Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization

ArticleinFertility and Sterility 72(3):406-11 · October 1999with10 Reads
DOI: 10.1016/S0015-0282(99)00289-7 · Source: PubMed
Abstract
To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. A prospective, randomized controlled trial. Hospital-based IVF Unit. Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. Ovarian stimulation patterns and IVF outcome. A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.
    • "Initially, several trials (prospective nonrandomized studies with historical control) on the use of " GnRH agonist stopped protocol " in poor responders reported a reduction in the amount of gonadotropin administered and improved laboratory results and clinical outcome [47, 63, 64] . Unfortunately , two prospective randomized controlled trials did not confirm improvements in reproductive outcome when this stimulation regimen is used compared to standard stimulation protocols [65, 66] . Similarly, in a recent metaanalysis no statistically significant difference was present in clinical pregnancy rates per cycle randomized between the " GnRH agonist stopped protocol " and the standard agonist protocol. "
    [Show abstract] [Hide abstract] ABSTRACT: Despite the fact that in the last two decades an enormous number of papers on the topic of poor ovarian response have been published in the literature, so far it has been impossible to identify any efficient treatment to improve the ovarian response and the clinical outcome of this group of patients. The incidence of poor ovarian responders among infertile women has been estimated at 9-24% but according to recent reviews, it seems to have slightly increased. The limitation in quantifying the incidence of these patients among the infertile population is due to the difficulty of a clear definition in literature. A recent paper by the Bologna ESHRE working group on poor ovarian response has been the first real attempt to find a common definition. Current literature proposes new risk factors which could be the cause of a reduction in ovarian reserve, which also includes genetic factors. This represents the first necessary step towards finding applicable solutions for these patients. To date, there is a substantial lack of literature that identifies an ideal protocol for these patients. The use of the "Bologna criteria" and the introduction of long acting gonadotropin in clinical practice have given rise to new promising stimulation protocols for this group of patients.
    Full-text · Article · Jul 2014
    • "Many different modified GnRH agonist protocols for poor responders, mostly by altering the dose and timing of GnRH agonist administration (stop or microdose flare-up protocols ), were reported. Although there is evidence that lowering the GnRH agonist dose when stimulating poor responders may decrease gonadotropin requirements and increase oocyte yield121314, two prospective, randomized trials in poor responders, comparing the long GnRH agonist protocols to GnRH agonist stop protocols, failed to find a significant difference in clinical PRs between the two protocols [14,15]. Craft et al. [16] first reported better oocyte retrieval and higher pregnancy rates in poor responders treated with a multiple-dose GnRH antagonist protocol compared to previous results with a long luteal GnRH agonist protocol. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders. Study design: This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0-4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II). Results: Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P=NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P=NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P=NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P=0.03). Conclusions: Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.
    Full-text · Article · Sep 2012
    • "The results are rather contradictory; two prospective randomized controlled trials for the ‘stop’ versus ‘non-stop’ GnRH agonist protocols showed no statistically significant increase in pregnancy rates, (16, 17). Conversely, different prospective trials using different drugs demonstrated better outcomes. "
    [Show abstract] [Hide abstract] ABSTRACT: The ovarian stimulation of poor responders still remains a challenging task for clinicians. There are numerous strategies that have been suggested to improve the outcome in poor responders but there is still no one pituitary down-regulation protocol that best suits all women with such condition. Traditional GnRH agonist flare and long luteal phase protocols do not appear to be advantageous. Reduction of GnRH agonist doses, "stop" protocols, and microdose GnRH agonist flare regimes all appear to improve outcomes, although the proportional benefit of one approach over another has not been convincingly established. GnRH antagonists improve outcomes in this patient population, although, in general, pregnancy rates appear to be lower in comparison to microdose GnRH agonist flare regimes.
    Full-text · Article · Jul 2012
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