Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development

Abstract

BACKGROUND: The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS: Randomized patients in both groups (antagonist: n 5 26; long agonist: n 5 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin b. The primary outcome was E 2 level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS: Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E 2 ) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E 2 was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml 21 , P < 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS: In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.

Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study

“…Even though other studies reveal lack of association between IVF outcome and the LH level on the beginning [49,50] and during [51][52][53][54] COH, they did not concern PCOS patients. Study by Lainas et al [55] described significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group among PCOS women. But these study did not consider the influence of LH on IVF outcome.…”

Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial

“…The absence of pituitary suppression during the first few days of COS may have caused the follicular asynchrony, and starting the GnRH antagonist earlier during COS may theoretically improve asynchrony among follicles, thereby increasing the oocyte yield and eliminating the potential detrimental effects of early follicular exposure to LH and E 2 [8]. However, controversy emerged regarding whether earlier GnRH antagonist administration would increase the gonadotropin dose requirement, increase E 2 levels on the day of hCG, or have any effects on pregnancy outcomes and the incidence of OHSS [891121]. …”

“…Such a sample size (80 patients per group) is not easily achieved even in a multicenter study, when studying a small proportion of the population, such as PCOS patients who undergo IVF. The previous two studies on this topic reported 49 patients [10] and 78 patients [11] and we initiated this study because we thought we could provide useful clinical information, even with small number of subjects.…”

“…Additionally, early administration of the GnRH antagonist may increase the oocyte yield by eliminating the asynchrony (size discrepancy) among growing follicles [9]. In two previous studies, the early antagonist protocol showed a similar number of oocytes retrieved, a similar pregnancy rate, and reduced OHSS rates compared to the long agonist protocol in PCOS patients [10,11]. …”

Controlled Ovarian Stimulation Using a Long Gonadotropin-Releasing Hormone<b> </b>Antagonist Protocol: A Proof of Concept and Feasibility Study

“…Oral contraceptive [24,25,26] and luteal progesterone pretreatment [24] have also been studied in the same context. In addition, early initiation of the GnRH antagonist on cycle day 1 has been studied in normo- [27] or high-responding [28] patients. Recently, two studies evaluated the consequences on GnRH antagonist cycle dynamics of early follicular phase short-term antagonist administration [29,30].…”