Effect of altrenogest on endogenous progesterone during early pregnancy in recipient mares

Abstract

Altrenogest is commonly utilised for hormonal support of pregnancy, with undefined effects. We investigated effects of altrenogest supplementation on endogenous progesterone (P4) production in embryo recipient mares (RM). RM were managed onsite and selected on the basis of ‘best tone' on transfer day. Thirty RM received a 150mg depot altrenogest intramuscularly from transfer, at 7-day intervals, through to 42 days (ALT), a further 31 RM received no altrenogest (CON). Blood was collected at 7-day intervals, starting 7 days after transfer and P4 assayed by amplified enzyme-linked immunoassay. Data were analysed by total (tP4, ng/ml) and P4 corrected by number of corpora lutea (CL; cP4). Statistical comparisons of non-parametric data were performed by Kruskal-Wallis ANOVA and Friedman repeated measures; values presented as median and 95% confidence interval. Odds ratios (OR) were calculated to evaluate associations between ALT and secondary ovulation, and tP4 values of <3ng/ml. In ALT, tP4 was lower on days 21, 28 and 35 when compared to days 14 and 42 (p<0.01), and no difference was seen between days 14 and 42 (p=0.715). The same pattern was seen with cP4 lower on days 21, 28 and 35 compared to days 14 and 42 (p<0.01), and no difference between days 14 and 42 (p=0.273). A similar profile was seen in CON, with tP4 loweron days 21, 28 and 35 compared to days 14 and 42 (p<0.01) and no difference between days 14 and 42 (p=0.095). However, compared to day 14, cP4 was lower on days 21, 28, 35 (p<0.01), and also on day 42 (p=0.026). When compared to days 21, 28 and 35 there were no differences with day 42 (p>0.10). Secondary CL occurred in 17.24% CON and in 26.67% ALT (OR 1.55; 0.45-5.28, p=0.487). Total P4 was lower in ALT 4.8 (3.9-6.3), compared with CON 6.0 (5.4-7.3, p=0.04), and in ALT 4.7 (3.9-5.3), compared with CON 5.7 (5.1-7.4, p=0.02) at 21 and 28 days respectively. This held true for cP4 at 21 (ALT 3.7; 2.8-4.3 versus CON 4.7; 3.7-6.6, p=0.03) and 28 days (ALT 3.4; 2.5-4.3 versus CON 5.0; 4.0-5.8, p=0.005) where effect of multiple ovulations was nullified. In 40% of ALT, tP4 was <3.0 at ≥1 time-point compared to 3.2% in CON. The odds of a mare having a tP4 concentration <3.0 at any time-point was greater for ALT (OR 11.2; 1.37-91.83, p=0.024). Three ALT (10%) and no CON had tP4 ≤3.0 at 42 days (p=0.212). In conclusion, altrenogest led to suppressed endogenous P4 production with the greatest magnitude at 28 days of gestation; we hypothesize that this is mediated via negative feedback of altrenogest on pituitary LH release and effective reduction of its luteotrophic influence.