A714
Reproduction Management - 
Estrus Synchronization and Heat Detection

prostaglandins | GnRH-PGF2a based synchronization protocols | follicular waves | ovsynch | heatsynch | presynch | select synch | MGA-PGF2a system | CDIRs (the eazi-breed) | heat detection

Estrus Synchronization Programs:

1. Prostaglandins: The foundation of any dairy cow synchronization program is prostaglandin. 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.
   
   The PGF2a-based breeding program requires a set-up injection of PGF2a 14 days prior to the end of the voluntary waiting period (VWP), followed by another injection at the end of the VWP. Animals are inseminated to detected estrus over the next 5 days. Animals not inseminated following the first injection are re-injected 14 days later and observed for estrus for another 5 days (Figure #1).
   
   Figure #1:
   
   
   There are four categories of eligible cows that should receive the PGF2a injection:
   • All open cows that are approaching or are just past the voluntary waiting period (VWP = 45-60 days following calving in most herds).
   • Cows not responding to the previous prostaglandin injection. (Animals not responding to three successive injections should be checked by the veterinarian for cyclicity.)
   • Inseminated animals that have been diagnosed open by palpation.
   • Early postpartum cows. Early postpartum injections have therapeutic benefits in helping cows with low-grade uterine infections to clean. Additionally, "short cycling" cows with prostaglandin may help to improve the fertility of subsequent heat cycles. Prostaglandin given two weeks prior to the VWP will also increase the percentage of animals in the proper stage of the cycle to respond at the first breeding injection.
   
   Injection Frequency: The frequency of injections will vary depending on herd size and other management factors. Prostaglandin programs work by allowing producers to systematically schedule reproductive management procedures into a short time period for "groups" of eligible cows. While large herds (> 400 cows) may have dozens of eligible cows each week, smaller herds (< 60 cows) may only have 1 or 2 eligible animals. Therefore, smaller herd owners may choose to inject groups of cows at 2 or 3 week intervals, while larger herd owners will inject weekly.
   
   The key to any of these programs is to choose a specific day of the week for injections that will complement labor availability for heat detection and breeding, and to inject all eligible cows on each injection day regardless of the number of weeks since the previous injection. This facilitates simplicity and minimizes confusion.
   
   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.
   
   Additionally, when using the 11-day interval, 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. 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.
   
   Advantages of Prostaglandin Programs:
   1. Improved Heat Detection: A major benefit of prostaglandin programs is to group cows so they all come into heat at the same time. This facilitates more efficient use of labor for heat detection. Mounting activity also increases two-to-four fold with multiple cows in heat. Thus, not only can time and labor be focused to a period when cows should be in heat, but the cows are also more willing to display the many signs associated with estrus. During such active periods, many naturally cycling cows are likely to be detected that otherwise would have gone unnoticed.
      
      
   2. Reduced Days to First Service: The more efficient a producer is at detecting heat, the greater the impact on "days to first service." However, prostaglandin programs also have a more direct impact on this variable. With a voluntary waiting period of 60 days between calving and breeding, the average days to first service would typically be around 70 days (if all cows cycled and were detected during that 21 day period). In a herd on a prostaglandin program, responding animals are generally inseminated 3-4 days after each injection. Thus, on average, days to first service are cut by about 7 days for each responding animal.
      
      
   3. Possible Increased Conception: Most herds on a prostaglandin program have experienced increased conception rates. Prostaglandin has no direct effect on fertility; however, better heat detection results in fewer cows getting bred when they are not actually in heat.
      
      
   4. Allows a Greater Focus on Cyclicity: Organized prostaglandin programs "force" producers to focus more attention on the cyclicity of their herds. Any non-cycling cow on the program will be diagnosed as a problem within 2-3 weeks of her VWP. A producer can then seek veterinary intervention early to get her back on track. Equally important is the fact that the cows that are cycling and healthy get inseminated early. These are the cows that make money for an operation.
      
      
   5. Flexibility: Some producers limit the number of animals bred during the warm summer months. In the fall and winter, cows may be injected weekly. Gradually back the program off to once every 2 weeks or 3 weeks as a higher percentage of the herd becomes pregnant. In the spring, prostaglandin programs can be used to get more animals pregnant before the summer breeding slump arrives.
      
      For producers investigating seasonal dairying, a synchronization program such as this is a must. To have a strict milking season, there must be a strict calving season which dictates a strict breeding season.
      
      
   6. The program is simple and easy to schedule and administer.
      
      
   7. It is the least expensive of all popular synchronization programs.
      
      
   Disadvantages and Precautions:
   1. Possible Abortions: Prostaglandin programs require accurate identification of cows and excellent record keeping systems. Because they may abort, a producer must be certain that previously inseminated or pregnant cows are not mistakenly injected with prostaglandin.
      
      
   2. No Fixed-time AI: Although prostaglandin labels may recommend breeding cows at 80 hours after the injection, this is not conducive to optimum fertility. Breeding at 80 hours may be implemented to help settle some cows that are hard to catch in heat; however, it should not be used as standard practice on all cows. Considerable variation exists in the interval from PGF2a injection to estrus; therefore, PGF2a alone is not conducive to fixed-time AI. Additionally, breeding an animal at 80 hours without observation of standing estrus closes the door on all reproductive management options until the animal returns to estrus or is palpated for pregnancy. If the animal was not cycling, this could be a costly mistake. It is best to inseminate cows based on observation of standing estrus when using prostaglandin.
      
      
   3. Daily Heat Detection: Although prostaglandin programs allow producers to focus heat detection during a short period of time, some heat detection should be done each day to detect naturally cycling animals and possible returns to estrus of previously inseminated animals.
      
      
   4. It is not effective on early cycle or anestrous animals.
      
      
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. The following is a brief description of follicular waves in cattle.
   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. Because virgin heifers do not respond to GnRH injections as consistently as mature cows, use of GnRH-based synchronization protocols is not currently recommended.
      
      
   GnRH-PGF2a Based Synchronization Options:
   1. 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 #2). 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 #2:
      
      
      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.
      
      
   2. 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. GnRH is the hormone that is used to induce ovulation in the Ovsynch protocol discussed previously.
      
      To induce ovulation, 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 about an hour, 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 7 days later with a PGF2a injection. 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 interval to fixed-time AI is 72 hours after PGF2a (48 hours after ECP) for Heatsynch, compared with 56-64 hours after PGF2a (8-16 hours after GnRH) for Ovsynch.
      
      The biggest difference that producers will immediately notice between Heatsynch and Ovsynch is the percentage of cows that will show visual signs of estrus. ECP 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.
      
      
   3. 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, 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.
      
      
   4. Select Synch: With the Select Synch system, cows are injected with GnRH and PGF2a 7 days apart (Figure #3). 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, sometimes called the Hybrid system (combination of Select Synch and Ovsynch), is to heat detect and Al until 72 hours after the PGF2a injection and then mass-Al and give GnRH to those cows that have not exhibited estrus.
      
      Figure #3:
      
      
      When comparing estrus response, conception and pregnancy rates for Select Synch and the two-shot PGF2a system in 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 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 group (60-70%) to standing heats. Estrous detection can be terminated at 48-60 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, drug costs are reduced because only 30 to 40% of the group will receive the second GnRH injection. Additionally, if less than 40-50% of the group is detected in estrus by 72 hours, the mass mating can be aborted, saving drugs, money, and semen that might be wasted on anestrous cows.
      
      
3. MGA - PGF2a System: The MGA-PGF2a system (Figure #4) is a time tested, proven method for synchronizing estrus in dairy heifers. MGA is not approved for use in lactating dairy animals. 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 #4:
   
   
   Success of the MGA system depends on adequate bunk space and proper feeding rates so the appropriate daily dosage is consumed by each heifer. 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 often 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.
   
   
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 7-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 6 after insertion and implant removal on day 7, 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.
   
   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. Numerous other studies have evaluated the use of the CIDR within the Ovsynch protocol (e.g., insert CIDR and inject GnRH; remove CIDR and inject prostaglandin (Lutalyse) 7 days later). Most of these studies suggest improved reproductive performance in animals using the CIDR approach.
   
   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.

Heat Detection: