I was wondering if you had any thoughts on an older mare we have who has driven us nuts for 3 years now. She is an SPS Hanoverian mare imported from Germany 9 years ago, now 18, and has had 6 previous foals by both fresh and frozen semen. Her last foal was 2003 I believe.
She has been somewhat of a mystery, as she will get pregnant as noted by u/s on day 12-13 or so, but then when checked on day 17-18 it is gone. This occurs despite treatment with Regumate and we've had her progesterone levels checked in 2007 and they are supposedly fine.
She does usually have fluid when you go to breed and has one very small cluster of cysts (less than 12mm) in one horn. We use oxytocin protocol before and after breeding, and now she has been confirmed pregnant 4 of 6 times bred over three years.
We biopsied her last year and she received a score of IIA, which as I understand is not terrible. We also note her cervix does not open very wide during estrus.
We had been told by other breeders to have her checked for Cushings and thyroid function as they have something to do with maintenance of pregnancy. Apparently there are mares that will only carry when on these meds, and otherwise do similar things to this mare when not treated as far as losing the pregnancy. The tests were somewhat inconclusive and we were told sometimes not accurate. We started her on Pergolide and Thyro-L just in case. She is a big air fern with a cresty neck and is slow to shed, so she somewhat fits the physical characteristics of a pre-Cushings horse.
We just checked her after breeding 2 weeks ago and she is again in foal at about 12 days (this was Tuesday). She is still on all the meds plus Regumate - trying to pull out all the stops.
My question is, what does the pituitary gland/thyroid have to do with maintenance of pregnancy (if anything) and do you have any other ideas for this mare if she still loses this pregnancy despite the meds - other than she's one heck of an ET candidate ;). What else could the problem be, issue with uterine quality? She always loses the pregnancy before 16 days or so. Thanks so much - she is a fantastic mare and we are DYING to have a foal from her (she has produced two approved stallions previously), but obviously we want to quit throwing money into the pit if there is nothing else left to try.
Okay, this is my area as I work in human medicine - but this is a hugely complicated topic and one that I cannot begin to discuss in detail here, so here are the basics of all basics.
In order to properly diagnose and treat your mare, you need to figure out if she has a problem with her pituitary gland, or whether she is having localized problems with her thyroid and/or pancreas (you mentioned Cushings). This can be expensive and you have to decide whether it's worth it. The treatment of same can also be very expensive and must be given meticulously and without fail every single day exactly as prescribed, and you must be extremely regimented with her feed - the type of feed and quantity.
It is best you do a lot of your research on university medical faculty web sites or faculty of vet medicine web sites, or the official web sites of hyperpituitarism/hypopituitarism and/or hyper or hypothyroidism organization web sites. Don't accept advice from john or jane doe web sites because there is too much misinformation out there.
In both people and horses, the pituitary gland is the boss when it comes to hormone regulation. It controls a tremendous amount of stuff when it comes to our basic body function - everything from our sleep/wake cycle, hunger/satiety, temperature/sweat regulation, impacts our excretions (urine/stool - a hypothyroid person tends towards severe constipation), blood pressure/heart rate, cortisol levels, stress hormones, and it controls every single endocrine gland in the body, such as the pancreas, adrenal glands, thyroid, and the sex glands (ovaries and testicles). In growing kids and foals, the pituitary gland controls growth rates. A failure in growth stimulating hormone causes failure to grow. It controls hydration levels, mineral levels (calcium, sodium, potassium, phosphorous, all needed for basic muscle function - that includes your heart muscle! - and skeletal support), tells the kidneys when we're overhydrated and thus pull excess water out in the urine, along with any other excessive levels of the sodium, phosphourous and K+ (potassium) out too. There's more but this is overwhelming enough.
If there is a general overall pituitary gland failure, the entire body is impacted in a huge way and is usually fatal without extremely aggressive treatment. The good news is that 9 times out of 10, the pituitary gland just doesn't up and quit. Parts of it, however, might be affected by a little benign tumor that cause things to go awry.
Keep in mind this one important fact - the only difference between a benign tumor and a malignant one is that the malignant one goes tromping off around the entire body and is fatal fairly quickly. A benign tumor still can keep growing in its original location and can still wreak havoc on the body and can still eventually lead to death albeit over a much slower period of time.
Sometimes the pituitary gland just has a localized failure in one little part of it - could be due to a mini-stroke or some other form of damage to one tiny piece of it.
Hormones are extraordinarily powerful chemicals.
2 possibilities - a failure of the pituitary gland to stimulate the thyroid; or failure of the thyroid to respond to the stimulation from the pituitary. Both result in failures to either get pregnant or maintain pregnancies. More discussed below.
Another 2 possibilities: Failure of the pituitary to stimulate the pancreas, or failure of the pancreas to respond to the stimulation from the pituitary gland, causing Cushings in both people and horses, diabetes, insulin resistance, etc., etc.
Personally, because you said your horse looks like she's pre-cushings and is also suffering repeated embryo loss, I'm leaning towards some failures in the pituitary gland to properly stimulate the pancreas and her sex hormones and levels.
You need to get this mare's blood tests done. Preferrably, a fasting glucose (no food for 12 hours), T3/T4/TSH and other studies as recommended by a vet who is experienced with endocrine problems.
Now, I'll try to explain this in the uttermost basics that I can:
The pancreas produces hormones which control hunger/satiety, blood glucose levels, and the production of insulin to maintain the latter. This also gets into the very complicated area of insulin resistance, etc.
When a horse develops Cushings or insulin resistance or flat out diabetes, it can be treated with medication and an extremely strict diet - no sugar foods, no alfalfa, NO GRAIN. No carrots, apples or horsie cookies. A very low low starch/carbohydrate, and very high fiber diet. Grass hay should be low-sugar types and should be tested. Surprisingly, hay fields which are non-irrigated tend to have higher sugar-producing grasses because the grass is stimulate to produce seed heads faster. You won't know for sure until you get your hay tested. Daily exercise to maintain glucose levels. Strict maintenance of weight. No spring-growth grass. Cushing's horses are extremely susceptible to repeated founder/laminitis, so owners have to work twice as hard to prevent this. At the first sign of soreness in the feet, get the horse onto anti-inflammatories and restrict movement and analyze your feeding program to ensure it is meeting the strict requirements required for these horses.
Cushings horses also tend towards long-haired, wiry hair, with failure of shedding of their winter coats, or shedding failure of their summer coat to bring on winter coat and obesity fat deposits in belly, crest and croup.
When strictly controlled, this problem can be worked around and a long and relatively healthy life can follow. If allowed to be uncontrolled, it causes complications with heart failure, uncontrolled blood glucose both of which can be fatal in relatively short order.
A failure of the pituitary to produce thyroid stimulating hormone (TSH) which stimulates the thyroid to produce its particular hormones and maintenance of said levels, will cause the thyroid gland to reduce and/or stop activity and production of T3 and T4 (there are also others, but like I said, this is an extraordinarily complicated matter and I'm trying to simplify as much as possible).
The body begins to "starve" so-to-speak of necessary hormonal balances which impact hair growth which becomes spindly, dry, brittle; the skin becomes dry, frail, and thin; weight control becomes excessively difficult usually gaining obesity but sometimes skinny, appetite can be increased/decreased, and depending on whether hyperthyroid or hypothyroid, fatigue and/or hyperactivity, nails (hooves) become brittle, cracked or don't grow properly, both a hyper or hypo situation can seriously impact the ovaries and uterus in a big, big way. With most women and mares, their cycles become very erratic or nonexistent. With mares, follicles may grow but she might still be anovulatory, and heats may stop or continue. Women and mares, if they can get pregnant, can't keep the pregnancies beyond a certain point, usually at the time the embryo needs to start latching to the uterine wall, because the lining is weak. Once the embryo can latch, it can start producing it's own maintenance hormones and you have a better chance of maintaining the pregnancy to term, but it is always a high risk pregnancy and one that needs close attention by an experienced professional.
With either a pituitary lack or a thyroid lack, she will still need T3/T4 replacement. With a hyper situation, usually the thyroid needs to be killed off and complete supplementation started.
Before you go off and say fine we'll just get her on medications, you should be aware of the following: The only way the mare will be properly medicated with the proper dosages is if you have the blood work done that tells you how much is being naturally produced, so that the calculations can be made to properly supplement.
Supplementation of the thyroid hormone takes a lot of tweaking to get it right for one horse's particular body. In people, a TSH level of 0.5 to 5.5 is considered normal, but some people react very strongly to the lower end of that spectrum and have considerable symptomatology and thus need medication anyway. The number is a tool, but not the most important factor. Treating the symptoms is the #1 thing that needs to be done.
Treatment also takes a few months to really make an impact.
I would suggest you stop breeding this mare this year. Work on getting her blood work figured out, her hormones levelled out, change her diet around, and if she does require medications, getting the proper dosages worked out. This could literally take all summer and fall! If she starts to appear more energetic and lively (but not spastic which would make us think she might be a bit over-medicated), and her coat and hoof growth starts to normalize then you know you are starting to achieve the right levels for her particular body. You could then try breeding her next year.
Alternatively, since she seems to be producing eggs and getting them fertilized, you could try flushing them out and placing in a host mare.
Reality is: Even with hormonal treatment with thyroid replacement, a pregnancy will take a considerable toll on her body and the changing demands will require continual assessment of her thyroid hormone levels and adjustment of her medication. This just might not be the right mare to breed if your finances or time resources can't cope with sort of demand.
Not soon enough, not often enough, and not long enough. Also, how much are you giving?
You need to start the oxytocin 4 hours after breeding (and treat before breeding if the mare is a "high risk" mare), and then treat every six hours at a minimum (some go to every four hours) until 3½ days after ovulation, not breeding.
There is a very good chance that your mare has breeding-induced endometritis, which can often be treated successfully with the use of an adequate oxytocin protocol (follow that link for details). Endometritis is the leading cause of early embryonic loss, and your mare appears to be exhibiting prime characteristic behaviour that would fit with that scenario.
So could that alone make that much of a difference (I guess it could or else you wouldn't mention it right?)? We have also used Settle with her as well which I understood is supposed to combat the inflammation.
I took a look at your article and noted that we've never lavaged her after breeding either. I'm just trying to decide do we try one more time and just try the intense oxy protocol and lavage as well possibly? It's so frustrating to see the embryo on u/s and then it's gone, and her biopsy is not too bad. She's also been cultured in the past and it was clean, she still lost.
We also notice her cervix never opens very wide at all even during peak of heat. Could this be an indication of the presence of fibrotic tissue and therefore another possible reason she loses it?
We have already sunk so much money it's almost like what's one more try... but then again do you think it's worth it? (tough question) Could the increased oxy really be the answer? Thanks so much for your help, I really appreciate it so much!!!
Correction - my vet said we did lavage her once the first year, and she did get in foal as usual, but then still lost it. Didn't seem to make any difference.
Jan Owen Senior Stallion or Mare Username: 1frosty1
Post Number: 2558 Registered: 04-2006
Posted on Monday, July 06, 2009 - 12:21 pm:
Hi Jennifer...my mare was 17 and we really wanted one more foal from her so after lots of $ and 3 AI tries we tried it all. We used "Settle", bred, and used the Jos posted Oxy protocol to the tee. My vet had never used it exactly that way and it worked. She delivered a healthy filly before right after her 18th birthday. Worth the try..she is a dream filly! I hope you have the success you want ant deserve. Good Luck!
Thanks so much for the heartwarming story! We are still holding out hope for a baby from this mare somehow, even if we have to do ET.
We use Settle also, and dang it if she's not pregnant every time. It's even more frustrating to see the baby and then have it be gone. So we are in a weird situation, she does get preg but then loses it each time at around 14-15-16 days. It's always small (8mm-ish) and then never seems to grow any more.
A low-grade endometritis can cause pregnancy loss in that manner. Can't say for sure that is the cause, but its a distinct possibility.
Settle has been demonstrated to have a positive impact in cases where there is a bacterial-based endometritis by stimulation of the immune system. You may not be dealing with such a situation, but rather a delayed uterine clearance (DUC) situation. Incidentally, there is a money-back guarantee with Settle if you want to go through the hassle of trying to get it.
Lavage is usually used in situations where there is an amount of fluid >2 cm in the uterus, however if there is an issue related to clearance of sperm or if there are uterine sacculations it can also be beneficial post-breeding.
When biopsied (or on cytology with a culture - you NEED a cytology not just a culture) have you seen inflammatory cell presence? That is likely to be indicative of a uterine issue, pathogenic or otherwise, but most likely pathogenic, even if there was no growth on culture.
The fact that she has a cervix that does no relax also points towards an issue related to DUC. Use of estrogen early in estrus and/or topical misoprostol cream (on the cervix) early in estrus can encourage relaxation in many cases. If the cervix is not relaxed, then - obviously - fluids placed within the uterus cannot drain, and you end up with DUC issues. Fibrotic tissue in the cervix is not necessarily going to be indicative of endometrial fibrosis as there is no correlation.
Oxytocin therapy carefully applied pre- peri- and post-breeding in these older and problam mares can make a hige difference in pregnancy rates. If this were my mare, I would put her on oxytocin 4 times a day when she comes in estrus, using just 10 iu (typically ½ ml in North America) right through to 3½ days after the mare ovulates. I would increase the dosage to 20 iu post-ovulation, and I would try and breed the mare just once, within 24 hours prior to ovulation (if using fresh or cooled semen -frozen is a different issue), and time it so that the breeding was no less than 2 hours after I had given the last dose of oxytocin, and I would give the next dose of oxytocin 4 hours after breeding (we like to give oxytocin at 6 and 12 around the clock, so when doing that we breed at 2 pm - 2 hours after the noon oxytocin and 4 hours before the 6 pm treatment). I would also use the estrogen and misoprostol cream I mentioned. We have had good luck with use of a protocol such as that but you have to be religious about giving the oxytocin - and treat more often rather than missing a dose (so if you have to go out at 4 pm and won't be back until 10 pm, rather than missing the 6 pm treatment, give one at 4, then again when you get home at 10 and then back on the routine at midnight).
Thanks for all your help - I have been sharing this info with our vet who is extremely dedicated to repro luckily!!!
Her cervix does relax SOME, I mean a small amount according to the vet - and when we see fluid on u/s pre-breeding and we do oxytocin it's definitely gone, or mostly gone, when she's rechecked. So it apparently IS able to escape at least.
Would you think trying again one more time would be prudent if we use the cream to relax the cervix and do the very tight oxy protocol? It just kill us to see the baby on u/s repeatedly but then lose it. Previously we've not seen fluid on u/s upon preg check at 12-13 days, but that doesn't mean there is not inflammation right? Would something like Banamine help at all?
I can't answer the "should I do it again" question for you... that's one you have to ponder!
What I will say is that using a tighter oxytocin protocol may well help and make a positive difference.
Or perhaps not!
You need to get any inflammation under control long before 12-14 days, which is why we do the intense treatments around estrus and breeding time. Banamine therefore is unlikely to help in the inflammatory area, but MAY assist with preventing prostaglandin release. The trouble is that you are going to have to use it repeatedly, and that can be hard on the digestive system. You might want to talk to your vet about using meloxicam which is available from BET Pharmacy and a single injection will have positive effect for up to three days, plus it is easier on the gut than Banamine or 'bute. If you do choose to use it, I would start it around 9 days post ovulation to hopefully assist in the maternal recognition process at around days 12-14.
Use of Dexamethasone around the time of breeding has been shown to be beneficial in reduction of uterine inflammation, so that might be worthy of consideration as well.
Would I give it another go if she were my mare? Well, if the cost factor isn't an issue, then yes I probably would.
Definitely, this further information does change the perspective a bit. Endometritis has a powerful impact on the uterus' ability to be healthy enough for an embryo to co-exist. Why? When an inflammatory response sets into motion, the whole immune system gets involved. Anything found residing in the uterus is considered foreign and is lethally attacked. An embryo is very much a foreign object, even though it's her embryo! Embryo's have their own genetic sequence, proteins, etc., etc., so the body considers it foreign. Quite frankly, the fact that the female of any species can get pregnant and stay pregnant is an amazing miracle, considering how powerful the immune system can potentially get against the foreign invader (embryo). Get the inflammatory response cooled down by removing the factors that cause the inflammation (infection, fluid, embryonic tissue from previous losses, and other "debris" as we call it in our human medicine) - in other words get her back to a clean slate. Then try breeding again, as long as you stay on top of any post-insemination inflammatory response that kicks up. The protocol Jos mentioned is absolutely the number one way to start getting it under control and then keeping it that way. In human medicine, when a woman loses her pregnancy in the first trimester, a doctor will always recommend she rest her body a few months before trying to conceive again to give the uterus a chance to clean up and settle down from the inflammatory response. In the wild, a mare who suffers a loss may or may not go into heat right away and may or may not get pregnant again for the rest of the season and she has a longer chance to clean up and settle down. In our regimented breeding plan, we don't have this sort of time, so we implement flushings and drugs to speed it up so we can get right back to it.
As an aside, I might suggest to keep on top of that crestiness appearance she has. Without actually seeing her, I would still lean towards her be pre-cushings and you can start nipping this now with diet/exercise controls. Pull her from grain, alfalfa and rich grass. Pregnant mares are susceptible already to colic and founder and a pre-cushings mare is doubly so. The leading cause for colic and founder/laminitis is STRESS (environmental/management stress, illness stress, dietary stress, exercise-related stress, just to name a few). Pregnancy is very stressful on the body, so don't add big sugar, big protein stresses to her body. Even pregnant, she'll do well with good quality plain grass hay, lots of ad lib exercise. There are a few Cushing's kibbles out there, so find one with about 10-12% protein. That's enough for fetus to draw from. You can supplement with a granular vitamin/mineral to ensure in utero foal has access to the various nutrients needed - phosphorous, magnesium, calcium, selenium, potassium, plus others, etc. As she progresses in her pregnancy, it's a great idea to take her for daily walks, 2-3 miles, if you can find the time to do this - not to mention it'll do the human some good too ;) Maybe a friend will come walking with you with a buddy horse? Get some tunes going.... LOL But seriously, it would do a pre-cushings preggie mare a lot of good - The walking will keep some muscle tone to her pelvic girdle, plus burn off some extra glucose and encourage good blood circulation, especially to the feet and legs.
Good luck! Do keep us posted... I'm very interested in this mare's progress and success.
When an inflammatory response sets into motion, the whole immune system gets involved. Anything found residing in the uterus is considered foreign and is lethally attacked. An embryo is very much a foreign object, even though it's her embryo! Embryo's have their own genetic sequence, proteins, etc., etc., so the body considers it foreign.
This is actually only partially correct, and only part of the story!
When the equine uterus is under the influence of progestins (of which progesterone is one that is present during early pregnancy, replaced by different progestins later in pregnancy), the uterine immune function is suppressed. This is why it is vitally important not to breed a mare on a mid-cycle diestrus follicle - when one introduces semen in that situation, one cannot avoid introduction of bacteria, and the uterine immune response is absent and unable to deal with it and one gets a bacterial "bloom".
So with a mare that develops a major uterine immune response at the time of breeding, there will be a suppression (to a major degree) of the immune response once the CL becomes functional (and secretes progesterone), but the "unpleasant environment" - upset pH (acidity/alkalinity), fluid presence etc. - that has been created by the immune response is what causes the issues for the embryo. On top of that, if there is enough irritation created by the inflammatory response during the tail-end of estrus, it may cause an interference (through Prostaglandin F2α release) in the formation of a fully functional CL - thereby impacting progesterone secretion (and a suppressive effect on uterine immune function, embryo nutrition and cervical closure); or it may even cause enough Prostaglandin F2α secretion that the CL is lysed prematurely, and the mare comes back into estrus - at which time the cervix relaxes and the embryo is lost through it.
}Some years ago after being devastated with a loss of a 7 year old mare that I had raised from a baby, my veterinarian told me it was possible to still get a foal out of an older AQHA mare that I had.
The mare was 21 years old when we first bred her. She caught the first time but was reabsorbing the embryo by day 18. Knowing this, we decided to try again and ultrasounded her at day 14 and confirmed a pregnancy. The protocol that we used on this mare (this was in Canada so I am not sure if you have the same drug availability) was for the first 6 months of the pregnancy she was given a shot of progesterone once a week (40cc) if I remember correctly.
We were successful in getting three foals out of this mare using the same protocol to check for a pregnancy early and then using the progesterone to keep it.
The interesting thing is that I had bred this mare when she was 16 years old, confirmed pregnant and shipped home from the stud farm and then came up empty later on so I didn't think that I would ever get a foal out of her. The history on the mare is that she had been a brood mare from age 6 to 13.
The veterinarian you use is really important and I was lucky enough to be using one whose main interest was equine reproduction in addition to being just a good all around vet.
Good luck. I hope you are successful.
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