7 common, tricky ovarian issues that can affect mare fertility
In July 2018 Lucy, a 12-year-old Quarter Horse mare, presented with typical signs of mild colic—pawing the ground and refusing to eat. When the veterinarian arrived, however, she found the mare’s gastrointestinal tract to be functioning normally. Because Lucy was in obvious discomfort, she was referred to the University of Illinois at Urbana-Champaign Veterinary Teaching Hospital, where Giorgia Podico, DVM, MSc, and her colleagues received her.
“At her arrival we did another thorough work-up for colic,” Podico says. “The exam did not reveal anything abnormal in her gastrointestinal system. But a transrectal ultrasound revealed that her left ovary was the size of a cantaloupe. The freshly formed ovarian hematoma was considered responsible for her colic signs.”
Ovarian hematomas, which are relatively common, typically form after ovulation. The follicular fluid contains higher-than-normal levels of anticoagulants, and hemorrhaging can occur. (This physiological process relies on anticoagulants in the follicular fluid to ensure the follicle’s contents release and reach the oviduct without being trapped in a blood clot when the follicle ruptures.) The swelling of a hematoma stretches and distorts the ovarian capsule, potentially causing intense pain if it gets excessively large.
Lucy was hospitalized for four days, given a potent painkiller, and monitored closely to make sure her abdominal pain didn’t worsen. Within this period, the hematoma stabilized. Usually with these cases, the blood resorbs and the ovary gradually returns to its normal size. If the ovary had continued to enlarge, cause pain, and disrupt the normal ovarian tissue, veterinarians would have had to surgically remove it.
Hematomas are only one of many ovarian abnormalities in mares.
“The ovary is one of the most dynamic organs in the body; its activity both in normal and pathological conditions can be influenced by many factors: photoperiodism (length of daylight), age, season, and the presence of associated metabolic conditions,” Podico says. “This plasticity makes some of the ovarian conditions, especially the neoplasms (involving abnormal tissue masses), more difficult to diagnose.”
Missed cycles caused by ovarian abnormalities are both frustrating and expensive; the costs of diagnostics and treatment and the loss of potential income from a future foal can add up. Even more aggravating, affected mares can have no clinical signs. Often, veterinarians only identify an abnormality as an incidental finding during a reproductive exam for breeding or during necropsy, says Podico.
Here’s a look at the ordinary, as well as not so ordinary, ovarian abnormalities you might encounter in your broodmares.
Common Ovarian Challenges
Veterinarians routinely recognize ovarian abnormalities when examining the broodmare reproductive tract both manually via palpation and visually through transrectal ultrasound. Recognizing if something is abnormal is imperative when determining how to best manage the mare. Issues might include:
Generally speaking, a hematoma is a pooling of blood, similar to a bad bruise. An ovarian hematoma is excessive bleeding that occurs around the time of ovulation.
“Ovarian hematomas usually regress without any signs; however, when they get very large and distend the ovarian capsule, they can cause discomfort,” says Wolfsdorf.
Meanwhile, the unaffected ovary continues to function and cycle normally. If the hematoma doesn’t regress with time and luteinization (forming a corpus luteum [CL], a group of cells that produces the hormone progesterone) occurs, veterinarians can administer prostaglandin, she says.
Hemorrhagic anovulatory follicles (ovulation failure)
Follicles that fail to release eggs are the most common ovarian abnormalities and occur in about 25% of mare cycles, says Podico. Their occurrence can be even more frequent in broodmares over age 16.
“These follicles can sit there for long periods of time and will either regress on their own when another follicle starts to grow, or they can luteinize,” explains Karen E. Wolfsdorf, DVM, Dipl. ACT, of Hagyard Equine Medical Institute, in Lexington, Kentucky.
Once veterinarians identify hemorrhagic anovulatory follicles, Wolfsdorf says they can analyze serum progesterone levels to guide treatment. These follicles can be normal in size or get extremely large. On ultrasound they’re thick-walled and full of speckles. Follicles with progesterone levels above 1 ng/dL respond well to exogenous (not derived from the mare) prostaglandin administration to cause CL regression.
Failure to ovulate is challenging because we do not know why it occurs or how to prevent it.
“Ovulation failure is a source of significant frustration for owners and veterinarians, but they cause no disease per se,” Podico says. “There are certain predisposing factors like metabolic conditions, the administration of certain drugs, or the time of the season that have been related to the development of dominant anovulatory follicles.”
Persistent corpus luteum (false pregnancy)
The CL forms when a follicle releases an oocyte. As previously noted, this structure produces progesterone, which is necessary to maintain pregnancy. If a mare doesn’t become pregnant during this time, the uterus releases prostaglandin and the CL regresses in about 14 days. Sometimes when a mare experiences early embryonic loss, luteolysis (breakdown) of the CL does not occur because the mare’s body thinks she is pregnant. As a result, she does not return to heat normally to be rebred.
“It’s also possible for a secondary follicle in diestrus (between estrous cycles) to ovulate,” says Wolfsdorf, a situation that results in a CL too young to respond to prostaglandin secreted late in disestrus. “This lengthens the time that the mare remains out of heat. Both scenarios can be treated with exogenous prostaglandin.”
Germinal inclusion cysts
These lesions develop on a wedge-shaped area on the ovary known as the ovulation fossa. They typically appear in mares at least 15 years of age, says Wolfsdorf.
“They can potentially affect ovulation by blocking the ovulation fossa, but unfortunately there is not much to do about them,” she says.
Mares not cycling
Anestrus in mares normally occurs during winter; as daylight increases, mares transition to cycling. Mares that do not can be manipulated with artificial lighting, hormone therapy, and/or acupuncture, says Wolfsdorf. Foaling mares can also go into anestrus, especially if they foal early in the year. Placing early foaling mares under lights prior to foaling can help reduce the incidence of anestrus.
Less Common Ovarian Abnormalities
Of all livestock, mares have the largest ovaries and follicles. On average, they’re 2 to 3 inches long, 1 to 1.5 inches tall, and 70 to 80 grams (about the weight of three AA batteries). The bean-shaped ovaries change sizes seasonally and, in the process, can develop abnormalities. Here are less-common defects to be aware of, which can be detected, again, via palpation and transrectal ultrasound:
Podico ranks ovarian tumors as one of the most important ovarian abnormalities to consider, despite them being relatively rare. Still, ovarian tumors are the most common type of tumor to develop in the mare’s reproductive tract, and they represent about 2.5% of all horse tumors, says Podico. Affected mares might display erratic estrous and stallionlike behavior.
Granulosa theca cell tumors are the most common ovarian tumors. Veterinarians diagnose them using ultrasound and palpation; typically, one ovary is enlarged and multilobulated, while the other is small and inactive.
“Many other tumors and non-neoplastic conditions in the ovary of mares can complicate the diagnosis,” says Alan Conley, BVCs, MS, PhD. “However, there are no other ovarian cancers or conditions that secrete such high levels of AMH (anti-Müllerian hormone, a sex hormone typically produced by testicular cells), inhibin-B, or testosterone, which is why hormonal assay tests are so valuable as indicators of granulosa cell tumors helping to distinguish them from other tumors.”
Conley, a professor at the University of California, Davis, School of Veterinary Medicine, who leads research on health and reproduction, explains the science behind the assay tests, which use monoclonal antibodies to recognize different parts of the inhibin-A and inhibin-B molecules.
Monoclonal antibodies are basically the same type of molecule as those used in human medicine to treat a wide range of conditions, including HUMIRA for osteoarthritis and even REGEN-COV for COVID-19. Each targets different molecules in the blood or tissues, says Conley.
“The assays for inhibin-A and inhibin-B use two different monoclonal antibodies (man-made proteins that act like and are identical to certain antibodies in the immune system) to each of the isoforms, and when they bind together on the target molecules, they form a sandwich that creates color,” he explains. “The more inhibin-B or inhibin-A in that sample, the more color develops.”
When veterinarians identify a granulosa cell tumor, they typically remove the affected ovary. Doing so allows the other ovary to recover with time, usually by the following breeding season, says Podico.
The most common chromosome abnormality in mares is Turner syndrome. Instead of having 64 chromosomes, a mare with Turner syndrome only has 63. This DNA mutation renders mares infertile (mules also have 63 chromosomes).
“Usually this becomes evident when mares have small, noncycling ovaries with a dysmature uterus and cervix during the late spring to summer months,” Wolfsdorf says. “Chromosomal analysis can help diagnose the abnormality.”
What’s on the Horizon?
One of the biggest challenges associated with ovarian abnormalities is the extreme physiological variability among mares. A mare can have no signs, always or never be in heat, or display stallionlike or aggressive behavior.
“The use of ovarian biopsy techniques can help identify and treat undiagnosable abnormalities earlier and more easily,” says Wolfsdorf.
These methods include transvaginal ultrasound-guided ovarian biopsy and in vivo antral (in the ovarian cavity) follicle wall biopsy.
Conley and his colleagues at UC Davis are excited about what they’re learning about equine ovaries through their intracytoplasmic sperm injection (ICSI) program. They have begun to sample and test the follicular fluid recovered when retrieving oocytes for this assisted reproduction technique for inhibin-A, inhibin-B, and AMH levels. Their hope is hormone concentrations in follicular fluid might predict which oocytes are the healthiest.
“We think that sampling follicular fluid might also be useful in identifying suspected developing granulosa cell tumors at an early stage when changes in blood are not yet elevated,” he says.
Another advancement Wolfsdorf points to is the use of AMH not only as a diagnostic tool for granulosa theca cell tumors but also to determine antral follicle numbers, which can potentially help guide reproductive expectations.
“The use of color Doppler during ultrasonographic examination can also help veterinarians determine the blood flow to structures within the ovary,” she says. “This can sometimes help determine if a follicle will ovulate or become anovulatory or a CL is active or not.”
Breeding mares isn’t as simple as allowing nature to take its course. Knowing about ovarian abnormalities and how they can impact a mare’s ability to conceive can help owners and veterinarians identify problems early, begin treatment, and breed the mare before the season ends. Advancements in detecting and treating these problems have helped vets solve challenges faster, but more research is needed to fully understand the conditions that lead to ovarian abnormalities.