Moderate elevations in serum progesterone concentrations are observed following the use of gonadotrophin-releasing hormone agonists during ovarian stimulation. The clinical significance of this phenomenon has been investigated, but findings have been inconclusive. This commentary proposes that progesterone concentrations are indeed important in endometrial advancement and oocyte/embryo development, which, may lead to asynchrony between endometrial and embryo development. Based on the two-cell, two-gonadotrophin model, this commentary proposes a hypothesis to describe how progesterone concentration increases during ovarian stimulation and three factors influencing this during ovarian stimulation are identified: the number of follicles, the FSH drive and the LH activity. It also suggests how differences in gonadotrophin preparations used for ovarian stimulation may have differential effects on progesterone synthesis. It remains to be tested whether routine measurement of late follicular progesterone concentrations may prove beneficial as suitable assay methods are now available. However, strategies that reduce follicular recruitment in high-responding women and gonadotrophins that contain LH activity may reduce the degree of progesterone elevation prior to luteinization.