ARTIFICIAL INSEMINATION IN FARM ANIMALS - Phenix-Vet

Reproductive Endocrinology Diseases: Hormone Replacement and Therapy for Peri/Menopause 281and begin after 5–6 days of gonadotropin stimulation, (Albano C, et al., 1997; Diedrich K, etal., 1994), or tailored to the response of the individual, starting treatment when the leadfollicle reaches approximately 13–14 mm in diameter. The individualized treatment regimengenerally requires fewer total doses and may yield better overall results (Ludwig M, et al.,2002). Alternatively, a single larger dose of cetrorelix (3.0 mg) will effectively prevent an LHsurge for 96 hours. If given on day 6–7 of stimulation, the interval of effective suppressionwill encompass the day of hCG administration in most women (75–90%); the remainder mayreceive additional daily doses (0.25 mg) as needed, ending on the day of hCG treatment(Olivennes F, et al 1995; Olivennes F, et al., 2000; Olivennes F, et al., 2003). The single doseantagonist treatment regimen also can be withheld until the lead follicle reaches 13–14 mmin diameter (Fanchin R, et al., 2003,2005).A common variation of the antagonist stimulation regimen uses preliminary treatment withan OC to control the onset of menses, typically ending approximately 5 days before thescheduled start, which also may help to synchronize the follicular cohort before stimulationbegins. Another variation advocated for poor responders uses micronized estradiol (2 mgtwice daily, administered orally, beginning on day 21 of the preceding cycle) to suppressFSH during the late luteal phase for the same purpose, ending on the day beforegonadotropins stimulation begins, (Fanchin R, et al 2003, 2005), or continuing through thefirst 3 days of gonadotropin stimulation (Hill MJ, et al., 2009). The improved folliculardynamics observed are similar to those achieved by down-regulation with a GnRH agonistin the long protocol. The rebound increase in endogenous FSH levels that follows thediscontinuation of estradiol treatment also may synergize with exogenous gonadotropins topromote multi-follicular development (de Ziegler D, et al., 1998; Fanchin R, et al., 2003).Results of a number of early trials comparing a fixed antagonist treatment protocol to thestandard long protocol suggested that the two stimulation regimens yielded similarpregnancy rates (Albano C, et al., 2000; Olivennes F, et al., 2000); The European Middle EastOrgalutran Study Group, 2001; Fluker M, et al., 2001). However, a 2006 systematic reviewand meta-analysis including 27 trials comparing different antagonist stimulation protocolswith the long GnRH agonist protocol observed a significantly lower clinical pregnancy rate(OR=0.84, CI=0.72–0.97) and ongoing pregnancy/live birth rate (OR=0.82, CI=0.69–0.98).Overall, the total dose and duration of gonadotropin stimulation required, peak serumestradiol levels, and the number of follicles and oocytes were lower in antagonist cycles.The explanation for the modestly lower pregnancy rates observed in antagonist treatmentcycles is not clear. It is possible, but unlikely, that GnRH antagonists may have adverseeffects on oocytes, embryos, or the endometrium (Hernandez ER 200; Ortmann O, et al.,2001). It is far more likely that early results reflected inexperience and improved with timeand further refinements in the treatment regimen like those described above. Many of theadvantages originally envisioned for GnRH antagonists already have been realized.Whether antagonists ultimately will replace agonists and become the standard ovarianstimulation regimen in ART cycles remains to be seen, but their place in the therapeuticarsenal already is firmly established. Whereas a single bolus injection of an agonist(leuprolide 0.5 mg, triptorelin 0.2 mg) triggers a physiologic LH surge that lasts less than 24hours, hCG levels remain elevated for several days and stimulate markedly higher estradioland progesterone concentrations (Fauser BC, et al., 2002).The antagonist treatment regimens currently in use have potential disadvantages for womenwith PCOS. Their tonically elevated LH levels will remain high until antagonist treatmentbegins. Consequently, LH levels may rise prematurely, particularly if antagonist treatment