecting the origin of the ovulatory follicle in heifers with induced luteolysis. Anim Reprod Sci 26:13–24, 1991.

87. Smith ST, Ward WR, Dobson H: Use of ultrasonography to help to predict observed oestrus in dairy cows after the administration of prostaglandin F2(. Vet Rec. 142:271–274, 1998.

88. McIntosh DAD, Lewis JA, Hammond D: Conception rates in dairy cattle treated with cloprostenol and inseminated at observed oestrus. Vet Rec 115:129–130, 1984.

89. Lucy MC, Stevenson JS, Call EP: Controlling first service and calving interval by prostaglandin F2a gonadotropin-releasing hormone and timed insemination. J Dairy Sci 69:2186–2194, 1986.

90. Young IM, Henderson DC: Evaluation of single and double artificial insemination regimes as methods of shortening calving intervals in dairy cows treated with dinoprost. Vec Rec 109:446–449, 1981.

91. Fetrow J, Blanchard T: Economic impact of the use prostaglandin to induce estrus in dairy cows. J Am Vet Med Assoc 190:163–169, 1987.

92. Stevenson JS, Lucy MC, Call EP: Failure of timed insemination and associated luteal function in dairy cattle after two injections of prostaglandin F2a. Theriogenology 28:937–946, 1987.

93. Archbald LT, Tran T, Massey R, Klapstein E: Conception rates in dairy cows after timed-insemination and simultaneous treatment with gonadotropin-releasing hormone and/or prostaglandin F2a. Theriogenology 37:723–731, 1992.

94. Heuwieser W, Oltenacu PA, Lednor AJ, Foote RH: Evaluation of different protocols for prostaglandin synchronization to improve reproductive performance in dairy herds with low estrus detection efficiency. J Dairy Sci 80:2766–2774, 1997.

95. Tenhagen BA, Drillich M, Heuwieser W: Synchronization of lactating cows with prostaglandin F2alpha: insemination on observed oestrus versus timed artificial insemination. J Vet Med Assoc 47:577–584, 2000.

96. Macmillan KL, Curnow RJ, Morris GR: Oestrus synchronization with a prostaglandin analogue : I. Systems in lactating dairy cattle. NZ Vet J 25:366–372, 1977.

97. Roche JF, Prendiville DJ: Control of estrus in dairy cows with a synthetic analogue of prostaglandin F2 alpha. Theriogenology 11:153–162, 1979.

98. White AJ, Dobson H: Effect of prostaglandin F2a on the fertility of dairy cows after calving. Vet Rec 127:588–592, 1990.

99. Stevens RD, Seguin BE, Momont HW: Evaluation of the effects of route of administration of cloprostenol on synchronization of estrus in diestrous dairy cattle. J Am Vet Med Assoc 207:214–216, 1995.

100. Young IM, Anderson DB, Plenderleith RWJ: Increased conception rate in dairy cows after early postpartum administration of prostaglandin. Vet Rec 115:429–431, 1984.

101. Etherington WG, Bosu WTK, Martin SW, et al: Reproductive performance in dairy cows following postpartum treatment with gonadotropin-releasing hormone and/or prostaglandin: A field trail. Can J Comp Med 48:245–250, 1984.

102. Benmrad M, Stevenson JS: Gonadotropin-releasing hormone and prostaglandin F2a for postpartum dairy cows: Estrus, ovulation and fertility traits. J Dairy Sci 69:800–811, 1986.

103. Wenzel JGW, Williamson NB, Seguin BE: Factors associated with use of prostaglandins in reproductive herd health programs for dairy cows. J Am Vet Med Assoc 206:347–353, 1995.

104. Thatcher WW, Wilcox CJ: Postpartum estrus as an indicator of reproductive status in the dairy cows. J Dairy Sci 56:608–610, 1973.

105. Young IM: Selection of specific categories of dairy cows for oestrus induction with dinoprost. Vet Rec 113:319–320, 1983.

106. Burton NR, Lean IJ: Investigation by meta-analysis of the effect of prostaglandin F2a administered post partum on the reproductive performance of dairy cattle. Vet Rec136:90–94, 1995.

107. Gonzalez-Padilla E, Ruiz R, LeFever DG, et al: Puberty in beef heifers. III Induction of fertile estrus. J Anim Sci 40:1110–1118, 1975.

108. Anderson LH, McDowell CM, Day ML: Progestin-induced puberty and secretion of luteinizing hormone in heifers. Bio Reprod 54:1025–1031, 1996.

109. Fike KE, Day ML, Inskeep EK, et al: Estrus and luteal function in suckled beef cows that were anestrous when treated with an intravaginal device containing progesterone with or without a subsequent injection of estradiol benzoate. J Anim Sci 75:2009–2015, 1997.

110. Imwalle DB, Patterson DJ, Schillo KK: Effects of melengestrol acetate on onset of puberty, follicular growth, and patterns of luteinizing hormone secretion in beef heifers. Bio Reprod 58:1432–1436, 1998.

111. Peters AR: Hormonal control of the bovine oestrous cycle. II Pharmacological principles. Br Vet J 142:20–29, 1986.

112. Pierson RA, Ginther OJ: Ultrasonic imaging of the ovaries and uterus in cattle. Theriogenology 29:21–37, 1988.

113. Savio JD, Thatcher WW, Morris GR, et al: Effects of induction of low plasma progesterone concentrations with a progesterone-releasing intravaginal device on follicular turnover and fertility in cattle. J Reprod Fertil 98:77–84, 1993.

114. Revah I, Butler WR: Prolonged dominance of follicles and reduced viability of bovine oocyte. J Reprod Fertil 106:39–47, 1996.

115. Lane EA, Austin EJ, Roche JF, Crowe MA: The effect of estradiol benzoate or a synthetic gonadotropin-releasing hormone used at the start of a progesterone treatment on estrous response in cattle. Theriogenology 56:79–90, 2001.

116. Wishart DF: Synchronization of oestrus in cattle using a potent progestogen (SC 21009) and PGF2a. Theriogenology 1:87–90, 1974.

117. Thimonier J, Chupin D, Pelot J: Synchronization of oestrus in heifers and cyclic cows with progesterone and prostaglandin analogue alone or in combination. Ann Biol Anim Biochim Biophys 15:437–449, 1975.

118. Beal WE: A note on synchronization of oestrus in post-partum cows with prostaglandin F2a and a progesterone releasing device. Anim Prod 37:305–308, 1983.

119. Macmillan KL, Thatcher WW: Effects of an agonist of gonadotropin-releasing hormone on ovarian follicles in cattle. Biol Reprod 45:883–889, 1991.

120. Macmillan KL, Peterson AJ: A new intravaginal progesterone releasing device for cattle (CIDR-B) for oestrous synchronization, increasing pregnancy rates and the treatment of post-partum anoestrous. Anim Reprod Sci 33:1–25, 1993.

121. Gyawu P, Pope GS: Fertility of dairy cattle following oestrus and ovulation controlled with cloprostenol, oestradiol benzoate and progesterone or progesterone and cloprostenol. J Steroid Biochem 19:857–862, 1983.

122. Xu ZZ, Burton LJ, Macmillan KL: Reproductive performance of lactating dairy cows following oestrus synchronization with progesterone, oestradiol and prostaglandin. NZ Vet J 44:99–104, 1996.

123. Abdullah P, Williamson NB, Parkinson TJ, Fathalla M: Comparison of oestrus synchronization programmes in dairy cattle using oestradiol benzoate, short-acting progesterone and cloprostenol, or buserelin and cloprostenol. NZ Vet J 49:201–210, 2001.

124. Johnson SN, Spitzer JC: Estrus and pregnancy after synchrony with lutalyse in conjunction with Synchro-Mate-B. Theriogenology 55:1787–1795, 2001.

125. Hansel W, Beal WE: Use of prostaglandin F2a and its analogues with progestational agents. Beltsville Symposia in Agri Res, Anim Reprod Hawks, Montclair NJ, Altenhed Osmon. 102–107, 1979.

126. Gyawu P, Ducker MJ, Pope GS, et al: The value of progesterone, oestradiol benzoate and cloprostenol in controlling the timing of oestrus and ovulation in dairy cows and allowing successful fixed time insemination. Br Vet J 147:171–182, 1991.

127. Tregaskes LD, Broadbent PL, Dolmar DF, Grimmer SP: Evaluation of Crestar, a synthetic progestogen regime, for synchronizing oestrus in maiden heifers used as recipients of embryo transfers. Vet Rec 134:92–94, 1994.

128. Macmillan KL, Taufa VK: Oestradiol concentrates the synchrony pattern in heifers treated with progesterone and prostaglandin F2a. Proc NZ Soc Anim Prod 57:238–241, 1997.

129. Penny CD, Lowman BG, Scott NA, Scott PR: Repeated oestrus synchrony and fixed-time artificial insemination in beef cows. Vet Rec 140:496–498, 1997.

130. Kerr DR, McGowan MR, Carroll CL, Baldock FC: Evaluation of three estrus synchronization regimens for use in extensively managed Bos indicus and Bos indicus/taurus heifers in northern Australia. Theriogenology 36:129–141, 1991.

131. Fitzpatrick LA, Finlay PJ: Fixed-time insemination for controlled breeding of Bos indicus heifers under extensive management conditions in north Queensland. Aust Vet J 70:77–78, 1993.

132. Folman Y, Kaim M, Herz Z, Rosenberg M: Reproductive management of dairy cattle based on synchronization of estrous cycles. J Dairy Sci 67:153–160, 1984.

133. Chupin D, Pelot J, Mauleon P: Control of oestrus and ovulation in dairy cows. Theriogenology 7:399–347, 1977.

134. Munro RK, Moore NW: Effects of progesterone, oestradiol benzoate and cloprostenol on luteal function in the heifer. J Reprod Fertil 73:353–359, 1985.

135. Ryan DP, Galvin JA, O’Farrell KJ: Comparison of oestrous synchronization regimens for lactating dairy cows. Anim Reprod Sci 56:153–168, 1999.

136. Mialot JP, Ponsart C, Gipoulou Ch, et al: The fertility of autumn calving suckler beef cows is increased by the addition of prostaglandin to progesterone and eCG estrus synchronization treatment. Theriogenology 49:1353–1363, 1998.

137. Macmillan KL, Taufa VK, Day AM: Combination treatments for synchronising oestrus in dairy heifers. Proc NZ Soc Anim Prod 53:267–270, 1993.

138. Xu ZZ, Burton LJ: Reproductive performance of dairy heifers after estrus synchronization and fixed-time artificial insemination. J Dairy Sci 82:910–917. 1999.

139. Xu Zz, Burton LJ: Estrus synchronization of lactating dairy cows with GnRH, Progesterone, and Prostaglandin F2a. J Dairy Sci 83:471–476, 2000.

140. Lammoglia MA, Short RE, Bellows SE, Bellows RA, MacNeil MD, Hafs HD. 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 F2a. J Anim Sci 76:1662–1670, 1998.

141. Salfen BE, Cresswell JR, Xu ZZ, Bao B, Garverick HA: Effects of the presence of a dominant follicle and exogenous oestradiol on the duration of the luteal phase of the bovine oestrous cycle. J Reprod Fert 115:15–21, 1999.

142. Welch JA, Hackett AJ, Cunningham CJ, Heishman JO, Ford SP, Nadaraja R, Hansel W, Inskeep EK: Control of estrus in lactating beef cows with prostaglandin F2a and estradiol benzoate. J Anim Sci 41:1686–1692, 1975.

143. Inskeep EK, Dailey RA, James RE, Peters JB, Lewis PE, Welch JA: Estradiol benzoate improves synchronization of estrus in cattle with prostaglandin F2a. 9th Int Congr Anim Reprod Artif Insem, Madrid Spain, 1980.

144. Dailey RA, James RE, Inskeep EK, Washburn SP: Synchronization of estrus in dairy heifers with prostaglandin F2a with or without estradiol benzoate. J Dairy Sci 66:881–886, 1983.

145. Dailey RA, Price JC, Simmons KR, et al: Synchronization of estrus in dairy cows with prostaglandin F2a and estradiol benzoate. J Dairy Sci 69:1110–1114, 1986.

146. Figueroa MR, Fuquay JW, Shipley SK: Synchronization of estrus in early diestral dairy heifers with prostaglandin F2a and estradiol benzoate. Theriogenology 30:1093–1097, 1988.

147. Price CA, Webb R: Steroid control of gonadotropin secretion and ovarian function in heifers. Endocrinology 122:2222–2231, 1988.

148. López-Gatius F: Effects of cloprostenol, human chorionic gonadotropin and estradiol benzoate treatment on estrus synchronization in dairy cows. Theriogenology 32:185–195, 1989.

149. López-Gatius F: Short synchronization system for estrus cycles in dairy heifers: a preliminary report. Theriogenology 54:1185–1190, 2000.

150. López-Gatius F, Vega-Prieto B: Pregnancy rate of dairy cows following synchronization of estrus with cloprostenol, hCG and estradiol benzoate. J Vet Med Assoc 37:452–454, 1990.

151. López-Gatius F: Reproductive performance of lactating dairy cows treated with cloprostenol, hCG and estradiol benzoate for synchronization of estrus followed by timed AI. Theriogenology 54:551–558, 2000.

152. Chenault JR, Kratzer DD, Rzepkowski RA, Goodwin MC: LH and FSH response of Holstein heifers to fertirelin acetate, gonadoreline and buserelin. Theriogenology 34:81–98, 1990.

153. Thatcher WW, Macmillan KL, Hansen PJ, Drost M: Concepts for regulation of corpus luteum function by the conceptus and ovarian follicles to improve fertility. Theriogenology 31:149–164, 1989.

154. Wolfenson D, Thatcher WW, Savio JD, et al: The effect of a GnRH analogue on the dynamics of follicular development and synchronization of estrus in lactating dairy cows. Theriogenology 42:633–644, 1994.

155. Schmitt EJ-P, Diaz TC, Barros CM, et al: Differential response of the luteal phase and fertility in cattle following ovulation of the first-wave follicle with human chorionic gonadotropin or an agonist of GnRH. Theriogenology 31:149–164, 1996.

156. Schmitt EJ-P, Drost M, Diaz TC, et al: Effect of gonadotropin-releasing hormone agonist on follicle recruitment and pregnancy rate in cattle. J Anim Sci 74:154–161, 1996.

157. Stevenson JS, Kobayashi Y, Thompson KE: Reproductive performance of dairy cows in various programmed breeding systems including Ovsynch and combination of gonadotropin-releasing hormone and prostaglandin F2a. J Dairy Sci 82:506–515, 1999.

158. LeBlanc SJ, Leslie KE, Ceelen HJ, et al: Measures of estrus detection and pregnancy in dairy cows after administration of gonadotropin-releasing hormone within an estrus synchronization program based on prostaglandin F2a. J Dairy Sci 81:375–381, 1998.

159. Stevenson JS, Kobayashi Y, Shipka MP, Rauchholz KC: Altering conception of dairy cattle by gonadotropin-releasing hormone preceding luteolysis induced by prostaglandin F2a. J Dairy Sci 79:402–410, 1996.

160. Pursley JR, Mee MO, Wiltbank MC: Synchronization of ovulation in dairy cows using PGF2a and GnRH. Theriogenology 44:915–923, 1995.

161. Twagiramungu H, Guilbault LA, Proulx JG, Dufour JJ: Influence of corpus luteum and induced ovulation on ovarian follicular dynamics in postpartum cyclic cows treated with buserelin and cloprostenol. J Anim Sci 72:1796–1805, 1994.

162. De Rensis F, Allegri M, Seidel GE Jr: Estrus synchronization and fertility in post-partum dairy cattle after administration of human chorionic gonadotrophin (HCG) and prostaglandin F2a analog. Theriogenology 52:259–269, 1999.

163. Thatcher WW, de la Sota RL, Schmitt EJ-P, et al: Control and management of ovarian follicles in cattle to optimize fertility. Reprod Fertil Dev 8:203–217, 1996.

164. Peters AR, Mawhinney I, Drew SB, et al: Development of a gonadotrophin-releasing hormone and prostaglandin regimen for the planned breeding of dairy cows. Vet Rec 145:516–521, 1999.

165. Silcox RW, Boden BK, Farnsworth JH: Synchronization of beef cattle using GnRH, prostaglandin (PGF), GnRH: effects on time to ovulation and fertility. J Anim Sci 73(Suppl 1):304, 1995.

166. Silcox RW, Powell Kl, Pursley JR, Wiltbank MC: Use of GnRH to synchronize ovulation in Holstein cows and heifers treated with GnRH and prostaglandin. Theriogenology 43:325, 1995.

167. Zeroual A, Twagiramungu H, Roy GL, et al: Fixed-time insemination after prostaglandin-induced luteolysis in beef cattle pretreated with Gn-RH. J Anim Sci 73( Suppl 1):224, 1995.

168. Geary TW, Whittier JC, Downing ER, et al: Pregnancy rates of postpartum beef cows that were synchronized using synchro-mate -B or Ovsynch protocol. J Anim Sci 76:1523–1527, 1998.

169. Britt JH, Kittok RJ, Harrison DS: Ovulation, estrus, and endocrine response after GnRH in early postpartum cows. J Anim Sci 39:915–919, 1974.

170. Pursley JR, Wiltbank MC, Stevenson JS, et al: Pregnancy rates per artificial insemination for cows and heifers inseminated at a synchronized ovulation or synchronized estrus. J Dairy Sci 80:295–300, 1997.

171. Pursley JR, Silcox RW, Wiltbank MC: Effect of time of artificial insemination on pregnancy rates, calving rates, pregnancy loss, and gender ratio after synchronization of ovulation in lactating dairy cows. J Dairy Sci 81:2139–2144, 1998.

172. Fricke PM, Guenther JN, Wiltbank MC: Efficacy of decreasing the dose of GnRH used in a protocol for synchronization of ovulation and timed AI in lactating dairy cows. Theriogenology 50:1275–1284, 1998.

173. Yamada K, Nakao T, Nakada K, Matsuda G: Influence of GnRH analogue (fertirelin acetate) doses on synchronization of ovulation and fixed-time artificial insemination in lactating dairy cows. Anim Reprod Sci 74:27–34, 2002.

174. Vasconcelos JLM, Silcox RW, Rosa GJM, et al: Synchronization rate, size of the ovulatory follicle, and conception rate after synchronization of ovulation with GnRH on different days of estrous cycle. J Dairy Sci 80(Suppl 1):148(abstr), 1997.

175. Vasconcelos JLM, Silcox RW, Rosa GJM, et al: Synchronization rate, size of the ovulatory follicle, and pregnancy rate after synchronization of ovulation beginning on different days of the estrous cycle in lactating dairy cows. Theriogenology 52:1067–1078, 1999.

176. Moreira F, de la Sota RL, Diaz T, Thatcher WW: Effect of day of the estrous cycle at the initiation of a timed artificial insemination protocol on reproductive responses of dairy heifers. J Anim Sci 78:1568–1576, 2000.

177. Keister ZO, DeNise SK, Armstrong DV, et al: Pregnancy outcomes in two commercial dairy herds following hormonal scheduling programs. Theriogenology 51:1587–1596, 1999.

178. Moreira F, Orlandi C, Risco C, Mattos R, Lopes F, Thatcher WW: Effects of presynchronization and bovine somatotropin on pregnancy rates to a timed artificial insemination protocol in lactating diary. J Dairy Sci 84:1646–1659, 2001.

179. Cartmill JA, El-Zarkouny SZ, Hensley BA, et al: Stage of cycle, incidence, and timing of ovulation, and pregnancy rates in dairy cattle after three timed breeding protocols. J Dairy Sci 84:1051–1059, 2001.

180. Jordan ER, Schouten MJ, Quast JW, et al: Comparison of two timed artificial insemination (TAI) protocols for management of first insemination postpartum. J Dairy Sci 85:1002–1008, 2002.

181. Burke JM, de la Sota RL, Risco CA, et al: Evaluation of timed insemination using gonadotropin-releasing hormone agonist in lactating dairy cows. J Dairy Sci 79:1385–1393, 1996.

182. Pursley JR, Kosorok MR, Wiltbank MC: Reproductive management of lactating dairy cows using synchronization of ovulation. J Dairy Sci 80:301–306, 1997.

183. Mialot JP, Laumonnier G, Ponsart C, et al: Postpartum subestrus in dairy cows: Comparison of treatment with prostaglandin F2a or GnRH + prostaglandin F2a + GnRH. Theriogenology 52:901–911, 1999.

184. Cartmill JA, Hensley BA, El-Zarkouny SZ, et al: An alternative AI-breeding protocol for dairy cows exposed to elevated ambient temperatures before or after calving or both. J Dairy Sci 84:799–806, 2001.

185. DeJarnette JM,  Salverson RR, Marshall CE: Incidence of premature estrus in lactating dairy cows and conception rates to standing estrus or fixed-time inseminations after synchronization using GnRH and PGF2a. Anim Reprod Sci 67:27–35, 2001.

186. Yamada K, Nakao T, Mihara N: Synchronization of ovulation and fixed - time insemination for improvement of conception rate in dairy herds with poor estrus detection efficiency. J Reprod Dev 45:51–55, 1999.

187. Momcilovic D, Archbald LF, Walters A, et al: Reproductive performance of lactating dairy cows treated with gonadotropin-releasing hormone (GnRH) and/or prostaglandin F2a ( PGF2a) for synchronization of estrus and ovulation. Theriogenology 50:1131–1139, 1998.

188. Xu ZZ, Burton LJ. Estrus synchronization of lactating dairy cows with GnRH, progesterone, and prostaglandin F2a. Theriogenology 83:471–476, 2000.

189. Xu ZZ, Burton LJ, McDougall S, Jolly PD: Treatment of noncyclic lactating dairy cows with progesterone and estradiol or with progesterone, GnRH, prostaglandin F2( and estradiol. J Dairy Sci 83:464–470, 2000.

190. Roy GL, Twagiramungu H: Time interval between GnRH and prostaglandin injections influences the precision of estrus in synchronized cattle. Theriogenology 51:413, 1999.

191. Thatcher WW, Drost M, Savio JD, et al: New clinical uses of GnRH and its analogues in cattle. Anim Reprod Sci 33:27–49, 1993.