Controlled ovarian hyperstimulation protocols for in vitro fertilization: two decades of experience after the birth of Elizabeth Carr

Objective: To critically discuss the current protocols for the management of controlled ovarian hyperstimulation in assisted reproduction technology. Design: Review of the literature and presentation of our experience. Main Outcome Measure(s): ovarian response (peak serum estrogen levels, number of oocytes retrieved, quality of oocytes and embryos) and pregnancy outcome (clinical, delivery, and multiple pregnancy rates). Result(s): Controversies still exist regarding selection of gonadotropin preparation, choice of adjuvant therapy with GnRH analogues, and use of oral contraceptive pills. Patients identified as intermediate responders have,an excellent outcome with adjuvant therapy with either a GnRH agonist (long protocol) or a GnRH antagonist, but tailoring of gonadotropin dose must be performed to achieve optimized results. High responders perform favorably with gentler gonadotropin stimulation that minimizes the occurrence of ovarian hyperstimulation syndrome. On the other hand, results in low responders remain suboptimal both in terms of ovarian response and oocyte/embryo quality in spite of a variety of stimulation regimens used. Conclusion(s): Ovarian stimulation is a critical step in in vitro fertilization therapy. A variety of controlled, ovarian hyperstimulation regimens are available and efficacious, but individualization of management is essential and depends on assessment of the ovarian reserve. Identification of the etiologies of poor olvarian response, constitutes a formidable challenge facing reproductive endocrinologists.