SEARCH

SEARCH BY CITATION

Keywords:

  • horse;
  • mare;
  • ovulation;
  • hCG;
  • dexamethasone

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

Reasons for performing study: Human chorionic gonadotropin (hCG) and dexamethasone have a role in the reproductive management protocols of mares susceptible to persistent mating-induced endometritis (PMIE). However, it is possible that there is interference between these 2 drugs.

Objectives: The objective of this retrospective study was to determine the efficacy of hCG to induce ovulation in mares treated with dexamethasone at breeding time.

Methods: Medical records from 152 mares and 223 cycles were analysed. In 113 cycles, mares susceptible to PMIE were treated with 1500 iu hCG and a single dose of 50 mg dexamethasone, 110 cycles were used as controls and subsequent ovulation was assessed ultrasonographically and compared.

Results: Dexamethasone did not inhibit ovulation in mares susceptible to PMIE.

Conclusions and potential relevance: Multiple administrations of dexamethasone to mares in early oestrus have induced ovulation failure. However, a single dose of dexamethasone, administered at breeding time, has been used as an effective modulator of PMIE in susceptible mares and does not interfere with efficacy of hCG to induce ovulation.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

Human chorionic gonadotropin (hCG) has been reported to be efficacious in inducing ovulation in cycling oestrous mares, where at least one 35 mm ovarian follicle is present (Day 1939; Loy and Hughes 1966; Sullivan et al. 1973; Voss et al. 1975; Webel et al. 1977; Ginther 1982; Michel et al. 1986; Duchamp et al. 1987; Wilson et al. 1990; Rossdale and Lambercht 1998; Barbacini et al. 2000). Induction of ovulation is widely used in the equine industry because of the long and variable length of oestrus and, more specifically, the long and variable interval from onset of oestrus to ovulation (Ginther 1982). Ovulation is generally induced to predict its time of occurrence and achieve synchronisation with breeding time. In natural breeding programmes, ovulation is usually induced to optimise stallion availability. When using frozen semen, timing between insemination and ovulation must be thoroughly synchronised (Pace and Sullivan 1975; Volkmann and van Zyl 1987; Pickett and Amann 1993; Katila et al. 1996).

Mares susceptible to persistent mating-induced endometritis (PMIE) should only be covered once during each oestrus cycle as multiple sperm challenges of the endometrium tend to aggravate their condition (Kotilainen et al. 1994; Troedsson 1995). Recently, corticosteroid treatment has been advocated as an effective means of modulating PMIE in susceptible mares (Dell'Aqua et al. 2006; Bucca et al. 2008). Bucca et al. (2008) reported improved conception rates in susceptible mares administered dexamethasone at breeding time.

In 1982, Asa and Ginther demonstrated in the mare that daily administration of dexamethasone from Day 10 after ovulation can interfere with ovulation and associated events (Asa and Ginther 1982). However, McKinnon et al. (1997) showed that administration of 20 mg of dexamethasone i.m. twice a day, from the detection of a 35 mm follicle and uterine oedema until ovulation had no effect on ovulation rates or days to ovulation (McKinnon et al. 1997). Recently, Ferris and McCue reported that twice daily administrations of dexamethasone to mares in early oestrus was associated with decreased uterine oedema, suppression of luteinising hormone (LH) and a high rate of ovulation failure (Ferris and McCue 2010).

It is possible that there is interference between a single dose of dexamethasone administered at breeding time and the use of hCG to induce ovulation in the mare. The objective of this retrospective study was to determine the efficacy of hCG to induce ovulation in mares treated with dexamethasone at breeding time.

Materials and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

The reproductive records of 152 mares, collected at an Irish studfarm from March to September during the 2006 and 2007 breeding seasons, were retrospectively analysed. Warmblood and Thoroughbred mares, ranging from 3 to 24 years of age, were used in this study for treated and control cycles.

A total of 223 cycles were examined; dexamethasone was administered at breeding time in 113 cycles of mares susceptible to PMIE and 110 cycles were used as control. Of the 152 mares examined, 59 were inseminated for 2 cycles (43 treated and 14 control) and 12 for 3 cycles (10 treated and 2 controls).

Mares received a thorough reproductive assessment at enrolment time and were examined by ultrasound daily to evaluate reproductive function. Ultrasound linear array technology (Sonosyte Titan) was used for this study, operating with a 6–8 MHz transrectal transducer. Nonfoaling mares entered the study after the first ovulation of the year had been detected and foaling mares on their second heat post foaling.

Human chorionic gonadotropin 1500 iu (Chorulon)1 was administered i.v. to oestrous mares, when at least one follicle ≥35 mm was detected. Only one injection of hCG 1500 iu per oestrous cycle was given. A single standard dose of dexamethasone 50 mg (Dexadreson)1, was administered i.v. within 1 h of breeding time, in treated cycles.

Mares were bred naturally or inseminated with fresh or chilled semen either when hCG was administered or later.

Further reproductive ultrasonographic examinations were performed at 24 and 48 h post hCG injection and subsequently at 24 h intervals until ovulation took place. Ovulation time was recorded as occurring: ≤24, >24, ≤48 and >48 h. When ovulation did not occur within 48 h of hCG administration, the mare was considered to have had an inappropriate response to treatment (Ginther 1982).

Data examined are presented as mean (± s.e.). Categorical variables were compared using contingency tables and Chi-square tests with P<0.05 considered significant.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

During the course of the study, the mean number of hCG injections received by each enrolled mare was 1.45. In the control group, ovulation occurred within 48 h of administration in 90.9% of cycles (100/110) and between 25 and 48 h in 83.6% of cycles (92/110). In 7.2% of cycles (8/110) ovulation was detected within 24 h whereas in 9.1% of cycles (10/110), mares showed an inappropriate response to treatment.

When dexamethasone was administered at breeding time, in 97.3% of cycles (110/113) ovulation took place within 48 h and in 77.8% (88/113 cycles) between 25 and 48 h. In 19.4% of cycles (22/113), ovulation was detected within 24 h. An inappropriate response to hCG was recorded in 2.6% of treated cycles (3/113).

A single dose of dexamethasone administered at breeding time did not decrease efficacy of hCG to induce ovulation in the mare (P>0.05). Furthermore, no statistically significant difference was identified in number of treated vs. controlled cycles, where ovulation occurred between 25 and 48 h (P>0.1). The mean number of hours between hCG and dexamethasone administration was 10.24 ± 10.47 (range 0–29.5 h). When synchronous administration of hCG and dexamethasone took place (29/113 treated cycles), ovulation always occurred within 48 h, with a 24.2% incidence (7/29 cycles) of ovulation within 24 h. When dexamethasone was administered between 1 and 6 h of hCG injection, ovulation occurred within 48 h in 96.8% of cycles (31/32), of which 68.7% (22/32) between 25 and 48 h and 28.1% (9/32) within 24 h. Dexamethasone did not decrease the efficacy of hCG to induce ovulation in the mare, when administered within 1–6 h after hCG (P>0.45) and a comparable response was also recorded between control and treated cycles, as ovulation occurred between 25 and 48 h (P>0.65).

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

Human chorionic gonadotropin was the first ovulatory agent to be used in the mare (Asa and Ginther 1982) and remains the drug of choice by many equine practitioners to this day. Human chorionic gonadotropin improves breeding efficiency as it facilitates prediction of ovulation time and synchronism with breeding. Several studies investigating the effects of hCG in hastening ovulation have demonstrated that the duration of oestrus and interval from onset of oestrus to ovulation are significantly reduced in treated mares (Day 1939; Loy and Hughes 1966; Sullivan et al. 1973; Voss et al. 1975; Webel et al. 1977; Ginther 1982; Michel et al. 1986; Duchamp et al. 1987; Wilson et al. 1990; Rossdale and Lambercht 1998; Barbacini et al. 2000). It has been previously reported that hCG is effective to induce ovulation within 48 h of administration in ≥80% of cases (Loy and Hughes 1966; Ginther 1982; Barbacini et al. 2000). Comparable results have been obtained in the control group of the present study since ovulation occurred within 48 h of hCG injection in 90.9% of cycles.

Current literature reports that ovulation is expected to take place within 25–48 h of hCG administration in 73–75% of the cases (Sullivan et al. 1973; Duchamp et al. 1987; Barbacini et al. 2000). An endogenous peak of LH appears to be responsible for ovulations occurring within 24 h of hCG administration (Freeman et al. 1991; Grondhal et al. 1993; Battut et al. 1998). In the present retrospective study, ovulation occurred within 25 and 48 h of hCG administration in 83.6% of cycles.

Breeding close to ovulation, to apply minimum contamination techniques, is pivotal to the successful management of susceptible mares and aims at preventing the detrimental effects of repeated endometrial exposure to sperm. Predicting time of ovulation, through a timely administration of ovulatory agents, will ultimately reduce the number of breeding per cycle. Susceptible mares fail to ‘turn off’ mating-induced endometritis within physiological time limits and the persisting inflammatory condition impacts negatively on fertility, by creating a poor uterine environment and hampering embryonic survival. Corticosteroids, have recently been proven an effective means of modulating PMIE in susceptible mares, by improving post breeding uterine environment, without altering major defence mechanisms (Dell'Aqua et al. 2006; Bucca et al. 2008).

The administration of hCG and dexamethasone at breeding time has been reported as an effective protocol in the management of susceptible mares (Bucca et al. 2008). Exogenous glucocorticoids in the horse have been associated with suppression of the hypothalamic-pituitary-adrenal axis (Toutain et al. 1984), immunosuppression (Tumas et al. 1994), laminitis (Johnson et al. 2002), suppression of sexual behaviour (Asa et al. 1980) and have been reported to have adverse effects on reproductive function (Asa and Ginther 1982; McNeill-Wiest et al. 1988; Thompson et al. 1991; Ferris and McCue 2010). Asa and Ginther (1982) demonstrated that in the mare, administration of 30 mg of dexamethasone i.m. once a day for 20 days from Day 10 after ovulation, inhibits follicular development and ovulation (Asa and Ginther 1982). A decrease in LH and follicle-stimulating hormone (LHL) has been recorded in ovariectomised pony mares following dexamethasone administration (0.125 mg/kg bwt, subcut., once per day) (McNeill-Wiest et al. 1988; Thompson et al. 1991). However, McKinnon et al. (1997) administered 20 mg dexamethasone i.m. twice a day, from detection of a 35 mm follicle and uterine oedema until ovulation, without adverse effects on ovulation rates or days to ovulation. More recently, Ferris and McCue (2010), administrated 50 mg dexamethasone twice a day to 6 mares in early oestrus and reported decreased uterine oedema, suppression of LH and a high rate of ovulation failure. In the present retrospective study, a single dose of 50 mg dexamethasone administered at breeding time did not adversely affect the efficacy of hCG to induce ovulation in the mare.

Conclusions

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References

Multiple administrations of dexamethasone to mares in early oestrus have induced ovulation failure. However, a single dose of dexamethasone, administered at breeding time has been used as an effective modulator of PMIE in susceptible mares and does not interfere with efficacy of hCG to induce ovulation.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Authors' declaration of interests
  9. Source of funding
  10. Acknowledgements
  11. Manufacturer's address
  12. References
  • Asa, C.S. and Ginther, O.J. (1982) Glucocorticoid suppression of oestrus, follicles, LH and ovulation in the mare. J. Reprod. Fert. Suppl. 32, 247-251.
  • Asa, C.S., Goldfoot, D.A., Garcia, M.C. and Ginther, O.J. (1980) Dexamethasone suppression of sexual behavior in the ovariectomized mare. Horm. Behav. 14, 55-64.
  • Barbacini, S., Zavaglia, G., Gulden, P., Marchi, V. and Necchi, D. (2000) Retrospective study on the efficacy of hCG in an equine artificial insemination programme using frozen semen. Equine vet. Educ. 12, 312-317.
  • Battut, I., Colchen, S., Fiéni, F., Tainturier, T. and Bruyas, J.F. (1998) Rates of success in non-surgical embryo collections at 144, 156 or 168 h after ovulation. Equine vet. J., Suppl. 25, 60-62.
  • Bucca, S., Carli, A., Buckley, T., Dolci, G. and Fogarty, U. (2008) The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis. Theriogenol. 70, 1093-1100.
  • Day, F.T. (1939) Ovulation and the descent of the ovum in the fallopian tube of the mare after the treatment with gonadotropin hormones. J. Agric. Sci. Camb. 29, 459-469.
  • Dell'Aqua, Jr J.A., Papa, F.O., Lopes, M.D., Alvarenga, M.A., Macedo, L.P. and Melo, C.M. (2006) Modulation of acute uterine inflammatory response after artificial insemination with equine frozen semen. Anim. reprod. Sci. 94, 270-273.
  • Duchamp, G., Bour, B., Combarnous, Y. and Palmer, E. (1987) Alternative solutions to hCG induction of ovulation in the mare. J. Reprod. Fert. Suppl. 35, 221-228.
  • Ferris, R.A. and McCue, P.M. (2010) The effects of dexamethasone and prednisolone on pituitary and ovarian function in the mare. Equine vet. J. 42, 438-443.
  • Freeman, D.A., Weber, J.A., Geary, R.T. and Woods, G.L. (1991) Time of embryo transport through the mare oviduct. Theriogenol. 36, 823-830.
  • Ginther, O.J. (1982) Reproductive Biology of the Mare, 2nd edn., Equiservices, Wisconsin. pp 233-290.
  • Grondhal, C., Grondhal Nielsen, C., Eriksen, T., Greve, T. and Hyttel, P. (1993) In vivo fertilisation and initial embryogenesis in the mare. Equine vet. J., Suppl. 15, 79-83.
  • Johnson, P.J., Slight, S.H., Ganjam, V.K. and Kreeger, J.M. (2002) Glucocorticoids and laminitis in the horse. Vet. Clin. N. Am. 18, 219-236.
  • Katila, T., Celebi, M. and Koskinen, E. (1996) Effect of timing of frozen semen insemination on pregnancy rate in mares. Acta vet. Scand. 37, 361-365.
  • Kotilainen, T., Huhtinen, M. and Katila, T. (1994) Sperm-induced leukocytosis in the equine uterus. Theriogenol. 41, 629-636.
  • Loy, R.G. and Hughes, J.P. (1966) The effect of human chorionic gonadotropin on ovulation, length of oestrus and fertility in the mare. Cornell Vet. 56, 41-50.
  • McKinnon, A.O., Perriam, W.J., Lescum, T.B., Walker, J., Vasey, J.R. and Trigg, T.E. (1997) Effect of a GnRH analogue (Ovuplant), hCG and dexamethasone on time to ovulation in cycling mares. World equine vet. Rev. 2, 16-18.
  • McNeill-Wiest, D.R., Thompson, D.L. Jr and Wiest, J.J. (1988) Gonadotropin secretion in ovariectomized pony mares treated with dexamethasone or progesterone and subsequently with dihydrotestosterone. Domest. anim. Endocrinol. 5, 149-155.
  • Michel, T.H., Rossdale, P.D. and Cash, R.S.G. (1986) Efficacy of human chorionic gonadotropin and gonadotropin releasing hormone for hastening ovulation in Thoroughbred mares. Equine vet. J. 18, 438-442.
  • Pace, M.M. and Sullivan, J.J. (1975) Effect of timing of insemination, numbers of spermatozoa and extenders components on the pregnancy rate in mares inseminated with frozen stallion semen. J. Reprod. Fert. Suppl. 23, 115-121.
  • Pickett, B.W. and Amann, R.P. (1993) Cryopreservation of semen. In: Equine Reproduction, Eds: A.O. McKinnon and J.L. Voss, Lea and Febiger, Philadelphia; London. pp 767-789.
  • Rossdale, P.D. and Lambercht, P. (1998) Comparison of the interval between administration of hCG or GnRH implant and ovulation in oestrus mares. Equine vet. Educ. 10, 76-79.
  • Sullivan, J.J., Parker, W.G. and Larson, L.L. (1973) Duration of estrus and ovulation time in non lactating mares given hCG during three successive estrous periods. J. Am. vet. med. Ass. 163, 895-898.
  • Thompson, D.L. Jr, Graza, F. Jr, George, R.L., Rabb, M.H., Barry, B.E. and French, D.D. (1991) Relationships among LH, FSH and prolactin secretion, storage and response to secretagogue and hypothalamic GnRH content in ovariectomized pony mares administered testosterone, dihydrotestosterone, estradiol, progesterone, dexamethasone or follicular fluid. Domest. Anim. Endocrinol. 8, 189-199.
  • Toutain, P.L., Brandon, R.A., de Pomyers, H., Alvinerie, M. and Baggot, J.D. (1984) Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland. Am. J. vet. Res. 45, 1750-1756.
  • Troedsson, M.T. (1995). Proc. Annu. Meet. Soc. Theriogenol., 130-135.
  • Tumas, D.B., Hines, M.T., Perryman, L.E., Davis, W.C. and McGuire, T.C. (1994) Corticosteroid immunosuppression and monoclonal antibody-mediated CD5+ T lymphocyte depletion in normal and equine infectious anemia virus-carrier horses. J. Gen. Virol. 75, 959-968.
  • Volkmann, D.H. and van Zyl, D. (1987) Fertility of stallion semen frozen in 0.5 ml straws. J. Reprod. Fert. Suppl. 35, 143-148.
  • Voss, J.L., Sullivan, J.J., Pickett, B.W., Parker, W.G., Burwash, L.D. and Larson, L.L. (1975) The effect of hCG on duration of oestrus, ovulation time and fertility in mares. J. Reprod. Fert. Suppl. 35, 557-561.
  • Webel, S.K., Franklin, V., Harland, B. and Dzuik, P.J. (1977) Fertility, ovulation and maturation of eggs in mares treated with hCG. J. Reprod. 51, 328-337.
  • Wilson, C.G., Downie, C.R., Hughes, J.P. and Roser, J.F. (1990) Effects of repeated hCG injections on reproductive efficiency in mares. J. equine vet. Sci. 10, 301-308.