Elaboration of a working model for the involvement of inhibin A as a mediator of the preovulatory rise of progesterone levels

During the final days of follicular development, exogenously administered follicle-stimulating hormone (FSH) produces a rise in serum progesterone level. The aim of the present study was to investigate the possible source and regulation of this preovulatory progesterone surge. Four sets of matching treatments with gonadotropins for in vitro fertilization and intracytoplasmic sperm injection were selected from a cohort of 953 treatments in 244 couples. Half of these four sets of treatments were selected based on the unusual course of the progesterone concentration during follicular development. The first set of I I cycles with early termination of gonadotropin administration for prolonged coasting were compared with a set of 12 cycles with similar estradiol levels but with uninterrupted ovarian stimulation. Another set of 12 cycles with low preovulatory progesterone levels (<2 nmol/l) were matched with ten cycles with normal preovulatory progesterone levels (>2 nmol/l). The sera of these four selected sets of treatments were stored for subsequent measurement of the concentrations of inhibin A, inhibin 13, activin A and leptin. During ovarian hyperstimulation serum levels of inhibin A correlated significantly with those of progesterone (p < 0.001), whereas this correlation disappeared after the withdrawal of FSH administration. The rapid fall of progesterone levels during prolonged coasting contrasts with the continuing rise of estradiol concentration and indicates that the theca interna, not the granulosa, is the major source of preovulatory progesterone. Women failing to produce any increment of progesterone levels at the end of follicular development had significantly lower levels of inhibin A (p < 0.05), indicating that inhibin A may well be involved in mediating the signal of FSH from the granulosa to the theca interna.