To investigate if exposure of antral cohorts to progesterone hormone during ovarian stimulation causes any aberrations in the molecular/luteal characteristics of the granulosa cells in the progestin-primed IVF cycles (PPOS) in comparison to the conventional GnRH antagonist cycles in normal responding IVF patients A total of 45 IVF patients comparable for age, BMI, duration of stimulation, daily and total gonadotropin dose and mode of trigger were selected for the study. The patients underwent ovarian stimulation either with PPOS (23) using medroxy progesterone acetate (5mg twice daily) or, with GnRH antagonist Cetrorelix acetate (22) and rec-FSH were included in the study. Luteal GCs obtained during oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging and hormone assays were utilized. Demographic and IVF characteristics of the patients undergoing ovarian stimulation with PPOS vs. GnRH antagonist were comparable (Table). The expression of the enzymes involved in uptake (LDL receptor), utilization (hormone-sensitive lipase (HSL), hydroxy-methyl glutaryl Co-enzyme-A reductase (HMG-CoA-R), storage (Sterol O-acyltransferase1) of cholesterol and sex steroid synthesis (StAR, aromatase, 3B-HSD) in the immunoblot analysis of the luteinized GCs of the PPOS cycles were totally comparable to those of the antagonist IVF cycles (Figure 1A). Both cycles were also similar for the expression of FSH and LH receptors at transcriptional and translational level (Figure 1B). Consistent with the findings above, basal and gonadotropin-induced up-regulation of StAR and P4 production of the luteinized GCs did not differ between the PPOS and the antagonist cycles (Figure 1C to 1E). Confocal imaging revealed similar patterns of expression for the steroidogenic enzymes (Figure 1F) and NBD cholesterol uptake (Figure 1G) in these two types of IVF cycles. Our study provides molecular evidence that exposure to progesterone hormone during follicular growth phase of antral cohorts under gonadotropin stimulation in PPOS cycles does not appear to have any detrimental effect in gonadotropin receptor expression, gonadotropin response and steroidogenic/luteal characteristics of the GCs in normal responding IVF patients. PPOS IVF cycles are similar to the conventional GnRH antagonist cycles not only for clinical IVF characteristics and but also for molecular steroidogenic/luteal features. [ABSTRACT FROM AUTHOR]