Optimizing the use of GnRH antagonists in ovarian stimulation protocols
- Author:
Howles Colin M.
- Publication Type:Journal Article
- MeSH:
GONADOTROPIN-RELEASING HORMONE;
OVULATION INDUCTION
- From:
Philippine Journal of Reproductive Endocrinology and Infertility
2005;2(2):88-
- CountryPhilippines
- Language:English
-
Abstract:
Unlike the GnRH agonists, which have been routinely used in ovarian stimulation protocols for almost 20 years, the GnRH-antagonist acts via a dose-dependent competetive blockade of the pituitary GnRH receptors. This results in an immediate suppression of gonadotrophin secretion (in particular LH) from the anterior pituitary. Despite the new advantages of this new class of substances, the controversial discussion about the influence of the antagonist of the implantation and embryo quality has been ongoing for the last few years. New data from recent meta analysis have demonstrated that the clinical pregnancy rate per cycle is equivalent between antagonist protocols, however there is a sugnificant reduction in the amount of FSH used and the incidence of OHSS.
Recently, flexible protocols where the GnRH antagonist is applied according to leading follicle size rather than a fixed of stimulation have been developed in order to prevent a premature LH surge. A recent meta-analysis of four randomised trials comparing fixed vs flexible starting day for the GnRH antagonist concluded there was no statistically significant difference in pregnancy rates, but a significant reduction in the amount of FSH utilized in favour of the flexible protocol.
A series of studies have however raised concern about late administration of the GnRH antagonist, as used in a flexible protocol. In the three studies, the implantation and pregnancy rates were higher when the antagonist was initiated on a fixed day (stimulation day 6) compared to administration in a flexible protocol according to follicle size (-15mm).
Whilst Kolibianakis, et al. reported no difference in overall pregnancy rate in flexible over fixed day antagonist administration, the implantation rate was lower in the flexible protocol, when there were no follicles of -15mm on the stimulation day 6. In this group, higher concentrations of LH and oestradiol were observed to antagonist administration. In a second study, Kolibianakis, et al reported that profound suppression of LH after GnRH antagonist suppression was associated with a significantly higher ongoing pregnancy rate. They argued that exposure of the genital tract/oocyte to LH may adversely affect the implantation rate, mainly by altering endometrial receptivity. One issue here that ma have complicated the interpretation of the results is the very late administration of the GnRH antagonist (-15mm). It is generally recommended that the antagonist should administered when the leading follicle is 14mm at he very latest.
Co-treatment with oral contraceptive pill (OCP) programming can also be utilized with GnRH antagonists in order to facilitate scheduling the start of FSH therapy, rather than waiting for the patient to have spontaneous menses. There are now a number of studies reporting the use of OCP pill programming with either daily 0.25mg or single dose 3mg Cetrotide in routine ART and also poor responder patients. Future studies in this area are needed to elucidate the optimal preparation protocol in GnRH antagonist cycles. However, the data that are emerging seem to support that previous cycle preparation can make a clinical contribution to the outcome of the antagonist treatment cycle.
