New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF

BACKGROUND: The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. OBJECTIVE AND RATIONALE: This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. SEARCH METHODS: A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. OUTCOMES: The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However, their medical and economic significance remains to be demonstrated. WIDER IMPLICATIONS: The use of luteal phase or follicular phase protocols with progestins could rapidly develop in the context of oocyte donation and fertility preservation not related to oncology. Their place could develop even more in the general population of patients in IVF programs. The strategy of total freezing continues to develop, thanks to technical improvements, in particular vitrification and PGS on blastocysts, and thanks to studies showing improvements in embryo implantation when the transfer take place far removed from the hormonal changes caused by ovarian stimulation.