Thank you to Stacey for the introduction, and see Animal Health are delighted to be sponsoring this webinar. Before we get started on the main act, I'd just like to take this opportunity to let you know of some changes to our PreDelta device. This has been advertising in practise, and emails have been sent, but for those of you who may have missed it, a quick heads up.
The applicator and the tail have both been improved to make it easier to both implant and remove the device. The print otherwise remains the same in progesterone levels and individual wrapping. This new print will be available in wholesalers from the first of August and will run as a separate item until current print stocks are depleted.
Please do contact our sales, marketing, or technical team if you have any further questions. Now it is with great pleasure that I introduce Professor Paul Fricke. Professor Fickie is a world renowned expert on dairy cow reproduction.
He was raised on his family's crop and dairy farm located near Papinon, Nebraska, where his family continues to farm today. Paul joined the faculty in the Department of Dairy Science at the University of Wisconsin Madison in 1998, and he was promoted to Associate Professor with tenure in 2004 and to full professor in 2009. His current position includes 70% extension and 30% research appointments in the dairy cattle reproduction.
Professor Frickie's research programme focuses on understanding the biology underlying the many reproductive problems presented by modern dairy cattle. In 2014, Professor Frickie was awarded a six month research to Pascal as a visiting scientist in Ireland. The goal of Professor Fricke's extension programme is to improve reproductive efficiency of dairy cattle by applying knowledge gained through scientific research to develop practical management strategies and assess new reproductive techno technologies and to disseminate that information throughout Wisconsin, the United States and the world.
Today, Professor Frie will speak on reproductive management strategies for high producing dairy herds and specifically the development of fertility programmes for these high producing dairy cows. Thank you, Paul. All right, great.
Well, I will say good morning to everybody out there. It's morning here in Wisconsin. It's just about 50 a.m.
So good afternoon to all of you, over in the UK and, and thanks for joining the webinar. And thank you to Siva for for sponsoring this. There, there's a lot of different topics that I, I could discuss.
I really enjoy doing these webinars for veterinarians that allows me to, to explore some of the more technical aspects of some of the things that we've done. And really what I wanna focus on today is this idea of of fertility programmes. And this is probably the newer aspect of, of what we've been working with, .
We have been able to, to programme, to, to use programmes to inseminate cows for a long time. This is the programme that we'll be, we'll be focusing in on. This is an OBSync protocol.
This is actually the original publication of the the first publication of OSync. This, this was published in 1995, just recognising, my colleague, Doctor Mila Wilbank here at the University of Wisconsin. His graduate student at the time, Doctor Richard Purley, he's at Michigan State University.
So these two guys, published this protocol in 1995, and it uses sequential treatments of H and prostate glandin. In the sequence that you see here, we call this an obsync protocol. And the thing I want to emphasise is that back in 1995, this protocol was not a fertility programme.
This was simply a protocol that allowed us to set up cows and inseminate them in a timely manner. In fact, the first studies that compared of sync directly with breeding cows to an asterisk would would have shown that There's really was not a difference in, in conception rate at that particular time. Conception rates were somewhere in the mid-30% range, whether you put a cow in an off sync protocol like this and inseminated them, or whether you inseminated them to an estis.
And so, The publication of this protocol was a game changer. It's the true, I think the term paradigm shift sometimes is, is a bit overused, but this truly was a paradigm shift. It really changed the way that we thought about what we could do with reproduction and lactating dairy cows.
And so what I want to move then to is looking at this protocol and We basically, in the years since OSync was developed, our kind of our quest from a reproduction, research standpoint was to see how can we modify this programme so that not only can we put semen into cows in a timely manner, in other words, we can increase the service rate, but are, are there things that we can do within the context of this protocol, to increase fertility? And that's really been the quest, lactating dairy cows are are not very fertile. Typically we see conception rates in the mid, mid 30 to 40% range when we breed these high producing lactating dairy cows to an asterisk.
That would be compared to a non-lactating heifer when we would expect conception rates to be in the, in the 50 to 60% range. And so, kind of our idea has been how can we modify this protocol? What can we do to try to increase fertility to time insemination.
I think by the time we get towards the end of the end of this webinar, you'll see that in fact that we've done that. So we've done a lot of manipulations. But I'll summarise right up front the manipulations that we've done, we've done with this take-home message.
And so we've done a lot of work with this, and this is really what it comes down to. The key factor affecting fertility to an obsync protocol is the response to each of the three sequential hormonal treatments. And we can define those responses using progesterone profiles.
So, What fertility to this programme really comes down to is if we can get a cow to do exactly what we want her to do in each of these sequential treatments during this protocol, if we can set them up to do better, for example, we can actually achieve pretty high fertility, higher fertility, in fact, to this protocol than we can get to breeding these high pricing lactating dairy cows to an asterisk. One of the first attempts, and, and I just want to launch into this, this is probably the most popular protocol, at least in North America, and on a lot of, a lot of dairy farms that I've been to around the world in, in Asia and in Europe. This is a very popular protocol to set up cows for first insemination.
And without getting into too much nitty gritty, if, if we could select a day of the cycle to start this OSIN protocol, in other words, to give this GRH treatment. Day 6 or 7 ends up being, being the best days that we could do that. And it's for a number of reasons.
Progesterone is, is not too low and it's not too high at that point during an extra cycle. And most cows are gonna have an obultory follicle that at least has a chance to ovulate to that GRH treatment. And this group in Florida back in 2001 published this protocol, and the idea is that if we can pre-synchronize cows with these two treatments of prostate glandin.
And, and this was a very common practise at the time, by the way, people in breeding pens would be giving prostaglandin to non-pregnant cows, breeding cows that come into asterisks, if they don't see them in asterisk, 14 days later they get prostaglandin. So this is really an old Astrosynchronization protocol. And really what happens is that most cows are going to be in asterisk on day 3 and 4 after this second prostate landing.
If you use a 10-day interval, then you're going to put them right at day 6 and 7. And so, so this protocol is, is quite popular with that regard. This is the way I like to show these protocols when I talk to dairy farmers, it's a lot easier to see them on a calendar.
I always encourage people to draw these, these things out so they can see how they work. Typically what people would do is they'd be on a Wednesday giving these processed landings. 14 days apart, 12 days later, in this example, you can start off sync.
And so really it sets up management on the farm to work pretty well where Mondays, these, animals are gettingation process and on Wednesdays, you're gettingation Prolan on Thursdays, you stack up a lot of cows to breed astri. So we have a lot of farms that are actually using this protocol, to, to set up cows for first breeding. And in this paper in 2001, And this, this becomes another key here.
There are non-cycling cows present in the population of all cows at the end of the voluntary waiting period. In this study, 23% of the cows an oar. You have to take those angular cows out because the pro lands aren't gonna really do anything to benefit them.
And when they looked at only cycling cows, this precinct of sync increased fertility compared to obsync alone. So it's really kind of the first step. To, to making it, making a fertility programme, you know, 1st, 1st step that we could actually increase fertility to a time of insemination.
What the industry did then is a lot of farms that will breed cows to estrus after these two prostaglandins. And so, you'll see a lot of cows coming into heat. The thing I want to point out about that though, are the cows that come into estrus here are the cows that are set up to have the increase in fertility, to the obscene protocol.
So if you choose to breed them, you kind of take, you negate this precinct effect and you no longer see an increase in fertility. And So one of the questions that has been asked is what would happen if we didn't cherry pick? In other words, what happens if we just send all the cows through 100% time to I versus cows that would get, would get inseminated after this prostate gland.
This is a meta-analysis that was published last year in 2016, a group in Germany. They reviewed 3 different papers, 3 randomised controlled studies. There were 1,689 cows.
My colleague Milo did one of these studies. I did the other one, so it's kind of focused on the work that we've done here in Wisconsin. What they concluded then was that the incorporation of of AI to Ester during a presyncoing protocol actually decreased the odds of pregnancy to first insemination by 35%.
So, Again, all this is saying that If you breed cows to estis, if you intervene and you breed cows to estrus, and you pull those cows that are pre-synchronized out, you lose the precinct effect. And so this meta-analysis would would support that concept. So, that kind of gets me into some of the different things that I want to talk about.
So this is the outline that I follow through my talk. I want to talk about effective obliatory response to that first GRH injection on, on fertility, the effect of progesterone during this protocol on fertility. The effect of progesterone at the last GNRH treatment on fertility to the protocol, and then addition of the second prostate glandin treatment and how that can be used to increase fertility.
If we have time as we get to the end, we'll talk about strategies for re-synchronization and I've got a little bit on HEPA protocols, at the, at the end of this thing as well. So this outline is really kind of the strategic way in which we kind of attack the problem as to how we can improve fertility to the protocol. So let's first talk about arbitrary response to that first generation injection of the protocol on fertility.
This paper we published in, in 2015 and this is just, the structure of progesterone and progesterone is very important throughout this protocol. It really has a lot to do with determining fertility to this protocol. So this is another paper that we published in 2012.
And what this paper illustrates is one of the problems that we have with using GNRH in these protocols. We challenged cows in a high progesterone environment. In other words, they had a, a day seven corpus ludium at this particular time versus a low progesterone environment.
This is after a corpus ludium had been regressed. And we challenged them with the, with 100 mcg of GRH. Now in the US we use Gnadery and acetate.
And this is the, the, the labelled dose of gamenatare and acetate. And what this graph is showing is that animals that had a corpus luteum. You have a, a very diminished LH surge in response to that generates treatment.
In the absence of progesterone, we have a good LH surge. And so what this illustrates is that there is a problem, although we want to get casts a 6 or 7 of the cycle to start. An offsy protocol, it sets them up at a time when they do have a corpus luteum and you, you actually run into a bit of a problem with that because you don't get a very good LA surge.
In other words, you, you decrease auditory response. So this, this kind of shows the way we have to kind of think about the physiology of this programme, what we want to have happen. And so there, there are good things about starting on day 6 or day 7, and there's a few downsides about day 6 or day 7, and this is one of them is that we're, we're setting them up to have progesterone.
So that gets into the idea of this particular experiment. It's, it's a, it's a very novel idea, I think, and, and it's kind of neat how it works out. We'll get into this.
This is a, a double ob sync protocol. We use this protocol in the context of our experiments. We have a lot of control over what happens during this particular programme, but the first obsync protocol, basically, if we get these animals to ovulate to this GRH treatment.
If we give a half dose of prostaglandin on day 5, we won't regress the corpus luteum that results from this GRH treatment. But what we do is we knock it down. So we'll knock down progesterone by giving this half dose of prostaglandin.
Theoretically then we can increase obligatory response to this firstH treatment. So the, the whole idea behind this experiment was to try to knock down progesterone. At the right time so that when we challenge with this GRH, we can increase ob response to the first GRH treatment.
So it's all focused around what happens if we could increase obulatory response to this first-gener treatment. How does that affect fertility to time insemination. So these are the results of this trial.
You can see at the bottom here, this is the the 2nd Osync protocol. We have GRH, prolein and GNRH. So this is that half dose of prostaglandin 2 days before, cows that did not give it.
Or did not receive this second, this half dose prostaglandin. They're just increasing progesterone as they normally would during the cycle, and then you regress that corpus luteum, with this prostaglandin. You can see that our treatment did exactly what we thought it would do.
We were able to knock down progesterone, so we have about 2 nanograms per mL less progesterone at the first GRH treatment when we give that half dose of proplein up front. Now that CL again on day 5, it's not gonna regress. You just knock down progesterone for a bit and then those CL actually recover and then they regress.
So this actually set them up, it's pretty neat how we, we were able to set them up and actually decrease progesterone at that first treatment. So what did that do to obitory response? These animals that, that were in a high progesterone environment that didn't get the half dose of prostaglandin.
This is just something that kind of philtre back in your mind. Only about 60% of animals normally ovulate to that first generation injection of an obsync protocol within the context of a double obsync protocol. Now that may seem lower than you might think it would be, but that's exactly what it is, and it's because there's some progesterone there.
By knocking down that progesterone, we were able to increase obit response by 21% points, and that's, we've done a lot of different things to try to increase obbi response to G1. This is probably the most effective way that we've been able to do that. So that's a very substantial increase in arbitrary response to G1.
So with all of that, then what we did is we looked at conception rates at 32, 46, and 67 days. So this is the first preg check and then the two rechecks. And you can see that although we were able to increase obligatory response by 21% points, we were not able to statistically increase conception rates.
So, The bottom line of these data is, it's just a kind of a theoretical experiment is that we were trying to see if we could increase obulory response to G1, how much of an impact does that have? Well, it has a big impact on obit response, but it does not have a big impact on fertility. And so one of the ways we can think about this is that You know, one of the things I run into with veterinarians, they want to go into a cow and ensure that she has a dominant follicle capable of ovulating before they put him on an offsy protocol.
It's a nice idea, but really looking at follicles doesn't do much as far as increasing fertility. To these particular programmes. This is kind of, just looking at Conception rate of cows that ovulated to G1 versus cows that didn't.
So it's a good thing if they do ovulate to G1, they have much higher fertility than if they don't. We did some calculations here just saying, OK, so we have cows that ovulate, we have cows that don't ovulate. We know the conception rate of the cows that ovulate, we know the conception rate of the cows that don't ovulate, and we calculated based on this, that we would only see a 3.4% increase in conception rate, based on increasing this fertility.
So again, this is just showing that Small increase in conception rate for a big increase in arbitrary response to G1, we kind of moved on from this and said, well, You know, focusing on getting more cows to ovulate the G1 is probably not a big issue. So now I just want to briefly go through kind of the way we started to think about another way to attack this problem. And that is simply to define what progesterone looks like, going through this protocol.
So what we're gonna look like at here is, is cows, as they go through this protocol, what does progesterone look like at G1 and what is progesterone look like at proslandin. So in other words, how does progesterone during off sync affect fertility? And so first we're gonna look at A large group of cows that we pulled blood samples at G1 and we ran progesterone.
So this is over 6000 cows. Each of the cows was on an experiment that we had done. This is a collapsed across many different experiments.
We pulled a blood sample. And ran progesterone. And what you can see is that we can stratify progesterone is from left to right as being very low in those blood samples or very high.
The height of the bars is the conception rate or pregnancies for artificial insemination. The numbers within the bars are the number of cows represented in each of these subgroups. And so the question is, does progesterone at G1 matter for fertility?
And the answer is yes. Cows that have very low progesterone have low fertility. Also, cows that have very high progesterone have about the same low fertility.
If you can get cows into these mid-level progesterone levels, these cows have pretty reasonable fertility. All this is really saying is that if you can get cows to day 6 or 7 of the ester cycle, you're gonna have better fertility, you know, by starting them G1 at that particular time than if you start them without a CL or you start them too late. In an est cycle.
So part of the idea then is that how do we get cows to day 6 and 7? How do we increase the proportion of cows that get to day 6 and 7, to see that increase in fertility? How do we eliminate these no progesterone cows?
How do we eliminate these cows that have, too high or too late in the ester cycle. So we want them to ovulate to G1. And then we had a group of cows 7 days later, this is 3,383 cows.
This is looking at progesterone at the prostate glandin. And what you can see is, is that if cows don't have a CL at the prostate gland and of these protocols, they have very low fertility. This is 20%, this is across many different studies.
Some of the studies actually are much lower than this. So one of the things to keep track of in your mind is that Cows, the best indicator of low fertility in these protocols are cows that fail to have a corpus luteum at the prostate glandin. When we get to re-synchronization, this is exactly why I like to look at cows at the prostaglandin of a protocol rather than at the first generate treatment.
And so you can see 20% if they didn't have a CL. We want cows to have as high progesterone as we can get at this particular point in the protocol at, at Prosland. You can see how high the fertility actually is in these cows.
Kind of a bimodal distribution, don't know exactly what's happening here. I would say that these are cows probably with one large CL. These are probably the cows that actually have two CLs within the protocol, and I can show you how that works once we get to, to double off sync.
So, understanding what we want medium-level progesterones that generate you and very high progesterone concentrations of this prostate glandin, how does precinct sync help us? Well, there's two big problems with the precinct opsync protocol. And the first one is that anovular cows are not affected by these prostate glandins.
And I'll show you in, in the next slide. About 25% of cows are not cycling. And so if they're not cycling, you send them through this protocol, about 25% of the cows start off sink in a low progesterone environment.
And if you remember the conception rates of the cows without a CL G1, they have very low fertility. So this programme doesn't do anything to resolve the annoular condition. And it And by way of that, it really doesn't get all of our cows on day 6 or 7, or it doesn't maximise the number of cows on, on day 6 or 7.
You don't really tightly pre-synchronize these cows. So this is just a study that we did, published back in 2009, looking at 5,818 cows across many different studies that we've done, looking at the incidence of an ovulation. It's about 1 in 4 cows.
It ranges from herd to herd. I could do a whole talk on, on an ovular conditions, but we, we always find this number is very repeatable, at least in our herds, we see, we see about 1 in 4 cows or so. It's related to body condition score, but not completely.
Lower condition score cows have a higher rate of anovulation than kind of these mid-level cows, but even the cows in good body condition have somewhere between 15 and 30% incidence of, of an ovulation. So this is a big problem, you know lactating dairy cows. Presync calsin does nothing to resolve this problem.
So that moves us into this protocol and this the protocols get more complicated. But hopefully what you're seeing is I'm kind of walking through this, the thought process, and this is, some work that Milo Wilbank did and published it. Now this has been almost 10 years ago now that this this was, this was first published in 2008.
So what Milo did is he, he basically took those ideas that I just shared with you. How do we get more cows to day 6 or day 7? At this particular point in the protocol.
And how can we deal with the non-cycling cows? In other words, can we resolve that an ocular condition before they start, this green ob sync, which is the obsync that we breed to. And so, what all, all he did was he took, took an off sync.
This is an off-sync protocol in red, it's a little modified. There's 3 days between prolennon and GRH. That's nothing magic other than to keep things between Monday and Friday.
. About 90% or more of these anovular cows will ovulate to a generate treatment. So they have follicles capable of ovulating. They're just not doing that.
So if we treat with GNRH, we get them to ovulate. If we get 90% of our cows to ovulate to this GRH treatment, then 90% of our cows will start off exactly on day 7. And so this protocol will resolve the anovular condition in most anovular cows, and it gets them set up, so a high proportion of cows actually start off sin exactly on day 7.
And so those are the two big Ideas behind a double sync protocol. Now, the first studies with double sync, I'll go through these quickly, comparing to 100% time insemination to presyncopsync versus double op sync, many of the first data sets, and this would be true with anecdotal data on farms, first lactation cows really had an increase in fertility when they went from presyncopsy to double opsync. Older cows in this study didn't see as big of an increase.
The problem with data is that it's not all completely consistent. This is a much larger study done in 2012. Again, this is from Milo Wilbank's lab.
In both cases in this study, there was an increase in fertility to double sync compared to a precinct sync. Now remember this is a 100% time insemination of precinct sync. There's no estisk detection done for first insemination here.
But the point I want to make is this, and, and really was the next kind of thing we try to tackle. What's going on with fertility in these older cows? Why, why is fertility lagging in the older cows compared to the younger cows?
This is very typical what we see, when we go into herds first lactation cows are always the highest fertility group, but really the question is when, when we're really manipulating. The, the ovarian function as much as we do. Why is it that we don't get high fertility in these, in these lactating dairy cows?
And to answer that question, what we did is we started to look at progesterone at the end of the protocol or at this last GRH treatment. So if I go back to the protocol, we've looked at progesterone at this point, we want it to be mid-level here. We want to get progesterone as high as we can get it here at this prostaglandin.
And then when we give prostaglandin, we want to get the CLs to regress quickly and completely. And this is a good illustration of some of the things again that happened with these kinds of protocols. We fix a lot of problems by doing certain things, but we create some other problems by doing things.
If cows ovulate to G1, we're setting them up to have at least one CL that is just acquiring ludiolytic capacity at this time. And it ends up that there is a subpopulation of cows, anytime we look, that do not fully regress their corpus luteum by this particular point in the protocol. I remember time insemination is going to happen out here and that's reflected by progesterone.
So we're going to look at progesterone at G2. So this is 3,148 cows that went through the protocol, blood sample collected at G2. Notice the progesterone levels are tenfold lower than any of the others that I've shown you.
Obviously, we've given prostaglandin, so we've at least knocked down progesterone to a great extent in most of these animals. What you can see is that anytime we do this kind of an analysis in our data sets, there's always a cut point. And in this data set, the cut point is 0.4 nanograms per mL.
If these cows regress their CL or have less than 0.4 nanograms per mL, they have relatively decent fertility. These animals, there's always a subpopulation, and this is on a double opsy protocol to first breeding.
It's always about 10 to 15% of these animals. They're not fully regressing their corpus luteum. And you can see what it does to fertility.
It really decreases fertility. Now, what we think is happening in this case is that a little bit of progesterone hanging around, especially when you go to do the time dissemination, probably inhibits gametete transport and probably decreases fertilisation rate, and there are some data that would, would suggest that that indeed is the case. And so, again, it's kind of a problem created by the protocol.
It tends to be a greater problem for the older cows as compared to the younger cows. There is an age effect on acquisition of luteolytic capacity with older cows acquiring ludiolytic capacity a little bit later. And so, in looking at the problem, you can try to come up with a solution.
And again, the solution here is to modify the protocol. And this gets into kind of maybe some of you have heard about what's being done in these protocols is adding a second prostate gland in treatment. So I wanted you to understand kind of why this was done, to understand that this is the problem.
The problem is that some cows are not fully regressing their, their CL in the context of this protocol. And so to remedy that, the first experiment that was tried was to add a second prostate gland in treatment. Again, this is some of my Wilbank's work from 2009.
And all he did was took this double off sync protocol. We knew that there was a problem with luteal regression. They're not fully regressing their CL.
So what Milo did is he added a second prostag glandin. So just to ensure that those regress, this second prostag glandin was added. All the experiments that we've done, it's simply a full dose of prostate glandin 24 hours after the first one.
This is a subset of, of, of a much larger data set. I'm just showing this because what it shows is the difference between one prostag glandin versus the two prostate glandins in these protocols. Note that first lactation cows, there's really not a difference in fertility.
Obviously, they have pretty good fertility. They're regressing their seals fine. They acquire luolytic capacity a little bit earlier.
It's these older cows that really benefit. So if you give one prostate glandin, their conception rate was 37%, adding the second prostate glandin, that bumped that 45%. What Milo did in this study was looked at the percent increase in pregnancies produced.
So by adding one prostag gland into this already complicated protocol, was able to increase the percentage of pregnant cows by 23%. And so really that's kind of the, I guess I would say the Rosetta Stone. That was kind of the, the big idea that really propelled us into this kind of idea of, of fertility programmes.
So, I want to quickly go through a couple very recent experiments that we've done. I'll just flip back to this. So we have a lot of farms now that have added this second process landing.
Almost down the line, the farms will say, when you add the second prostate glandin, there's a tremendous increase in fertility to time insemination. So there's no, there's no quibbling about that. The complaint is that you have to handle cows another day.
It's a real pain to, to add that second prostate glandin. So there's two experiments that we've recently done to try to, try to address this issue. And this is one of them.
And so, All we did is we had, this is in a recent protocol, but we had a standard sync protocol. This is our control group. This is our positive, this is our native control group.
This is our positive control group, the two prostate glandins 24 hours apart. We simply said, what would happen if we doubled the dose of prostate glandin at one time. So rather than having to give two prostaglandins 24 hours apart, we're just going to give a double dose of prostate glandin.
This experiment was done. With dinarost, by the way, which, which may be important. So we doubled the dose of, of dnarost at one time.
And the story is pretty simple. When we look at luteal regression, you can see with OSync with one prostaglandin, 87.5% luteal regression.
So again, there's the problem with luteal regression. When we add the second prostaglandin, we can drive that up to 94%, but doubling the dose of dnarost did not increase ludar regression. And I just want to make sure that everyone understands this.
I've heard some veterinarians saying that I said that you can increase the dose, and I'm not saying that at least with Dinarost, it does not appear that we can double the dose and get the same effect as the two prostaglandins 24 hours apart. These are conception rates. It's always harder to show statistical increases in conception rates.
They're not statistically different, but the conception rates follow, the luteal regression rate. So bad news if you want to just increase the dose of prostate glandin at a single time rather than giving the two prostate glandins 24 hours apart. This was another idea that we had then in a very recent experiment, we just presented this data at the dairy science meetings this, this summer.
So the idea was this. Here's our positive control again. We've got off sync with the two process plan it's 24 hours apart.
We gave one this is kind of our negative control here on day 7, and we said, well, rather than going on day 7 and day 8, what would happen if we just delayed? The treatment with prostate glandin in these protocols to day 8. So rather than, day 7, this allows the, the CL to be one day older when we challenge with the prostate landing.
I'll just briefly tell you exactly what happened and so that might be good. We're, we're treating an older CL but you don't get progesterone down fast enough, and we had the problem here with progesterone at G2. So let's look at the data very quickly.
These are conception rates have broken it out by parity. This was done in the summer on a farm in Wisconsin. We had heat stress, particularly in these older cows.
The conception rate in that group 3, delaying till day 8, is not a good idea. We had lower fertility in this group than we did in these first two groups. So, again, we tried this and it just didn't work.
This is where we took out the cows with a low progesterone at the prostate gland and there was 13% of them. And so, these are just conception rates of the cows that either didn't have a CL or had a CL at the pros Atlantic. So we took these cows out.
And this is just showing you the percentage of cows and progesterone greater than 0.5 gramme per mL. What's happening in that group 3 is just as I said, we're not, we're not regressing the CL fast enough.
About a third of the animals in this treatment had progesterone that was too high at that particular point in the protocol. So, at any rate, those are just a couple of the things that we've, we've done to try to, try to work with that second prostag gland and then to summarise that, I would say that At this point in time, we're still stuck with giving that second prostate gland in 24 hours after the first. This is kind of the culmination then of, of these protocols.
This is a paper that we just got accepted to the Journal of Dairy Science, and what we did is we set up cows on a fertility programme, double off sync with the second prostag glandin. For first insemination, which happened at 77 plus or minus 3 days in milk. One thing that had never been done before is setting up cows to come into Erik at exactly the same day in milk range.
This experimental design allowed us to compare fertility to a time insemination after a fertility programme to cows that are coming into estrus at the exact same day in milk. Don't get too caught up in this protocol. It's really just two processed landings 14 days apart, to bring the cows into estrus.
So the first thing I'll show you is conception rate. 50% conception rate in this, top group, 39%, in this, in this lower group. So there's about a 10% increase in fertility to the time dissemination programme.
But the thing you have to realise is that you breed 100% of the cows in this, in this scenario. So we breed 100% of the cows at a 50% conception rate. And the other thing that I, I just want you to realise.
All the non-cycling cows are in this group. All the cows with any kind of, you know, any kind of problems, whether they're, they have lameness problems or if they have nutritis or all the, all those cows are in this group, and they're all inseminated, and we get 50% conception rate. We were only able to catch 77% of these cows in Eris, and this was done with tail chalking and with the aid of a heat detection system.
On this, commercial dairy. So, I took these numbers on the right and I just put them into, I, I put him into this table. These, these are actually the finalised data actually from the paper.
So again, submission rate 100% versus 78%, conception rate at 33 days, 49 versus 39. If you do a kind of a pregnancy rate calculation and calculate the percent pregnant cows at 33 days, you have almost half of your cows pregnant 33 days after the end of the voluntary waiting period in this protocol, only 30%, that's 64% more pregnancies for time dissemination. At the recheck at 63 days, you can do these very same calculations, 23% more pregnant cows, or 58% more pregnant cows in the double oxy group as compared to the stro group.
I, I present these data to, to try to show you, and I realised that in the UK that there's not, the herds are not being this aggressive with synchronisation protocols, but I want you to understand kind of There are some dairies in the US that are doing this, and I wonder, I want you to understand why. It's a very powerful way to increase preg rate if you can get half of your cows pregnant, at the end of the voluntary waiting period. And so probably the best data out there right now showing this, this increase in fertility, due to these fertility programmes.
These protocols are not just for increasing. The proportion of cows that you breed, a double oxy protocol with the second prostaglandin is indeed a fertility programme that actually increases conception rate, to first service. All right.
I want to briefly talk about, resynchronization strategies. So I've talked a lot about kind of how we developed these, these fertility programmes. One of the interests I find, when I go to the UK, you know, so you're, you're in there doing preg checks and you got cows that are open and they might have a seal or might not have a seal.
What's the best kind of a resynchronization strategy that we can come up with? And so this is just looking at these strategies for re-synchronization. So this is actual data from a farm.
So this farm is doing an insemination here at day zero, so this may be 1st through 5th insemination. And the height of the bars are the number of cows and when they get reinseminated. So obviously these are cows that failed to conceive to that insemination.
You can see that there's a big surge of cows that come into asterisk anywhere from 18 to 34 days. And many farms, after that first insemination, this is the earliest non-pregnancy diagnosis you can do, and you can breed those cows to asterisk. Notice that most of the ester activity is over by day 32.
So typically what we'll do is we'll come in with the GRH treatment on day 32. We'll set up with GNRH. 7 days later, we'll do the pregnancy diagnosis.
Now, again, the reason this is done at the prostate glandin is because In the context of this protocol, the best time to look at cows is at this prostate gland and, and cows with or with or without a CL. That's really how we're, how we're gonna deal with these cows. I'll show you that in just a minute.
And then we can finish off by, by doing the resin. These are the cows that were previously synchronised. These are the cows that were an asterisks that they get rebred.
And so now we have a pretty good strategy for for resynchronization. The problem with that strategy, and, and we've worked with this for over 10 years, when farms started to do this, this is insemination number. And you can see this herd is used in a fertility programme for first breeding.
It's a double opsy protocol at this time just with a single prostag gland, and 47% conception rate for first breeding, and then it falls off, at these recincts. So, what this was telling us was that the resincts were not optimised. And so we did a lot of experiments to try to optimise the resincs, and I just want to show you.
The one study that kind of changed my thinking completely on this, so this was a study. Then I had a grad student that was ultrasounding cows at this point in this particular protocol. What you have to realise is that at this point in time, you can have a group of cows that have 2 CL.
In other words, there's a day 14 CL and a day 7 CL. There'd be a group of cows that only have a day 7 CL and there'd be a group of cows that only have a day 14 CL. So, my grad student Julio was able to look at that group, those three groups of cows, and This data changed everything about the way that I think about the problems with resynchronization.
So let's, let's take a look at it. Cows that had 1 day 14 CL at that point in the programme. They regress their CLs just fine.
So this is again, essentially the percentage of cows with incomplete luolysis used in progesterone and G2 as I was shown before. All this says is that if you have a day 14 CL, the cows regress extremely well, seals regress extremely well. There's a large group of cows that have then a day 7 and a day 14 seal, and they seem to regress pretty well.
Here is where the real issue comes in with the reins. There are, there is a group of cows that only have a day 7 seal. About a third of those cows fail to regress their seal and have poor fertility.
For those of you that do preg checks, I just want you to think about the percentage of animals that are open at a herd check that don't have a seal. If they don't have a seal when they start the protocol. And they ovulate to G1, you set them up to have this particular problem, and this is a big issue that I find.
Particularly in, in many herds here in Wisconsin in the US, particularly some herds in the UK. If your strategy at an open check is to put all of the no CL cows that are open on an obsync protocol. That is not the right way to deal with open cows.
If you put all of your no CL cows on an off synctogram, you're gonna end up setting them up so that they do not fully regress their corpus luteum. A better treatment for these cows would be a a rid sync protocol or even a GG GGPG protocol in which we set up with GenRH a week ahead of the herd check with GNRH. So, I don't know if there will be questions about this at the end.
I think this is a key aspect to understand, and I find still that there are veterinarians who want to take the non-pregnant cows without a CL and just put all those cows on a sin. You're gonna set them up to fail, if that's the way that you're handling the nonpregnant cows at a herd check. To maximise fertility in these recent programmes, this is what I was talking about.
This is kind of a GGPG type protocol. So we looked at the effect of adding GRH upfront. Adding a second prostag glandin.
It's not adding the GRH up front doesn't do that much, but if you collapse the data down to looking at plus or minus second process landing, that's where the effect is. We can go from 27 to 35% conception rate. So we have ways that we can increase conception rate to these cows at a resink.
What I did is I challenged my grad students a number of years ago to try to come up with all the, all the experiments. I haven't shown all the experiments that we've done. But based on everything that we know, what would be maybe the best strategy for a recent protocol.
And so this is really what we came up with. And so anywhere from day 25 to 32 after a previous insemination. You set him up with Gener H.
And again, the time that you want to look at him is at the prostaglandin. We can do an ultrasound very accurately determine whether or not cows have a CL. The key to the fertility to a resinc is segregating cows based on plus or minus CL.
If they have a CL, you can give prostaglandin. We've added the second prostag glandin to the resinc programmes and finished them off. If they don't have a seal, and I would say in our hands, about 85% of the cows are gonna have a CL if you set them up with the GRH up front.
By contrast, about 15% of the cows won't have a seal. What we do with those animals is we restart off sync. And we use progesterone.
It's important for the no CL cows, I think, to be using progesterone, you give the two prostaglandins to finish them off and do the time insemination. So this dealing with the no CL cows is really how we pull up fertility in this particular strategy. So just to kind of summarise in lactating dairy cows, this was 2007, so 10 years ago, this is over 8000 Holstein herds in the US.
A distribution of 21 day pregnancy rates. What I want to point out is that very few herds maintained a prey rate above 20%, and this was just 10 years ago. If you look at what's happened, And this is a summary of 2015.
You can see that this distribution is clearly shifted to the right. Obviously, we have good herds and bad herds, and, but the percentage of herds that can maintain above a 21% pregnancy rate, has just dramatically increased. I think in this distribution, about 45% of the herds were able to maintain a pregrate above 20%.
And I would say for those of you that are monitoring pregnancy rate, 20% is a low bar now for, for pregnancy rates. Our good herds are sitting in the mid-20s to the low 30s on their, on their 21 day pregnancy rates. All right, I've left myself just a couple minutes here to hit these heifer protocols.
Probably the best work that's done in this area has been done down at the University of Florida, Jose Santos, many of you probably know that name. In heifers, we're gonna use 5-day, protocols that, that look like this. Because we use a 5-day protocol, we have to include the second prostate glandin, and in heifers, we have to include, progesterone.
So, this is an experiment that they did. This is just putting in progesterone for 5 days, giving prostaglandin, finishing them off. Not that we do a 3-day interval here with a co-sync.
This is simply looking at the effect of the second prostate glandin, but this is Gen H up front and 2 prostate glandin. If you give GRH up front, you have to give the second prostaglandin. If you don't give up front, you don't have to give the second prostate glandin.
And this just shows the conception rates. You can see it, let's just look at day 60, the control group 49%, adding the second prostate glandin without gene generates up front doesn't get you much, but this protocol would generate you up front in the two prostate glandins. About 10% increase in fertility.
This conception rate is really about what we get when we breed cows, or excuse me, when we breed heifers to, to an asterisk. So we have protocols now and heifers that we can get about the same fertility to time insemination as we can get to. Breeding those cows to E, those heifers to Eris.
So I think I'm gonna skip this last little bit here and just get to the last thing. A study that we did, using, rids. And so we've taken this 5-day protocol and we've simply just left the red in an extra day.
One of the problems with these protocols is you have some heifers that come into heat before time insemination when you pull the, the prid early. And so what happens is, if you pull the pri at the first prostag glandin, about 12% of the heifers will come into estrus. We knock that down to 1% by leaving the print in for an extra day, and there was no effect on fertility.
So I think, you know, we can modify these HEPA programmes just a little bit to decrease the problem with increased expression of estis before the time of dissemination. So with that, I think I finished. I think I'm 1 minute over.
Again, I'm from the Department of Dairy Science at the University of Wisconsin-Madison, and I'll just go ahead at this point and open it up for questions. I know that I, I went through an awful lot of material, so let's see if, if anybody has any, any questions. Thank you very much, Paul, for your great webinar and I'm sure everyone who's watching found it very useful as well.
Just before we go to questions, if you have a look, a new tab should have opened up on your screen, with a survey, and I'm a massive survey nerd and I love statistics. So if you could spare a minute just to complete the feedback survey that, as I said, should have popped up in a new tab in your browser, we would be really grateful for that. So Paul, we've had a few questions submitted, and the first one being on luteal regression, why not use only a double dose of the second prostaglandin and do not use dinarost.
OK, so a double dose, we haven't tried, so a double dose on day 8. That's an interesting, interesting question whether or not that would work. I think the problem is It's not just in the timing or the dose at day 8, it's just that the interval from that prostaglandin on day 8 until when you do the time insemination isn't long enough.
And so, if I was gonna try something to modify, what I would do would be to go day 8. And then I would move the time dissemination out to day 56 or 6 hours, excuse me. So you got to modify the backing of the protocol to give enough time for little regression.
I don't think it's just a matter of dose. I think it's just a matter of time that that CL has to regress. And so, there's good things about that idea.
Now, I'm just speaking about ideas, so don't rush out and do this because you have no control group, right? So, the, the positive side is that you would probably get decent little regression and timing of insemination and all that would be great. The downside is that increasing the interval from G1 to the prostate gland to 8 days, you're going to lose some follicles that turn over and you're going to decrease synchronisation rate by some extent.
Now that could wash out any benefits you'd have modifying the protocol. So, I'm just going to tell you that these are things that we think about all the time. It's not until we actually have empirical data that we can make a recommendation.
So, I'm sticking with the, you know, the regular 7-day protocol with the second prostag gland and 24 hours later is better. Now your second issue, Dinarost versus chloroxtinol. We have some data that would suggest that increasing the dose of chlorosinol actually might increase lute regression rate.
But it's hard to increase. Fertility by just increasing the dose of chlorotinol. So again, you know, we've kind of compared 1 versus 2 and we've increased the dose.
In our hands, the two treatments 24 hours apart on day 7 and day 8 always end up being the best way to go. It's not the easiest way to do it, but it's, it's the most effective. So I hope, I hope that answers the question.
It's a good question. Thank you very much, Paul. A similar question here, what do you think would happen if you use double PGF without the precinct?
So the problem, the, the reason, that's a good question, OK? So the reason that the double prostate gland and becomes important. It is particularly in a presync sync protocol or a double ob sync protocol.
We've set the animals up or a lot of animals, to be right on day 6 or day 7, and, and by setting up most cows at that time, we set up the problem for lunar regression. If you don't pre-synchronize the animals. You probably are not going to see a big benefit of adding that second prostate glandin because you don't run into the issue with, with the problem with fluid regression.
It all has to, it all has to do with the fact that the seal acquires ludi litre capacity around day 6 or day 7, OK? And when you set cows up, to be on that day, you kind of set them up to have that problem. Another caution that I, I'll have for everyone out there, and I haven't, Didn't have time to really go into this.
What you may observe, if you put no CL cows on off sync. And you add the 2nd prostaglandin. Those animals tend to have very high fertility.
They also tend to have a lot of double ovulations. And we're doing an experiment now where we've set up cows to start off sync in a low progesterone environment versus a higher progesterone environment. If you set up cows in a low progesterone environment on these protocols and give the second prostaglandin, the double ovulation rate is threefold higher in the low progesterone animals.
So, I would be very careful. We do everything that we can do to get cows to be set up so that they have a CL. If they don't have a CL, that reinc protocol that I showed you guys with the two different forks, the two different decision points, becomes really important because you're identifying the no the no CL cows and you're treating those no CL cows with progesterone.
And, and we think that that's going to be beneficial as far as getting that double ovulation rate down. Obviously, double ovulation rate is highly correlated with twinning, and so you don't want to do things within the context of a herd that are gonna make things worse as far as, as twinning is concerned. So these things get a little bit complicated.
We're, we're still working through that story, but, but it's something that you need to kind of think about as you're working through these ideas. Brilliant. Thank you, Paul.
Another question, as most of these results relate to dairy herds, how do you think the results influence the design of synchronisation programmes in beef suckler herds? Oh, OK, so that's, that's it. No, that's an excellent question.
OK, so there's, there's two things that I want to refer you guys to. There's an organisation called the Dairy Cattle Reproduction Council, the National Dairy Cattle Reproduction Council. You have to Google that.
You can't Google DCRC or you come up with some other weird website. So it's the National Dairy Cattle Reproduction Council. If you get on the website, I'm on the board.
If you get on the website, there's a free end of that website and you can download protocol sheets. Those protocol sheets will be updated soon to reflect the second process plan. That's probably the best source of information you can go to to get the latest recommendations on these protocols for dairy.
Physio physiologic problems presented by beef cows are completely different than lactating dairy cows. There's a whole group of reproductive biologists that work in beef, and you have to go to the beef cattle reproduction task force. So if you Google beef cattle reproduction task force, you're gonna get to a website and they have comparable protocols for postpartum suckled beef cows and beef heifers, and those protocols.
Almost always involve the use of progestins because there's more anovular beef cows. But, but the bottom line, this is an excellent question. You would never want to put postpartum cycle beef cow in a double sync protocol.
Double sync programmes are, you know, beef cows won't ovulate the GNRH. They're anovular for different reasons. So, so be very careful.
You want to use the protocols that are recommended for postpartum suckled beef cows and beef heifers, and those protocols are available at that other website. So, really, really an outstanding question. Thank you.
Great. Thanks for those websites for. Next question, for heifers that are milking 3 times a day, the off sync 16 hour and 56 hours can be quite difficult.
What's the range in hours for this protocol with still good results, similar to the 32 and 16 hour intervals. Thanks. Yeah, that's a very common question because it's that after so, so let me, can everyone still see my screen?
Yes, we can, Paul. OK, so it's still up. Let's just go back.
It's, it's a, it's a really good question and, and so let's just go to a protocol here, . You know, just when you think you had a lot of those protocols, there we go. I'm gonna get to this.
OK, so let's, I just want to get to the straight up opposing protocol. The, the way we typically do this, so let's just look at this. The off-sync and green is the important one.
In this kind of a protocol, every treatment is going to be given in the morning with the exception of that GNRH right there. What we typically do to get the 56 hours is this treatment would be given in the morning, this treatment would be pushed as late in the afternoon as we can get it, and then breathe the next morning. So that really gets us that 56 and 16.
Those are not incredibly hard numbers. What I can tell you is there's different intervals that have different importance. What we know is that cows are gonna ovulate about 24 to 32 hours after that GRH treatment.
We want to breed about 8 to 12 hours before those animals ovulate. So, you know, doing these, the old coincts where you would give GNRH and breed at the same time. Does not optimise timing of insemination relative to ovulation.
So in my mind, this interval of 12 to 16 hours is the most important interval. So you got to preserve that. So what that means is even if you give this in the morning and this in the morning, you're going to be breeding, you know, later that day, and that doesn't work either.
I mean, it's the answer to your question is that sometimes these things are not the easiest thing to do and the biology doesn't match up with the easiest thing to do. It, you know, so I, I can't make any promises if you deviate away from kind of the 56 and 16 hours. What I can tell you is that the herds that can comply to these kinds of protocols get, get excellent fertility.
So, we're kind of stuck a little bit as far as, as how we do these programmes. I don't know if I'm answering the question is, I'm not answering the question, I think in the way that, that you were hoping that I would answer the question. I think the second best way that I would do this would be to give this treatment in the morning, this treatment in the morning, and then try to breathe, you know, 12 to 16 hours later in, in the afternoon, but That's kind of the way it works out with these protocols, unfortunately.
Thank you, Paul. Are you OK for a couple more questions? Yeah, I'm fine.
That's great. Thank you. Next question, I will start with, compliment.
Many thanks, Paul, great overview and a really great improvement to our old offsync. However, we are really struggling here, as in with many herds, with a poor understanding of the herd's economy. So any additional dose of PGF or GNRH is seen in a very negative light on the grounds of additional cost rather than handling.
How to help these farmers to see the additional cost in the light of improved fertility. I guess you probably have these clients like that as well, smiley face. Yeah, yeah, no, it's a, it's that that's an excellent question.
It's, it's a very common question and . There was a there was a famous poet and playwright. His name was Oscar Wilde, I believe he's an Irishman.
I walked by his statue last week when I was in Ireland, and he has a, he has a great quote. He said a cynic is a man who knows the cost of everything and the value of nothing. And I think dairy farmers are cynics in in that exact definition, because the problem is everyone can count up exactly how much each of these treatments costs, everyone knows exactly how much semen costs.
You might even be able to estimate. You know, How much labour it's gonna take to do, to do a protocol like this. But nobody thinks about what is the value of a pregnancy.
And when you do the economics of these protocols, it ends up that pregnancies, when you look at the value of making a cow pregnant, if you make a cow pregnant at the right time, OK, so time is involved as well, but if you get a cow pregnant at the right time, that is probably worth hundreds of dollars, at least $200 and maybe up to $500 or $600. And the value of that pregnancy so overwhelms the cost of the treatments. And the cost to give the treatments.
So any economic model we've ever done. These protocols are, as long as they're complied to and as long as you get the performance out of them that you can get, they're profitable to do that. So, let's go back to, to Milo's data here.
So this would, this is a good illustration I think of, of where your clients are. So you're, I'm saying here, add that second prospect landing, and they're gonna baulk at that and they're gonna say, well, that's expensive to give that a second prospect landing. Well, here's the way I would approach it.
Ask them what is the cost of the prospect land, extra prospect landing? Well, in the US it's cheap. It's about $2.
I don't know what it is in the UK. Let's say it's triple that. Let's say it costs $6 to give an extra prostic landing.
You get 23% more pregnancies, and each of those pregnancies is worth, let's say $300. The, the numbers just skew completely toward the fact that that second prostaglandin is pretty negligible to get that percent increase in the proportion of pregnant cows. Now, I, I do know that the costs that you guys pay over there for prostate glandin are more than we pay.
In the US. I don't understand, those markets. I don't understand why, why that's the case, but, but that is the case, and I have a, a former student who basically did an analysis.
He, he was trying to ask the question, how expensive would these treatments have to get before it's prohibitive to use them? And in other words, at what point do the treatments break even with the increase in pregnancies? And it's like $40 per treatment.
OK, so it's, it's outrageously high. So I think the way that I approach it with farmers here in the US is I just try to, I try to frame that and I try to emphasise the value of a pregnancy as compared to the cost up front of, of the treatments. And, and that's kind of, that's kind of how I do that.
So anyhow, that's kind of a long answer to that question, but it's a good question. Great, thank you, Paul, and I think the final question, what is your advice to medium input, medium output, dairy herds of about 8000 litres from your experience in Ireland? Do you advise the same protocols?
No, that's another really, really good question. OK, so, so it does go back to my experience, in Ireland, and, in Ireland, I worked down in the south at Chagas Moore Park. And those animals are, are different.
They're genetically different. They've been selected to be different. They're smaller, they're not as angular.
They, those animals give about a third of the amount of milk that are high producing dairy cows will give because they're on grass, and because they're actually selecting against milk volume, they're actually selecting for fat and protein. So, my experience was with those animals is that they're already fertile. We don't see conception rates in the 30% range in those lower producing grazed animals.
You know, I saw conception rates. In fact, the experiment that I did over in Ireland, I put them on a double offsync protocol just to manipulate and we had a high versus low progesterone group, and it ends up that conception rates were like 63%. If you breed those animals to an estisk, they have over 50% conception rates.
So, Fertility programmes are fertility programmes in these very high producing dairy cows. In a low producing herd like a, a, a grazing-based herd, those animals are basically managed kind of like, more like a beef herd. I mean, they want them to calve every year.
They don't have a problem with fertility. So the way I would use the protocols in that context, I would breed as many cows to asterisk as I possibly could. And then I would deal with the an ovular cows by using a synchronisation approach.
And that's going to involve using probably arid sync type of protocol. You got to have a, a progestin in there. So I can't go into exactly what I would do, but I'm trying to flesh it out a little bit.
But you're gonna want to use the protocols, not as fertility programmes, but you're gonna want to use them more to treat. The anovular cows and, and make sure that you have a progestin in, in the protocol. But again, it's a, a really, really good question.
And so, it's those cows just don't have the fertility problems that we see in the, in the very high producing dairy cows, probably because of the liver metabolism hypothesis that the Milo's been working with and the increased feed intake. I didn't really get into that whole story, but. Amazing.
Thank you very much, Paul, again for your brilliant webinar and sharing all your vast knowledge. We really appreciate it. Thank you.
You bet. Thanks. It's been great.
A big thank you to Kay and Siva for sponsoring this webinar and thank you to everyone who joined us on the live webinar. It's always great to have your company and providing feedback on our webinars. And last but not least, thank you to my office mates, Paul and Holly for co-hosting on this webinar with me.
I can, I hope you can join us again on another webinar soon and enjoy the rest of your day.
