For a successful domestic species, the fertility rate of the horse is surprisingly low. Coupled with an 11-month gestation period and a single offspring per year, producing a foal is a significant investment for any breeder. So, if you're determined to breed horses rather than something easier, like re-assembling car engines, it pays to do everything you can to ensure that your broodmares are healthy, that breeding is successful on the first cover as often as possible, and that your careful management results in a trouble-free pregnancy and a robust and energetic foal.
Unfortunately, Mother Nature sometimes has other ideas. One of the most persistent and frustrating situations a breeder can face is a mare which, mysteriously, refuses to "catch." A season or more of this labels her a barren mare--one with a potential fertility problem. Getting to the root of that fertility problem sometimes can feel like blundering around in a cave without so much as a flashlight. So, let's take a look at the various causes of infertility in mares, at the treatments currently available, and at what new research has turned up.
Causes of Infertility
The causes of infertility in mares can be broken down into three categories: Mares which fail to cycle (ovulate) at all; mares which cycle and either fail to conceive or lose the pregnancy before 35 days; and mares which conceive and lose the pregnancy after 35 days (aborting or reabsorbing the fetus).
Of these three, Michelle LeBlanc, DVM, Diplomate American College of Theriogenology, an expert in mare infertility at the University of Florida's College of Veterinary Medicine, says that failure to cycle is the most common client complaint. Mares can be extremely variable in their heat cycles, both in terms of frequency and length, and in the signs they show. Owners should remember that just because a mare shows signs of estrus (heat) does not necessarily guarantee that an ovum has been released.
In fact, because mares are seasonal breeders which usually (though not always) go into anestrus (lack of heat periods) in the winter, they experience a "transition phase" every spring. During the transition to breeding readiness, they frequently produce a follicle that does not ovulate--and if they do produce an ovum that is fertilized, they are at risk of very high embryonic loss rates (up to three times higher than the norm). By the second estrous cycle, most mares' hormonal systems have settled into a rhythm, and there is a much greater chance that ovulation has occurred, that she will "catch" if bred, and that she will keep the developing fetus.
The reproductive cycle of a mare is influenced by the length of the daylight, rather than the ambient temperature, of the approaching spring. Increased hours of daylight will kickstart her reproductive system, initiating follicle development in her ovaries. In the Northern Hemisphere, left to her own devices, a mare usually will show the first signs of estrus in March, and she will be ready to breed at her second heat in April. Many breeders, however, hoping to produce foals born as close to January 1 as possible, find they must "trick" mares into ovulating earlier. The most effective way to do that is to expose the mare to artificial daylight by putting her under 200 watt lights for several hours every evening, beginning on Dec. 1. Alternatively, a single hour of artificial light, 10 hours after dusk, for 60 days, can be as effective as several hours of artificial light in the afternoon and evening--and it certainly saves on electricity. The best way to deliver this type of "light therapy" is to use pre-set timers. Interestingly, artificial light seems to be more effective if added at the end of the day rather than the beginning; the reason for this is still unclear. When exposed to either method of lighting, mares generally will begin ovulating within 60 days.
A simple way of testing whether you have adequate light intensity in the barn is to use a 35-mm camera with a "through-the-lens" light meter. Place a Styrofoam cup around the lens to diffuse the light and average out your light sources, and check the light meter to see whether you have a "green light" at 400 ASA/0.25 sec/f5.6.
Even if placed under the lights consistently, however, a mare's fertility still might
be compromised by trying to get her to cycle, and conceive, before her natural timing usually would allow. Some studies have indicated that mares which become pregnant early in the year are more likely to lose their fetuses because of extreme fluctuations in hormone levels. If there is no pressure to breed your mare before May 1, it might be better to let your mare begin cycling naturally.
Failure to Ovulate
Older broodmares, over the age of 16, frequently suffer from infertility problems. They take longer to make the transition from anestrus to active estrus, and because of the changes in reproductive conformation that carrying several foals produces, they are more susceptible to uterine adhesions and infections (more on this later).
Recent research has indicated that "aging eggs" might be more to blame for falling conception rates; the ova of an older mare are more likely to be defective, which means that a fertilized embryo might die before pregnancy can be detected. Some researchers have suggested one of the superovulation techniques (as are sometimes used with infertile women) as a possible solution to this problem, but for the moment, it's more common to simply expect an older mare to require more covers by a stallion to become pregnant with a healthy embryo. (For information on multiple ovulations see The Horse of January 1997, page 21.)
Chromosomal abnormalities, while rare in horses, also can account for the inability of some mares to conceive. These abnormalities can be detected by karyotyping, a test in which blood lymphocytes are cultured and their DNA examined (a process that takes three to five weeks). Chromosomal defects can include:
Gonadal Dysgenesis--Mares with this condition (first identified in 1975) lack one of the pair of sex chromosomes and are almost always infertile, small in size for their age and breed, and have small, inactive ovaries. (The equivalent condition in humans is called Turner Syndrome.) Documented in many breeds, it is probably the result of spontaneous genetic mutation, and it is not inherited.
Gonadal Dysgenesis or XY Sex Reversal--This is sometimes also known as testicular feminization. Though these mares are of normal or even large size, and can have successful performance careers, genetically, they have an extra Y (male) chromosome in addition to the normal two X (female) chromosomes. They will have inactive or non-existent ovaries, and fertility is extremely uncommon, although it has been reported. This condition is most frequently described in Arabians, but also has been reported in Thoroughbreds, Quarter Horses, Appaloosas, Morgans, Standardbreds, and ponies.
Balanced reciprocal translocations--Only recently described in horses, this is a chromosomal rearrangement that has been associated with reduced fertility in humans, pigs, and cattle. Researchers expect that more cases of reciprocal translocation will turn up as karyotyping becomes more widely used.
More common as a cause of failure to ovulate are ovarian tumors. On rectal palpation, one ovary of an affected mare will be abnormally large, with no palpable ovulation fossa; the opposite ovary is usually small, firm, and inactive. Ultrasound examination usually suggests a multicystic character. (Hematomas also can appear on the ovaries, by themselves or in combination with an ovarian tumor, and this can complicate diagnosis in many mares.) Behavior changes also can be a tip-off to the development of an ovarian tumor--watch for stallion-like behavior, a lack of observable estrus, nymphomania, or irregular cycles. Some tumors are operable by arthroscopy, and the prognosis for future fertility is as good as before the tumor developed.
Cervical adhesions (usually as a result of past complications with a pregnancy) can make it difficult for the sperm to enter or the cervix to seal after estrus. A manual exam during estrus usually will reveal the defect. Cervical adhesions sometimes will allow conception, but they make it difficult for the mare to sustain the pregnancy. Cysts also can develop in the uterine lining, particularly in older mares. If small, they are of little concern, but they can affect pregnancy rates if they become larger than 25 mm in diameter, or if there are several present.
Sometimes an assumed failure to ovulate is really just a failure to demonstrate a visible heat--something fairly common in maiden mares or those retired from long performance careers, particularly when there is no stallion on the premises. Rectal palpation and ultrasound can detect estrus if your mare has "silent" heats, and a vaginal speculum can help determine the stage of estrus to pinpoint the time of ovulation. Measurement of serum progesterone levels also can be helpful.
William Ley, DVM, a specialist in equine reproduction at the Virginia-Maryland Regional College of Veterinary Medicine, recently has been looking at another cause of infertility in older mares--uterine tubal patency. Patency refers to the "openness" of the oviduct, the slender channel through which eggs travel from ovary to uterus. Many mares with fertility problems, Ley says, have blockages in their oviducts which make it impossible for an egg to be fertilized, or for an embryo to make its way to safe haven in the womb. The blockage sometimes consists of scar tissue--a result of inflammation in previous pregnancies--but more frequently it's composed of unfertilized eggs, which haven't descended to the uterus and build up in the narrow channel. By the time a mare is in her mid-teens, she is at risk of a blockage, particularly if she has never carried a foal.
Until recently, tubal patency has been difficult to diagnose.
"Ultrasound doesn't work well in this instance," notes Ley, "and it's been particularly difficult to determine whether the problem is in the left oviduct, the right, or both."
He has been experimenting with a new technique in which tiny fluorescent micro-spheres are placed on top of the ovaries with a 22-inch needle designed for embryo transfer techniques. Transvaginal ultrasound (requiring a special probe which most veterinary hospitals now have) helps guide the needle, and different fluorescent colors are used for the left and right ovaries. These microspheres will make their way along the oviduct to the uterus if the passage is clear; after 48 hours, the uterus is flushed, and the concentrations of the microspheres of both colors are determined. A low concentration of microspheres of one or both colors can indicate a blockage or blockages.
"Once a blockage is demonstrated, it can be surgically corrected," says Ley, "or, if only one oviduct is affected, you can breed the mare according to follicle development on the 'good' side."
He adds, "The technique is still being refined, but we hope to make it available to owners of broodmares by mid-1997 or so. It's a procedure that can be done at most veterinary hospitals, or even on-farm if the veterinarian has the right kind of ultrasound probe."
Early Pregnancy Loss
Loss of pregnancy in the 35-90 day period indicates that the mare's reproductive hormones are functioning properly, at least up to a point. Sometimes, however, the hormones that make a pregnancy possible fail to support it once the embryo has made its way to the uterus. An insufficiency of progesterone (due to a partial failure of the corpus luteum, which secretes the hormone) will cause mares to lose the normal tone of the cervix and uterus, and abort the fetus. As a result of this, it has become standard practice for some veterinarians to administer artificial progesterone (brand name Regumate) during the early stages of pregnancy to mares with a history of infertility, and occasionally up to the seventh or eighth month of gestation. But studies, so far, have failed to demonstrate reliably that this therapy is really advantageous--and Regumate might be contraindicated if a mare has a history of endometritis (chronic inflammation of the uterus).
Cervical incompetency also can account for some cases of early pregnancy loss. If the cervix is damaged in a prior foaling, it can be over-stretched, scarred, or have adhesions that prevent it from sealing tightly. The majority of these lesions can be detected on rectal palpation, and some can be repaired surgically, although many practitioners feel it's difficult, perhaps impossible, to correct an over-stretched cervix (one that allows easy passage of one or two human fingers through the cervical canal). Adhesions have been treated with ointments, including Panalog and creams containing vitamins A, D, or E, with questionable results.
Mares with lymphatic lacunae (a compromised lymph system in the area of the uterus) also tend to lose their pregnancies in the 60-90 day range. Just why this occurs is not clear. During diestrus (between heat periods), the lymphatics clear large particulate matter from the uterine lumen (cavity), and in estrus, they absorb fluid within the uterine wall, but the exact function of the lymphatics during pregnancy is still being studied. It's assumed, however, that a lymph system that's partly dysfunctional would have difficulty sweeping away excess fluids and inflammatory by-products, creating a possibly toxic environment for the fetus.
Failing to Conceive
A significant portion of mares which ovulate, but fail to conceive, might harbor acute infections in their reproductive tracts. "Dirty" mares, as they're often called, usually have a purulent discharge, and bacteria are readily cultured from a swab taken in the first or second day of estrus. Once your veterinarian has an idea which organism(s) he or she is dealing with, an appropriate antibiotic can be prescribed, and there's a 60-70% chance the infection can be cured and the mare successfully bred at her next estrus. (See the AAEP AnswerLine in The Horse of November 1996, page 70.)
Any mare with an acute infection should be evaluated at the time the infection is noted, because her conformation might predispose her to re-contamination. An excessive angulation of the vulva is the most common defect; it allows air, feces, and/or urine to enter into the reproductive tract, causing recurring bacterial opportunities. Mares with "tipped" vulvas usually are treated with a Caslick's operation, in which the vulva is partiatially stitched to prevent contamination of the reproductive tract. (See The Horse of May 1997, page 28.)
Long-standing, stubborn infections are trickier to deal with. Usually caused by bacteria such as Klebsiella, Pseudomonas, or any of several yeasts, these infections sometimes do not respond to standard antibiotic treatments. Uterine lavage (to wash away pus and other infectious by-products), saline, and DMSO all are treatments that have had varying degrees of success. The University of Florida's LeBlanc notes that in her experience, these mares often respond better to rest than anything else. Left to clear up on their own over the fall and winter, some of these mares are healthy and ready to be bred by spring, but the prognosis varies.
Even more significant than acute infection, according to LeBlanc, is a condition that she rates the number one cause of infertility in mares--endometritis, a lingering inflammation of the uterus. Since 1989, LeBlanc has been investigating the causes, diagnosis, and treatment of endometritis, and she has come up with some interesting findings.
"It's important to realize," LeBlanc says, "that all mares experience inflammation in their reproductive tracts when they are bred. It's a natural reaction to the irritating qualities of sperm itself. The difference between normal mares, and those with endometritis, is that normal mares are able to clear away the products of the inflammatory response from the sperm within a couple of days."
Ordinarily, the products of an inflammatory response are rapidly eliminated from the uterine lumen through the cervix or via lymphatics draining the uterus. In an infertile mare, however, excess fluid, and enzymes and proteins that result from the inflammatory response, tend to "pool" in the uterus for days or weeks, a situation called "delayed uterine clearance." Bacteria have a chance to multiply and overwhelm uterine defense mechanisms...and to contribute to the death of a new embryo.
Horses are unique in that newly formed embryos take a leisurely five days to make their way down the oviduct to the uterus. Another 12 days are taken up in the "migration" from one horn of the uterus to the other before the embryo finally attaches to the uterine wall at Day 17 or so. The exact mechanism by which excess fluid causes the death of the embryo is still unclear--LeBlanc suspects that either the enzymes in the fluid are toxic to the fragile new lifeform, or that the excess fluid interferes with the embryo's migration across the uterine horns.
Like many other causes of infertility, delay in uterine clearance seems to occur most often in mares older than 12, and frequently in mares which have borne several foals and thus might have a thickened, edematous (fluid-retaining), or pendulous uterus. Inflammation and infection can be detected with a standard culture and cytology. Various yeasts and bacteria can be cultured from these mares (although the recovery of organisms, without the presence of inflammation, is not regarded as evidence of endometritis). Uterine cytology, which measures the number of neutrophils (a type of infection-fighting white blood cell) from a sample, is a more definitive indicator of active inflammation.
To definitively identify horses with persistent delays in uterine clearance, LeBlanc and her colleagues use nuclear scintigraphy, a technique whereby a radioactive liquid is infused into the uterus, and the amount that had been "cleared" from the vaginal area is measured three days later. (The liquid emits gamma rays that can create an image much like an X ray. ) "We began with tiny radioactive beads," she notes, "which gave an accurate diagnosis, but weren't really suitable for use in client-owned mares due to the long half-life of the radioactivity. This led to the design of a new technique in which a much smaller amount of radioactive liquid was infused into the uterus."
The results were conclusive.
"Mares with persistent endometritis were unable to clear any of the substance within four hours," says LeBlanc. "In our original study, seven out of 10 mares who were infertile had trouble 'clearing.' The other three had similar histories, but didn't demonstrate difficulty in uterine clearance when we did the scintigraphy. We're working on a simpler method of diagnosing endometritis, but I can't say anything about it just yet."
Based on evidence that suggested equine sperm took approximately two hours to make their way to the ovum, and that neutrophil populations in the female reproductive tract tend to peak about eight hours after breeding, LeBlanc suspected that a drug administered in that window of opportunity at approximately four to eight hours after breeding might help mares clear excess fluid and inflammation without endangering the new embryo, still safely tucked away in the oviduct. She hit the jackpot on the first drug she tried--oxytocin, a hormone previously used only to induce contractions in foaling mares.
"With oxytocin, all of the mares cleared (the radioactive fluid in their uteri) within 30 minutes."
Since that first drug trial in 1993, the administration of oxytocin, four to eight hours after breeding, has proven very effective in helping mares to clear--so that by the time the embryo drops into the uterus at Day 5, the uterus is healthy and ready to receive the embryo. This treatment often is combined with uterine lavage, which helps clear residual inflammatory products. In one study, the use of these two procedures produced viable pregnancies in 27 of 32 previously infertile mares (84%) after breeding during one estrus. Oxytocin does, LeBlanc notes, cause the oviducts to contract as well, "but we don't know if that has any effect on the embryo. So far, I'd say that, if anything, it has a beneficial effect, because mares are getting pregnant."
LeBlanc recommends that oxytocin be used in low doses of about 10 to 20 international units, injected intra-muscularly.
"I see a lot of practitioners using higher doses than that, but it's not necessary, and it's quite painful to the mare! You need to be careful about higher doses, too, because it's possible there are oxytocin receptors elsewhere in the body. If they exist in the gut, for example, you might risk triggering a colic. It's just a guess at this point that they're there, but I wouldn't want to take the chance."
Although the administration of oxytocin has become routine for many veterinarians, LeBlanc suggests caution there, too. "I only use it for mares with a demonstrated problem," she says.
While originally it was suspected that the inflammatory product in a semen sample was the seminal fluid, it's now becoming clearer that the irritant is the sperm itself. Frozen semen seems to be the most irritating of all, since in the process of thawing it, some sperm cells lyse (burst), releasing irritating enzymes.
"I see the worst inflammatory responses with frozen semen," says LeBlanc, "and I often suggest that live cover, or cooled semen, might be a better way to go if the mare has endometritis."
Recent work at the University of Florida has focused on mares which retain fluid within the uterine wall as well as in the lumen (uterine cavity). In these mares (which account for about 20% of the infertile mares LeBlanc sees in her practice), the lymphatic channels around the uterus seem to be blocked. LeBlanc says you can detect the condition by rectal palpation ("the uterus feels 'boggy' with fluid") and by ultrasound or biopsy. The drug of choice for this condition is cloprostenol, a prostaglandin analogue that causes the uterine wall to contract less strongly than oxytocin, but for a longer period (five hours, on average, as compared to 45 minutes for oxytocin). "It's a cattle drug that's been around a while," notes LeBlanc, "but this is a new application for horses."
A delay in physical clearance of the uterus should not be presumed to be the cause of infertility based on a mare's reproductive history, stresses LeBlanc. Scintigraphy is an expensive technique to which all veterinary hospitals don't have access, but ultrasound examinations of mares which have been bred one to 10 days after ovulation can easily identify mares with persistent endometritis. The disadvantage is that if the ultrasound is positive for retained fluid, the breeder has to wait for the next estrus to try again.
If, despite all your best efforts, your mare still has not settled after three consecutive cycles in which she's been bred, the chances are very low that she is going to get pregnant, says LeBlanc. By then, her system is likely so inflamed and acidic (a result of the lysosomal enzymes in sperm) that it would be impossible for it to support an embryo. Provided you're sure she has really been cycling (something that can be confirmed by palpation), the best cure at this point is rest for at least 30 to 45 days. Many mares, given the chance to clear the inflammation on their own, will "bounce back" and be ready for breeding again later in the season.
About the Author
Karen Briggs is the author of six books, including the recently updated Understanding Equine Nutrition as well as Understanding The Pony, both published by Eclipse Press. She's written a few thousand articles on subjects ranging from guttural pouch infections to how to compost your manure. She is also a Canadian certified riding coach, an equine nutritionist, and works in media relations for the harness racing industry. She lives with her band of off-the-track Thoroughbreds on a farm near Guelph, Ontario, and dabbles in eventing.
POLL: University Equine Hospitals