Optimal stimulation protocols for in vitro fertilization

Objective: To update clinicians on different gonadotropin regimens for ovarian stimulation for IVF including the use of urinary and recombinant gonadotropins, the value of added LH to FSH in the stimulation regimen, the use of GnRH agonists and antagonists, and the role of minimal stimulation protocols. Design: Literature review and critical analysis of major articles during the last five years on ovarian stimulation for IVF. Conclusion(s): Urinary and recombinant gonadotropins, for ovarian stimulation for IVF, are probably equally safe and effective. The higher cost for recombinant products limits their worldwide use in IVF. Conflicting data exist regarding the benefit of adding LH to FSH in the stimulation regimens. The use of different GnRH-agonists, of varying potency, may account for different levels of LH suppression. Adding LH should be considered in severe situations of LH suppression such as with the use of potent GnRH-agonists or when GnRH-antagonists are introduced during the course of stimulation. GnRH-antagonists provide advantages to patients in terms of fewer injections, shorter stimulation days, and avoidance of adverse effects of agonists. The incidence of ovarian hyperstimulation syndrome is probably less with antagonists compared to agonists, with the option to use an agonist as a surrogate LH surge. Fixed and early start of the antagonist is probably more effective than an individualized and late start. The earlier reported lower pregnancy rates with antagonists compared to agonists is not fully understood and needs to be continually monitored. Minimal stimulation protocols using a combination of clomiphene citrate and gonadotropins are attractive and should be considered in some patients owing to lower costs and acceptable success rates. The optimal stimulation protocol for IVF should be an individualized regimen based on the patient's ovarian physiology and prior IVF experience, if any.