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Andrew V Schally - One of the best experts on this subject based on the ideXlab platform.

  • the effect of lhrh antagonist Cetrorelix in crossover conditioned media from epithelial bph 1 and stromal wpmy 1 prostate cells
    Hormone and Metabolic Research, 2013
    Co-Authors: Agnieszka Siejka, Andrew V Schally, Nektarios Barabutis
    Abstract:

    Stromal cells strictly modulate the differentiation of the normal prostate epithelium. In benign prostatic hyperplasia (BPH) tissue, the ratio of stromal to epithelial cells reaches a 5:1 ratio. In this study, we evaluated the effects of crossover conditioned media (CM) of stromal and epithelial prostate cells before and after treatment with LHRH antagonist Cetrorelix. WPMY-1 human prostate stromal cells and BPH-1 human benign prostatic hyperplasia cells were cultured in vitro and the effects of crossover conditioned media (CM) from those cells were studied. We evaluated the effect of Cetrorelix on the expression of PCNA and p53 in those cells. We then studied the effect of Cetrorelix on BPH-1 cells cultured with the CM from WPMY-1 cells, as well as the mechanisms which govern these interactions. CM from WPMY-1 cells strongly stimulated the proliferation of BPH-1 cells in a dose dependent manner, while CM from BPH-1 cells only slightly increased the proliferation of WPMY-1 cells. Cetrorelix inhibited the proliferation of both cell lines and the expression of PCNA, while the expression of p53 was increased. Cetrorelix also inhibited the proliferation of BPH-1 cells stimulated with the CM from WPMY-1 cells. In the crossover experiment, conditioned media from WPMY-1 and BPH-1 cells increased the expression of phosphorylated ERK1/2 and STAT3. Our results support previous observations on the bidirectional stromal-epithelial interactions in prostate gland and shed more light on the mechanistic action of those effects. Our study strongly supports the hypothesis that LHRH antagonists may be beneficial for BPH prevention and treatment.

  • lhrh antagonist Cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia
    The Prostate, 2011
    Co-Authors: Ferenc G Rick, Andrew V Schally, Gabor Halmos, Norman L Block, Roberto Perez, Jesus B Fernandez, Irving Vidaurre, Luca Szalontay
    Abstract:

    BACKGROUND Recent findings suggest that BPH has an inflammatory component. Clinical trials have documented that therapy with LHRH antagonist Cetrorelix causes a marked and prolonged improvement in LUTS in men with symptomatic BPH. We investigated the mechanism of action and effect of Cetrorelix in a rat model of BPH. METHODS Adult male Wistar rats were used. BPH was induced in rats by subcutaneous injections of TE 2 mg/day for 4 weeks. Control animals received injections of corn oil. After induction of BPH, rats received depot Cetrorelix pamoate at the doses of 0.625, 1.25, and 12.5 mg/kg on days 1 and 22 and TE-control rats received vehicle injections. Whole prostates were weighed and processed for RNA and protein. Real-time RT-PCR assays for numerous inflammatory cytokines and growth factors were performed. Quantitative analyses of prostatic LHRH receptor, LHRH, androgen receptor (AR) and 5α-reductase 2 were done by real-time RT-PCR and immunoblotting; serum DHT, LH, PSA, and IGF-1 by immunoassays. RESULTS mRNA levels for inflammatory cytokines IFN-γ, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, IL-15, and IL-17 and for growth factors EGF, FGF-2, FGF-7, FGF-8, FGF-14, TGF-β1, and VEGF-A were significantly reduced by Cetrorelix 0.625 mg/kg (P < 0.05). Prostate weights were also significantly lowered by any dose of Cetrorelix. CONCLUSIONS This study suggests that Cetrorelix reduces various inflammatory cytokines and growth factors in rat prostate and, at doses which do not induce castration levels of testosterone, can lower prostate weights. Our findings shed light on the mechanism of action of LHRH antagonists in BPH. Prostate 71:736–747, 2011. © 2010 Wiley-Liss, Inc.

  • luteinizing hormone releasing hormone lhrh i antagonist Cetrorelix inhibits myeloma cell growth in vitro and in vivo
    Molecular Cancer Therapeutics, 2011
    Co-Authors: Yongdong Feng, Andrew V Schally, Chad C Bjorklund, Michael Wang, Robert Z Orlowski, Bing Liao, Jacqueline Ohare, Youli Zu, Chung Che Chang
    Abstract:

    The objective of this study was to determine the effects of an luteinizing hormone-releasing hormone (LHRH)-I antagonist, Cetrorelix, on human multiple myeloma (MM) cells and to elucidate the mechanisms of action. We showed that LHRH-I and LHRHR-I genes were expressed in MM cell lines and primary MM cells. Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, including cell lines resistant to arsenic trioxide, bortezomib, or lenalidomide. Cetrorelix induced apoptosis in myeloma cells including primary myeloma cells. In addition, Cetrorelix inhibited the growth of human myeloma cells xenografted into mice without any apparent side effects. Cetrorelix downregulated the nuclear factor-kappa B (NF-κB) pathway activity and the expression of cytokines, including interleukin 6, insulin-like growth factor 1, VEGF-A, and stromal-derived factor 1, important for myeloma cell growth and survival in myeloma cells and/or marrow stromal cells from myeloma patients. Cetrorelix decreased the phosphorylation of extracellular signal regulated kinase 1/2 and STAT3 in myeloma cells, two crucial pathways for myeloma cells growth and survival. Moreover, the expression of p21 and p53 was increased, whereas that of antiapoptotic proteins Bcl-2 and Bcl-xL was reduced by Cetrorelix. Our findings indicate that Cetrorelix induces cytotoxicity in myeloma cells through various mechanisms and provide a rationale for investigating Cetrorelix for the treatment of MM. Mol Cancer Ther; 10(1); 148–58. ©2010 AACR .

  • mechanisms of inhibition of human benign prostatic hyperplasia in vitro by the luteinizing hormone releasing hormone antagonist Cetrorelix
    BJUI, 2010
    Co-Authors: Agnieszka Siejka, Andrew V Schally, Norman L Block, Nektarios Barabutis
    Abstract:

    OBJECTIVE To assess the mechanism by which the luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix exerts its effects in men with benign prostatic hyperplasia (BPH), as it produces a long-lasting improvement in lower urinary tract symptoms that is only partly accounted for by the transient reduction in testosterone levels, and the beneficial results could be due to direct inhibitory effects of Cetrorelix on the prostate exerted through prostatic LHRH receptors. MATERIALS AND METHODS Using the BPH-1 cell line we evaluated the effects of Cetrorelix in vitro on the proliferation and the expression of receptors for LHRH, epidermal growth factor (EGF), α1A-adrenergic receptor, STAT-3 transcription factor and the response to growth factors insulin-like growth factor (IGF)-1 and -II and fibroblast growth factor (FGF)-2. RESULTS There was expression of LHRH receptors in the human BPH-1 cell line. Cetrorelix had inhibitory effects on the proliferation rate of BPH-1 cells, also reflected by the decrease in the expression of the proliferating cell nuclear antigen (PCNA). Cetrorelix inhibited the stimulatory effect of the growth factors IGF-I and -II and FGF-2 on the proliferation of this line. Cetrorelix also downregulated the expression of the receptors for LHRH and EGF, as well as of α1A-adrenergic receptors, and inhibited the activation of the STAT3 transcription factor. CONCLUSIONS The results show that in vitro Cetrorelix can directly inhibit the proliferation rate of the human BPH-1 cell line by counteracting growth factors like IGF-I and -II and FGF-2, and downregulating the LHRH receptor and α-adrenergic receptors, as well as transcription factors.

  • LHRH antagonist Cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia.
    The Prostate, 2010
    Co-Authors: Ferenc G Rick, Andrew V Schally, Gabor Halmos, Norman L Block, Roberto Perez, Jesus B Fernandez, Irving Vidaurre, Luca Szalontay
    Abstract:

    BACKGROUND Recent findings suggest that BPH has an inflammatory component. Clinical trials have documented that therapy with LHRH antagonist Cetrorelix causes a marked and prolonged improvement in LUTS in men with symptomatic BPH. We investigated the mechanism of action and effect of Cetrorelix in a rat model of BPH. METHODS Adult male Wistar rats were used. BPH was induced in rats by subcutaneous injections of TE 2 mg/day for 4 weeks. Control animals received injections of corn oil. After induction of BPH, rats received depot Cetrorelix pamoate at the doses of 0.625, 1.25, and 12.5 mg/kg on days 1 and 22 and TE-control rats received vehicle injections. Whole prostates were weighed and processed for RNA and protein. Real-time RT-PCR assays for numerous inflammatory cytokines and growth factors were performed. Quantitative analyses of prostatic LHRH receptor, LHRH, androgen receptor (AR) and 5α-reductase 2 were done by real-time RT-PCR and immunoblotting; serum DHT, LH, PSA, and IGF-1 by immunoassays. RESULTS mRNA levels for inflammatory cytokines IFN-γ, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, IL-15, and IL-17 and for growth factors EGF, FGF-2, FGF-7, FGF-8, FGF-14, TGF-β1, and VEGF-A were significantly reduced by Cetrorelix 0.625 mg/kg (P 

Kate Groot - One of the best experts on this subject based on the ideXlab platform.

  • effect of long term treatment with low doses of the lhrh antagonist Cetrorelix on pituitary receptors for lhrh and gonadal axis in male and female rats
    Proceedings of the National Academy of Sciences of the United States of America, 2004
    Co-Authors: Judit Horvath, Andrew V Schally, Gabor L Toller, Ana M Bajo, Kate Groot
    Abstract:

    Our previous studies showed that treatment of female rats with large doses of Cetrorelix, an antagonist of luteinizing hormone-releasing hormone (LHRH), reduces levels of serum LH, estradiol, progesterone, and the concentration of pituitary LHRH receptors (LHRH-Rs) and their mRNA expression. Serum LH and testosterone levels and pituitary LHRH-R in male rats are also decreased by high doses of Cetrorelix. This approach can be used for therapy of sex hormone-dependent cancers. However, in conditions where an incomplete hormone deprivation is indicated, lower doses of Cetrorelix may suffice. Thus, we investigated the effect of a 30-day treatment with a low-dose depot formulation of Cetrorelix (20-24 μg per kg per day) on the pituitary-gonadal axis of male and female rats. In both sexes, lower serum LH levels were observed on day 4 after administration. In males, LH returned to control levels by day 10, whereas in females, a rebound LH elevation occurred. Testosterone levels in male rats were decreased up to day 20, but on day 30, the values were similar to controls. In females, serum estradiol was reduced on day 4; however, by day 10 it returned to normal. Progesterone levels were diminished through the entire period. Female rats showed diestrous smears during the first week of treatment and prolonged estrous periods thereafter. The weights of testes and ovaries were significantly lower, but not the weights of prostate, seminal vesicles, and uterus. Pituitary LHRH-R mRNA and LHRH-R protein levels were not significantly different from the controls. Thus, the treatment with low doses of Cetrorelix did not seriously impair gonadal functions. The results suggest that Cetrorelix in low doses induces only a partial pituitary-gonadal inhibition and might be indicated for treatment of endometriosis, leiomyomas, and benign prostatic hyperplasia.

  • effects of long term treatment with the luteinizing hormone releasing hormone lhrh agonist decapeptyl and the lhrh antagonist Cetrorelix on the levels of pituitary lhrh receptors and their mrna expression in rats
    Proceedings of the National Academy of Sciences of the United States of America, 2002
    Co-Authors: Judit Horvath, Andrew V Schally, Magdolna Kovacs, Ana M Bajo, Francine Herbert, Kate Groot
    Abstract:

    The effects of depot formulations of the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl (25 μg/day) for 30 days or LHRH antagonist Cetrorelix pamoate (100 μg/day) for 30 days and daily injections of 100 μg of Decapeptyl for 10 days on the expression of mRNA for pituitary LHRH receptor (LHRH-R) and the levels of LHRH-R protein were evaluated in rats. Serum sex steroid concentrations and the weights of the reproductive organs were greatly reduced in all groups treated with analogs, demonstrating an efficient blockade of the pituitary–gonadal axis. Decapeptyl microcapsules elevated serum LH in female rats, but decreased it in male rats. LHRH-R mRNA expression in female pituitaries was reduced to 41% and 56–65% on days 10 and 30, respectively, whereas LHRH-R protein was 64% of control on day 10 and returned to pretreatment levels on day 30. Decapeptyl microcapsules reduced LHRH-R mRNA expression in male pituitaries to 58% on day 30 but not LHRH-R protein. Daily injections of Decapeptyl caused a desensitization of LH responses in female rats, while raising LHRH-R mRNA expression in female rats by 23% and LHRH-R protein levels by 119%. Cetrorelix pamoate reduced serum LH in female rats and diminished LHRH-R mRNA to 30% and 26% and LHRH-R protein to 57% and 48% on days 10 and 30, respectively. Elevated LHRH-R protein levels of ovariectomized rats were reduced after 10-day treatment with Cetrorelix or 100 μg/day Decapeptyl. Thus, changes in the mRNA expression after treatment with Cetrorelix, but not always Decapeptyl, paralleled those of LHRH-R protein. The inhibitory effect of Cetrorelix on serum LH, pituitary LHRH-R mRNA, and LHRH-R protein was greater than that of Decapeptyl.

  • inhibition of growth of es 2 human ovarian cancers by bombesin antagonist rc 3095 and luteinizing hormone releasing hormone antagonist Cetrorelix
    Cancer Letters, 2001
    Co-Authors: Ioulia Chatzistamou, Andrew V Schally, Kate Groot, Karoly Szepeshazi, Francine Hebert, Jose M Arencibia
    Abstract:

    Abstract We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, and the luteinizing hormone–releasing hormone (LH–RH) antagonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-3095 at a dose of 20 μg/day and Cetrorelix (100 μg/day), significantly reduced the volume of ES-2 tumors by 63.0% ( P P P P P

  • luteinizing hormone releasing hormone antagonist Cetrorelix sb 75 and bombesin antagonist rc 3940 ii inhibit the growth of androgen independent pc 3 prostate cancer in nude mice
    The Prostate, 1997
    Co-Authors: Andreas Jungwirth, Gabor Halmos, Jacek Pinski, Kate Groot, Georg Galvan, Karoly Szepeshazi, Andrew V Schally
    Abstract:

    BACKGROUND Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and luteinizing hormone-releasing hormone (LH-RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen-independent prostate cancer. METHODS LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured. RESULTS When the treatment was started, tumor volume in all groups was 70–80 mm3. After 4 weeks, tumor volume in the control animals injected with saline was 871 ± 233 mm3 and that of animals treated with Cetrorelix only 197 ± 61 mm3. The BN/GRP antagonist RC-3940-II also significantly reduced PC-3 tumor volume in nude mice to 122 ± 20 mm3. The combination of Cetrorelix and RC-3940-II produced no additional inhibition. High-affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC-3940-II. CONCLUSIONS These findings demonstrate that LH-RH antagonists and BN/GRP antagonists inhibit the growth of the androgen-independent prostate cancer cell line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down-regulation of EGF receptors. Prostate 32:164–172, 1997. © 1997 Wiley-Liss, Inc.

  • inhibition of growth of androgen independent du 145 prostate cancer in vivo by luteinising hormone releasing hormone antagonist Cetrorelix and bombesin antagonists rc 3940 ii and rc 3950 ii
    European Journal of Cancer, 1997
    Co-Authors: Andreas Jungwirth, Gabor Halmos, Jacek Pinski, Manuel Vadillobuenfil, Kate Groot, Georg Galvan, Karoly Szepeshazi, Andrew V Schally
    Abstract:

    The aim of this study was to test the antagonist of LH-RH (Cetrorelix), agonist [D-Trp6]LH-RH (triptorelin) and new bombesin antagonists RC-3940-II and RC-3950-II for their effect on the growth of an androgen-independent prostate cancer cell line, DU-145, xenografted into nude mice. Xenografts were grown in male nude mice and after 4 weeks, the animals were treated either with saline (control) or with one of the analogues. One group of mice was given a combination of Cetrorelix and RC-3950-II. Treatment was given for 4 weeks. Tumour and body weights and tumour volumes were measured. At sacrifice, tumours were dissected for histological examination and receptor studies. Serum was collected for measurement of hormone levels. The final tumour volume in control animals injected with saline was 577 ± 155 mm3 and that of animals treated with Cetrorelix only 121.4 ± 45 mm3 (P < 0.01). Bombesin antagonists RC-3940-II and RC-3950-II also significantly reduced DU-145 tumour volume in nude mice to 84.9 ± 19.9 and 96.8 ± 28 mm3, respectively. Agonist [D-Trp6]LH-RH did not significantly inhibit tumour growth. Serum levels of LH were decreased to 0.08 ± 0.02 ng/ml (P < 0.05) in the Cetrorelix treated group as compared to 1.02 ± 0.1 ng/ml for the controls and testosterone levels were reduced to castration levels (0.01 ± 0.01 ng/ml). Specific receptors for EGF and LH-RH in DU-145 tumours were significantly downregulated after treatment with Cetrorelix, RC-3940-II and RC-3950-II. Although LH-RH could be a local regulator of growth of prostate cancer, the fall in LH-RH receptors is not fully understood and the inhibitory effects of Cetrorelix and bombesin antagonists on DU-145 tumour growth might be attributed at least in part to a downregulation of EHF receptors. Since Cetrorelix and bombesin antagonists inhibit growth of androgen-independent DU-145 prostate cancers, these compounds could be considered for the therapy of advanced prostate cancer in men, especially after relapse.

K Diedrich - One of the best experts on this subject based on the ideXlab platform.

  • the effects of Cetrorelix and triptorelin on the viability and steroidogenesis of cultured human granulosa luteinized cells
    in Vivo, 2012
    Co-Authors: Chryssa Metallinou, Frank Koster, K Diedrich, N Nikolettos, Byron Asimakopoulos
    Abstract:

    BACKGROUND: We investigated the effects of the gonadotropin-releasing hormone (GnRH) agonist triptorelin as well the GnRH antagonist Cetrorelix those of on the viability and steroidogenesis in human granulosa luteinized (hGL) cell cultures. MATERIALS AND METHODS: The hGL cells were obtained from 34 women undergoing ovarian stimulation for IVF treatment. The cells were cultured for 48 h with or without 1 nM or 3 nM of Cetrorelix or triptorelin in serum-free media. The cell viability was evaluated by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The concentrations of estradiol and progesterone in culture supernatants were measured by ELISA. RESULTS: Treatment with triptorelin slightly increased cell viability, whereas treatment with 3 nM Cetrorelix led to a significant decrease. Estradiol concentrations were reduced with 3 nM triptorelin. Cultures treated with high-dose of either Cetrorelix or triptorelin tended to secrete less progesterone than controls. CONCLUSION: Cetrorelix significantly reduces the viability of hGL cells. Triptorelin and Cetrorelix may have minor effects on steroidogenesis. These results suggest that GnRH analogues may influence ovarian functions.

  • presurgical short term treatment of uterine fibroids with different doses of Cetrorelix acetate a double blind placebo controlled multicenter study
    European Journal of Obstetrics & Gynecology and Reproductive Biology, 2007
    Co-Authors: Jorg B Engel, Alain Audebert, R Frydman, Jaroslav Zivny, K Diedrich
    Abstract:

    The objective was to assess the efficacy and safety of different dosing schedules of Cetrorelix acetate as a short term treatment for 4 weeks prior to surgery in patients with uterine fibroids. A Randomized double-blind placebo-controlled study was used and the patients were 109 premenopausal women with at least one uterine fibroid more than 4 cm in diameter. Groups 1-3 received placebo 5 and 10 mg of Cetrorelix on days 1 8 15 and 22 respectively group 4 received 10 mg of Cetrorelix on days 1 and 15. MRI scan was performed at screening and on day 29. The main outcome measure was the reduction of uterine volume on day 29 and response defined as >30% size reduction. Mean (+or- S.D.) reduction of uterine volume on day 29 (MRI scan) was 5.1 +or- 32.1% with placebo 15.6 +or- 20.2% with 4 x 5 mg 15.4 +or- 34.6% with 4 x 10 mg and 0.6 +or- 30.6% with 2 x 10 mg Cetrorelix. Significant response versus placebo ( p < 0.05) occurred in the 4 x 10 mg group (42.3% versus 11.1%) Best objective response after 4 weeks of treatment was achieved after therapy with 4 x 10 mg of Cetrorelix acetate. Short term presurgical treatment with the LHRH-antagonist Cetrorelix is a flexible treatment protocol without any major side effects. (authors)

  • comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the gnrh antagonist Cetrorelix and gnrh agonists
    European Journal of Obstetrics & Gynecology and Reproductive Biology, 2000
    Co-Authors: N Nikolettos, Thomas Reissmann, Hilde Riethmullerwinzen, R Felberbaum, S Alhasani, L C Demirel, B Schopper, R Sturm, K Diedrich
    Abstract:

    This retrospective study was performed to examine the implantation and pregnancy rates of frozen–thawed pronuclear stage oocytes obtained with the use of a GnRH antagonist, Cetrorelix (Cetrotide® ASTA-Medica, Frankfurt/M, Germany) used in a multidose protocol with hMG, and to compare these results with those obtained after a conventional long GnRH analogue protocol (Decapeptyl-Depot, Ferring, Kiel, Germany). The study population consisted of 31 infertile couples with frozen–thawed pronuclear stage oocytes after ICSI treatment using the GnRH antagonist Cetrorelix (Cetrorelix®) and 31 infertile couples with frozen–thawed pronuclear stage oocytes after ICSI treatment using the long GnRH analogue protocol. Patients underwent ICSI after down regulation with a GnRH agonist (Decapeptyl) and stimulation with hMG, or a GnRH antagonist (Cetrorelix) and hMG. The supernumerary pronuclear stage oocytes were cryopreserved and transferred in a later mildly stimulated cycle. The implantation and pregnancy rates for frozen–thawed pronuclear stage oocytes derived from the GnRH antagonist compared with the GnRH agonist were 3.26% versus 3.73% (P=1.0000) and 8.33% versus 10.25% (P=1.0000), respectively. To our knowledge we report here the first pregnancies obtained by the transfer of cryopreserved pronuclear stage embryos generated from ICSI using a GnRH antagonist in the collecting cycle. The use of Cetrorelix in a multiple dose protocol in combination with hMG does not demonstrate a negative effect on viability, implantation potential or pregnancy outcome as compared to 2PN conceptuses obtained from a long GnRH agonist-hMG protocol.

  • significant reduction of the incidence of ovarian hyperstimulation syndrome ohss by using the lhrh antagonist Cetrorelix cetrotide in controlled ovarian stimulation for assisted reproduction
    Archives of Gynecology and Obstetrics, 2000
    Co-Authors: Michael Ludwig, Hilde Riethmullerwinzen, P Devroey, R Felberbaum, C Albano, A Schuler, W Engel, K Diedrich
    Abstract:

    A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO °II and °III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

  • ovarian stimulation with hmg results of a prospective randomized phase iii european study comparing the luteinizing hormone releasing hormone lhrh antagonist Cetrorelix and the lhrh agonist buserelin
    Human Reproduction, 2000
    Co-Authors: Carola Albano, Hilde Riethmullerwinzen, Jorg B Engel, K Diedrich, R Felberbaum, J Smitz, P Devroey
    Abstract:

    In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the Cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the Cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received Cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the Cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received Cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

P Devroey - One of the best experts on this subject based on the ideXlab platform.

  • the impact of lh serum concentration on the clinical outcome of ivf cycles in patients receiving two regimens of clomiphene citrate gonadotrophin 0 25 mg Cetrorelix
    Reproductive Biomedicine Online, 2003
    Co-Authors: Asimina Tavaniotou, Carola Albano, Andre Van Steirteghem, P Devroey
    Abstract:

    Abstract Clomiphene citrate treatment with the association of gonadotrophins and the GnRH antagonist Cetrorelix 0.25mg was analysed in two different stimulation protocols for IVF. In protocol I, 18 patients were sequentially stimulated with clomiphene citrate and gonadotrophins. In protocol II, 28 patients started the gonadotrophin injections during the clomiphene citrate administration. LH values significantly dropped after the first 0.25 mg Cetrorelix injection in both protocols. A total of 22% and 7% of cycles were cancelled in protocols I and II, respectively, because of poor follicular development. The clinical pregnancy rate following embryo transfer was 18.1% in protocol I and 29.1% in protocol II. In two (11.1%) cycles stimulated according to protocol I and in eight (28.5%) cycles from protocol II, premature LH surges occurred. In patients with premature LH surge, significantly fewer metaphase II oocytes were obtained. The clinical pregnancy rate following embryo transfer was 12.5% in patients with surge compared with 29.6% in patients without. LH values were lower before HCG injection in patients who achieved pregnancy in the study cycle. In conclusion, sequential clomiphene citrate and gonadotrophin administration is not recommended for clomiphene citrate/gonadotrophin/Cetrorelix 0.25 cycles. Cetrorelix 0.25 mg/day was associated with a high incidence of premature LH surges and premature LH surges were associated with an adverse cycle outcome.

  • significant reduction of the incidence of ovarian hyperstimulation syndrome ohss by using the lhrh antagonist Cetrorelix cetrotide in controlled ovarian stimulation for assisted reproduction
    Archives of Gynecology and Obstetrics, 2000
    Co-Authors: Michael Ludwig, Hilde Riethmullerwinzen, P Devroey, R Felberbaum, C Albano, A Schuler, W Engel, K Diedrich
    Abstract:

    A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO °II and °III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

  • ovarian stimulation with hmg results of a prospective randomized phase iii european study comparing the luteinizing hormone releasing hormone lhrh antagonist Cetrorelix and the lhrh agonist buserelin
    Human Reproduction, 2000
    Co-Authors: Carola Albano, Hilde Riethmullerwinzen, Jorg B Engel, K Diedrich, R Felberbaum, J Smitz, P Devroey
    Abstract:

    In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the Cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the Cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received Cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the Cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received Cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

  • comparison of different doses of gonadotropin releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation
    Fertility and Sterility, 1997
    Co-Authors: Carola Albano, Hilde Riethmullerwinzen, Johan Smitz, Michel Camus, Andre Van Steirteghem, P Devroey
    Abstract:

    Abstract Objective: To assess the minimal effective dose of a GnRH antagonist (Cetrorelix; Asta Medical, Frankfurt, Germany) to prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technologies. Design: In 69 patients COH was carried out with the association of hMG, starting on day 2 of the menstrual cycle, and a GnRH antagonist (Cetrorelix) was administered from day 6 of the hMG treatment (day 7 of the menstrual cycle) every day up to and including the last day of the hMG injection. In 32 and 30 patients, 0.5 mg and 0.25 mg of Cetrorelix were administered, respectively. Seven patients received 0.1 mg of Cetrorelix. Setting: Tertiary referral center. Result(s): No premature endogenous LH surge occurred in patients treated with 0.5 and 0.25 mg of Cetrorelix, and serum LH concentrations were maintained constantly low during the entire follicular phase in both groups. Follicle-stimulating hormone, LH, E 2 , and P expressed as area under the curve were similar in both groups. A premature LH surge (18 mIU/mL; conversion factor to SI unit, 1.00) with a concomitant P rise (1.7 μg/L; conversion factor to SI unit, 3.180) occurred in one of the seven patients treated with 0.1 mg Cetrorelix; therefore, treatment with this dose was discontinued. Conclusion(s): The minimal effective dose of Cetrorelix able to prevent premature LH surge in COH cycles is 0.25 mg administered daily.

  • endocrinologyhormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin releasing hormone antagonist Cetrorelix
    Human Reproduction, 1996
    Co-Authors: Carola Albano, Hilde Riethmullerwinzen, K Diedrich, Johan Smitz, Michel Camus, Andre Van Steirteghem, M Siebertweigel, P Devroey
    Abstract:

    A third-generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P< 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2122 ± 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.

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  • Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/Cetrorelix protocol and buserelin long protocol – a randomized study
    Gynecological Endocrinology, 2020
    Co-Authors: Jiann-loung Hwang, Kok-min Seow, Bih-chwen Hsieh, Lee-wen Huang, Chi-ruey Tzeng
    Abstract:

    This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/Cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/Cetrorelix protocol (Cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the Cetrorelix group than in the buserelin group (mean ± standard deviation (SD): 11.1 ± 4.0 vs. 17.3 ± 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the Cetrorelix than in the buserelin group (mean ± SD: 2600.58 ± 1189.11 vs. 3293.46 ± 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17....

  • Effect of Cetrorelix dose on premature LH surge during ovarian stimulation
    Reproductive Biomedicine Online, 2020
    Co-Authors: Kok-min Seow, Lee-wen Huang, Heng-ju Chen, Chi-ruey Tzeng, Bin Chwen Hsieh, Jiann-loung Hwang
    Abstract:

    Previous studies have shown that ovarian stimulation with clomiphene citrate (CC), human menopausal gonadotrophin (HMG), and multiple-dose gonadotrophin-releasing hormone (GnRH) antagonist is associated with a high rate of premature LH surge. This study assessed whether administration of the GnRH antagonist Cetrorelix at an incremental dose or at a high dose (0.5mg) from the start could prevent premature LH surge. Couples with male factor or unexplained infertility who were going to undergo intrauterine insemination were randomized into two stimulation protocols. All women were stimulated with CC and HMG. In protocol A, Cetrorelix was given at 0.25 mg per day when the leading follicles reached 14 mm, and increased to 0.5 mg when the leading follicles were 16 mm. With protocol B, Cetrorelix was given at 0.5 mg per day when the leading follicles reached 14 mm. The primary outcome measure was the incidence of premature LH surge. Premature LH surge occurred in 21.6% of patients undergoing protocol A, and in 18.9% of patients undergoing protocol B. Cetrorelix at incremental dose or at 0.5 mg per day does not prevent premature LH surges associated with the CC/HMG/multiple-dose Cetrorelix stimulation protocol.

  • Impact of estradiol patterns in clomiphene citrate/human menopausal gonadotropin/Cetrorelix protocol.
    Gynecological Endocrinology, 2020
    Co-Authors: Kok-min Seow, Lee-wen Huang, Heng-ju Chen, Jiann-loung Hwang, Chi-ruey Tzeng
    Abstract:

    The importance of serum estradiol changes associated with gonadotropin-releasing hormone antagonists is not clear. The purpose of the present study was to analyze the impact of estradiol changes after Cetrorelix injection on the outcome of intracytoplasmic sperm injection (ICSI) cycles. This was a prospective observational study. One hundred and thirteen women with male-factor infertility who were undergoing first ICSI cycles were reviewed for this study. Excluding seven cycles with incomplete data, 106 cycles were included in the analysis. The women were stimulated with clomiphene citrate and human menopausal gonadotropin (hMG). Cetrorelix acetate (2.5 mg) was given when the leading follicles reached 14 mm. After Cetrorelix administration, serum estradiol rose in 48 cycles (45.3%), plateaued in 26 cycles (24.5%) and dropped in 32 cycles (30.2%). Mean age and day-3 follicle-stimulating hormone, luteinizing hormone and estradiol levels were similar among the three groups. The mean ampoules of hMG used, est...

  • safety and efficacy of mixing Cetrorelix with follitropin alfa a randomized study
    Fertility and Sterility, 2010
    Co-Authors: Kok-min Seow, Bih-chwen Hsieh, Jiann-loung Hwang, Yuanmay Chang, Chii Ruey Tzeng
    Abstract:

    OBJECTIVE: To assess the safety and efficacy of mixing Cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology. DESIGN: Prospective, randomized study. SETTING: An IVF center in a teaching hospital. PATIENT(S): One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups. INTERVENTION(S): In the M group, rFSH and Cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and Cetrorelix were administered separately. MAIN OUTCOME MEASURE(S): The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability. RESULT(S): Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups. CONCLUSION(S): Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.

  • Safety and efficacy of mixing Cetrorelix with follitropin alfa: a randomized study
    Fertility and Sterility, 2009
    Co-Authors: Yuanmay Chang, Kok-min Seow, Bih-chwen Hsieh, Jiann-loung Hwang, Chii Ruey Tzeng
    Abstract:

    Objective To assess the safety and efficacy of mixing Cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology. Design Prospective, randomized study. Setting An IVF center in a teaching hospital. Patient(s) One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups. Intervention(s) In the M group, rFSH and Cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and Cetrorelix were administered separately. Main Outcome Measure(s) The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability. Result(s) Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups. Conclusion(s) Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.