GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Abstract

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Figure 1

GnRH agonist protocols. Long Protocol: GnRH agonist 0.1 mg starting in follicular phase or luteal phase (Cycle Day 21) of the previuos cycle until hCG administration . Short Protocol: GnRH agonist 0.1 mg starting on day 1 or 3 of stimulation until hCG administration. Ultrashort Protocol: GnRH agonist 0.1 mg administered on day 2–4 of stimulation.

Figure 2

GnRH antagonist protocols. Fixed day 6 protocol: 0.25 mg GnRH antagonist/daily until hCG administration (Albano et al.,F&S 1997)[23]. Single dose protocol. 3 mg GnRH antagonist at day 7 of stimulation (Olivennes et al.,HR 1998)[22]. Flexible dose protocol: 0.25 mg GnRH antagonist when follicles reach >14 mm (Diedrich et al., HR 1994).[21]

Figure 3

Linear regression analysis between patient’s age and number of oocytes in the GnRH agonist group (A) and the GnRH antagonist group (B). In GnRH antagonist protocol it was observed a positive correlation between number of oocytes and patient’s age: the luteo-follicular transition induces FSH levels above the treshold for a short-period until hormonal feedback occurs, leading to the initiation of follicular growth of a few leading follicle. After exogenous FSH administration, FSH levels arise above threshold again and will initiate several additional follicles to grow, leading to a less synchronization of the follicular cohort, and a more natural recruitment of follicles. In GnRH antagonist protocol no correlation was observed between number of follicles and patient’s age. In GnRH agonist protocol, FSH levels remain above the threshold following pituitary downregulation and FSH exogenous administration, resulting in a more synchronized follicular recruitment (Depalo et al., Gynecol Endocrinol. 2009).[45]