Administration of a gonadotropin-releasing hormone antagonist during the 3 days before the initiation of the in vitro fertilization/intracytoplasmic sperm injection treatment cycle: Impact on ovarian stimulation. A pilot study

Centre for Reproductive Medicine, Brussels, Belgium.
Fertility and sterility (Impact Factor: 4.59). 02/2011; 95(5):1714-9.e1-2. DOI: 10.1016/j.fertnstert.2011.01.028
Source: PubMed


To investigate the impact on the number of cumulus-oocyte complexes (COC) when a 3-day course of GnRH antagonist treatment precedes the initiation of controlled ovarian stimulation with gonadotropins in a GnRH antagonist protocol for IVF/intracytoplasmic sperm injection (ICSI).
Randomized controlled trial.
Tertiary referral center.
Sixty-nine women undergoing controlled ovarian hyperstimulation for IVF/ICSI.
The control group (n = 36) received a standard treatment with daily injections of recombinant FSH (rFSH), starting on day 2 of the cycle at a dose of 150-225 IU/day, and GnRH antagonists from cycle day 7 onward. In the pretreatment group (n = 33), a GnRH antagonist was administered from day 2 of the menstrual cycle onward during 3 consecutive days; thereafter controlled ovarian stimulation was initiated with the same protocol as used in the control group.
The primary endpoint was the number of COCs at egg retrieval.
Both groups had comparable baseline characteristics. The duration of rFSH stimulation and consumption of gonadotropins were similar in both groups. The number of COCs was higher in the pretreatment group (12.8; SD, 7.8) compared with in the control group (9.9; SD, 4.9), although this increment was not significant (between-group difference of 2.9 [95% confidence interval {CI} -0.2 to 6.0]). The ongoing pregnancy rates per started cycle of 14/33 (42%) versus 12/36 (33%) for pretreatment versus control did not differ significantly (between-group difference, 9.1%; 95% CI, -13% to 30%).
Among women under 36 years old, early follicular phase GnRH antagonist pretreatment in a fixed GnRH antagonist protocol results in a trend toward a higher number of retrieved oocytes but does not yield significantly higher pregnancy rates.

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    ABSTRACT: This randomized controlled trial analyses the ability to control the oocyte retrieval schedule of gonadotrophin-releasing hormone antagonist cycles through the administration of oestradiol valerate during the luteo-follicular transition period prior to the initiation of ovarian stimulation. Eighty-six women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection were enrolled in the study. The control group (n = 42) received a standard ovarian stimulation protocol. In the pretreatment group (n = 44), patients were administered oestradiol valerate at a daily dose of 2 · 2 mg from day 25 of the preceding cycle onwards, during 6–10 consecutive days, depending on the day of the week. The primary endpoint was the proportion of patients undergoing oocyte retrieval during a weekend day (i.e. Saturday or Sunday), which was significantly lower in the pretreatment group (1/37, 2.7%) compared with the control group (8/39, 20.5%; P value = 0.029). The clinical pregnancy rates per started cycle were similar in the pretreatment group (38.6%) compared with the control group (38.1%). Pretreatment with oestradiol valerate results in a significantly lower proportion of patients undergoing oocyte retrieval during a weekend day and can be a valuable tool for the organization of an assisted reproduction centre.
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    ABSTRACT: In reproductive medicine, the aim is to establish an optimal balance between cost-effectiveness, success rate and safety for the patient. In this thesis, a series of clinical studies are presented that all revolve around the optimisation of ovarian stimulation with GnRH antagonist co-treatment. Basal hormonal levels at the start of ovarian stimulation are mandatory to obtain acceptable pregnancy rates. In view of this, we focused on the impact of cycle day 2 progesterone levels on treatment outcome. By interfering in the early follicular phase, we tried to synchronise the follicular cohort and to increase the number of retrieved oocytes. Innovative treatment protocols based on GnRH antagonists should lead to a more flexible and better controlled schedule of oocyte retrievals. The inability to program the start of gonadotrophin stimulation and hence to minimise weekend oocyte retrievals is a major impediment to the widespread implementation of the GnRH antagonist protocol in fertility clinics. Because treatment schedule is important both for the patients, who wish to undergo reproductive treatment at their own convenience, and for the ART clinic, to organise the workload, we attempted to bring the schedule of egg retrievals in a GnRH antagonist protocol under improved control. Another important aim of our clinical research was to diminish patient discomfort and reduce side effects by a simplification of GnRH antagonist ovarian stimulation protocols. We also focused on significant reduction of FSH consumption by substitution of FSH by low dosages of hCG during the mid-late follicular phase, without impairing outcome in terms of oocyte yield and ongoing pregnancy rate or live birth rate.
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