Pre-hCG elevation of plasma progesterone: good, bad or otherwise

Sir, In the pre-GnRH analogue (GnRH-a) era, late follicular phase elevation of progesterone in IVF was taken as evidence of premature LH elevation and hence, correctly named ‘premature luteinization’. The advent of GnRH-a, rapidly adopted in all IVF centres, allowed reliable suppression of LH throughout controlled ovarian hyperstimulation (COH) and thus, prevented premature luteinization. In the mind of all therefore, GnRH-a had definitively erased the pitfalls of pre-hCG progesterone elevation and its adverse consequences on IVF outcome. The reprieve, however, was going to be short-lived. In 1991, a report from Schoolcraft et al. (1991) drew attention to the fact that in certain patients, progesterone still rose above normal follicular phase levels prior to hCG administration in spite of gonadotropin suppression by GnRH-a. In their patients, this was associated with an ominous prediction of IVF outcome. Soon, however, other reports came out with different conclusions on this issue, which created vast confusion. Attempting to separate the wheat from the chaff in the lingering debate over the consequences of pre-hCG progesterone elevation, Venetis et al. (2007) conducted a meta-analysis of published data. From their results, pre-hCG progesterone elevation did not adversely affect IVF outcome. We do not intend to minimize the value of this report but yet, we agree with the arguments voiced by Bosch (2007) and Fleming (2008) in Human Reproduction Update about the limitations of this meta-analysis.