Each year the American Association of Equine Practitioners convention kicks off with a rapid-fire run through some of the most important surgery, medicine, and reproduction studies of the previous 12 months. The 2018 edition, held at the Dec. 1-5 meeting in San Francisco, California, featured Regina Turner, VMD, PhD, Dipl. ACT, chief of the Section of Reproduction and Behavior at the University of Pennsylvania’s New Bolton Center, in Kennett Square, presenting reproduction research. Here were her top selections:
How Ceftiofur Sodium Affects Pregnant Mares
In this study researchers from Florida, Georgia, and Kentucky evaluated the pharmacokinetics (how drugs are processed and maintained in the body) of the broad-spectrum antibiotic ceftiofur sodium (Naxcel) in pregnant mares to see if this drug might be an effective placentitis (inflammation of the placenta) treatment.
“It makes great intuitive sense because most placentitis cases are caused by Streptococcus equi subspecies zooepidemicus, and ceftiofur sodium is very effective against (that pathogen),” said Turner.
The researchers administered intramuscular ceftiofur sodium to 11 pregnant study ponies daily, measured drug levels in their blood plasma, and took placental fluid samples. They found that plasma levels were the same in the pregnant mares as in nonpregnant horses but detected no ceftiofur sodium in placental fluid during gestation or in placental fluid or tissues immediately after foaling.
Their take-home? Ceftiofur sodium does not cross the fetal membranes and is not a good option for treating placentitis, said Turner, adding that it’s still useful for treating Streptococcus infections in other body regions in both pregnant and nonpregnant mares (the drug is labeled in horses for use against respiratory infections). Additionally, she said, it is useful for treating nonpregnant mares with endometritis (inflammation of the inner lining of the uterus) caused by Streptococcus, because it’s been shown to reach good levels in the uterine lining.
Macpherson ML, Giguère S, Pozor MA, et al. Pharmacokinetics of ceftiofur sodium in equine pregnancy. J Vet Pharmacol Ther. 2017 Dec;40(6):656-662.
Appropriate Antimicrobials for Treating Metritis in Mares
To guide metritis (uterine wall inflammation) treatment recommendations in horses, University of Georgia researchers evaluated the most frequent causative agents, their antimicrobial susceptibility, and the prevalence of multidrug resistance (MDR) in such cases. This is important because these mares are often very sick, so treatment must begin immediately—usually days before test results identifying the bacteria species are available.
In their retrospective study the researchers looked at more than 80 organisms found on uterine cultures of 45 postpartum mares with metritis. They found that 62% of mares harbored more than one bacterial species, with the most common ones being Escherichia coli, S. zooepidemicus, and other Streptococcus spp.
“These organisms represent both Gram-negative and Gram-positive species,” said Turner. Gram-negative and gram-positive organisms are often sensitive to different classes of antimicrobials. Therefore, the presence of both bacteria types in the uterus is concerning because choosing a single antimicrobial empirically (without knowing the results of culture and antimicrobial sensitivity testing) is likely to be ineffective against at least one or the other, she said.
As for treatment, the researchers found that the antimicrobial trimethoprim/sulfonamide (TMS) was not a good option, having less than 49% efficacy against the most commonly isolated organisms. Gentamicin with penicillin was more effective at 65%. While the study authors concluded that a combination of penicillin and amikacin or enrofloxacin might be preferable to penicillin and gentamicin, Turner said these choices might be cost-prohibitive or impractical.
Lastly, the team found MDR in around 60% of organisms and in 85% of Gram-negative bacteria.
“This is making me feel very worried, as it is pointing to a significant increase in bacterial drug resistance,” said Turner.
Ferrer MS, Palomares R. Aerobic uterine isolates and antimicrobial susceptibility in mares with post-partum metritis. Equine Vet J. 2018 Mar;50(2):202-207.
Two Noninvasive Treatments for Oviduct Blockage in Mares
Turner compared two studies in which researchers evaluated noninvasive treatments for subfertile mares suspected of having blocked oviducts. Historically, veterinarians have had to perform laparoscopy to treat suspected oviduct blockages. Although minimally invasive, this surgical procedure can cost upward of $4,000.
In the first study Japanese researchers evaluated the efficacy of hysteroscopic hydrotubation of the oviduct, a procedure in which the veterinarian passes an endoscope into the uterus and, through it, threads a stylet (a slender probe) and tubing to the tip of the uterine horn and into the oviduct. He or she administers sterile saline through this tube to mechanically flush out any blockage. Of the 28 subfertile mares suspected of having blocked oviducts that underwent this procedure in this retrospective study, 26 (93%) became pregnant after treatment, suggesting that this technique is an effective method for clearing blockages, said Turner.
In the second study researchers from Brazil tested an even easier approach: topical administration of the drug misoprostol (a form of prostaglandin E that can cause the oviduct to dilate and increase oviduct contractions, which move ova down the tubes to the uterus) through a flexible insemination pipette. After inserting the pipette through the cervix into the uterus, the veterinarian manually guides it transrectally to the uterine horn tip adjacent to the oviduct opening. Then, he or she injects misoprostol through the pipette onto the opening.
“The idea is that the misoprostol will pass into the oviduct, where it will cause the oviduct to contract, thus forcing the blockage out,” said Turner. The researchers reported a 73% pregnancy rate in the 22 treated mares.
“Now we have two noninvasive, less expensive, apparently effective treatments. This is a big jump forward in ease of treatment,” said Turner. “While (hysteroscopic hydrotubation) is more difficult and expensive (around $800 to $1,000, compared to misoprostol’s approximately $200 price tag), it gives you the bonus of being able to see inside the uterus and evaluate the health of the uterine lining in these infertile mares.”
Inoue Y, Sekiguchi M. Clinical application of hysteroscopic hydrotubation for unexplained infertility in the mare. Equine Vet J. 2018 Jul;50(4):470-473.
Alvarenga MA, Segabinazzi LG. Application of Misoprostol as a Treatment of Unexplained Infertility in Mares. J Equine Vet Science. 2018 Dec;71:46-50.
Length of Estrus Affects Recipient Mare Pregnancy Rates
Mares’ natural length of estrus can be variable, ranging from three to 7 days. When we manipulate the estrous cycle with prostaglandin (short-cycling), the variation can be even more extreme. Researchers have previously shown that longer estrous periods are associated with increased pregnancy rates, but it was unknown whether this was due to an effect on the oocyte, the oviduct, the uterus, or some combination of these.
Dutch scientists wanted to narrow down the mechanism by which estrus duration affects pregnancy rates and early embryonic loss by determining whether there a longer estrus has a positive effect on the uterus’ ability, specifically, to support early pregnancy. To accomplish this, they looked at pregnancy rates in a large group of embryo transfer recipient mares and determined if estrous length preceding embryo transfer affected recipients’ pregnancy rates. For embryo transfer, the fertilized oocyte comes from the donor mare; the recipient mare essentially only provides the uterine environment. Therefore, by focusing on pregnancy rates in recipient mares, these researchers could eliminate the oocyte and oviduct from the equation.
Endometrial edema (an increase in fluid within the tissues lining the uterus) is a hallmark of estrus and a normal response to high levels of circulating estrogen and low levels of progesterone. Using uterine edema as a marker for an estrogen-dominated uterine environment, these researchers looked at data on 231 recipient mares and found that those with significant uterine edema for at least three days prior to ovulating had an 83% pregnancy rate following embryo transfer. Mares with fewer than three days of edema had a 64% pregnancy rate, and those with none had a 50% rate. The authors concluded that adequate estrogen priming during estrus is key to uterine receptivity and embryo survival.
“Mares that ovulate quickly and show the development of little to no uterine edema prior to ovulation are less likely to become pregnant, and this is due, at least in part, to an effect on the uterine environment,” said Turner.
Cuervo-Arango J, Claes AN, Ruijter-Villani M, et al. Likelihood of pregnancy after embryo transfer is reduced in recipient mares with a short preceding oestrus. Equine Vet J. 2018 May;50(3):386-390.
Colic Surgery and Broodmare Careers
Large colon volvulus (twisting) is one of the most common postpartum problems in mares and is a surgical emergency, said Turner. To measure its future impact, researchers from Colorado, Kentucky, and Michigan looked at the long-term reproductive careers of broodmares that underwent surgery to correct this type of colic. In their retrospective study they found that 82% of mares bred post-surgery produced at least one foal. Forty-seven percent foaled in the year following volvulus surgery (so they were successfully bred the same year as the surgery). Younger mares (ages 3 to 11) produced more foals after surgery than did older mares, but Turner noted that foal production was no different than that seen in age-matched mares that did not have surgery.
The authors concluded that large colon volvulus surgery does not affect broodmare careers. “Age at the time of surgery and not the surgery itself has an effect on how long these mares will continue to produce foals,” said Turner. “Base a decision to go to surgery on a mare’s age and value and not on a concern that the surgery itself will shorten her reproductive career.”