ganirelix
Sources réglementaires consultées
Indications approuvées
- Prévention des pics prématurés de LH chez les femmes soumises à une hyperstimulation ovarienne contrôlée pour une procréation médicalement assistée.
Contre-indications
Absolues
- Hypersensibilité au ganirélix, à la GnRH, à ses analogues ou aux excipients.
- Insuffisance rénale ou hépatique modérée ou sévère.
- Grossesse ou allaitement.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer une anaphylaxie, un angio-œdème ou une urticaire même après la première dose ; arrêter et traiter immédiatement en cas d’hypersensibilité. — CIMA/AEMPS, ficha técnica 00130001
- Mise en garde majeure · Le syndrome d’hyperstimulation ovarienne est un risque de la procédure nécessitant une surveillance et une prise en charge spécialisées. — CIMA/AEMPS, ficha técnica 00130001
Interactions médicamenteuses
- ModéréeMédicaments libérant de l’histamine
Mécanisme: Une majoration des réactions d’hypersensibilité ne peut être exclue.
Recommandation: Renforcer la surveillance et disposer d’un traitement d’urgence.
CIMA/AEMPS, ficha técnica 00130001
Effets indésirables
Communs (≥1%)
Réaction cutanée locale au site d’injection
Rares mais graves
Anaphylaxie, angio-œdème et syndrome d’hyperstimulation ovarienne sévère
Grossesse et allaitement
Contre-indiqué pendant la grossesse et l’allaitement. Il est utilisé uniquement dans le cadre de protocoles de stimulation ovarienne contrôlée.
Bibliographie récente (PubMed)
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.
This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.
This study aimed to conduct computer searches in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, Wanfang, and CBM databases. Literature was screened and data extracted according to the inclusion and exclusion criteria. RevMan 5.3 was used to assess the methodological quality of the included studies, while Stata 14.0 was employed to rank the efficacy and safety of the five interventions. This analysis included 20 randomised controlled trials involving a total of 2,400 patients. The cumulative probability ranking results showed that, for improving clinical pregnancy rate (CPR), leuprorelin (97.8%) ranked highest, followed by cetrorelix (70.7%), triptorelin (47.9%), buserelin (18.2%), and ganirelix (15.3%). For improving the live birth rate (LBR), leuprorelin (99.9%) ranked highest, followed by triptorelin (44.1%) and cetrorelix (5.9%). For reducing the incidence of ovarian hyperstimulation syndrome (OHSS), cetrorelix (96.9%) ranked highest, followed by buserelin (58.7%), ganirelix (57.5%), leuprorelin (21.2%), and triptorelin (15.7%). Cetrorelix demonstrated superior performance in reducing the risk of OHSS, while leuprorelin was more effective in improving CPR and LBR. For women with polycystic ovary syndrome at high risk of OHSS, cetrorelix is recommended. For patients with the primary goal of improving CPR or LBR, leuprorelin is the more appropriate choice. Key Words: Polycystic ovary syndrome, Infertility, GnRH agonist, GnRH antagonist, Assisted reproduction.
Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.
The endothelin-B (ETB) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E2) on ETB receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E2 exposure modulates ETB receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m2) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E2 (0.1 mg/day, Vivelle-Dot patch) was added back on days 4-10. We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on day 4 (GnRHant) and day 10 (GnRHant + E2) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ETB receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ETB receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ± 5%CVCmax, P = 0.004). E2 administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant + E2: 89 ± 8%CVCmax, P = 0.036). Furthermore, cutaneous vasodilatory responses during ETB receptor blockade were blunted after E2 administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVCmax, P = 0.047). These data demonstrate that ovarian hormones, specifically E2, modulate ETB receptor function and contribute to the regulation of microvascular endothelial function in young women.NEW & NOTEWORTHY The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enh