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

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel
Fertility and Sterility (Impact Factor: 4.59). 10/1999; 72(3):406-11. DOI: 10.1016/S0015-0282(99)00289-7
Source: PubMed


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.

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    • "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 meta-analysis no statistically significant difference was present in clinical pregnancy rates per cycle randomized between the “GnRH agonist stopped protocol” and the standard agonist protocol. "
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    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 · BioMed Research International
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    • "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. "
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    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 · Journal of Reproduction and Infertility
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    • "The most prevalent approaches for treating poor responder are always the GnRH agonist flare protocol. Compared to traditional long GnRH agonist protocol, there is no significant difference in clinical pregnancy rates [12,13]. Our data showed that increased doses of gonadotropins were not able to influence ovarian response in poor responders (group C), the pregnancy rate for poor-responder patients and number of oocytes retrieved are lower than the two other groups (group A and group B). "
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    ABSTRACT: There are still some patients who show poor response to ovarian stimulation prior to evidence of normal ovarian reserve in vitro fertilization. However, there are few studies about how to treat the unexpectedly ovarian poor responder in vitro fertilization. The main aim of this study evaluate the effect of prolonging administration follicle-stimulating hormone in woman with the unexpectedly ovarian poor responder in vitro fertilization on implantation rate, clinical pregnancy rate and live birth rate. 922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups. The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C. Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.
    Full-text · Article · Mar 2010 · Reproductive Biology and Endocrinology
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