Effect of a single dose of a proprietary extended-release oxytocin formulation on corpus luteum function in cycling mares

Abstract

There is increasing clinical use of oxytocin treatment to prolong function of the corpus luteum (CL) to suppress estrus in performance mares. A common oxytocin treatment protocol involves administering 60 units of oxytocin intramuscularly (IM) once daily on days 7 to 14 after ovulation (day 0). In an effort to eliminate the need for daily administration, we have been evaluating the use of a proprietary extended-release formulation of oxytocin (ER-OT). We previously demonstrated that IM administration of 2,400 units ER-OT on day 7 and again on day 10 resulted in prolonged CL function in 75% of the treated mares (Sarnecky, et al., J Equine Vet Sci. 2019;77:28-30). That two-injection protocol reduced the number of treatments by 75% (i.e., two injections vs. eight injections from day 7 to 14). We hypothesized the number of ER-OT treatments can be further reduced to one and still maintain efficacy. In an initial study evaluating a single dose of ER-OT, IM administration of 4,800 units of ER-OT once on Day 8/9 resulted in prolonged CL function in 50% of the treated mares compared to 12.5% in untreated control mares (P>0.1), which although promising, indicated further work was needed (Clement et al., Clinical Theriogenology. 2022;14:280). The objective of this study was to evaluate the effect on CL function of a single dose of 4,800 units ER-OT on day10. Mares were examined via transrectal palpation and ultrasonography to determine the day of ovulation (day 0) and then randomly assigned to a nontreated control group and an ER-OT-treated group (n = 9 mares/group). Mares in the treated group received 2.0 mL of ER-OT containing 4,800 units oxytocin IM once on day 10. Starting 15 minutes before treatment, mares were monitored visually every 15 minutes for three hours and no signs of colic were observed. Jugular blood samples were collected on day 0 and then every Monday, Wednesday and Friday for 50 days for determination of the serum progesterone concentration. Mares were classified as having prolonged CL function if their progesterone concentration remained >1.0 ng/mL continuously for at least 30 days. The proportion of mares in each group with prolonged CL function was compared using Fisher's Exact Test (GraphPad Software, Inc., San Diego, CA). There was a tendency for CL function to be prolonged in more ER-OT-treated mares than control mares (6/9 [67%] vs. 2/9 [22%], respectively; P = 0.08). Although these results did not reach statistical significance, the 67% incidence of prolonged CL function in the ER-OT-treated mares suggests a single dose of ER-OT has the potential to be efficacious though additional work is still needed.