Effects of in-vitro exposure to HCG on subsequent HCC-responsiveness of human granulosa cells obtained following treatment with GnRH analogue and gonadotrophins: an in-vitro model for luteal phase support

Abstract

The pregnancy rate in patients undergoing assisted conception treatment following pituitary desensitization with GnRH analogue and ovarian stimulation with gonadotrophins has been reported to be higher when ovarian function is supported in the luteal phase by exogenous human chorionic gonadotrophin (HCG). In the present study, we have examined the effects of culturing monolayers of granulosa cells, collected from such patients at oocyte retrieval, for various time intervals in the presence or absence of HCG on their subsequent ability to secrete progesterone (P4) either spontaneously or in response to further challenge with HCG. When cultured in the absence of HCG, granulosa cells demonstrated a rapid decline in both the spontaneous P4 secretion rate and the ability to secrete P4 in response to HCG. Maintenance in the presence of HCG inhibited the rapid decline in ability to secrete P4 spontaneously and also significantly enhanced the ability to respond to subsequent HCG stimulation. These results suggest that HCG support in the luteal phase in GnRH analogue-treated patients may have a cellular basis for its action both in maintenance of P4 secretion and also in rendering the corpus luteum more sensitive to rescue by conceptus-derived HCG.

The significance of plasma progesterone levels during early pregnancies achieved after in vitro fertilization (IVF) treatment

“…Our findings are supported by those of Fritz et al (5), who have proven that human corpus luteum exhibits distinct age-dependent patterns of steroid secretion in response to hCG stimulation (6). Furthermore, Edgar and colleagues have shown that granulosa cells from patients treated with GnRH-a and gonadotropin maintained their ability to increase the PP secretion rate in response to hCG if previous support with hCG was administered until day 8 after ovulation (7). The ideal time to start this support in GnRH-hMG induced cycles is up to Day 5 postovulation (7).…”

“…Thus, for high levels of hCG, there is a maximal use of the corpus luteum functional capacity (a plateau effect), i.e., a subsequent increase in hCG, that does not result in a significant enhancement of the steroidogenic output. This can be explained by Edgar's work, which demonstrates that under hCG sensitization, there is an increase in the number of granulosa cell receptors, whereas the actual number of cells do not change (Edgar et al, 1991).…”

Induction of Ad4BP/SF-1, Steroidogenic Acute Regulatory Protein, and Cytochrome P450scc Enzyme System Expression in Newly Established Human Granulosa Cell Lines

“…Basal progesterone production declined when granulosaluteal cells obtained from IVF units were cultured in the absence of hCG (12,13). Culturing such cells for several days on a native basement membrane produced by bovine corneal endothelial (BCE) cells increased their basal progesterone output as well as their steroidogenic response to hCG, compared with cells on uncoated culture dishes (14).…”

Luteal Phase Support

“…In addition to stimulating progesterone production and inducting its own cytoplasmic receptor, Edgar et al 6 reported that luteal cells cultured in the presence of hCG had a diminished decline in their ability to secrete progesterone spontaneously and also had a significantly enhanced ability to respond to subsequent hCG stimulation.…”