Mares might be prone to early pregnancy loss for several reasons besides predisposing factors such as age. “There are very few evidence-based strategies which have been shown to increase pregnancy maintenance as well as increase viability,” said Karen Wolfsdorf, DVM, Dipl. ACT, of Hagyard Equine Medical Institute, in Lexington, Kentucky, during her presentation at the 2024 American Association of Equine Practitioners Convention held Nov. 29-Dec. 3 in San Diego, California. “So, a lot of treatments are extrapolated from research into a clinical setting.” Wolfsdorf defined early embryonic loss (EEL) as the loss of a conceptus (i.e., the embryo and associated membranes) between fertilization and Day 40 of gestation.

Oocyte Quality in Breeding Mares

Older mares have lower pregnancy rates and increased EEL rates due to decreased mitochondrial function in old oocytes and a change in the follicular fluid that nourishes the oocyte and leads to poor-quality embryos. N-3 fatty acids, which have anti-inflammatory and antioxidant properties, have been shown to improve oocyte metabolic function and embryo development. Ovum pickup (OPU) and intracytoplasmic sperm injection (ICSI) can take “the aged oocyte out of the poor follicular milieu and (put) it into that better-growing environment to produce a better quality embryo,” Wolfsdorf said.

Equine Embryonic Development

The embryo must be an appropriate size to grow and move throughout the uterus for maternal recognition of pregnancy to occur. The hormones progesterone and estradiol both influence the production of histotroph, which provides food to the developing embryo. In addition, progesterone enhances uterine tone and estradiol improves endometrial (uterine lining) vascularity, aiding in embryonic growth.

Checking progesterone levels at Day 6 of pregnancy can help decide whether to supplement with exogenous (originating outside the body) progesterone. “We need to continue to monitor those mares,” Wolfsdorf said. Researchers found decreases in progesterone production by mares who received supplemental progesterone early in pregnancy, she said. In that case the mare might need to stay on the supplemented progesterone until the endometrial cup forms and secondary corpus luteal formation stimulates progesterone production.

Equine Uterine Environment

Identifying underlying endometritis as a cause of EEL is an important step in improving a mare’s pregnancy rates, says Wolfsdorf. The drugs N-acetylcysteine and misoprostol; bActivate (a bacterial growth medium); and kerosene have emerged as methods to identify bacteria found deep in the uterus, she said. “We can try to break down the biofilm and mucus (with these) to identify the bacteria so appropriate treatment can decrease the colony-forming units of these bacteria.” Veterinarians commonly see inflammation with endometritis, pooling urine, and pneumovagina, and might use firocoxib, a non-steroidal anti-inflammatory drug (NSAID) that selectively blocks an enzyme called cyclooxygenase-2 (COX-2), to treat this inflammation. “Unlike other anti-inflammatory products, firocoxib does not impede embryonic mobility,” says Wolfsdorf.

Chronic Degenerative Endometrial Changes in Mares

“It’s not necessarily the grade of the endometrium that you have on an endometrial biopsy—it’s the abnormalities that are present,” Wolfsdorf said. Practitioners use this biopsy to look for inflammation, fibrosis, and sclerosis of the vasculature. Strangled blood vessels due to degenerative changes cannot dilate as needed, decreasing blood flow to the endometrium and the embryo. Aspirin and the drug pentoxifylline both increase blood flow to the uterus. Newer approaches to improving the degenerative changes in the endometrium include injecting mesenchymal stem cells (MSCs) into the endometrium, injecting amniotic-derived acellular bioscaffold under the epithelial lining, and ozone therapy.

Endometrial Cysts

Cysts are dilations of the lymphatic system due to poor uterine clearance and fibrosis. They can block embryos, impede mobility, and can decrease absorption of nutrients because they interfere with endometri contact. Though various treatment options for removing cysts exist, Wolfsdorf said the important thing to remember is that cysts are a sign of an underlying problem—blocked lymphatics. Therefore, the uterus needs help contracting to improve fluid movement and drainage.

Reproductive Conformation

There are three barriers to environmental (air and bacterial) contamination of the uterus, the cervix, hymen, and vulva. When any become compromised, EEL can occur. Veterinarians should also be aware of pooling urine in the uterus, and if medical management with oxytocin, flushing, and acupuncture do not resolve this issue, a urethra extension might be needed. Good perineal conformation is imperative, so reconstruction might be necessary for some mares and can include a Caslick’s vulvoplasty, a Pouret (perineoplasty), or the Gadd technique (aka a deep Caslick’s or a episioplasty).

Take-Home Message

Veterinarians should first identify the cause of EEL to effectively treat it. Mares need correct reproductive conformation to increase the likelihood of delivering a healthy foal. In mares with a poor uterine environment, endometrial cysts, or chronic degenerative changes, veterinarians should consider the age of the mare and the owner’s goals for her when choosing a treatment method.