GnRH receptor GnRH R levels

GnRH receptor (GnRH-R) levels are elevated in decidualized stromal cells, suggesting a function for the GnRH–GnRH-R pathway in the early implantation events. Both GnRH and GnRH-R have been shown to be present in preimplantation embryos and the fallopian tubes at both mRNA and protein levels (). Two forms of GnRH-R (GnRH-R I and GnRH-R II) exist and have functional roles in multiple and diverse extra-pituitary mammalian tissues and BRD4770 (Cheng and Leung, 2005, Chen et al., 2007), including the endometrium. GnRH can modulate matrix metalloproteinases and their endogenous inhibitors, tissue-specific inhibitors, both of which play a key role in cyclic remodelling events in the human endometrium in preparation for implantation (). GnRH agonists induce apoptosis in endometrial cells in vitro (), and GnRH-R have also been shown to be present in the endometrium with highest levels reported in the secretory phase (Shemesh, 2001) followed by a decline in GnRH-R numbers in the decidua (). Therefore, GnRH analogues administered during IVF have the potential to act on the endometrium and on the embryo during the very early stages of implantation via GnRH-R. Most studies on the early stages of implantation have used single and daily doses of GnRH agonists rather than long-acting forms (), as currently used for endometrial priming, as they are more convenient for patients included in oocyte donation programmes with ovarian function (). A recent study designed for determining predictive factors in an oocyte donation programme, in which all the available embryos were cryopreserved (), reported that the use of pituitary down-regulation with long acting GnRHa before endometrial priming had a negative effect regardless of the age of the recipient, as an independent factor. Recipients of donated eggs who underwent short-acting GnRH agonist administration (single dose of 0.1 mg triptoreline) 6 days after intracytoplasmic sperm injection, compared with placebo, showed an improvement in implantation and lower twin pregnancy rates with no increase in miscarriage rates, which culminated in a higher birth rate in the agonist group (). This finding excludes any possible effect of GnRH agonist on oocyte quality and suggests that GnRH agonist administration at the time of implantation enhances embryo developmental potential, probably by a direct effect on the embryo. Other in-vitro studies have suggested that daily agonist or antagonist have no detrimental effect on the specific events of trophoblastic invasion and stromal cell decidualization in vitro nor the invasive potential of the blastocyst in the early stages of implantation (); furthermore, GnRH analogue administration does not seem to have major direct effects on gene expression of human endometrial epithelial cells in vitro (). Previous studies have evaluated the influence of GnRH antagonist administration in oocyte donation recipients during the endometrial priming at a dose of 0.25 mg per day, concomitant with egg donor administration, and maintained until ovulation induction. This differs from the present study in which the antagonist is given during the first 7 days of endometrial priming in premenopausal recipients allocated to the antagonist group. In one of them () pointed out that GnRH antagonist administration in menopausal oocyte recipients during the proliferative phase at a dose of 0.25 mg per day until the day before the donor HCG does not seem to adversely affect endometrial receptivity. The other prospective, observational, non-randomized study confirmed that administration of GnRH antagonists coinciding with egg donor antagonist administration during endometrial preparation in premenopausal oocyte recipients compared with recipients suppressed with GnRH agonist, did not affect pregnancy rates (). In the present study, a higher percentage of vitrified–warmed oocytes were used in the GnRH antagonist group compared with the GnRH agonist group; however, this did not decrease the OPR in this group, and reinforces previously published data that cryopreserved donated oocytes are convenient to use with Cryotop vitrification ().