IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY


To illustrate the use of prostaglandin for elective pregnancy termination, 185 abortions were induced with once-daily intramuscular injections of clo- prostenol administered during the period of eCG production.21 Three to four daily injections were necessary. Reportedly, in 90% of the abortions, no manual veterinary intervention was necessary.21 Exogenous prostaglandin treatment caused luteoly- sis and increased endogenous prostaglandin pro- duction, altogether causing uterine contractions, subsequent cervical softening, and expulsion of the fetus.18 Once eCG production subsides, multiple daily


doses of prostaglandin are still necessary to achieve abortion. Approximately 66% to 75% of 21 pony and 25 horse mares, respectively, aborted within the first week of administration of daily prostaglandin (product not specified) when it was administered at 100 to 245 days of gestation.22 Some mares re- quired up to 4 weeks of daily prostaglandin to achieve abortion.22 Later in gestation, at approxi- mately 10 months of gestation until near to term, both natural prostaglandin and the analogue flupro- stenol did not reliably cause parturition when ad- ministered several times in one day.23 It is also worthwhile to note that, depending on stage of ges- tation, dystocia may occur.


4. Late-Gestation Progestogen and Estrogen Monitoring


Systemic diseases that affect the gravid mare can affect hormone production by the fetus and placenta. Serial serum progestogens can be periodically mon- itored in mares as an indicator of pregnancy health. Commercially available progesterone assays cross- react considerably with the pregnanes and other progestogens produced by the feto-placental unit. Thus, diagnostic laboratories will use their proges- terone assay to measure total progestogens, which is the sum of both progesterone and other cross- reacting feto-placental progestogens.24 Note that laboratory assays for progesterone vary in their ability to cross-react and quantify the various equine progestogens. Thus, total progestogens de- termined on a serum specimen from a gravid mare and assayed at two different laboratories, running two different progesterone assays, may show consid- erable differences in the total values. It is best to stay with one laboratory when submitting serial specimens for pregnant-mare total progestogen de- termination. Normal reference ranges have been determined by means of the assay at BET Labora- tories in Kentucky.3 Total progestogens normally ranged from 4 to 10 ng/mL until approximately 300 to 320 days of gestation. After this time, progesto- gens may increase to above 40 ng/mL.3,25 Total progestogen concentrations are generally performed in a serial fashion so that a trend of rising, stable, or falling, becomes evident.25 Pro- gestogens have been shown to rise abnormally and prematurely in the compromised mid- to late-gesta-


354 2013  Vol. 59  AAEP PROCEEDINGS


tion pregnancy.26 In severe cases of pregnancy compromise, in which fetal death is imminent, acute decreases in progestogens have been identified both in naturally occurring pregnancy conditions26 and in experimentally induced placentitis.27 Increases in progestogens before that normally identified in the last several weeks of gestation are a cause for concern and indicate ongoing fetal stress and com- promise, with premature activation of the fetal pi- tuitary adrenal axis.28 The mechanism for this occurrence is the increased fetal adrenal production of the precursor P5, which is metabolized by the placenta to more progestogens.2 Response to treat- ment may be assessed indirectly. For example, if progestogens fall back to a normal range, then im- provement in the clinical condition of the fetus and placenta is suggested. Alternatively, failure of pro- gestogens to rise can be identified in mares with fescue toxicity or uterine pathology and prolonged gestation.29 Estrogen production can likewise be determined


in serum obtained from the mare and used as an indicator of feto-placental health. Total estrogen concentrations may also be taken serially but can be helpful if only a single specimen is assayed.25 As discussed above, the fetal gonads produce estrogen precursors that are then metabolized at the level of the placenta into various estrogenic hormones. Estrogens peak in the second trimester and then fall gradually.1,2 Normal reference ranges have been determined by means of the assay at BET Labora- tories in Kentucky. Total estrogens normally were at least 1000 pg/mL from approximately 150 to 300 days of gestation. After this time, estrogens will normally be lower as term approaches.3 Low total estrogens have been found in cases of placentitis. Retrospectively, Douglas25 found that in naturally occurring cases of placentitis at ges- tational ages between 150 and 280 days, it was common to find both abnormally elevated total progestogens and low total estrogens in mares that aborted. Mares that maintained their preg- nancy (with various treatments administered) had normally low progestogen and normally high estrogen.25


5. High-Risk Mares and Reproductive Hormone Supplementation


The discussions above lead to the question of hormone supplementation for the high-risk preg- nant mare with a compromised feto-placental unit. Questions one might ask are: If progestogens are elevated in abnormal pregnancies, then why admin- ister additional progestins to the mare? What is the argument for this administration? Further- more, is progestin supplementation safe for the fetus? The argument for administration of progestins to later-term pregnant mares with at-risk pregnancies is that the treatment maintains uterine quiescence. As was discussed above, progestogens continue to


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