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GnRH Antagonist

Yavuz Emre Şükür, Batuhan Özmen, Elif Didem Özdemir, Mehmet Murat Seval, Erkan Kalafat, Murat Sönmezer, Bülent Berker, Ruşen Aytaç, Cem Somer Atabekoğlu
Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS). Infertile patients treated with GnRH antagonist protocol between January 2014 and March 2016 were recruited. Patients with high serum oestradiol levels on HCG day (>3000 pg/ml) indicating a risk of OHSS consisted of the study groups (A and B). Patients with serum oestradiol levels less than 3000 pg/ml consisted of the control group (C)...
October 17, 2016: Reproductive Biomedicine Online
Stefano Salciccia, Alessandro Gentilucci, Susanna Cattarino, Alessandro Sciarra
On the basis of the trials available, are we ready to consider GnRH antagonists better than agonists? Is there a population of patients who may benefit from antagonists more than agonists?We specifically focused our analysis on the significance of oncological results obtained in phase III trials directly comparing Degarelix with GnRH agonists. Oncological results were evaluated only in 1 trial (CS21) with some subanalysis and they were not the primary endpoints of the study. The follow-up duration was 364 days, and therefore, the number of events (all causes deaths and prostate cancer (PC), Prostate Specific Antigen (PSA), Hazard ratio (HR)-related deaths) was very low in both groups and this aspect strongly reduces the significance of overall survival evaluation...
October 15, 2016: Urologia
Rashid Sayyid, Andrew Evans, Karen Hersey, Ranjena Maloni, Antonio Hurtado-Coll, Girish Kulkarni, Antonio Finelli, Alexandre R Zlotta, Robert Hamilton, Martin Gleave, Neil Fleshner
PURPOSE: Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over LHRH analogues in terms of avoiding "testosterone flare" and lower FSH levels. We set out to determine if pre-operative degarelix influenced surrogates of disease control in a randomized phase II study. EXPERIMENTAL DESIGN: 39 patients were randomly assigned to one of 3 different neo-adjuvant arms: degarelix only, degarelix/bicalutmaide, or LHRH agonist/bicalutamide...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ashraf Alyasin, Shayesteh Mehdinejadiani, Marzieh Ghasemi
Routinely, a bolus of 5.000-10.000 IU human chorionic gonadotropin (hCG) is used for the final follicular maturation and ovulation as a standard method. HCG has the same effect of luteinizing hormone (LH) with long half-life. It has the long lutheotrophic effect which increases the risk of ovarian hyper stimulation syndrome (OHSS). Recently, gonadotropin-releasing hormone agonist (GnRH-a) trigger has been used for the induction of final follicular maturation and ovulation with the aim of reducing the OHSS risk...
September 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Subathra Poopalasundaram, David Chambers, Anthony Graham, Pierre-Marc Bouloux
The hypothalamic gonadotrophin releasing hormone (GnRH) neurons are a small group of cells that regulate the reproductive axis. These neurons are specified within the olfactory placode, delaminate from this structure and then migrate to enter the forebrain before populating the hypothalamus. We have employed microarray technology to analyse the transcriptome of the olfactory placode at a number of key time points for GnRH ontogeny using the chick embryo. This resulted in the identification of a large number of genes whose expression levels change significantly over this period...
October 12, 2016: Endocrinology
W Decleer, K Verschueren, S Vandeginste, K Osmanagaoglu, P Devroey
OBJECTIVE: To demonstrate the feasibility of scheduling an IVF cycle, without disadvantages, in the new patient friendly stimulation protocol using the long acting Corifollitropin Alfa, in combination with GnRH-antagonist protection and GnRH-agonist triggering. STUDY DESIGN: Two groups of ten patients were admitted in the study. Both received the same stimulation protocol with Corifollitropin Alfa in combination with GnRH-antagonist protection. After ultrasound evaluation on day 7 individually dosed Menopur was added...
December 28, 2015: Facts, Views & Vision in ObGyn
Maryam Eftekhar, Sepideh Miraj, Zahrasadat Mortazavifar
BACKGROUND: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. OBJECTIVE: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. MATERIALS AND METHODS: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included...
August 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Imre Farkas, Csaba Vastagh, Erzsébet Farkas, Flóra Bálint, Katalin Skrapits, Erik Hrabovszky, Csaba Fekete, Zsolt Liposits
Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R...
2016: Frontiers in Cellular Neuroscience
Albert Stuart Reece, Mervyn Rees Thomas, Amanda Norman, Gary Kenneth Hulse
Whilst disturbances of female reproductive hormones and function are commonplace in opioid dependence, their pathophysiological interrelationships are not well understood. Hormonal levels in females were compared in 77 opioid dependent patients (ODP) and 148 medical controls (MC) including 205 and 364 repeat studies. Significant changes in FSH, LH, oestradiol, testosterone and SBG were noted including power functions with age. The FSH/LH was lower in ODP (P=0.0150) and the ratio inversion point occurred at 28...
September 20, 2016: Reproductive Toxicology
Georgios Christopoulos, Antonios Vlismas, Anna Carby, Stuart Lavery, Geoffrey Trew
A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had ≥18 follicles ≥11mm or serum oestradiol >18,000pmol/l on the day of trigger...
September 2016: Human Fertility: Journal of the British Fertility Society
Bülent Haydardedeoğlu, Esra Bulgan Kılıçdağ
OBJECTIVE: Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. MATERIAL AND METHODS: In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015...
2016: Journal of the Turkish German Gynecological Association
Leena Wadhwa, Rupali Khanna, Taru Gupta, Sangeeta Gupta, Sarika Arora, Sumi Nandwani
AIMS AND OBJECTIVE: To evaluate the role of GnRH antagonist in prevention of premature LH surge and increasing pregnancy rates in IUI cycle with mild ovarian hyperstimulation (MOH). STUDY DESIGN: Prospective parallel, randomised controlled study. MATERIAL AND METHODS: Couples diagnosed with unexplained, male factor subfertility and with one or both tubes patent were randomised to receive either a GnRH antagonist (study group) or no intervention (control group)...
October 2016: Journal of Obstetrics and Gynaecology of India
Karolina Skorupskaite, Jyothis T George, Johannes D Veldhuis, Robert P Millar, Richard A Anderson
CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with NK3R antagonist followed by transdermal estradiol to induce LH secretion 48hr later, with kisspeptin-10 or vehicle infusion during estrogen administration in a two-way cross-over study...
September 16, 2016: Journal of Clinical Endocrinology and Metabolism
B Lawrenz, F Beligotti, N Engelmann, D Gates, H M Fatemi
STUDY QUESTION: Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? SUMMARY ANSWER: The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. WHAT IS KNOWN ALREADY: Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome...
September 12, 2016: Human Reproduction
Giuseppe Benagiano, Sun-Wei Guo, Paola Bianchi, Patrick Puttemans, Stephan Gordts, Felice Petraglia, Ivo Brosens
INTRODUCTION: Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed at an earlier stage when the endometrioma may be smaller, less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important...
October 2016: Expert Opinion on Pharmacotherapy
Hannah Demond, Tom Trapphoff, Deborah Dankert, Martyna Heiligentag, Ruth Grümmer, Bernhard Horsthemke, Ursula Eichenlaub-Ritter
Delayed ovulation and delayed fertilization can lead to reduced developmental competence of the oocyte. In contrast to the consequences of postovulatory aging of the oocyte, hardly anything is known about the molecular processes occurring during oocyte maturation if ovulation is delayed (preovulatory aging). We investigated several aspects of oocyte maturation in two models of preovulatory aging: an in vitro follicle culture and an in vivo mouse model in which ovulation was postponed using the GnRH antagonist cetrorelix...
2016: PloS One
Seon-Mi Kim, Minhee Lee, So Young Lee, Euisun Park, Soo-Min Lee, Eun Jeong Kim, Min Young Han, Taekyung Yoo, Jihyae Ann, Suyoung Yoon, Jiyoun Lee, Jeewoo Lee
We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound...
October 13, 2016: Journal of Medicinal Chemistry
Alice Luddi, Angela Capaldo, Riccardo Focarelli, Martina Gori, Giuseppe Morgante, Paola Piomboni, Vincenzo De Leo
BACKGROUND: The status characterized by the imbalance between pro-oxidants and antioxidants molecules, defined as oxidative stress, has been suggested to be involved in the pathogenesis of subfertility in females. This study aims to evaluate the impact of a complete micronutrients supplementation on oxidative stress levels in follicular microenvironment as well as on in vitro fertilization (IVF) outcome. METHODS: This preliminary study was conducted between January 2014 and July 2015 at the Siena University Hospital Infertility Clinic...
2016: Reproductive Biology and Endocrinology: RB&E
J Gobernado, C Alvarez-Colomo, L Rodriguez-Tabernero, L Barrero, J M F Fernández-Gómez, J Schneider
BACKGROUND: In Spanish public hospital Reproduction Units it is very problematic to perform programmed intrauterine insemination (IUI) on weekends, if indicated. Small previous pilot studies suggest that using a GnRH antagonist to avoid an LH weekend surge would allow to perform IUI on the following Monday, not impairing the expected pregnancy rate. METHODS: Between 1st January 2007 and 31st December 2015, 4.782 intrauterine inseminations were performed at Valladolid University Clinic, Spain, corresponding to 1...
2016: Reproductive Biology and Endocrinology: RB&E
Kenta Miki, Hiroshi Sasaki, Masahito Kido, Hiroyuki Takahashi, Manabu Aoki, Shin Egawa
BACKGROUND: Neoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare. However, normalization of serum testosterone levels following completion of neoadjuvant ADT in either form of treatment has never been compared in clinical trials...
2016: BMC Cancer
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