Ganirelix Research & Studies

This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model.

Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50-55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Interestingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas.

Is oral medroxiprogesterone acetate (MPA) non-inferior compared to ganirelix with respect to the number of mature oocytes (MII) retrieved at ovum pick-up (OPU) in oocyte donation cycles?

Gonadotropin-releasing hormone (GnRH) antagonists for controlled ovarian stimulation (COS) were only recently introduced into China. The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter, controlled, open-label study, in which Chinese women were randomized to either ganirelix (n = 113) or a long GnRH agonist protocol of triptorelin (n = 120). The primary end point was the amount of recombinant follicle-stimulating hormone (rFSH) required to meet the human chorionic gonadotropin criterion (three follicles ≥17 mm). The amount of rFSH needed was significantly lower for ganirelix (1272 IU) vs. triptorelin (1416 IU; P< 0.001). Ongoing pregnancy rates per started cycle were 39.8% (ganirelix) and 39.2% (triptorelin). Although both treatments were well tolerated, cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) was less frequent with ganirelix (1.8%) than triptorelin (7.5%) (P = 0.06). Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol, with fewer reported cases of OHSS and similar pregnancy rates.

Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia.

This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises).

To assess the clinical efficacy and safety of the gonadotropin-releasing hormone (GnRH) antagonist, ganirelix (Orgalutran), treatment in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women.

To evaluate controlled ovarian stimulation cycles using the GnRH antagonist ganirelix in combination with the recombinant FSH, follitropin-beta, in women with polycystic ovary syndrome (PCOS).

To establish long-term safety, follow-up data on pregnancy, birth and neonatal outcome were collected during clinical development trials with ganirelix (Orgalutran) in women undergoing controlled ovarian stimulation for conventional IVF or ICSI.

The gonadotrophin-releasing hormone antagonist ganirelix has recently become available to clinicians. Its indication, prevention of premature luteinizing hormone surges in assisted reproduction programmes, has been investigated extensively in numerous studies. This article summarizes the major results from pharmacokinetics studies, a double-blind dose-finding trial and three large-scale phase III randomized clinical trials, comparing ganirelix and the most commonly used gonadotrophin-releasing hormone agonists, buserelin,leuprolide and triptorelin, in a long protocol. It is concluded that controlled ovarian hyperstimulation with ganirelix offers significant advantages in terms of convenience of treatment as reflected in a considerably reduced treatment period.Safety and tolerance as well as overall clinical outcome are good.

To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH).

This multicentre, randomized study was performed to assess the efficacy and safety of 0.25 mg ganirelix (Orgalutran, Antagon) treatment, using triptorelin (Decapeptyl) in a long protocol as a reference treatment. In total, 236 subjects were randomized to treatment with ganirelix (0.25 mg, s.c.) and 119 to triptorelin (0.1 mg, s.c.) treatment (treatment ratio 2:1). Treatment with ganirelix started on day 6 of stimulation, whereas treatment with triptorelin started on menstrual cycle day 21 to 24 of the previous cycle (i.e. the midluteal phase). The ganirelix regimen was on average 17 days shorter (9 versus 26 days) compared to the triptorelin regimen. The median total dose of recombinant FSH (Puregon) used was 450 IU less (1350 versus 1800 IU) in the ganirelix protocol. The initial follicular growth was faster and, consequently, oestradiol concentrations were higher in the ganirelix group. On the day of human chorionic gonadotrophin (HCG), the mean number of follicles > or = 11 mm was 10.1 and 10.7 and the median serum oestradiol concentration was 1090 and 1370 pg/ml in the ganirelix and triptorelin groups respectively. Per attempt, 7.9 and 9.6 oocytes (mean) were retrieved in the ganirelix and triptorelin groups respectively. The fertilization rates (64.0% ganirelix and 64.9% triptorelin) and the mean number of good quality embryos (2.7 and 2.9) were comparable in both treatment groups. The implantation rate was identical (22.9%). The ongoing pregnancy rate per attempt was 31.0 and 33.9% in the ganirelix and triptorelin groups respectively. The ganirelix regimen showed an improved local tolerance in that the percentage of subjects with at least one local skin reaction was 2-fold lower than in the triptorelin group (11.9 versus 24.1%). Taking all data together, it may be concluded that ganirelix offers a new treatment regimen in ovarian stimulation that is short, safe and well-tolerated, optimizing convenience for the patient.

A multicentre, open-label, randomized study of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix (Orgalutran((R))/Antagon((TM))) was performed in women undergoing ovarian stimulation with recombinant FSH (rFSH: Puregon((R))). The study was designed as a non-inferiority study using a long protocol of buserelin (intranasal) and rFSH as a reference treatment. A total of 730 subjects was randomized in a treatment ratio of 2:1 (ganirelix:buserelin) using an interactive voice response system which stratified for age, type of infertility and planned fertilization procedure [IVF or intracytoplasmic sperm injection (ICSI)]. The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group, whereas the median total rFSH dose was 1500 IU and 1800 IU respectively. In addition, in the ganirelix group the mean duration of stimulation was 1 day shorter. During ganirelix treatment the incidence of LH rises (LH >/=10 IU/l) was 2.8% versus 1.3% during rFSH stimulation in the buserelin group. On the day of triggering ovulation by human chorionic gonadotrophin (HCG), the mean number of follicles >/=11 mm diameter was 10.7 and 11.8, and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively. The mean number of oocytes per retrieval was 9.1 and 10.4 respectively, whereas the mean number of good quality embryos was 3.3 and 3.5 respectively. The fertilization rate was equal in both groups (62.1%), and the same mean number of embryos (2.2) was replaced. The mean implantation rates were 15.7% and 21.8%, and the ongoing pregnancy rates per attempt were 20.3% and 25.7% in the ganirelix and buserelin groups respectively. Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated. The overall incidence of ovarian hyperstimulation syndrome was 2.4% in the ganirelix group and 5.9% in the reference group. The results of this study support a safe, short and convenient treatment regimen of ganirelix, resulting in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI.

To assess the dose-proportionality and pharmacodynamic properties of multiple doses of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands).

To determine if daily subcutaneous doses of ganirelix will suppress and maintain E2 < or = 30 pg/mL (conversion factor to SI unit, 3.671), the serum profiles of LH and FSH during and after cessation of treatment, the time-course of the resumption of normal ovarian function after ganirelix cessation, and to identify side effects of daily treatment.

A procedure for the radioimmunoassay (RIA) of ganirelix in plasma or serum at concentrations as low as 0.050 ng/ml is described. Antiserum was produced by coupling the N-terminus glycyl analog of ganirelix to BSA by a carbodiimide reaction and immunizing rabbits with this conjugate. The antiserum did not crossreact with LHRH or with various ganirelix peptide fragments. For RIA, 125I labeled ganirelix was used as the tracer and a double antibody procedure was used to separate the free and bound fractions. No purification of the analyte was required prior to RIA. Accuracy of the method was assessed by adding known quantities of ganirelix to ganirelix-free plasma and determining the ratio of measured to added analyte. Linear regression analysis for the concentration range 0.050-50.0 ng/ml yielded a regression equation of y = 0.97x + 0.18, r = 0.999, where x is the amount added and y is the amount measured. Additional validation was obtained from an in vivo study in which [3H]-ganirelix was administered to monkeys and plasma clearance profiles were determined by RIA and an HPLC-radiochemical method. The results were in agreement within experimental error of the two methods. Linear regression analysis of the comparative data gave the equation y = 0.92x + 33.7, r = 0.980, where x is the amount measured by RIA and y is the amount measured by HPLC-radiochemical analysis.