A714
Reproduction Management -
Estrus Synchronization and Heat Detection

prostaglandins | GnRH-PGF2a based synchronization options | MGA-PGF2a | CIDRs (the eazi-breed) | heat detection

Estrus Synchronization Programs:

1. Prostaglandins: Prostaglandin F2a (PGF2a) is a naturally occurring hormone. During the normal estrous cycle of a non-pregnant animal, PGF2a is released from the uterus 16 to 18 days after the animal was in heat. This release of PGF2a functions to destroy the corpus luteum (CL). The CL is a structure in the ovary that produces the hormone progesterone and prevents the animal from returning to estrus. The release of PGF2a from the uterus is the triggering mechanism that results in the animal returning to estrus every 21 days. Commercially available PGF2a (Lutalyse, Estrumate, Prostamate, In-Synch) gives the herd owner the ability to simultaneously remove the CL from all cycling animals at a predetermined time that is convenient for heat detection and breeding.
   
   The major limitation of PGF2a is that it is not effective on animals that do not possess a CL. This includes animals within 6 to 7 days of a previous heat, prepubertal heifers, and postpartum anestrous (not cycling) cows. Despite these limitations, prostaglandins are the simplest method to synchronize estrus in cattle.
   
   Two-shot PGF2a Protocol: The most common method of synchronization with PGF2a is to inject all animals, and breed those that come into heat over the next 5 to 7 days. Animals not detected in estrus after the first injection are reinjected 14 days later and bred over the next 5 to 7 day period (Figure #1). Animals detected in standing heat should be inseminated 8-12 hours later. If labor availability is a limitation, all heat detection and breeding can be delayed until after the second PGF2a injection. This allows the producer to breed a high percentage of the herd during a single 5-7 day period, but requires two doses of PGF2a/head versus 1.3 to 1.5 doses/head if animals are bred after each injection. Overall estrus response rates may be slightly reduced (approximately 5%) when animals are bred only after the second injection because some animals that responded to the first injection may not respond again to the second.
   
   Figure #1:
   
   
   Although historic recommendations were to inject PGF2a at 11-day intervals, from a scheduling consideration, the 14-day interval is much easier to implement. The second injection is always 2 weeks down on the calendar from the first, and all activities (injections, heat detection, breeding) are conducted on the same days of the week from one week to the next. Also, animals that respond to the first injection but are not detected in estrus will be between day 7 and 9 of the cycle at the next injection using the 11-day interval. These "early" CLs typically do not respond to PGF2a as well as older more mature ones. Using a 14-day interval, a missed heat from the first injection will be on days 10 to 12 of the cycle at the second injection. This 3-day difference significantly improves the probability of the animal responding again.
   
   6-Day Heat Detection Plus PGF2a: A lower cost alternative is to breed animals to natural heats for 6 days and then inject the unbred animals with PGF2a and breed over the next 5 to 7 days. This system allows all cycling animals to be bred during a two week period and requires only 0.75-0.8 PGF2a injections/head. Although this system is conservative in terms of hormone usage, it is probably one of the more labor intensive synchronization options. If <20% of the animals have been inseminated following 6 days of heat detection, there may be a cycling problem. Do not waste time and money trying to synchronize a herd of cows that are not cycling. Instead, re-evaluate the body condition, herd health, and nutrition program in the herd.
   
   PGF2a Limitations: Fixed-time insemination after single or double injections of PGF2a alone seldom yields acceptable results. Because of this, it is usually not recommended.
   
   A major limitation of PGF2a is that it only works in cycling animals. Therefore, PGF2a-based protocols work very well in properly managed beef breeding programs. However, even in the best of management scenarios, research suggests as many as 50% of postpartum, suckled beef cows may still be anestrus at the beginning of the breeding season. For these reasons, use of PGF2a alone for estrus synchronization is not recommended for beef herds or in any situation wherein the herd cyclicity status is in question. In these situations, use of PGF2a in combination with GnRH and/or a progestin source are much more effective options.
   
   
2. GnRH-PGF2a Based Synchronization Protocols: Numerous new synchronization protocols currently recommended for cows use gonadotropin-releasing hormone (GnRH) in conjunction with PGF2a. A naturally occurring hormone, GnRH is more popularly known by the commercial brand names of Cystorelin, Factrel, and Fertagyl.
   
   Each GnRH-based protocol uses the same basic framework, which involves an injection of GnRH, followed 7 days later with an injection of PGF2a. The way animals are subsequently handled for heat detection and breeding is where the protocols begin to vary. To understand the benefits of GnRH-based synchronization protocols and how they work, an understanding of the concept of follicular waves in cattle must be gained.
   
   
   1. Follicular Waves: Follicles are blister-like structures that grow on the ovaries. Each follicle contains an unfertilized egg that will be released if the follicle ovulates. Research has revealed that follicular growth occurs in waves throughout the estrous cycle and that 2-3 follicular waves may occur during an 18-24 day cycle. Each wave is characterized by rapid growth of numerous small follicles. From this wave of follicles, one follicle is allowed to grow to a much larger size than the others (12-15 mm). This large follicle is called the dominant follicle because it has the ability to regulate and restrict the growth of other smaller follicles. A few days after reaching maximum size, the dominant follicle begins to regress. As the dominant follicle regresses, it begins to lose the ability to restrict the growth of other follicles. Thus a new follicular wave is initiated coinciding with the regression of the previous dominant follicle. From the new follicular wave, another dominant follicle will be selected.
      
      Any dominant follicle has the capacity to ovulate provided the inhibitory effects of progesterone can be removed at an opportune time. Prostaglandins serve this function by destroying the CL; however, PGF2a has no direct effect on the normal pattern of follicular waves. Thus the stage of follicular development at the time of PGF2a injection will affect the interval from injection to standing estrus. Animals injected when the dominant follicle is in the growing phase will display estrus within 2 to 3 days; whereas, animals with aged or regressing dominant follicles may require 4 to 6 days before a new follicle can be recruited for ovulation. Thus the interval from PGF2a injection to estrus and ovulation is highly variable between cows due to differences in the stage of follicular development at the time of PGF2a injection.
      
      
   2. Follicular Waves and GnRH: An injection of GnRH causes a release of luteinizing hormone (LH) from the pituitary gland in the brain. This LH "surge" results in ovulation or luteinization of most large dominant follicles. A new "synchronized" follicular wave is initiated in these animals 2 to 3 days later. Because GnRH stimulates development of luteal tissue in place of the dominant follicle, a higher percentage of cows will possess sufficient luteal tissue to respond to PGF2a 7 days later. Injecting cows with PGF2a 7 days after a GnRH injection synchronizes luteal regression in animals with previously synchronized follicular development. The result is a higher estrus response rate and much tighter synchrony of estrus when compared to PGF2a alone.
      
      Although GnRH synchronizes follicular development in most cows, some cows do not respond to the first GnRH injection. If the GnRH injection fails to luteinize a follicle in animals that were due to show heat naturally around the time of the PGF2a injection, the treatment fails to prevent those animals from displaying estrus. Research in both beef and dairy cows has consistently revealed that 5 to 10% of cows treated with GnRH will display standing estrus 6 to 7 days later. These natural heats should be bred when detected, and subsequent injections are not administered.
      
      
      
GnRH/ECP-PGF2a Based Synchronization Options:
1. Select Synch: With the Select Synch System, cows are injected with GnRH and PGF2a 7 days apart (Figure #2). Heat detection begins 24-48 hours before the PGF2a injection and continues for the next 5-7 days. The PGF2a injection is excluded for cows detected in estrus on day 6 or 7. Animals are inseminated 8 to 12 hours after being observed in standing estrus. An alternative method of using the Select Synch program is to heat detect and Al until 48 to 60 hours after PGF2a and then mass-Al the rest of the herd at 72 hours and give GnRH to those cows that have not exhibited estrus.
   
   Figure #2:
   
   
   When comparing estrus response, conception and pregnancy rates for Select Synch and the two-shot PGF2a system in beef cows, Select Synch resulted in more cows in standing estrus, equal or better conception rates, and ultimately more cows pregnant during the synchronized breeding period. These benefits are particularly evident in anestrus cows. The Select Synch system can more than double the percentage of anestrous cows that become pregnant during the synchronized breeding period.
   
   Major benefits of the Select Synch system are simplicity and tighter synchrony of estrus. Most animals will display standing estrus 2 to 4 days after the PGF2a injection. Overall, estrus response rates in well-managed beef herds average approximately 70 to 75% with no adverse effect on conception rates (60 to 70%), resulting in synchronized pregnancy rates that average between 45 and 50%.
   
   Select Synch followed by heat detection and 72 hour fixed-time Al is an option that allows producers to maximize potential pregnancy rates while minimizing labor requirements for estrus detection. Heat detection is used to catch the early heats and to breed the majority of the herd (60 to 70%) to standing heats. Estrous detection can be terminated at 48 to 60 hours after PGF2a, followed by mass-Al of the non-responders at 72 hours with GnRH. This option gives all cows an opportunity to conceive and, compared to strict fixed-time Al options such as Ovsynch and Cosynch, drug costs are reduced because only 30 to 40% of the herd will receive the second GnRH injection. Additionally, if less than 40 to 50% of the herd is detected in estrus by 72 hours, the mass mating can be aborted, saving drugs, money, and semen that might otherwise be wasted on anestrous cows.
   
   
2. Select Synch Plus: If feeding MGA is not an option in the herd, another method of boosting pregnancy rates over Select Synch is the Select Synch Plus Protocol. This system simply adds another GnRH injection 7 days prior to starting Select Synch program. The added GnRH provides an additional opportunity to induce cyclicity in anestrous cows and may improve synchrony of follicular development in both cyclic and anestrous cows.
   
   Although this system had no effect on the incidence of "early" heats, a large field trial found the Select Synch Plus protocol to increase synchronized Al pregnancy rates by an average of 6% across 10 different herds. Five of these herds realized a 9 to 14% increase in synchronized pregnancy rate in response to the Select Synch Plus treatment. Like the Short-Term MGA-Select study, the majority of the fertility benefit came from the significantly higher conception rates of non-responders mass inseminated at 72 hours. The Select Synch Plus protocol is also an excellent option for late calving cows that do not fit the Long-Term MGA-Select program.
   
   
3. Ovsynch: Ovsynch is a fixed-time Al synchronization protocol that has been developed, tested, and used extensively in dairy cattle. It has also proven to be a reliable timed Al program for beef cows.
   
   The protocol builds on the basic GnRH-PGF2a format by adding a second GnRH injection 48 hours after the PGF2a injection (Figure #3). This second GnRH injection induces ovulation of the dominant follicle recruited after the first GnRH injection. All cows are mass inseminated without estrous detection at 8 to 18 hours after the second GnRH injection.
   
   Figure #3:
   
   
   Across large numbers of dairy cattle, pregnancy rates to Ovsynch generally average in the 30 to 40% range. Although these numbers may not appear impressive at first, it is important to understand them in terms of an applied reproductive management program. Records from DHIA processing centers suggest that the average dairy producer only detects 50% of the heats in his/her herd and then only gets 40 to 50% of the inseminated animals to conceive. Thus, in a 21 day period, the effective pregnancy rate in the average dairy herd is approximately 25% (50% detected in heat x 50% conception = 25% pregnant). In that context, a 30 to 40% pregnancy rate to a single fixed time Al without heat detection is quite acceptable.
   
   Recent research suggests Ovsynch pregnancy rates in dairy herds can be significantly improved if cows are set-up or "pre-synchronized" to be in the early luteal phase of the estrous cycle at the time of the first GnRH injection. This can be accomplished with 2 injections of PGF2a given at 14-day intervals, with the last injection administered 14 days prior to starting Ovsynch. This option is particularly amendable in dairy herds that routinely administer therapeutic injections of PGF2a during the early postpartum period.
   
   Although Ovsynch allows for acceptable pregnancy rates with no heat detection, it does not eliminate the need for heat detection. Ovsynch treated animals should be observed closely for returns to estrus 18 to 24 days later. Additionally, natural heats can occur on any given day and Select Sires' research has found that as many as 20% of treated dairy or beef cows will display standing estrus between days 6 and 9 of the Ovsynch protocol. Conception rates in these animals will be compromised if bred strictly on a timed Al basis.
   
   
4. Co-Synch: Although Ovsynch has proven to be a reliable timed Al program for beef cows, Ovsynch requires four trips through the working chute. Research at Colorado State University demonstrated that comparable pregnancy rates can be achieved with only three trips through the working chute with all animals being inseminated at the time of the second GnRH injection (hence the name Co-Synch) (Figure #4). As with any fixed time Al protocol, results to the Co-Synch system can be variable. Although Co-Synch can achieve pregnancy rates >50% in beef cattle, overall averages are more often in the 40 to 45% range. As with Ovsynch, pregnancy rates are maximized if the early heats are visually detected and bred using the AM/PM rule.
   
   Figure #4:
   
   
   
   

5. Heatsynch: Because ECP has been taken off the market, this protocol is currently not feasible. Heatsynch is a newly developed synchronization protocol that uses the less-expensive hormone ECP in place of the second GnRH injection of the Ovsynch protocol. However, because of differences in how these hormones work, there also are several important differences in protocol implementation. ECP is a commercially available form of the natural hormone, estrogen. Estrogen is the hormone that causes cows to show the many signs of heat when they come into estrus, and it creates a surge-type release of gonadotropin-releasing hormone (GnRH) from the brain. GnRH, in turn, causes the release of luteinizing hormone (LH), which results in ovulation of the mature follicle.

   To induce ovulation in cattle, an LH surge must be induced. GnRH has a direct and almost immediate effect on the release of LH, while ECP has a delayed effect. A recent study found that cows injected with GnRH have an LH surge within an hour or so, while the LH surge of ECP treated cows was not detected for about 41 hours. This difference in time to LH surge means the hormone injection intervals must also be altered when substituting ECP for GnRH. Both Ovsynch and Heatsynch call for a GnRH injection followed seven days later with an injection of PGF2a. Heatsynch then prescribes a one-milligram injection of ECP 24 hours later, while Ovsynch-treated cows receive GnRH 48 hours later. Because of the delayed interval to the LH surge, the recommended interval to fixed-time AI is 72 hours after PGF2a (48 hours after ECP) for Heatsynch, compared with 56 to 64 hours after PGF2a (eight to 16 hours after GnRH) for Ovsynch.

   The biggest difference that producers immediately will notice between Heatsynch and Ovsynch is the percentage of cows that will show visual signs of estrus. ECP, as with all estrogens, stimulates estrus expression following injection. Heatsynch cows detected in estrus should be bred according to the "a.m./p.m. rule" or at 72 hours after PGF2a whichever comes first. In contrast, the second GnRH injection of Ovsynch induces the LH surge and ovulation almost immediately, shutting down estrogen production from the growing follicle and thus, very few cows will show heat even though they are ovulating.

   The increased estrous activity from Heatsynch certainly makes producers and technicians feel better about breeding cows, but that does not necessarily mean it is a better synchronization protocol. In one study, even though 40 percent of Heatsynch cows were detected in estrus compared to only 8 percent for Ovsynch, only 59 percent of Heatsynch cows ovulated following PGF2a injection compared to 83 percent for Ovsynch. Additionally, some producers have found this increased estrous activity of Heatsynch is not necessarily a plus if footing surfaces are less than optimal. This is particularly important to remember during the icy winter months.

   Cows that show heat almost always will have better conception rates than those that do not. However, controlled studies directly comparing Heatsynch and Ovsynch basically indicate the two have achieved identical overall pregnancy rates. The major advantages of Heatsynch compared to Ovsynch are reduced hormone costs, more efficient use of expensive semen in higher conception-rate cows that are allowed to express estrus, and somewhat easier scheduling and implementation, since all injections and AI are at 24-hour intervals. Researchers in Florida found that Ovsynch is more effective in cystic cows, while Heatsynch appeared more effective in cows that were in heat a few days before the start of treatment.
    

6. Presynch: Presynch uses 2 injections of PGF2a at 14 day intervals to pre-synchronize most of the cycling animals. Fourteen days after the 2nd PGF2a injection, these cows will be in the proper stage of the estrous cycle to respond to the first GNRH injection in the Select Synch, Heatsynch, Cosynch, or Ovsynch system. Preliminary results using Presynch in front of Ovsynch suggests pregnancy rates were improved by 10-20 percent. In many herds, therapeutic use of PGF2a in the early postpartum period is standard practice; Presynch simply coordinates this use of PGF2a for optimum results with a GnRH-based breeding protocol. Also, Presynch should eliminate most early heats.

    

3. MGA - PGF2a System: The MGA-PGF2a system (Figure #5) is a time tested, proven method for synchronizing estrus in beef and dairy heifers. Metengestrol Acetate (MGA) is a synthetic form of the naturally occurring hormone, progesterone. For best results, mix MGA with 3 to 5 lbs of a grain supplement and feed at a rate of 0.5 mg/head/day for 14 days. Top-dressing or mixing MGA in a ration can work, but intake (and thus results) tends to be more variable. Within 3 to 5 days after MGA feeding, most heifers will display standing heat. DO NOT BREED at this heat because conception rates are reduced. Wait 17 to 19 days after the last day of MGA feeding and inject all heifers with a single dose of PGF2a. For the next 5 to 7 days, inseminate animals 8 to 12 hours after detected estrus. Although the MGA-PGF2a system has traditionally used a 17-day interval between MGA feeding and the PGF2a injection, recent research suggests a 19-day interval results in slightly higher response and synchrony of estrus.
   
   Figure #5:
   
   
   Success of the MGA system depends on adequate bunk space and proper feeding rates so the appropriate dosage is consumed by each heifer on a daily basis. In addition to stimulating cyclicity in many prepubertal and anestrous animals, researchers at the University of Kentucky found the MGA-PGF2a system to result in higher estrus response and conception rates when compared to synchronization using PGF2a alone. With good heat detection of well-managed heifers at the proper age, weight, and body condition, synchronized pregnancy rates of 50-70% can be achieved.
   
   Because the synchrony of heats following the MGA-PGF2a protocol can be variable, pregnancy rates to single, fixed time inseminations are also variable. However, very acceptable pregnancy rates (45 to 55%) have been achieved to a single insemination at 72 hours or by double inseminating at 60 and 96 hours following the PGF2a injection. On average, timed Al with this system will probably result in a 5 to 10% (or more) reduction in pregnancy rates relative to what is possible with heat detection and breeding to standing heats.
   1. Long-Term MGA-Select: The Long-Term MGA-Select is possibly the best choice for optimum synchronized pregnancy rates in postpartum beef cows. This system simply superimposes the MGA heifer protocol on the Select Synch protocol. Cows are fed MGA (0.5 mg/head/day) for 14 days and treated with Select Synch starting 12 days after the last day of MGA feeding (Figure #6). Like the Select Synch program, cows are bred to observed heats for 5 to 7 days after PGF2a or until 72 to 80 hours after PGF2a with mass Al & concurrent GnRH to non-responders.
      
      Figure #6:
      
      
      Not only does MGA "jump start" cyclicity in many anestrous cows, the system induces this sub-fertile heat to occur prior to the insemination period. MGA also presynchronizes cycling cows for optimum response to Select Synch. A University of Missouri study observed a 70% synchronized Al pregnancy rate in response to the Long-Term MGA-Select protocol, and "real world" applications suggest this was no accident. In well-managed herds, the Long-Term MGA-Select system yields synchronized Al pregnancy rates ranging from 50 to 65% on a very consistent basis. Fixed-time Al at 72 to 80 hours after PGF2a has also produced very acceptable pregnancy rates. Like the heifer protocol, DO NOT breed cows detected in estrus within 10 days of MGA feeding.
      
      
   2. Short-term MGA-Select: The short-term MGA-Select System is the newest protocol introduced as a result of Select Sires research program. With this system (Figure #7), all cows are treated with a Select Synch protocol (GnRH day 0 and PGF2a day 7) and are then fed MGA (0.5 mg/ head/day) from the day after the GnRH injection of Select Synch (day 1) until the day before the PGF2a injection (day 6).
      
      Figure #7:
      
      
      The MGA feeding helps to "jump start" anestrous cows and eliminates most early heats. Therefore, cows are only observed for estrus from 24 to 60 hours after PGF2a. At 72 hours after PGF2a, all cows that have not been inseminated are mass-bred, and those that have not displayed estrus are also injected with GnRH. Although the percentage of cows detected in estrus may be reduced by the short-term MGA treatment, the overall pregnancy rate tends to be higher due to the significantly higher conception rates at the 72-hour mass-insemination. Compared to Select Synch without MGA, the short-term MGA-Select System allows producers to achieve equal or greater pregnancy rates with reduced time and labor required for estrous detection. Preliminary results suggest this system may also yield very acceptable pregnancy rates to a single fixed time Al at 60 to 72 hours after PGF2a. The short-term MGA-Select protocol is an excellent option for late calving cows that will not fit into the Long-Term MGA-Select program.
      
      

4. CIDRs (The Eazi-Breed): The Eazi-Breed CIDR (Controlled internal drug-releasing device) cattle insert, or CIDR as it is most commonly called, is the newest synchronization product available in the U.S. market. Developed and used extensively in New Zealand and marketed in the United States by Pharmacia Animal Health, the CIDR is a vaginal insert that delivers the natural hormone progesterone throughout the seven-day implant period. This progestin stimulation helps to induce cyclicity in anestrous cows and advances puberty in heifers.
   
   In studies that used an injection of prostaglandin (Lutalyse) on day six after insertion and implant removal on day seven, research has shown the CIDR to be an effective means of synchronizing estrus in virgin beef and dairy heifers, and in postpartum beef cows. The CIDR is now approved for use in lactating dairy cattle.

   Animals may either be bred to detected estrus for three or four days after CIDR removal or fixed-time inseminated at 48 to 54 hours after implant removal. Although labeled for a day 6 prostaglandin (Lutalyse) injection, practical implementation in most other countries usually involves moving the prostaglandin (Lutalyse) to day 7, which eliminates one animal handling with no indications of reduced efficacy.

   Reusing CIDRS: The following are a few reasons not to reuse a CIDR: Aside from legal issues, there are no studies available to document the efficacy of a used CIDR to induce cyclicity. In fact, the U.S. version was designed to have minimal residual progesterone upon removal, which would suggest they would not be effective if reused. Last, but certainly not least, regardless of how they are cleaned, the sanitation of a used CIDR is compromised and reuse increases the risk of disease transmission within the herd.
   
   Response: Although the rumors of 90 percent estrous-response rates are true, these are exceptions and not the averages. One of the studies that was used to demonstrate efficacy for the U.S. Food and Drug Administration (FDA) approval showed that although pregnancy rates in excess of 50 percent are certainly possible, data suggests that even when working with the improbable case of 100 percent cyclicity, pregnancy rates in excess of 50 percent are not guaranteed. Other studies have evaluated the use of the CIDR within the Ovsynch and Cosynch protocols (e.g., insert CIDR and inject GnRH; remove CIDR and inject prostaglandin (Lutalyse) 7 days later) and suggest improved reproductive performance in beef cows using the CIDR approach.