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: 4.3). 02/2011; 95(5):1714-9.e1-2. DOI: 10.1016/j.fertnstert.2011.01.028
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aims: To evaluate the feasibility of a long protocol of controlled ovarian stimulation prior to in vitro fertilization (IVF) and embryo transfer with a gonadotropin-releasing hormone (GnRH) antagonist used for pituitary and ovarian suppression. Methods: Thirty patients undergoing IVF/intracytoplasmic sperm injection were randomized into two groups. The control group (n = 16) received a standard flexible GnRH antagonist protocol. Ovarian stimulation consisted of 225 IU/day of recombinant follicle-stimulating hormone for 5 days, followed by 225 IU/day of human menopausal gonadotropin until human chorionic gonadotropin (hCG) administration. The study group (n = 14) received 0.25 mg of GnRH antagonist daily for 7 days, thereafter, upon confirmation of pituitary and ovarian suppression, ovarian stimulation was commenced with the same protocol as used in the control group. Hormone and follicle dynamics, as well as laboratory characteristics and cycle outcome, were compared for both groups. Results: Both groups were comparable in baseline characteristics. Pituitary and ovarian suppression were effectively achieved in 12/14 patients in the study group. The duration of ovarian stimulation and gonadotropin consumption were similar in both groups, as was also the number and size of follicles on hCG day. Conclusion: The results of our study confirm the feasibility of a long GnRH antagonist protocol. This regimen could become another option to optimize GnRH antagonist protocols, and should thus be further explored.
    Gynecologic and Obstetric Investigation 07/2013; 76(2). DOI:10.1159/000351570 · 1.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate whether delaying the start of ovarian stimulation with GnRH antagonist improves ovarian response in poor responders. Design Retrospective study. Setting Academic medical center. Patient(s) Thirty patients, who responded poorly and did not get pregnant with conventional estrogen priming antagonist IVF protocol. Intervention(s) Delayed-start antagonist protocol (estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation). Main Outcome Measure(s) Number of dominant follicles and mature oocytes retrieved, mature oocyte yield, and fertilization rate. Result(s) The number of patients who met the criteria to proceed to oocyte retrieval was significantly higher in the delayed-start protocol [21/30 (70%)] compared with the previous conventional estrogen priming antagonist cycle [11/30 (36.7%)]. The number of dominant follicles was significantly higher in the delayed-start (4.2 ± 2.7) compared with conventional (2.4 ± 1.3) protocol. In patients who had oocyte retrieval after both protocols (n = 9), the delayed start resulted in shorter ovarian stimulation (9.4 ± 1.4 days vs. 11.1 ± 2.0 days), higher number of mature oocytes retrieved (4.9 ± 2.0 vs. 2.2 ± 1.1), and a trend toward increased fertilization rates with intracytoplasmic sperm injection (ICSI; 86 ± 17% vs. 69 ± 21%) compared with conventional protocol. After delayed start, the average number of embryos transferred was 2.8 ± 1.4 with implantation rate of 9.8% and clinical pregnancy rate of 23.8%. Conclusion(s) The delayed-start protocol improves ovarian response in poor responders by promoting and synchronizing follicle development without impairing oocyte developmental competence.
    Fertility and sterility 05/2014; 101(5). DOI:10.1016/j.fertnstert.2014.01.050 · 4.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    03/2012; 4(3):203-12.