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SUMMARY ICI‐81008, a synthetic prostaglandin analogue structurally related to Prostaglandin F2α, was shown to be a safe and effective luteolytic agent in mares. It consistently induced luteolysis in Welsh Pony mares at a dose of 125 μg and only produced detectable adverse side effects when given at more than six times this dose. Of 63 Thoroughbred mares in prolonged dioestrus which were treated with ICI‐81008, 55 returned to oestrus and ovulated; 40 per cent of the mares covered during the induced oestrus conceived. A total of 144 Thoroughbred mares in prolonged dioestrus were treated with another prostaglandin analogue, ICI‐79939; 134 returned to oestrus and ovulated and 46 per cent of those covered during the induced oestrus conceived. However, ICI‐79939 produced marked adverse side effects in mares when given at only three to four times the normal therapeutic dose. This study supported previous findings that the majority of non‐pregnant mares which are not showing regular oestrous cycles during the breeding season are in prolonged dioestrus rather than anoestrus. RÉSUMÉ On a démontré l'innocuité et l'efficacité du produit, ICI 81,008, un analogue synthétique de la prostaglandine et qui est structurellement apprenté avec la prostaglandine F2α, comme agent luteolytique chez les juments. En administration dans une dose de 125 mcg (microgrammes) la substance induit une répons luteolytic constante chez les juments de la race poney gallois. Des effets collaterau néfastes sont decelables seulement après l'administration des doses 6 fois plus grandes. De 63 juments pur sang en dioestrus prolongé, qui ont reçu ce traitment avec l'ICI 81,008, 55 sont revenues en oestrus avec ovulation ulterieure. 40% des juments couvertes pendant cet oestrus induit ont conçu. Un total de 144 juments pur sang en dioestrus prolongé ont reçu un traitement avec un autre analogue de prostaglandine (le composé denommé ICI 79,939); 134 sont revenu en oestrus, avec ovulation; 46% des juments couvertes pendant cet oestrus induit sont devenues gravides. Pourtant le composé ICI 79,939 produisit des effets collateraux indésirables marqués chez les juments même dans les doses qui ne depassent le niveau therapeutic normal que par un facteur de 3 à 4. Cette investigation confirme les observations anterieures; elle montre que la plupart des juments non‐gravides qui ne presentente pas des cycles d'oestrus regulaires pendant la monte se trouvent en effet en dioestrus prolongé, plutôt que dans un état d'anoestrus. ZUSAMMENFASSUNG Es wurde gezeigt, dass ICI‐81008, ein synthetisches Prostaglandin, strukturanalog zum Prostaglandin F2α ein sicheres und wirksames luteolytisches Agens für Stuten darstellt. Eine Dosis von 125 μg löste bei Welsh‐Pony‐Stuten durchweg Luteolyse aus und verursachte nachweisbare nachteilige Nebenwirkungen erst nach einer sechsfachen Dosierung. Von 63 Vollblut‐Stuten mit verlängertem Diöstrus, die mit ICI‐81008 behandelt wurden, kamen 55 in Brunst und ovulierten: 40% der Stuten, die während dieser induzierten Brunst belegt wurden, kon...

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SUMMARYThe potency, toxicity and clinical value of two synthetic analogues of Prostaglandin F 2-(ICI-7()939 and ICI-8ioo8) for inducing luteolysis in mares is discussed. Measurement of peripheral plasma progestagen levels in over 4 oo Thoroughbred mares has demonstrated that abnormal persistence of luteal function (prolonged dioestrus) is the major cause of the failure of nonpregnant mares to exhibit regular oestrous cycles during the breeding season.

SUMMARYTwo single intramuscular injections of 500 t t g of ICI 8 0 , 99 6 separated by a period of i days was shown to be an effective method of controlling oestrus and ovulation in cycling heifers. One hundred and seventy one of one hundred and seventy five heifers exhibited oestrus between 4 8 and g6 hours, and no fewer than 159 of these came into heat between 4 8 and 72 hours after the second injection. Changes in plasma concentrations of LH, progesterone and oestradiol-17P around the oestrus following luteolysis induced by ICI 8 0 , 99 6, were closely similar to those occurring around a spontaneous oestrus. The corpus luteum formed following ovulation after the controlled heat was fully functional and the oestrous cycle following treatment was of normal length.These results suggest that fertility associated with the controlled ovulation is likely to be normal and this is confirmed by preliminary conception data.

A clinical trial involving 359 mares was conducted to ascertain the clinical value of a synthetic prostaglandin analogue (fluprostenol, ICI-81,008) structurally related to PGF2oc for treating mares in prolonged dioestrus. Some 263 mares (73.3%) displayed oestrus within 5 days of a first intramuscular injection of 250 mug fluprostenol and, of those mares later examined for pregnancy, 108 (40%) were found to have conceived during the first induced oestrus. A further 21 mares (8%) cycled normally and conceived to services during the second oestrus. Most (80.3%) of the plasma samples obtained from 242 mares prior to treatment showed a progesterone concentration greater than 1 ng/ml, thereby indicating the presence of functional luteal tissue in the ovaries. The results support earlier observations that most non-pregnant mares which fail to cycle during the breeding season are in a state of prolonged dioestrus rather than anoesturs.