Progesterone elevation on the day of hCG: methodological issues

Sir, Two recent interesting and learned articles in Human Reproduction Update concerning elevations of progesterone (P) in the follicular phase of controlled ovarian stimulation (Venetis et al., 2007; Bosch, 2008) address a number of issues which deserve further comment. The comments relate to technical issues (steroid hormone measurement and study design) as well as biological/biochemical concepts. Both articles addressed specific critical concentration points of P in the follicular phase, and Bosch indicated the imprecise nature of selecting a single value (0.9 ng/ml). If we first set aside the debate over specific concentrations of circulating P demonstrating negative clinical consequences, presumably through advancing endometrial development, we must consider whether the assays used are reliable at the values observed. Most commercial assays were developed to determine the standard clinical question for the clinical biochemistry laboratory—whether a patient has ovulated or not. This requires an operating concentration sensitivity some 5–10-fold higher than those of the follicular phase. Correspondingly, little development has been undertaken for these automated and semi-automated platforms to examine the more subtle changes taking place prior to ovulation. This matter was addressed in preparation for the study by Adonakis et al. (1998), and there are important lessons to be learned which I would like to discuss below.