Efficacy of altrenogest administration to postpone ovulation and subsequent fertility in mares

A recent report suggested administration of altrenogest during the follicular phase could postpone ovulation. Based on these results, two questions were generated. We first hypothesized that by initiating a altrenogest treatment earlier in the estrous cycle, a greater and/or more consistent delay in ovulation would result. Second, we hypothesized that exposure to elevated progestin concentrations might alter viability of the ovulatory follicle and oocyte. The focus of the first experiment was to determine if initiation of altrenogest treatment at different stages of the estrous cycle would yield a more predictable time to ovulation, whereas the second experiment was designed to determine whether mares receiving altrenogest during estrus had compromised fertility. In the first experiment thirty mares of mixed light breed, ranging in age from 5-15 years, were randomly assigned to one of three groups. The two treated groups received altrenogest (0.088 mg/kg of body weight) for two days once a follicle of 30 or 35 mm in diameter was detected. Control mares were not treated. Mares treated with altrenogest whether initiated at the detection of a 30 or 35 mm follicle demonstrated similar (P>.05) day to ovulation interval when adjusted to 35 mm (5.4 and 5.6 days, respectively). Both treated groups demonstrated a delayed interval (P<.05) when compared to control (3.9 days). Thirty-six mares of similar breed and age, were randomly assigned to two groups for use in the second experiment. All mares were monitored daily via transrectal ultrasonography from the time a 35 mm or greater follicle was detected until ovulation. Treated mares received daily doses of altrenogest (0.088 mg/kg of body weight) for two days once a follicle of 35 mm or greater was detected. Control mares received no treatment. Fertility data were collected from mares inseminated every other day with 500 million motile spermatozoa from one of two stallions with proven fertility. Pregnancy data were collected via transrectal ultrasonography at days 12, 14 and 16 post-ovulation. Ovulation data were collected from 27 control cycles and 26 treated cycles. Contrary to previous reports and Experiment 1, no difference (P=0.35) was noted between groups with respect to days to ovulation. Control mares averaged 4.14 days and treated mares averaged 4.7 days to ovulation from initial detection of a 35 mm follicle. Fertility data were also similar (P=0.8) between control and treated mares (66.6% and 61.5% per cycle, respectively). Interestingly, a greater number (P=0.017) of treated cycles (5/26) resulted in follicular regression than did control cycles (0/27). While these data suggest that this dosage of altrenogest may not postpone ovulation, it did appear related to increased incidence of follicular regression. Fertility was unaffected, however, in those mares that ovulated. Further studies are needed in which initiation at different stages of estrus and different doses of altrenogest are used.     

Evaluation of Injectable Sustained Release Progestin Formulations for Suppression of Estrus and Ovulation in Mares

Thirty-one mares were used in an experiment to evaluate the effectiveness of three sustained-release injectable formulations of altrenogest and one formulation of medroxyprogesterone acetate (MPA) for long-term suppression of estrus and ovulation. Luteolysis was induced by injection of prostaglandin-F_2α (Lutalyse) on day 0 (6th day after the previous ovulation) and was immediately followed by treatment with 1) no injection (controls; n = 7), 2) 1.5 mL of an altrenogest solution in sustained-release vehicle (LA 150, 1.5 mL; 225 mg altrenogest; n = 6), 3) 3 mL (450 mg altrenogest) of the same solution (n = 6), 4) 500 mg altrenogest in lactide-glycolide microparticles suspended in 7-mL vehicle (MP 500; n = 6), or 5) 1.0 g MPA as a 5-mL suspension. Mares were checked for estrus daily, and their ovaries scanned every other day until a 25-mm or greater follicle was detected, after which they were scanned daily. Control mares returned to estrus an average of 3.9 days after Lutalyse administration; all the single-injection altrenogest formulations increased (P < .05) the days to return to estrus, with the greatest increase occurring in mares receiving MP 500. Return to estrus was not affected by MPA treatment. Time of ovulation was determined by serial ultrasound scans and confirmed by daily plasma luteinizing hormone (LH) and progesterone concentrations. Control mares ovulated an average of 8.8 days after Lutalyse administration. Treatment with 1.5 or 3 mL of LA 150 increased (P < .05) the mean days to ovulation to 16.5 and 21.2 days, respectively; MP 500 increased (P < .05) the days to ovulation to 33.5 days. Administration of MPA did not affect (P > .1) days to ovulation relative to control mares. The MP 500 treatment provided long-term suppression of estrus and ovulation and could prove useful for that purpose. Treatment with the LA 150 solutions provided shorter-term suppression, and a relatively tight grouping of the individual mares around the mean days to ovulation; these one-shot formulations could be useful for synchronizing ovulation in cyclic mares and inducing normal estrous cyclicity in vernal transitional mares exhibiting erratic, anovulatory estrous periods.     

Dynamics of the Equine Preovulatory Follicle and Periovulatory Hormones: What's New?

Recent studies (2005–2008) on the interrelationships among the preovulatory follicle and periovulatory circulating hormones are reviewed. Close temporal and mechanistic relationships occur between estradiol/inhibin and follicle-stimulating hormone (FSH), between estradiol and luteinizing hormone (LH), and between progesterone and LH. Estradiol from the dominant follicle forms a surge that reaches a peak 2 days before ovulation. Estradiol, as well as inhibin, has a negative effect on FSH, and estradiol has a negative effect on LH. When estradiol decreases, the negative effect diminishes and accounts for the beginning of an FSH increase and a transition from a slow to rapid increase in LH on the day of the estradiol peak. The decrease in estradiol and the reduction or cessation in the growth of the preovulatory follicle beginning 2 days before ovulation are attributable to the development of a reciprocal negative effect of LH on follicle estradiol production when LH reaches a critical concentration. The LH decrease after the peak of the LH surge on the day after ovulation is related to a negative effect of a postovulatory increase in progesterone. Measurable repeatability within mares between consecutive estrous cycles occurs during the preovulatory period in diameter of the ovulatory follicle and concentrations of LH and FSH. Hormone-laden follicular fluid passes into the peritoneal cavity at ovulation and transiently alters the circulating concentrations of LH and FSH. Double ovulations are associated with greater estradiol concentrations and reduced concentrations of FSH.     

Use of a GnRH antagonist,antarelix, associated or not with hCG,to control ovulation in cyclic pony mares

The GnRH antagonist antarelix (Teverelix™) was administered to mares (0.01 mg/kg, i.v., twice a day) during the periovulatory period. In Experiment 1, 20 mares were divided into a treated (A3d−) and a control (Control−) group. A3d− mares received antarelix for 3 days from the day when the dominant follicle (F1) reached 32 mm (D0). In Experiment 2, 10 mares were divided into a treated (A6d+) and a control (Control+) group. A6d+ mares received antarelix for 6 days from D0 and hCG was injected in all animals (1600 IU, i.v.) on D1. Pregnancies were determined 13 days after ovulation. In both experiments, antarelix interrupted or totally abolished the LH surge. In Experiment 1, 5/10 of the A3d− mares (with maximum LH concentrations of 11.6 ng/ml at the beginning of treatment) ovulated at the same time as the Control− mares; the other five mares (with LH concentrations under 5.4 ng/ml) ovulated 13.4±0.6 days later. In Experiment 2, all the A6d+ mares ovulated at the same time as the Control+ mares. In treated mares which ovulated during the treatment, progesterone concentrations and fertility did not differ from control mares. These results demonstrate that in mares: (1) a small elevation of endogenous LH can induce ovulation, (2) ovulation can be postponed approximately 13 days after a 3-day antarelix treatment if initiated just before the preovulatory LH surge, (3) ovulation can be induced by hCG on depressed levels of endogenous LH, (4) the inhibition of the post ovulatory LH surge has no effect either on the corpus luteum or on fertility.     

Effects of a gonadotropin-releasing hormone antagonist and altrenogest on luteinizing hormone concentration and ovulation in the mare

The objective of Experiment 1 was to determine a dose and frequency of gonadotropin-releasing hormone (GnRH) antagonist administration to effectively suppress serum luteinizing hormone (LH) concentration and to delay ovulation when administered to mares. The objectives of Experiment 2 were 1) to determine the effects of subcutaneous or intravenous administration of a GnRH antagonist or oral altrenogest on serum LH concentration in the estrual mare; and 2) to determine the effectiveness of human chorionic gonadotropin (hCG) in inducing ovulation in mares with suppressed LH concentrations. In Experiment 1, mares (N = 20) were randomly assigned and treated with either 5% mannitol (control, single subcutaneous injection, 1 mL, at time 0; n = 5); low-dose GnRH antagonist (single subcutaneous injection, 0.01 mg/kg, at time 0; n = 5); frequent low-dose GnRH antagonist (subcutaneous injections, 0.01 mg/kg, at 0, 6, 18, and 24 hours; n = 5); or high-dose GnRH antagonist (single subcutaneous injection, 0.04 mg/kg, at time 0; n = 5). Both the frequent low-dose and high-dose GnRH antagonist treatments resulted in significantly lower LH concentrations compared with controls at 90, 102, and 114 hours after treatment (P < .05). In Experiment 2, mares (N = 38) were randomly assigned and treated with subcutaneous sterile saline (control), altrenogest (oral), subcutaneous GnRH antagonist, or intravenous GnRH antagonist. LH concentration for the altrenogest group was lower than the control group at 3, 4, 18, and 30 hours after treatment (P < .05). LH concentration for both the subcutaneous and intravenous GnRH antagonist groups were lower compared with the control group at several time points (P < .05). Based on these data, dose but not frequency of administration of a GnRH antagonist lowered LH concentration in the estrous mare but did not delay ovulation. In addition, serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG. This indicates that serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG.     

The Effect of Sulpiride Treatment During the Periovulatory Period on Prolactin Concentration and Ovulation in the Mare

Sixteen estrous cycles from 10 cyclic mares were randomly assigned to a control or sulpiride group (n = 8 each). All mares received 1,500 IU of human chorionic gonadotropin (hCG) (hour 0) during estrus with a follicular diameter ≥32 mm. Mares were scanned every 12 hours until ovulation. In the treatment group, beginning at hour 0, each mare received 1.5 mg/kg of sulpiride every 12 hours intra-muscularly until ovulation or formation of a luteinized unruptured follicle (LUF). Concentrations of luteinizing hormone (LH) and prolactin (PRL) were measured by radioimmunoassay. In each group, there were 10 preovulatory follicles for the eight cycles. The ovulation rate (9/10, 90%) was similar in the control and sulpiride groups. Two mares formed an LUF, which was first detected at hours 48 and 72 for the sulpiride and control mares, respectively. The interval from hCG to ovulation was 49.5 ± 11.1 and 43.5 ± 5.8 hours, for the control and sulpiride groups, respectively (P > .5). LH followed the typical preovulatory surge pattern, with no difference between groups (P > .5). Sulpiride administration increased PRL concentration in treated mares at 24 (P < .1), 36, and 48 hours (P < .05) after treatment. In conclusion, sulpiride administration every 12 hours increased PRL concentration in treated mares after 24 hours of the beginning of treatment. However, at this time window and concentration, PRL did not have any effect on ovulation. The control mare that developed an LUF had a PRL concentration similar to other ovulatory control mares (always ≤10 ng/mL).     

Efficacy of Medroxyprogesterone Acetate in Suppression of Estrus in Cycling Mares

The effects of compounded medroxyprogesterone acetate (MPA) on follicular activity and estrous behavior were evaluated. Eighteen cycling mares were assigned to one of three treatment groups. Mares in the MPA group (n = 6) were injected intramuscularly with 1,600 mg MPA (week 1), then 400 mg weekly for the next 5 weeks. Saline mares (n = 6) were injected intramuscularly weekly for 6 weeks. Altrenogest mares (n = 6) received 10 mL orally daily for 7 weeks. Mares were teased daily for 60 days and categorized as displaying estrous, diestrous, or neutral behavior. Transrectal ultrasound examinations were performed three times weekly, or daily when a 30-mm follicle was identified, until ovulation. Blood samples were harvested weekly for analysis of progesterone concentration and daily from days 14 to 23 for analysis of luteinizing hormone (LH) concentration. Mares treated with saline or MPA showed normal intervals of diestrus and estrus during the study. All altrenogest mares showed behavioral diestrus during treatment. All mares in the saline and MPA groups showed normal follicular development and ovulations. No altrenogest mares ovulated during treatment; four mares returned to estrus and resumed normal follicular development after treatment ceased. Progesterone analyses agreed with transrectal ultrasonographic ovarian activity for all mares. LH levels were lower for altrenogest-treated mares compared with MPA-treated and saline-treated mares during the treatment period. In conclusion, compounded MPA at dose rates and intervals used in this study was not effective in suppression of estrus, follicular development, or LH secretion in mares.     

Evaluation of the ability of altrenogest to control the equine estrous cycle

In our experience, altrenogest has not always been able to exert predictable control over the estrous cycle of the mare. Therefore, we examined 12 mares that were treated with altrenogest to identify reasons for its failure to control the estrous cycle. The mares were fed altrenogest for 15 to 20 days and were examined for follicle development, ovulation, and corpus luteum formation during treatment. Through the use of real-time ultrasonography and radioimmunoassay for progesterone, we concluded that altrenogest was unable to suppress the growth of follicles to preovulatory size in some mares, leading to ovulation during treatment or earlier than expected after the end of treatment. In addition, altrenogest did not appear to shorten the life-spans of the corpora lutea that were formed during treatment; in 4 mares, this resulted in the persistence of corpora lutea after the end of the suggested 15-day periods of treatment. The latter findings led us to suggest that if a luteolytic dose of prostaglandin had been given at the end of altrenogest treatment, there would have been improved control over the estrous cycle. The results of our study confirmed our clinical impressions that altrenogest may be satisfactory to control the equine estrous cycle under some circumstances, but it should not be used when precise control over ovulation is required.     

Timing of preovulatory LH surge and ovulation in superovulated sheep are affected by follicular status at start of the FSH treatment.

The aims of this study were to evaluate the chronology of periovulatory events (oestrus behaviour, LH surge and ovulation) in 16 superovulated Manchega sheep and to determine whether follicular status at start of the FSH supply might affect their occurrence. Mean timing for onset of oestrus behaviour was detected at 28.1 +/- 0.7 h after sponge withdrawal; the preovulatory LH surge and ovulation started at 37.2 +/- 0.7 h and 65.4 +/- 0.7 h after progestagen withdrawal, respectively. The intervals between oestrus, LH surge and ovulation were affected by a high individual variability, which might be the cause for reported decreased efficiency in embryo production. Current results also addressed the role of follicular status at start of the superovulatory treatment on the preovulatory LH surge and the ovulation. The interval LH surge-ovulation was increased in ewes with a growing dominant follicle at starting the FSH treatment (32.3 +/- 0.9 vs 28.6 +/- 0.5 h, p < 0.05). The developmental stage of the largest follicle at starting the superovulatory treatment also affected occurrence of LH surge and ovulation; follicles in growing phase advanced the occurrence of the LH surge and ovulation when compared to decreasing follicles (33.0 +/- 1.0 vs 43.5 +/- 1.1 h, p < 0.05, for LH peak and 60.7 +/- 1.1 vs 72.8 +/- 1.2 h, p < 0.05, for ovulation). Thus, only ewes with growing follicles ovulated prior to 55 h after sponge withdrawal; conversely, no sheep with decreasing follicles ovulated earlier than 67 h, when an 85.7% of the ewes bearing growing follicles has ovulated at 63 h.     

Follicle Diameter and Systemic Hormone Interrelationships during Induction of Follicle Collapse with Intrafollicular Prostaglandin E2 and F2α in Mares

The objectives were to determine: (i) whether intrafollicular administration of PGE2 and PGF2α to mares would hasten follicle collapse and (ii) the differences in reproductive hormone characteristics in mares with spontaneous and prostaglandin‐induced follicle collapses. Six mares were followed for two oestrous cycles each: when the mares reached a follicle diameter of 30–35 mm and showed mild‐to‐moderate endometrial oedema, mares were administered a single 0.5 ml dose containing 500 μg PGE2 and 125 μg PGF2α (treatment cycle) or a placebo (0.5 ml of water for injection; control cycle) into the preovulatory follicle (Hour 0). Blood samples were collected, and serial ultrasound examinations were performed until follicle collapse. Treated mares showed follicle collapse significantly earlier (20.0 ± 5.9 h) than the control mares (72.0 ± 10.7 h). The LH, progesterone, total oestrogens and oestradiol concentrations did not differ between groups; however, the progesterone concentration increased more between 48 and 72 h after follicle injection in the treatment compared to the control cycles (P < 0.05). In conclusion, intrafollicular treatment with PGE2 and PGF2α hastened follicle collapse in mares without the simultaneous use of an inductor of ovulation; despite the early induction of follicle collapse, the profiles of LH and oestradiol were not altered. This study provides information on the role of prostaglandins (PGs) in the process of follicle wall rupture and collapse and suggests that this may happen even before the beginning of the sharp rise in circulating LH at the final stage of the ovulatory surge.     

Attempt to control the day of ovulation in cycling pony mares by associating a GnRH antagonist with hCG

With the objective of controlling the day of ovulation, 40 mares were assigned to a control or three treated groups: A3d, A4d, and A5d. The treated groups received antarelix (Teverelix 0.01 mg/kg, i.v., twice a day) for 3, 4, or 5 days from the day the dominant follicle (F1) reached 28 mm (=D0), and one injection of hCG (1600 IU, i.v.) on D1, D2, or D3, respectively. Control mares received one injection of hCG when F1 reached 35 mm. Plasma LH, FSH, progesterone, and total estrogens were assayed. In the A3d, A4d, and A5d groups, 9 (90%), 6 (60%), and 5 (50%) out of 10 mares, respectively, ovulated on the expected day (i.e. between 24 and 48 h after hCG injection). In the control group, 7/10 (70%) presented the typical response to hCG. For 3 mares in both the A4d and A5d groups, the dominant follicle at the time the treatment was started did not ovulate and ovulation was postponed for between 11 and 15 days after the end of treatment. In the treated mares, the LH surge was abolished, and total estrogens were depressed during the preovulatory peak but the concentrations of FSH were not modified. Endocrine parameters were not altered in postponed cycles. Fertility did not differ in treated and control cycles. These results demonstrate that in mares: (1) ovulation can be programmed on a specific day of a 3-day period, with a success rate of 67%, by a treatment associating antarelix and one injection of hCG; (2) nevertheless in 20% of cases the dominant follicle regresses and does not ovulate; (3) for these mares ovulation is postponed by approximately 2 weeks; (4) terminal growth of the preovulatory follicle only requires low circulating concentrations of LH but atresia induced by a GnRH antagonist is significant when this treatment is administrated for more than 18 h.     

Comparison of two dosage regimens of the GNRH agonist deslorelin acetate on inducing ovulation in seasonally anestrous mares

This study investigated the efficacy of two dosage regimens of a potent GnRH analogue (GnRHa), deslorelin acetate, in inducing ovulation in seasonally anestrous mares. Forty-five seasonally anestrous mares were randomly assigned according to follicular size to one of three treatment groups: control, increasing GnRHa dose, and constant GnRHa dose. Treatment began on February 28 and continued until ovulation or for a maximum of seven treatments. Mares were palpated every other day until a 35 mm follicle was detected, then every day until ovulation or regression of the follicle occurred. Blood samples were taken from five randomly chosen mares in each treatment group and analyzed for LH levels.Twenty percent of mares in both deslorelin treatment groups ovulated, while no control mares ovulated during the treatment period. There was no difference in the number of mares that ovulated between treatment groups. Four of the six mares that ovulated were in transitional anestrus at the initiation of treatment, while only two were in deep anestrus.Concentrations of LH were greater (p=0.0008) in both GnRH-treated groups than in the control mares. Concentrations of LH did not differ between the two GnRH-treated groups until day 12 of treatment, when mares treated with a constant dosage had higher (p=0.0358) levels of LH than those treated with an increasing dosage. It is possible that administration of larger amounts of the GnRH agonist lowered the sensitivity of the pituitary to stimulation by GnRH.Deslorelin acetate did stimulate follicular growth and ovulation in a limited number of anestrous mares. Further investigation into the potential of this short-term implant to shorten the onsent of the breeding season is recommended.     

Effect of eFSH on Ovarian Cyclicity and Embryo Production of Mares in Spring Transitional Phase

The use of equine FSH (eFSH) for inducing follicular development and ovulation in transitional mares was evaluated. Twenty-seven mares, from 3 to 15 years of age, were examined during the months of August and September 2004, in Brazil. Ultrasound evaluations were performed during 2 weeks before the start of the experiment to confirm transitional characteristics (no follicles larger than 25 mm and no corpus luteum [CL] present). After this period, as the mares obtained a follicle of at least 25 mm, they were assigned to one of two groups: (1) control group, untreated; (2) treated with 12.5 mg eFSH, 2 times per day, until at least half of all follicles larger than 30 mm had reached 35 mm. Follicular activity of all mares was monitored. When most of the follicles from treated mares and a single follicle from control mares acquired a preovulatory size (≥35 mm), 2,500 IU human chorionic gonadotropin (hCG) was administered IV to induce ovulation. After hCG administration, the mares were inseminated with fresh semen every other day until ovulation. Ultrasound examinations continued until detection of the last ovulation, and embryo recovery was performed 7 to 8 days after ovulation. The mares of the treated group reached the first preovulatory follicle (4.1 ± 1.0 vs 14.9 ± 10.8 days) and ovulated before untreated mares (6.6 ± 1.2 vs 18.0 ± 11.1 days; P < .05). All mares were treated with prostaglandin F_2α (PGF_2α), on the day of embryo flushing. Three superovulated mares did not cycle immediately after PGF_2α treatment, and consequently had a longer interovulatory interval (22.4 vs 10.9 days, P < 0.05). The mean period of treatment was 4.79 ± 1.07 days and 85.71% of mares had multiple ovulations. The number of ovulations (5.6 vs 1.0) and embryos (2.0 vs 0.7) per mare were higher (P < 0.05) for treated mares than control mares. In conclusion, treatment with eFSH was effective in hastening the onset of the breeding season, inducing multiple ovulations, and increasing embryo production in transitional mares. This is the first report showing the use of FSH treatment to recover embryos from the first cycle of the year.     

Estradiol and progesterone concentrations resulting from the administration of an exogenous hormone regimen in diestrous embryo transfer recipients

Estradiol and progesterone concentrations were evaluated from diestrous embryo transfer recipient mares (5 to 14 days post-ovulation) which were treated with an exogenous hormone regimen. Upon detection of the donor mare's ovulation (0 hours), 10 mg PGF_2α was given to the recipient mare; at 12, 24 and 36 hours 20 mg estradiol cypionate; at 48 hours, 500 mg progesterone in oil and then 22 mg altrenogest at 60, 72 and 96 hours. Altrenogest (22 mg/day) was continued until end of the trial (detection of a fetal heart beat). Embryos were transferred non-surgically 6 or 7 days after the start of treatment.Plasma samples were evaluated over three periods; period 1-between recipient mare ovulation and prior to PGF_2α period 2-between PGF and embryo transfer and period 3-post-transfer. During periods 2 and 3, estradiol was higher (P<.05) for mares which were 10 to 14 days post-ovulation (late diestrous) as compared to mares which were 5 to 9 days post ovulation (mid-diestrous) when treatment began. Progesterone concentrations were higher (P<.05) for the mid-diestrous mares in the same periods. The pregnancy rate was higher for the late diestrous mares than the mid-diestrous mares (58% (7/12) vs 10% (1/10)). However, no difference (P>.05) was detected in estradiol or progesterone in the late diestrous mares which were pregnant or open. During period 2, estradiol was higher (P<.05) in the pregnant than open mares. Whereas, during period 3, progesterone was higher (P<.05) in the open mares.These data suggest that estradiol is important for the establishment of pregnancy in the mare. Furthermore, hormone treatment developed in this study appears to have some potential in synchronization of diestrus mares to be used as embryo recipients.     

Safety of altrenogest in pregnant mares and on health and development of offspring

Fifty-one light-horse mares were utilized to evaluate the safety of an oral progestin, altrenogest, administered throughout gestation on: gestation length, embryonic and fetal loss, periparturient events, health and development of offspring, and future reproductive capabilities of the mares. Pregnancies were established by inseminating mares with 250 × 10⁶ progressively motile spermatozoa from the same stallion every other day throughout estrus or by non-surgical transfer of embryos. Mares were randomly assigned to 1 of 2 treatments upon confirmation of pregnancy on day 20: 1) controls, 2 ml of neobee oil orally per 44.5 kg of body weight; and 2) treated, 2 ml of altrenogest dissolved in neobee oil at a concentration of 2.2 mg/ml orally per 44.5 kg of body weight. Treatments were administered daily from day 20 to 320 of gestation.There were no significant differences between treatment groups for duration of gestation, placental weight, time to placental expulsion and incidence of retained placental membranes. Number of female foals born from altrenogest treated mares (14 of 23) was greater (P<.05) than the number from untreated control mares (4 of 16). Female foals born from altrenogest treated mares had larger clitori (P<.05) than those from control mares. Times to sternal recumbency, standing and nursing were similar for the 2 groups (P>.05). Body weight and height at withers, heart girth circumference and length and width of cannon were measured at time of birth and at 2, 4, 6, 8, 12 and 16 weeks of age. Measurements did not differ (P>05) between treated and control foals for any development parameters.Beginning on day 20 postpartum, mares were teased daily. During estrus, mares were inseminated every other day with 250 × 10⁶ motile spermatozoa. Teasing and/or insemination was continued for 2 cycles or until mares were 35 days pregnant. The number of mares pregnant after 1 cycle and after 2 cycles of insemination was similar (P>.05) for treated and control mares. Nineteen of 21 treated mares and 15 of 16 control mares were pregnant after 2 cycles of insemination. Number of cycles per pregnancy was similar (P>.05) for treated and control mares (1.37 vs 1.13) as was number of days mares exhibited estrus (6.30 vs 6.13). Number of inseminations per cycle did not differ (P>.05) between treated and control mares (2.92 vs 3.00). In summary, there was no effect of treatment with altrenogest from day 20 to 320 of gestation on periparturient events, viability and growth of offspring and subsequent reproductive performance of mares.     

Effects of gonadotropin-releasing hormone infused in a pulsatile or continuous fashion on serum gonadotropin concentrations and ovulation in the mare.

Studies were conducted to compare continuous vs pulsatile i.v. infusion of GnRH on serum gonadotropin concentrations and ovulation in seasonally anestrous mares and in cycling mares. Anestrous mares (Exp. 1) received no treatment (control; n = 3), 2, or 20 micrograms of GnRH/h continuous infusion (CI) (n = 4 and n = 6, respectively), or 20 micrograms of GnRH/h pulsatile infusion (PI) (n = 5). After initiation of GnRH infusion, serum LH levels increased earlier, and to a greater extent, in the PI group than in other groups (P less than .05). In contrast, serum FSH concentrations did not differ among groups. The number of days to development of the first 35-mm follicle was not different among GnRH treatment groups; however, mares receiving PI ovulated on d 9.4 of treatment, 2.8 d earlier than those receiving 20 micrograms of GnRH/h CI (P less than .05). Mares given 2 micrograms of GnRH/h CI failed to ovulate spontaneously after 16 d of treatment, but each one ovulated within 2 to 4 d after injection of 2,000 IU of hCG on d 16. Control mares did not ovulate or show any significant follicular development throughout the experiment. Cycling mares (Exp. 2) received no treatment (control; n = 6), 20 micrograms of GnRH/h CI, or 20 micrograms of GnRH/h PI (n = 4) beginning on d 16 of an estrous cycle (d 0 = day of ovulation). Serum LH concentrations in all groups increased after initiation of treatment; however, on the day of ovulation LH concentrations were lower in the CI group than in the PI or control groups (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal Relationships and Repeatability of Follicle Diameters and Hormone Concentrations within Individuals in Mares

Data were collected daily from 23 mares during two consecutive interovulatory intervals (IOIs). Several significant (p < 0.05) new observations on temporal relationships were made. The FSH increase that begins before ovulation temporarily plateaued on the day of discharge of follicular fluid into the peritoneal cavity in association with ovulation. During the declining portion of the pre-ovulatory oestradiol surge, an abrupt reduction in the rate of decrease occurred in synchrony with the peak of the LH surge and is consistent with a negative effect of LH on oestradiol. Repeatability within mares was based on the following positive and significant correlations between the two IOIs: (i) length of the interval between ovulations and between ovulation and the beginning of follicle deviation; (ii) diameter of the pre-ovulatory follicle on days -3 to -1; (iii) number of follicles in diameter classes of 2–5 mm (correlation for 22/23 days of the IOI), 5.1–10 mm (18/23 days), 10.1–15 mm (12/23 days) and 15.1–20 mm (12/23 days) and (iv) concentrations of FSH (18/23 days) and LH (22/23 days). The greatest repeatability for the follicle-diameter classes occurred in the 2–5 mm class, and thereafter the repeatability progressively decreased as the diameters for the classes increased. Results demonstrated measurable repeatability within mares for several end points between consecutive IOIs.     

Effect of deslorelin acetate on gonadotropin secretion and ovarian follicle development in cycling mares

OBJECTIVE: To evaluate gonadotropin secretion and ovarian function after administration of deslorelin acetate to induce ovulation in mares. DESIGN: Randomized controlled trial. ANIMALS: 16 healthy mares with normal estrous cycles. PROCEDURE: 8 control mares were allowed to ovulate spontaneously, whereas 8 study mares received deslorelin to induce ovulation when an ovarian follicle > 35 mm in diameter was detected. Follicle development and serum concentrations of gonadotropins were monitored daily during 1 estrous cycle. Pituitary responsiveness to administration of gonadotropin-releasing hormone (GnRH) was evaluated 10 days after initial ovulation. RESULTS: Interovulatory intervals of mares treated with deslorelin (mean +/- SD, 25.6 +/- 2.6 days) were longer than those of control mares (22.9 +/- 1.8 days). Diameter of the largest follicle was significantly smaller during 2 days of the diestrous period after ovulation in deslorelin-treated mares than in control mares. Concentrations of follicle-stimulating hormone (FSH) were lower in deslorelin-treated mares on days 5 through 14 than in control mares. Concentrations of luteinizing hormone were not different between groups during most of the cycle. Gonadotropin release in response to administration of GnRH was lower in mares treated with deslorelin acetate than in control mares. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of deslorelin was associated with reduction in circulating concentrations of FSH and gonadotropin response to administration of GnRH during the estrous cycle. Low concentration of FSH in treated mares may lead to delayed follicular development and an increased interovulatory interval.     

Follicle Development during Luteal Phase and Altrenogest Treatment in Pigs

Synchronization of the oestrous cycle of gilts using altrenogest treatment has been found to increase ovulation rate. The current experiment investigated if the increase in ovulation rate after altrenogest treatment is related to increased follicle size at the end of altrenogest treatment compared with late luteal phase follicles. Crossbred gilts (n = 15) received altrenogest during 18 days [20 mg Regumate (Janssen Animal Health, Beerse, Belgium)], starting 5-7 days after onset of first oestrus. Control gilts (n = 15) did not receive altrenogest. At days 10-12 of the oestrous cycle [i.e. in the presence of corpora lutea (CL)], average follicle development was 2.51 +/- 0.20 mm (assessed with ultrasound) in altrenogest-treated gilts and 2.58 +/- 0.16 mm in control gilts (p > 0.10). During the last days of altrenogest treatment (i.e. when CL had gone into regression), average follicle size had increased to 3.01 +/- 0.31 mm (p < 0.05). Subsequent ovulation rate was 16.6 +/- 1.7 in altrenogest treated gilts and 15.1 +/- 1.2 in control gilts (p < 0.05). Altrenogest treatment resulted in increased follicle size after regression of the CL, showing that suppression of follicle growth by altrenogest alone is less severe than suppression by endogenous progesterone (either with or without altrenogest). Altrenogest treatment also resulted in a higher ovulation rate. However, it is unclear if the increased follicle size and higher ovulation rate after altrenogest treatment are causally related, as the relation between the two on an animal level was not significant.     

Effect of a Nonsurgical Embryo Transfer Procedure and/or Altrenogest Therapy on Endogenous Progesterone Concentration in Mares

Endogenous progesterone levels may decline after transcervical embryo transfer in some mares. Progestogen therapy is commonly used to support endogenous progesterone levels in embryo transfer recipient mares or those carrying their own pregnancy. The goal of this study was to determine the effects of the transcervical transfer procedure and/or altrenogest therapy on luteal function in mares. Mares were assigned to one of six treatment groups: group 1 (untreated control; n = 7 cycles), group 2 (sham transfer, no altrenogest; n = 8 cycles), group 3 (sham transfer plus altrenogest; n = 8 cycles), group 4 (pregnant, no altrenogest; n = 9 mares), group 5 (pregnant plus altrenogest; n = 9 mares), and group 6 (nonpregnant plus altrenogest; n = 10 cycles). Mares in groups 4-6 were bred and allowed an opportunity to carry their own pregnancy. Blood samples were collected for 22 days beginning on the day of ovulation. Sham embryo transfer (groups 2 and 3, combined) did not result in a decline in endogenous progesterone levels compared with control mares (group 6). However, sham embryo transfer did result in luteolysis and an abrupt decline in endogenous progesterone levels in one of the 16 (6.2%) sham-transferred mares. Altrenogest therapy in sham-transferred mares (group 3) was associated with lower endogenous progesterone levels on days 10, 12, and 13 postovulation when compared with sham-transferred mares that did not receive altrenogest (group 2). Administration of altrenogest to pregnant mares (group 5) was associated with lower concentrations of endogenous progesterone from days 14 to 18 and on day 21 compared with endogenous progesterone levels in pregnant mares not administered altrenogest (group 4). In conclusion, a transcervical embryo transfer procedure can cause luteolysis in a low percentage of mares. Altrenogest therapy may be associated with a reduction in endogenous progesterone secretion, presumably mediated by a reduction in pituitary luteinizing hormone (LH) release and a decrease in luteotropic support.