for the delayed adoption of ET in equine practice (Squires et al. 1999).
Although many ovarian stimulatory treatments were tested in mares, few
yielded more than an approximate doubling of the ovulation rate (for
review see McCue 1996); treatments examined included eCG (Day 1940),
GnRH (Ginther and Bergfelt 1990), porcine pituitary FSH preparations
(Fortune and Kimmich 1993), growth hormone (Hofferer et al. 1991;
Cochran et al. 1999), equine pituitary gonadotrophin extract (EPE:
Douglas et al. 1974; Hofferer et al. 1991; Dippert et al. 1992) and both
active (McKinnon et al. 1992) and passive (McCue et al. 1993)
immunisation against inhibin. The uniform failure to induce commercially
useful rates of superovulation led to a widespread belief that high ovulation
rates were unachievable in the mare, probably because of the combination
of the unusual anatomy of the equine ovary and a relative insensitivity of
the equine FSH receptor to commercially available gonadotrophins; the
latter presumably has its origin in mutations in the equine FSH receptor
that have evolved to avoid over-stimulation of the ovaries by eCG during
pregnancy (Combarnous et al. 1998). With regard to the anatomical
peculiarities, the equine ovary is ‘inside-out’, such that the very large
ovulatory follicles develop centrally within a tough connective tissue
capsule, and ovulation can take place only via a single, small germinalepithelium lined ‘ovulation fossa’ (Mossman and Duke 1973); this was
thought to pose an insurmountable barrier to the simultaneous growth and
ovulation of multiple follicles on the same ovary. Interest in the
development of equine superovulatory treatments was, however, rekindled
by experiments in which high rates of ovulation were achieved in mares
immunised passively against inhibin (4.5 per cycle; Nambo et al. 1998)
and, in particular, in mares injected twice daily with EPE starting before the
emergence of the mid-cycle dominant follicle and ending when the follicles
reached 35mm in diameter and human chorionic gonadotrophin (hCG)
was administered to complete follicle maturation and synchronise the
ovulations (7.1 ovulations and 3.5 embryos per cycle: Alvarenga et al.
2001). Subsequent studies aiming to optimize the EPE administration
regime have yielded slightly less dramatic results (4.7 ovulations per cycle;
Scoggin et al. 2002), but have demonstrated that respectable ovulation
rates can also be achieved with once daily EPE administration. Moreover,
results were sufficiently promising to lead to the development of the first
commercial superovulatory product for mares, eFSH (Bioniche Animal
Health, Ontario, Canada), an equine pituitary extract partially purified for
FSH. In practice, eFSH treatment results in an approximate tripling in
embryo recovery rates (from 0.65 to 2 embryos per cycle) at a cost of
approximately US$500 per treatment cycle (pers. comm. E. Squires,
Colorado State University). However, as with any superovulatory
treatment, responses vary markedly between individual mares and a
proportion fail either to ovulate any follicles or to produce any embryos.
This variability may, in part, relate to one of the intrinsic limitations of a
brain extract such as eFSH; the exact gonadotrophin composition, in
particular the ratio of FSH to LH, is likely to differ between batches and this
may contribute to variability in response; too low a dose of FSH would
result in a poor superovulatory response, while too high a dose (or too high
15-‐18
February
2016
East
London
Convention
Centre,
East
London,
South
Africa
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