In normal, apparently healthy mares, the incidence of early embryonic loss (EEL)—defined as loss of the conceptus anytime from fertilization to Day 40 of gestation—is about 18%. This can skyrocket to 80% in subfertile mares. Understanding the potential causes of EEL allows veterinarians to devise strategies to improve pregnancy maintenance, viability, and development of the foal to parturition.
According to Karen Wolfsdorf, DVM, Dipl. ACT, of Hagyard Equine Medical Institute, signs of impending embryonic loss include intraluminal uterine fluid, edema of endometrial folds, prolonged mobility of the embryonic vesicle, decreased size for embryonic age, abnormal shape of the vesicle, and loss of heartbeat.
“From a clinical perspective we need to try to determine what the cause of EEL is so when we rebreed the mare we can monitor and treat her appropriately to increase our chances of success,” said Wolfsdorf.
Veterinarians have few evidence-based strategies to help achieve this goal; however, Wolfsdorf did itemize several risk factors for EEL, including oocyte quality, embryonic development/uterine synchrony, oviductal and uterine factors, reproductive conformation, and endocrine abnormalities.
Oocyte Factors Contributing to EEL in Mares
“Old mares produce old oocytes, which produce poor-quality embryos,” said Wolfsdorf. “Old oocytes can have large vesicles in their ooplasm, increased incidence of chromosome malalignment, and decreased mitochondrial numbers and function.”
Obese mares also have increased EEL, and their follicular fluid has increased levels of insulin, leptin, and cytokines. These changes can be potentially mitigated by supplementing a mare’s diet with a complex of nutrients with n-3 fatty acids and antioxidants.
Embryo-uterine asynchrony, which means the embryo is not the appropriate size for its days of gestation, can also contribute to EEL.
“Changes in the oocyte can decrease embryonic growth, which can impede fixation and influence maternal recognition of pregnancy,” Wolfsdorf explained. “This can affect serum progesterone levels and estrogen signaling by the embryo, diminishing the production of histiotroph that ‘feeds’ the embryo and aids in embryonic development.”
Low Progesterone
Exogenous progesterone might aid in fixation by increasing uterine tone and, therefore, pregnancy maintenance in this situation, although no scientific studies have corroborated this. Increasing blood flow with pentoxifylline or aspirin might increase histiotroph and aid in embryonic growth. Wolfsdorf also described an algae-derived omega-3 fatty acid dietary supplement that can potentially alter the maternal uterine environment and modify expression of genes in the preimplantation equine conceptus. This might be of use in the future.
“There are a number of reasons for low serum progesterone levels,” she said. “For example, endometritis and the associated release of prostaglandins can cause lysis of the corpus luteum (CL), failure of maternal recognition of pregnancy leads to normal regression of the CL, systemic endotoxemia can induce lysis of the CL, as can stress.
“If progesterone levels are low, identifying the cause and providing treatment should restore levels to normal,” she continued. “In addition, increasing blood flow to the ovary can enhance progesterone production by the CL by incorporating aspirin or pentoxifylline into the regime.”
Endometrial Abnormalities
Identifying an underlying endometritis and treating it appropriately can improve pregnancy rates and decrease EEL in mares.
“This can be challenging as microorganisms can be trapped in mucus, hide within a biofilm, or remain dormant in endometrial glands. With appropriate treatment, pregnancy maintenance is possible,” asserted Wolfsdorf.
The risk of EEL also rises with increasing mare age, increased number of live foals, and the presence of endometrial cysts, all of which contribute to degenerative changes.
“Old mares have a baggy, saggy uterus, and a uterine biopsy can give a predictive foaling index and help identify specific abnormalities present,” said Wolfsdorf. “This will help determine how to treat the mare so that the uterus is a more hospitable environment for the developing embryo.”
She added, “Fibrosis around individual glands and nesting of glands can reduce nourishment of the developing embryo, while sclerosis or fibrosis of the vessels can decrease blood flow to the endometrium and subsequently the embryo. Dilated lymphatic lacunae provide evidence of blocked lymphatics and poor uterine clearance.”
Until recently, researchers had not identified a treatment to improve fibrosis; however, Segabinazzi et al. demonstrated that injecting mesenchymal stem cells into the endometrium improved endometrial biopsy scores by decreasing endometrial fibrosis, decreasing endometrial collagen type 3, and increasing progesterone receptor distribution.
Wolfsdorf said further studies are needed to see if this translates into improved pregnancy rates and decreased EEL. She said additional research using an acellular amniotic-derived product injected into the endometrium to regulate inflammation and potentially provide a bioscaffold for regenerative properties is also underway, which might be useful in the future.
“In addition, mares that have vascular degeneration and decreased uterine clearance may benefit from aspirin and pentoxifylline to increase blood flow to the old saggy, baggy uterus,” Wolfsdorf said. Protocols incorporating acupuncture and Chinese herbal remedies might also be beneficial.
Endometrial cysts are signs of blocked lymphatics and degenerative endometrial changes. They can impede embryonic mobility, which is needed for maternal recognition of pregnancy. Horses develop increased numbers of cysts with age, resulting in decreased pregnancy rates.
Wolfsdorf said veterinarians can use different procedures to remove endometrial cysts, but with multiple multilobulated cysts she prefers using a laser during diestrus to heat and puncture the cysts, initiating regression. Cysts might recur, as the laser does not alleviate the underlying problem. Therefore, she recommends removing cysts prior to the beginning of the breeding season.
Concluding Thoughts on EEL in Mares
“In summary, a methodical approach should be taken to identify the cause of EEL so appropriate treatment and management can be initiated,” said Wolfsdorf. “Then, continued monitoring of the fetoplacental unit throughout gestation can aid in identifying and managing problems so that a viable foal can be delivered.”
