Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With “Genuine” Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF

Orvieto, Raoul; Kirshenbaum, Michal; Galiano, Valentina; Elkan-Miller, Tal; Zilberberg, Eran; Haas, Jigal; Nahum, Ravit

doi:10.3389/fendo.2020.00182

Cited by 12 publications

(28 citation statements)

References 21 publications

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“…Moreover, in accordance with our previous study [6], the use of the combined Stop GnRH-ag with multiple-dose GnRH-ant resulted in significantly higher oocytes’ yield and more TQEs. It is well known that the long GnRH-ag protocol pretreatment results in better synchronized response and its cessation prior to gonadotropin administration might improve the ovarian response.…”

Section: Discussionsupporting

confidence: 90%

“…Diluting the number of GnRH receptors, together with the immediate LH suppression provided by the GnRH-ant (competitive inhibitor), vigorously suppress premature LH surge and inhibit the possibility of progesterone elevation. Moreover, in accordance with our previous study [6], the use of the combined Stop GnRH-ag with multiple-dose GnRH-ant resulted in significantly higher oocytes' yield and more TQEs. It is well known that the long GnRH-ag protocol pretreatment results in better synchronized response and its cessation prior to gonadotropin administration might improve the ovarian response.…”

Section: Discussionsupporting

confidence: 90%

“…Recently, our group demonstrated that combining the Stop GnRH-agonist (-ag) protocol with GnRH-ant protocols in poor ovarian responders revealed significantly higher number of oocytes retrieved and top-quality embryos (TQEs), with a reasonable clinical pregnancy rate [6]. The rationale behind the sequential treatment of the combined Stop GnRH-ag with multiple-dose GnRH-ant protocol stems from the advantages of its components.…”

Section: Introductionmentioning

confidence: 99%

“…Based on the valuable addition of the combined Stop GnRH-ag with multiple-dose GnRH-ant to the OS protocols armamentarium [6], we started offering patients with progesterone elevation during the late follicular phase of OS, the combined Stop GnRH-ag with multiple-dose GnRH-ant protocol. In the present study, we sought to examine the role of Stop GnRH-ag combined with multiple-dose GnRH-ant in preventing the undesired elevation of progesterone during the late follicular phase of an OS cycle.…”

Section: Introductionmentioning

confidence: 99%

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Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

Orvieto

Kirshenbaum

Galiano

et al. 2020

Gynecol Obstet Invest

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The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. Patients and Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multipledose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). Conclusions: The combined Stop GnRH-ag/ GnRH-ant OS protocol is a valuable tool in the armamentari-um for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients' subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

Orvieto

Kirshenbaum

Galiano

et al. 2020

Gynecol Obstet Invest

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“…The mid-luteal GnRH-ag pre-treatment causes down regulation of the GnRH receptors with the consequent suppression of pituitary LH secretion for as long as 10 days after the last dose of the agonist. This effect, together with the immediate LH suppression provided by the GnRH-ant, will eliminate premature LH surge and might improve the quality of the embryos generated (10). This protocol was successfully used in poor responder patients (10), those with poor embryos quality (11) and those with elevated peak serum progesterone levels (12).…”

Section: Introductionmentioning

confidence: 99%

GnRH Agonist Ovulation Trigger in Patients Undergoing Controlled Ovarian Hyperstimulation for IVF with Stop GnRH-agonist Combined With Multidose GnRH-antagonist Protocol.

Orvieto

Nahum

Frei

et al. 2021

Preprint

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Backround: Recently, the Stop GnRH agonist protocol has been used successfully in poor responder patients , those with poor embryos quality and those with elevated peak serum progesterone levels. The aim of the present study was to evaluate, whether GnRH-agonist trigger in patients undergoing the Stop protocol combined , will result in an optimal response/trigger, as reflected by post trigger LH >15 mIU/mL Methods: A retrospective cohort study. All consecutive women admitted to our IVF unit from February 2020 through November 2020 who reached the ovum pick-up stage. Patients triggered with GnRH-ag alone, or combined with hCG for final oocyte maturation were included in the study. LH levels were measured 12 hours post trigger.Results: Five out of the 32 patients (15.6%) demonstrated suboptimal response as reflected by LH levels <15 IU/L 12 hrs post GnRH-agonist trigger. Moreover, while no differences were observed in oocytes recovery rate, maturity or embryos quality between the different study groups, those achieving a suboptimal response to the GnRH-agonist trigger (post trigger LH <15 mIU/mL) demonstrated significantly higher number of follicles and peak estradiol levels at the day of trigger.Conclusions: The Stop GnRH-agonist combined with GnRH-antagonist protocol, enables the substitution of HCG with GnRH-ag for final oocyte maturation. However, caution should be taken in high responders, where the dual trigger with small doses of hCG (1000-1500IU) should be considered, aiming to avoid suboptimal response (post trigger LH levels <15IU/L).

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The effects of flexible short protocol with gonadotropin-releasing hormone antagonist on preventing premature ovulation in poor responders

Zhang,

Wang,

Zhang

et al. 2023

Arch Gynecol Obstet

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Purpose The proportion of patients with poor ovarian response (POR) is increasing, but effective treatment remains a challenge. To control the hidden peaks of luteinizing hormone (LH) and premature ovulation for poor responders, this study investigated the efficacy of flexible short protocol (FSP) with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day. Methods The 662 cycles of POR patients were retrospectively analyzed. The cohort was divided into control and intervention groups. The intervention group (group A) with 169 cycles received a GnRH-ant given on trigger day. The control (group B) with 493 cycles received only FSP. The clinical outcomes of the two groups were compared. Results Compared with group B, with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day in group A the incidences of spontaneous premature ovulation decreased significantly (2.37% vs. 8.72%, P < 0.05). The number of fresh embryo-transfer cycles was 45 in group A and 117 in group B. There were no significant differences in clinical outcomes, including implantation rate, clinical pregnancy rate, live birth rate and the cumulative live birth rate (12.0% vs. 9.34%; 22.22% vs. 21.93%; 17.78% vs. 14.91%; 20.51% vs. 20%, respectively; P > 0.05) between the two group. Conclusion FSP with GnRH-ant addition on trigger day had no effect on clinical outcomes, but could effectively inhibit the hidden peaks of luteinizing hormone (LH) and spontaneous premature ovulation in POR. Therefore, it is an advantageous option for POR women.

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Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With “Genuine” Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF

Abstract: Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients.

Cited by 12 publications

References 21 publications

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

GnRH Agonist Ovulation Trigger in Patients Undergoing Controlled Ovarian Hyperstimulation for IVF with Stop GnRH-agonist Combined With Multidose GnRH-antagonist Protocol.

The effects of flexible short protocol with gonadotropin-releasing hormone antagonist on preventing premature ovulation in poor responders

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