Over the past decades many of us have contributed to the controversy surrounding the origins and consequences of premature progesterone elevation during controlled ovarian stimulation. In this article, we attempt to retrace the progression of information on this complex subject which required reviewing a number of publications that often contradicted one another. The definition of premature progesterone elevation, the pathophysiological mechanisms underlying the high peripheral progesterone levels, and the debated consequences of this event on in vitro fertilixation-embryo transfer outcome will be addressed from a historical perspective.
Adequate availability and FSH sensitivity of ovarian antral follicles and coordination of their growth during controlled ovarian hyperstimulation (COH) rank among factors that may determine outcome, particularly in patients presenting ovarian function defects and so-called "poor responders." Growing evidence indicates that both factors are positively influenced by steroid hormone pretreatments. First, data from studies conducted in both animals and in women exposed to virilizing androgen doses indicate that androgen pretreatments may increase follicle responsiveness to FSH and/or the number of growing follicles in the ovary, thereby constituting an interesting perspective in the management of "poor responders." Second, overcoming pre-COH heterogeneities in antral follicle sizes, which are more pronounced in "poor responders," to achieve adequate coordination of multiple follicular growth during COH also is contributive. For this, suppression or attenuation of the premature FSH increase during the preceding late luteal phase using sex steroid pretreatments (oral contraceptives, synthetic progestogens, or estradiol), or additional strategies such as premenstrual GnRH antagonist administration has been shown to be effective. The present paper will critically review proposed mechanisms and clinical results of sex steroid hormone pretreatments in these two different indications as an effort to optimizing COH outcome.
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