Human granulosa cells in vitro: influence of GnRH/GnRH-agonist on steroidogenesis and on IVF outcome.

Steroidogenic activities of the granulosa cells (GCs) from 84 IVF trials were evaluated with respect to a set of ovarian stimulation regimens. Oestradiol (E2) synthesis of the GCs in vitro (obtained at oocyte retrieval) was compared to the maximal serum E2 levels of the same patients at induction of ovulation. Three stimulation regimens were employed: human post-menopausal gonadotrophin (hMG) alone; hMG accompanied by daily doses of a gonadotrophin releasing hormone agonist (GnRH-a); hMG preceded by a single depot application of the GnRH-a. Plots of E2 synthesis in vitro against serum E2 levels indicated that the GnRH-a directly inhibited E2 synthesis in the granulosa cells. This was confirmed in vitro by adding the agonist to the culture medium: both progesterone (P) and E2 syntheses were reduced in the presence of GnRH-a. Despite this drawback, the success of in vitro fertilization (IVF), as gauged by pregnancies achieved, was best for the group which received the GnRH-a as a single depot dose during the previous menstrual cycle, prior to the commence of stimulation. This success is attributed to the lower incidence of cancellations because of premature leuteinizing hormone (LH) surges which happen sometimes during ovarian stimulation. The implications of a direct influence of GnRH-a on E2 synthesis need to be further investigated.