cetrorelix and ganirelix

For many patients, the typical treatment protocol for in vitro fertilization (IVF) is both physically and psychologically demanding. An alternative approach to use of gonadotropin-releasing hormone (GnRH)-agonists traditionally used to prevent premature ovulation, is use of GnRH-antagonists. The aim of this article is to describe advantages and disadvantages of using GnRH-antagonists in IVF.. The paper is based on literature identified through a non-systematic search in PubMed, and more than ten years of clinical experience with use of GnRH antagonists in IVF.. To maintain a similar pregnancy rate as that with GnRH-agonists, one can use GnRH-antagonists at an earlier time-point during stimulation of the ovaries and a lower dose of follicle stimulating hormone (FSH). A less intensive stimulation implies a lower risk of complications and side effects and a shorter treatment period before egg collection (from four-five weeks to less than two weeks). The main disadvantage of the GnRH-antagonist protocol is that ovarian stimulation cannot be programmed to the same extent as that with use of a GnRH-agonist.. Stimulation with a GnRH-antagonist instead of a GnRH-agonist in IVF, is less physically and psychologically demanding for the patients and maintains the same birth rate.

Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovary; Ovulation; Pregnancy; Pregnancy Rate; Treatment Outcome; Ultrasonography, Prenatal

To compare the administration of GnRH antagonist in gonadotropin intrauterine insemination (IUI) cycles with cycles where no intervention took place.. Meta-analysis of published prospective randomized trials.. Five hundred twenty-one patients who were administered a GnRH antagonist and 548 conservatively treated patients who served as control subjects were included in the meta-analysis.. Prospective trials were retrieved from Medline and Cochrane Library (last update October 2006). Random effect analysis was used in this meta-analysis. Two independent reviewers performed data extraction.. Clinical pregnancy rates.. Six comparisons were retrieved including 1,069 patients. Higher pregnancy rates were found in the randomized controlled trials (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.05-2.33) when a GnRH antagonist was added to a gonadotropin superovulated IUI protocol. Early published studies with smaller sample sizes showed stronger associations (OR 2.31, 95% CI 1.15-4.63) than later studies (OR 1.32, 95% CI 0.79-2.23).. From the randomized controlled trials of this meta-analysis, it is clear that allowing for follicle growth and avoiding premature LH rise, increased pregnancy rates are observed with GnRH antagonist administration. A parallel trend for multiple pregnancy rates in the GnRH antagonist group was observed, although this did not reach statistical significance. The flexible regimen was widely used. This meta-analysis of early data might enhance further research in this direction.

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Insemination, Artificial; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Time Factors

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menstrual Cycle; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate

Topics: Drug Therapy, Combination; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Pregnancy; Pregnancy Outcome

This article is a systematic review of the literature on utilization of gonadotrophin-releasing hormone antagonists (GnRH-ant) for ovarian stimulation for IVF in special patient groups. Summarized by meta-analysis are the data from randomized controlled trials (RCT) in which GnRH-agonist (GnRH-a) and GnRH-ant were compared (eight RCT for poor response, four RCT for PCOS). Also reviewed are the data from two RCT and 13 retrospective or observational trials in which patients at risk of ovarian hyperstimulation syndrome (OHSS) were triggered with GnRH-agonist instead of HCG. For poor responders, no differences in clinical outcomes were found, except a significantly higher number of cumulus-oocyte complexes in GnRH-antagonist multiple dose protocol as compared to GnRH-agonist long protocol (P=0.05). For PCOS patients, no differences in outcomes were found, except a significantly shorter duration of stimulation, when GnRH-antagonist multiple dose protocol and GnRH-agonist long protocol are compared (P<0.01). However, sample sizes are still small and power to detect subtle differences is therefore limited. For OHSS risk patients triggered with GnRH-agonist, reports on the efficacy of this measure vary in the literature. GnRH-agonist triggering appears to be associated with a reduction in the incidence of mild and moderate OHSS. For prevention of severe OHSS, as yet, only very limited evidence is available.

Topics: Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Odds Ratio; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

Gonadotrophin-releasing hormone (GnRH) plays a key role in the secretion of gonadotrophins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which regulate steroidogenesis and folliculogenesis. Two GnRH antagonists, Cetrorelix and Ganirelix, deprived of histaminergic side-effects, have been introduced into ovarian stimulation protocols to prevent premature LH surges and proved their safety in clinical trials. At present, most of the published studies have not found significant differences in follicular recruitment, oocyte quality, and so on, except for a decrease in pregnancy and implantation rates in in vitro fertilization and embryo transfer (IVF-ET) cycles when the GnRH antagonist rather than the agonist was used. This decrease in pregnancy rates was in relation with a necessary learning curve of the physicians. Another possibility is the impact of the GnRH antagonist on endometrium through its GnRH receptor; this effect was cancelled after cryopreserved embryo transfers because the pregnancy rates were similar between GnRH antagonist and agonist in this case. GnRH antagonists were also interesting in poor responders and polycystic ovarian syndrome, where the agonists have not permitted to obtain the better results in IVF-ET cycles. Similarly, the GnRH antagonists could prevent the LH surge in the intrauterine insemination cycles.

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocytes; Pregnancy; Reproductive Medicine

Gonadotrophin-releasing hormone (GnRH) antagonists have been introduced in IVF to prevent premature LH surge. They bind competitively to pituitary receptors and prevent endogenous GnRH from exerting any stimulus on pituitary cells, avoiding the initial 'flare-up' effect and decreasing gonadotrophin secretion within a few hours. Pituitary reserve and gonadotrophin synthesis are not affected; therefore, the recovery of pituitary function is rapid. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day 6-7 of stimulation, or when the leading follicle is 14-15 mm, until human chorionic gonadotrophin (HCG) administration. The single-dose protocol involves the single administration of 3 mg cetrorelix on day 7-8 of stimulation. Both antagonists with either regimen seem to be equally effective in the prevention of the LH surge. Compared with a long luteal agonist protocol, the treatment is shorter and requires a smaller amount of gonadotrophins. Pregnancy rate seems to be lower, but a decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) is reported by several studies. A promising aspect of antagonists may be the possibility of making treatment less aggressive. Finally, in antagonist cycles, ovulation triggering is possible by GnRH agonists, avoiding the deleterious effect of HCG and thus preventing OHSS.

Topics: Chorionic Gonadotropin; Clinical Protocols; Clinical Trials as Topic; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pituitary Gland

The outcome of freeze-thaw cycles with pronuclear stage oocytes or embryos, derived from collecting cycles stimulated with gonadotropin-releasing hormone (GnRH)-antagonists' protocols, was reviewed.. The viability of cryopreserved pronuclear stage oocytes and embryos, the quality of transferred embryos and the pregnancy rates of the freeze-thaw cycles seem to be satisfactory regardless of the type and dose of GnRH-antagonist.

Topics: Cryopreservation; Embryo Implantation; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteolytic Agents; Oocytes; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Receptors, LHRH; Triptorelin Pamoate

Gonadotropin-releasing hormone (GnRH) antagonists have been tested extensively in ovarian stimulation protocols for assisted reproductive techniques (ART). GnRH antagonists immediately and rapidly inhibit gonadotropin release by the anterior pituitary gland by competitive blockage of the GnRH receptor, preventing and interrupting luteinising hormone surges in controlled ovarian hyperstimulation for infertility treatment. A review of the available literature on GnRH antagonists for ART is presented, focusing on the pharmacological and clinical properties of the two compounds available on the market, cetrorelix and ganirelix. Both cetrorelix and ganirelix are well tolerated and effective drugs for controlled ovarian hyperstimulation and are of comparable value for infertility treatment. Cetrorelix is available as a 0.25mg preparation for daily injections and as a 3mg intermediate depot preparation. Ganirelix is available as a 0.25mg preparation for daily injections.Currently, two treatment protocols are used in clinical practice: the GnRH antagonist multiple-dose protocol and the GnRH antagonist single-dose protocol. Both protocols are effective and well tolerated. Cetrorelix and ganirelix have not yet been directly compared in a clinical trial; nor have the single-dose and the multiple-dose approaches been compared in a randomised, controlled trial. Data to compare these compounds in clinical terms can be extrapolated only from results of phase II dose-finding studies and phase III studies comparing GnRH agonist cycles with GnRH antagonists in single- and multiple-dose protocols. Therefore, all conclusions on clinical differences between cetrorelix and ganirelix should remain tentative, as they are based on a limited amount of available data.Randomised, controlled trials comparing cetrorelix and ganirelix are warranted to further evaluate benefits and drawbacks of individual GnRH antagonists. Furthermore, more data are needed to determine the efficacy and safety of cetrorelix and ganirelix in established treatment protocols in patients other than those included in clinical trials investigating new drugs, such as "poor responders", patients with polycystic ovaries, patients with a history of allergy or overweight patients.

Topics: Clinical Trials as Topic; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted

Modern gonadotrophin-releasing hormone (GnRH) antagonists such as cetrorelix and ganirelix reliably prevent premature LH surge in controlled ovarian hyperstimulation for assisted reproductive technologies. Nevertheless, GnRH antagonists do not allow homogenization of the follicle cohort, as observed with GnRH agonists. Administration of estrogens, progestogens or contraceptive pill in previous late luteal phase, may improve the size homogeneity of antral follicles. The coordination of follicular development may optimize ovarian response to r-FSH/GnRH antagonist protocols.

Topics: Estrogens; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Norethindrone; Ovulation Induction; Progestins

Introduction of the antagonist: on a determined day or depending on follicular growth? GnRH antagonists prevent LH surge in IVF cycles. GnRH antagonist can be administrated at a fixed day (day 6) or according to mean follicle size and estradiol levels (flexible regimen). Less monitoring is required for IVF cycles with the fixed regimen. For the flexible regimen, GnRH antagonist should be initiated on the day when the leading follicle reaches 14 mm diameter. Flexible regimen should decrease total antagonist and gonadotropin doses. Similar pregnancy rates are observed between the fixed and the flexible GnRH antagonist regimens.

Topics: Clinical Protocols; Drug Administration Schedule; Drug Monitoring; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy Rate; Time Factors

Gonadotrophin-releasing hormone (GnRH) antagonists have recently been introduced into clinical practice. They appear to offer a promising alternative to the long-established GnRH agonist regimens for prevention of a premature LH surge during ovarian stimulation for assisted reproductive techniques. Clinical outcomes achieved with antagonists are comparable with those of a long GnRH agonist protocol, while treatment times and gonadotrophin requirements are reduced and safety is improved. In particular, the antagonists appear to be associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) than do agonists. Patient surveys suggest a preference for antagonist over agonist treatment cycles. These benefits suggest that GnRH antagonists have the potential to replace agonists as the treatment of choice in ovarian stimulation for assisted reproductive techniques. Two agents, cetrorelix and ganirelix, are currently in clinical use. Cetrorelix is available in single- and multiple-dose formulations, offering increased flexibility compared with ganirelix.

Topics: Amino Acid Sequence; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Molecular Sequence Data; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins

The different schemes of application of gonadotrophin-releasing hormone (GnRH) antagonists in ovarian stimulation protocols for assisted reproduction are reviewed. Starting from the initial schemes of single and/or multiple doses, the efficacy of GnRH antagonists in 'soft' protocols of ovarian stimulation has been evaluated in natural cycles, and the possibility of inducing the final oocyte maturation under antagonists either with native luteinizing hormone-releasing hormone or with GnRH agonists. The largest clinical studies carried out with cetrorelix or with ganirelix and published to date were analysed. Apart from the benefits of reducing the duration of the treatment, gonadotrophin requirements and ovarian hyperstimulation syndrome incidence, there is still a serious debate on the potential deleterious effect of GnRH antagonists on implantation and pregnancy rates. More specific aspects such as cycle programming, application of GnRH antagonists in protocols for poor responders etc., were also reviewed in this survey.

Topics: Buserelin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction; Pregnancy; Reproductive Techniques, Assisted

The safety of ovarian stimulation procedures or the procedure of assisted reproduction in general can be estimated by various parameters. Two of the most important are the health of children born after the procedure and the incidence of ovarian hyperstimulation syndrome (OHSS). The latter is important because it is the most severe, potentially life-threatening complication of any stimulation procedure. The use of gonadotrophin-releasing hormone (GnRH) antagonists in ovarian stimulation protocols has had no impact on the health of children born. This was proven in 227 children born after the use of cetrorelix and in 73 children born after the use of ganirelix. To analyse the incidence of OHSS and the impact of GnRH antagonists on clinical pregnancy rates compared with the long protocol, a meta-analysis was done. This showed a reduction of OHSS with the use of cetrorelix. Furthermore, when compared with the long protocol, clinical and ongoing pregnancy rates were not significantly reduced with the use of cetrorelix. Taken together, the use of GnRH antagonists are safe with regard to children's health. The incidence of OHSS does not increase with ganirelix, and a reduction can be expected with cetrorelix.

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

The introduction of the gonadotrophin-releasing hormone(GnRH) antagonists offers new potential for in vitro fertilization (IVF) clinics. Compared with GnRH agonists, the use of the GnRH antagonists significantly reduces the dose of gonadotrophin and duration of treatment required, and also reduces unwanted side-effects. Patients also tend to prefer treatment with GnRH antagonists compared with agonists. The GnRH antagonists are useful in both good and poor responders, and there is some flexibility in treatment protocols. A single dose of GnRH antagonist may be used in patients who do not want or require more aggressive stimulation. Promising data indicate advantages of GnRH antagonists in terms of reduced incidence of ovarian hyperstimulation syndrome and reduced impairment of luteal function. It is anticipated that, as a result of further development of treatment protocols, pregnancy rates with the GnRH antagonists will become at least equivalent to those achieved with GnRH agonist protocols.

Topics: Clinical Trials, Phase III as Topic; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction

Before gonadotropin-releasing hormone agonists (GnRHa) became available, approximately 20% of stimulated cycles within an in vitro fertilization (IVF) program were cancelled due to premature LH surges. By using the GnRHa to prevent LH surges via gonadotrope GnRH receptor down-regulation and desensitization, this percentage decreased to about 2%, and concomitantly, the IVF and pregnancy rates per cycle initiated were increased. Several treatment schedules currently are in use, including the so-called "long protocol," in which the GnRHa is begun in the luteal phase and down-regulation occurs before the start of the gonadotropin-stimulation treatment phase. This is generally the most effective regimen and is presently the most frequently used protocol. However, it has some disadvantages, such as hypoestrogenic side effects and an increase in the number of ampules of FSH or hMG required for adequate stimulation. There is a new generation of GnRH antagonists now clinically available, that has been able to minimize the potential side effects and provide reliable antagonism at the GnRH receptor. These agents seem better suited than GnRHa for assisted reproductive technology (ART) cycles inasmuch as they can prevent LH surges without requiring complete gonadotropin suppression. We have reviewed the current literature concerning their use in IVF cycles.

Topics: Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction; Pregnancy

Over the last two decades, a long protocol of Gonadotrophin-releasing hormone agonist (GnRHa) to prevent premature LH surges has been the standard treatment for ovarian stimulation in assisted reproduction. In the long protocols (with GnRHa started either in the mid luteal phase or in the early follicular phase of the preceding cycle) gonadotrophin administration is delayed until pituitary desensitization has been achieved, which usually takes 2-3 weeks. Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This will result in dramatic reduction in the duration of treatment cycle and will avoid estrogen deprivation symptoms associated with GnRH agonist induced down-regulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens.. To compare the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception.. Search strategies included on-line searching of the MEDLINE and EMBASE databases and the Cochrane Menstrual Disorders and Subfertility Group's Specialised Register from 1982 to 2001, and hand searching of bibliographies of relevant publications and reviews, and abstracts of scientific meetings.. Only randomised controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review.. Data were extracted into 2 x 2 tables. For the primary outcomes, clinical pregnancy per woman randomised and prevention of premature LH surge, the overall common odds ratio (OR) and the risk difference with 95% confidence interval (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. Secondary outcomes considered were the number of oocytes retrieved, clinical pregnancy per oocyte retrieval and per embryo transfer, spontaneous abortion, incidence of severe ovarian hyperstimulation syndrome and the amount of gonadotrophins used. Where relevant data were missing or unclear the authors were consulted.. Five trials comparing the new fixed protocol of GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria and were included. In four studies, the multiple low-dose (0.25 mg) antagonist regimen was applied and in one study, the single high-dose (3 mg) antagonist regimen was investigated. In all trials, reference treatment included a long protocol of GnRHa (buserelin, leuprorelin or triptorelin) starting in the mid-luteal phase of the preceding cycle. In comparison to the long protocol of GnRHa, the overall OR for the prevention of premature LH surges was 1.76 (95% CI 0.75, 4.16), which is not statistically significant. There was a significantly fewer clinical pregnancies in those treated with GnRH antagonists (OR 0.78, 95% CI 0.62, 0.97). The absolute treatment effect (ATE) was calculated to be 5%. The number needed to treat (NNT) was 20. There was a statistically significant reduction in incidence of severe ovarian hyperstimulation syndrome, (RR 0.36, 95% CI 0.16, 0.80) using antagonist regimens as compared to the long GnRHa protocol.. The new fixed GnRH antagonist protocol (i.e. with antagonist start fixed on day 6 of gonadotrophin stimulation) is a short and simple protocol with a significant reduction in incidence of severe OHSS but a lower pregnancy rate compared to the GnRH agonist long protocol. There is a non significant difference between both protocols regarding prevention of premature LH surge. The clinical outcome may be further improved by developing more flexible antagonist regimens taking into account individual patient characteristics. The GnRH antagonist flexible regimen should be the area of research in the near future.

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction; Prospective Studies; Randomized Controlled Trials as Topic

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.

Topics: Chorionic Gonadotropin; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Odds Ratio; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Reproductive Techniques, Assisted

New GnRH antagonists are available in clinical practice. The different studies have confirmed the efficacy of these antagonists in preventing the LH surge. Two protocols have been described: in the multiple dose regimens, small doses of antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG. In the single dose protocol, one injection of a larger dose (3 mg) is proposed in the late follicular phase. Local and general tolerance of the two compounds is very good. The results obtained with both regimens as compared with GnRH agonists in long protocols are showing a reduction in the stimulation length, in the consumption of gonadotrophins and in the incidence of the OHSS. The pregnancy rates are comparable in the good prognosis patients selected in the published studies. When the final tuning of these new protocols will be done, the advantages of GnRH antagonists in reducing the complications and side effects of ovarian stimulation will give to GnRH antagonists an important place in IVF.

Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

The gonadotrophin-releasing hormone (GnRH) antagonists Cetrorelix and Ganirelix have been used in recent years in clinical studies to prove that these compounds reliably prevent the onset of premature luteinizing hormone (LH) surges during ovarian stimulation. Cetrorelix has been applied in single and multiple dose protocols, while Ganirelix has until now only been used in the multiple dose protocol. In the latter protocol, ovarian stimulation is started on day 2 or 3 of the spontaneous cycle with human menopausal gonadotrophin or recombinant follicle stimulating hormone. Daily administration of the GnRH antagonist at its minimum effective dose (0.25 mg/day s.c.) occurs from the sixth day of stimulation onwards until ovulation induction by human chorionic gonadotrophin. In the single dose protocol, 3 mg of the GnRH antagonist Cetrorelix was injected on day 8 of the stimulation cycle. Both protocols have been proven to be safe and effective. Fertilization rates of >60% in in-vitro fertilization and >70% in intracytoplasmic sperm injection, as well as clinical pregnancy rates of approximately 30% per transfer, sound most promising. The incidence of a premature LH surge is below 2%. The incidence of severe ovarian hyperstimulation syndrome seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened.

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Menotropins; Ovulation Induction; Randomized Controlled Trials as Topic; Recombinant Proteins; Sperm Injections, Intracytoplasmic

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle?. A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle.. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle.. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05.. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo.. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01).. This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use.. This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle.. None.. EudraCT number 2009-010952-81.. 21 September 2009.. 30 October 2009.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Treatment Outcome

In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles, the current study aimed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist, and if so, to what extent the progesterone rise affects the probability of pregnancy.. Overall 190 patients were randomized: 94 in the GnRH-agonist group and 96 in the GnRH-antagonist group. The GnRH-agonist long protocol started on Day 21 of the preceding cycle with intranasal buserelin (600 mg per day). The GnRH-antagonist protocol started on Day 6 of the stimulation with ganirelix or cetrorelix (each 0.25 mg). All blood samples were analysed with the Elecsys analyzer. An intention-to-treat analysis was applied.. A progesterone rise >1.5 ng/ml was noticed in 23.0% of the antagonist group, comparable with 24.1% incidence within the agonist group. Per patient randomized, delivery rates were also comparable: 28.1% in the antagonist group and 24.5% in the agonist group (odds ratio = 1.21, 95% confidence interval: 0.63-2.31, P= 0.56). However, there was a reduction in delivery rates when progesterone exceeded the threshold of 1.5 ng/ml, both in the agonist group (9.5 versus 31.8%, P= 0.03) and in the antagonist group (14.3 versus 34.3%, P= 0.07).. Although the incidence of a progesterone rise was similar between the two analogues, our findings reconfirm previous observations that insufficient progesterone control (>1.5 ng/ml) on the day of ovulation triggering is related to poor delivery rates in both protocols. The current study has shown that the reproductive outcomes with the two GnRH analogues are comparable. Possible modes of action to circumvent late follicular progesterone rise should be explored.. NCT01191710.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Pregnancy; Pregnancy Outcome; Progesterone; Prospective Studies; Sperm Injections, Intracytoplasmic

To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.. Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.. There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.. The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.

Topics: Adult; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Outcome

To compare the safety and efficacy of single-dose cetrorelix acetate (3 mg) and daily ganirelix acetate (0.25 mg) in the inhibition of premature LH surge in women undergoing cycle-programmed ovarian stimulation before Assisted Reproductive Technology (ART).. Prospective, open-label, randomized, comparative study.. Sixteen ART centers in the United States.. One hundred eighty-five infertile patients undergoing ART.. Single injection of cetrorelix (3 mg SC) or daily dose of ganirelix (0.25 mg SC) was administered when the lead follicle was > or =14 mm. Daily cetrorelix (0.25 mg) was administered if the criteria for hCG administration were not met 4 days after receiving 3 mg of cetrorelix.. Percentage of patients who did not have a premature LH surge, defined as LH <10 IU/L on the day of hCG administration. The IVF and embryo transfer (ET) outcomes were assessed.. No patient in either treatment group had a premature LH surge. There were no statistically significant differences between treatments for any IVF/intracytoplasmic sperm injection (ICSI) or ET outcomes, including pregnancy rate (PR). However, cetrorelix required significantly fewer injections than ganirelix. Similar safety profiles were observed.. Cetrorelix and ganirelix effectively prevented LH surges in oral contraceptive (OC) pill-programmed, flexible protocols, with similar safety profiles and PRs; however, cetrorelix required significantly fewer injections, increasing patient convenience.

Topics: Adult; Analysis of Variance; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Pregnancy; Pregnancy Rate; Prospective Studies; Reproductive Techniques, Assisted

A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols.. A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016-2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups.. Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88-2.28; P < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99-2.74; P < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69-2.63, P < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28-1.99; P < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P < 0.05). No significant difference was observed in other patients between different protocols.. It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China.

Topics: Adult; China; Chorionic Gonadotropin; Cryopreservation; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Logistic Models; Multivariate Analysis; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Treatment Outcome; Triptorelin Pamoate

The aim of the presented study is to investigate the impact of progesterone change in the late follicular phase on the pregnancy rates of both agonist and antagonist protocols in normoresponders.. A total of 201 normoresponder patients, who underwent embryo transfer were consecutively selected. 118 patients were stimulated using a long luteal GnRH agonist protocol and 83 using a flexible antagonist protocol. The level of change in late follicular phase progesterone was calculated according to the progesterone levels on the hCG day and pre-hCG day (1 or 2 days prior to hCG day) measurement.. Clinical pregnancy rates were comparable between long luteal and antagonist group (35.6 and 41%, respectively). The incidence of progesterone elevation on the hCG day was 11% in long luteal and 18% in antagonist group (p = 0.16). In pregnant cycles, p levels both on the hCG day and pre-hCG day measurement were significantly higher in antagonist than agonist cycles (p = 0.029, p = 0.038, respectively). The change of p level was statistically significant in non-pregnant cycles both for the agonist (-0.17 ± 0.07; 95% CI: -0.29 to -0.37) and antagonist groups (-0.18 ± 0.07; 95%CI: -0.31 to -0.04).. Late follicular phase progesterone levels were stable during the cycles of pregnant patients irrespective of the protocols and were shown to be higher in pregnant patients in antagonist cycles when compared to agonist cycles.

Topics: Adult; Case-Control Studies; Embryo Transfer; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Luteinizing Hormone; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Sperm Injections, Intracytoplasmic

To evaluate the effects of an ovulation triggering agent, human chorionic gonadotropin (hCG), versus a gonadotropin-releasing hormone agonist (GnRHa) on early embryo development in vitro using a time-lapse system.. Retrospective analysis of a prospectively collected database. A total of 739 embryos from 152 infertile couples undergoing intracytoplasmic sperm injection cycles.. Embryo culture in a time-lapse incubator (EmbryoScope, Vitrolife, Göteborg, Sweden).. Embryo morphokinetic parameters.. In the 152 women, 252 embryos were derived from GnRHa-triggered cycles compared with 487 embryos derived from hCG-triggered cycles. Time-lapse analysis revealed that embryos from cycles triggered by a GnRHa cleaved faster than embryos derived from hCG-triggered cycles.. Triggering with a GnRHa in in vitro fertilization cycles affects embryo kinetics.

Topics: Adult; Azoospermia; Chorionic Gonadotropin; Embryo Culture Techniques; Embryonic Development; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Kinetics; Male; Ovarian Reserve; Ovulation Induction; Retrospective Studies; Sperm Injections, Intracytoplasmic; Time-Lapse Imaging; Triptorelin Pamoate

To determine if there is any association of serum progesterone (P) level at the time of human chorionic gonadotropin (hCG) injection and pregnancy outcome in in vitro fertilization (IVF) cycles using gonadotropin releasing hormone (GnRH) antagonists for controlled ovarian hyperstimulation (COH).. A retrospective analysis of IVF cycles over a six and a half-year period where either cetrorelix or ganirelix was used with COH and at least two embryos were transferred. Female partners were < or = 35. Four different serum progesterone (P) ranges were evaluated from < or = .5 ng/ml to 1.9 ng/ml; P was measured by ELISA.. There was no significant difference in pregnancy rates or even a trend in that direction with increasing serum P levels with either GnRH antagonist.. At least with COH cycles using GnRH antagonists and where serum P is measured by ELISA there does not seem to be any disadvantage of higher serum P levels up to 2 ng/ml at the time of hCG in IVF-ET cycles.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Pregnancy; Pregnancy Outcome; Progesterone; Reproductive Control Agents; Retrospective Studies

To compare pregnancy rates following the transfer of thawed frozen embryos according to the type of GnRH antagonist or agonist used during controlled ovarian hyperstimulation (COH).. Retrospective review of frozen embryo transfers according to whether a GnRH agonist or antagonist was used. Furthermore to determine if a specific antagonist/agonist resulted in higher pregnancy rates than the other.. The pregnancy rates in two different age categories were similar whether the COH regimen used the GnRH agonist leuprolide acetate or the GnRH antagonist cetrorelix. However, lower pregnancy rates were found with the GnRH antagonist ganirelix.. These data reached similar conclusions as was found comparing these three agents in fresh embryo transfer.

Topics: Adult; Embryo Transfer; Endometrium; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Outcome; Retrospective Studies

This study evaluated women with a high body mass index (BMI) (>40 kg/m(2)) and low BMI (<18 kg/m(2)) undergoing assisted reproduction treatment and determined whether the type of gonadotrophin-releasing hormone (GnRH) analogue used has an impact on cycle parameters and outcome. The study analysed 65 women with high BMI and 118 with low BMI. In the former group, polycystic ovarian syndrome was significantly more prevalent in the agonist long protocol (ALP) group (P=0.01) and gonadotrophin consumption was lower, peak oestradiol concentrations and total number of oocytes retrieved were higher in the ALP group compared with the antagonist (ANT) group. Implantation rate (IR), pregnancy rate (PR) per embryo transfer and early pregnancy loss rate (EPLR) were similar in both stimulation groups, with overall rates of 21.6%, 55.4% and 44.4%, respectively. In women with low BMI, peak oestradiol concentrations, total oocytes retrieved, mature oocytes and transferred embryos were higher in the ALP group compared with ANT group. IR, PR/embryo transfer and EPLR were similar in both groups, with overall rates of 24.3%, 52.5% and 16.1%, respectively. In all patients, no difference was found between ALP and ANT protocols concerning treatment outcome. Contrary to the reasonable EPLR observed in women with low BMI, the high rate found in women with high BMI is remarkable.

Topics: Abortion, Spontaneous; Adult; Body Mass Index; Embryo Implantation; Embryo Transfer; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies

Early studies on gonadotrophin-releasing hormone (GnRH) antagonists pointed out histamine-mediated anaphylactic reactions as a potential adverse effect of these drug candidates. In this study we have compared the histamine-releasing potential of four approved and marketed antagonists, degarelix, cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples.. Human skin samples were obtained during cosmetic plastic surgery and kept in oxygenated saline solution. The samples were incubated either without or at different concentrations of the antagonists (3, 30 or 300 µg ml(-1) for all, except for ganirelix 1, 10 or 100 µg ml(-1) ). The drug-induced effect was expressed as the increase relative to basal release. The histamine-releasing capacity of the skin was verified by a universal histamine releaser, compound 40/80.. Degarelix had no significant effect on basal histamine release in the 3 to 300 µg ml(-1) concentration range. The effect of ganirelix was moderate causing a nonsignificant increase of 81 ± 27% at the 100 µg ml(-1) concentration. At 30 and 300 µg ml(-1) concentrations abarelix (143 ± 29% and 362 ± 58%, respectively, P < 0.05) and cetrorelix (228 ± 111% and 279 ± 46%, respectively, P < 0.05) caused significantly increased histamine release.. In this ex vivo human skin model, degarelix displayed the lowest capacity to release histamine followed by ganirelix, abarelix and cetrorelix. These findings may provide indirect hints as to the relative likelihood of systemic anaphylactic reactions in clinical settings.

Topics: Gonadotropin-Releasing Hormone; Histamine; Histamine Release; Humans; Oligopeptides; Skin

To determine if controlled ovarian hyperstimulation (COH) regimens using the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate result in higher pregnancy and implantation rates than COH regimens using the GnRH antagonists cetrorelix or ganirelix following fresh and frozen embryo transfer.. Retrospective analysis was performed evaluating the pregnancy rates with the first fresh and first frozen embryo transfer cycles according to which protocol was used. A haphazard decision was made on which protocol to use. Women were required to be < 40 years of age and have had > or = 5 eggs retrieved.. Significantly lower implantation rates were seen with ganirelix compared to leuprolide acetate or cetrorelix.. These data should hopefully encourage interest in a prospective study to determine if conclusions about the inferiority of ganirelix are not merely fortuitous.

Topics: Adult; Cryopreservation; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pregnancy; Pregnancy Rate; Retrospective Studies

To describe the distribution of E2 change after antagonist treatment and evaluate the prognostic implications on cycle outcomes.. We reviewed all antagonist IVF cycles from 2002 to 2007 in a university clinic, if E2 levels preantagonist and postantagonist administration were available (N = 287). Distributions of E2 response (defined as posttreatment/pretreatment E2 ratio) to antagonist treatment were composed and categorized by quartiles, and outcomes were analyzed (oocyte yield, clinical pregnancy and live birth rates).. Cycles in the upper quartile had higher oocyte yield (15.2 +/- 7.5 vs. 13.1 +/- 7.9 vs. 11.8 +/- 5.6, upper, middle and lower quartiles, p<0.01), clinical pregnancy (45.9% vs. 28.7% vs. 25.0%, p=0.01) and live birth rates (38.6% vs. 22.3% vs. 20.0%, p=0.02) than cycles in middle and lower quartiles. However, cycles in the lowest quartile did not have significantly different outcomes from the majority of cycles in the cohort (middle quartiles of E2 distribution).. Our study suggests that E2 rise after antagonist initiation is positively associated with higher oocyte yield and clinical pregnancy. However, women with the lowest increases in E2 do not have significantly worse outcomes than most women using antagonist IVF protocols.

Topics: Adult; Age Factors; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Pregnancy; Pregnancy Rate; Prognosis; Treatment Outcome

To determine if the choice of gonadotropin releasing hormone antagonist influences subsequent pregnancy rates in women with diminished egg reserve.. Retrospective determination of pregnancy rates following embryo transfer in women with day 3 FSH >12 mIU/ml using lower dose gonadotropin stimulation regimen.. Though no significant differences were found there was a trend for lower pregnancy rates with ganirelix vs cetrorelix.. The trend for lower pregnancy rates with ganirelix vs. cetrorelix seen in women with diminished egg reserve is consistent with the findings of a study performed in women with normal egg reserve using a normal gonadotropin stimulation regimen. It is not clear if the adverse effect is on the endometrium or the embryo.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Maternal Age; Ovarian Follicle; Pregnancy; Pregnancy Outcome; Retrospective Studies

HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of GnRH antagonists on endometrial receptivity, we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles.. Prospective case-control study.. University academic medical center.. Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation with recombinant FSH and used either a GnRH antagonist or a GnRH agonist; seven control subjects underwent natural cycles.. Pipelle endometrial biopsies were obtained 11 days after hCG administration or spontaneous LH surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma.. Endometrial HOXA10 protein expression.. HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist-treated cycles compared with GnRH agonist-treated cycles or natural cycle control subjects. There was no significant difference in glandular cell HOXA10 expression among the three groups.. Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells and thus may affect endometrial receptivity.

Topics: Adult; Biopsy; Case-Control Studies; Endometrium; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Homeobox A10 Proteins; Homeodomain Proteins; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Prospective Studies; RNA, Messenger; Stromal Cells

Three antagonists of gonadotrophin-releasing hormone are currently clinically available. Cetrorelix (Cetrotide) and ganirelix (Orgalutran/Antagon) have been safely used in assisted reproduction since 1999 and 2000 respectively. The structurally similar abarelix (Plenaxis) has been approved for the therapy of advanced androgen sensitive prostate cancer. However, due to the occurrence of allergic reactions, its use is restricted to only a subgroup of patients. These allergic side effects may not be due to abarelix, as the drug itself does not have a strong histamine liberating potential in vitro, but could be attributed to carboxymethylcellulose (CMC), which only Plenaxis, but not Cetrotide or Orgalutran/Antagon contain. CMC is used to obtain the sustained-release characteristics of Plenaxis. Since 1973, numerous case reports and studies have been published regarding allergic reactions and specific immunoglobulin E antibodies against CMC. Thus, the allergic side effects of Plenaxis could be rather due to CMC than to abarelix.

Topics: Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Hypersensitivity; Oligopeptides; Pregnancy

Recently, GnRH antagonists (GnRHants) have been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). Here we investigated whether the GnRHants cetrorelix and ganirelix exert effects on the human ovarian IGF system. Since controversy exists on the action of GnRH agonists in the human ovary, we also tested the effect of triptorelin on IGF-II, IGF-binding protein-2 (IGFBP-2) and pregnancy-associated plasma protein-A (PAPP-A) in cultured human granulosa-lutein cells.. In vitro cell culture study in a research laboratory of a university hospital.. Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin or cetrorelix. Cells were treated with triptorelin, cetrorelix or ganirelix, 1 nmol/l each, for 48 h. IGF-II, IGFBP-2 and PAPP-A were measured by RIA and enzyme immunoassay respectively.. GnRHants and triptorelin did not affect IGF-II, IGFBP-2 or PAPP-A.. We conclude that GnRHants do not exert any significant effects on the IGF system of granulosa-lutein cells and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Topics: Cells, Cultured; Female; Gonadotropin-Releasing Hormone; Granulosa Cells; Hormone Antagonists; Humans; In Vitro Techniques; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor II; Luteolytic Agents; Pregnancy-Associated Plasma Protein-A; Triptorelin Pamoate

GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells.. Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue.. Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production.. We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Topics: Cells, Cultured; Female; Gonadotropin-Releasing Hormone; Granulosa Cells; Hormone Antagonists; Humans; Lutein; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Steroids; Triptorelin Pamoate

Topics: Contraceptive Agents, Male; Female; Genital Diseases, Female; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Male; Prostatic Neoplasms; Reproductive Techniques

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction

Recent suggestions that gonadotrophin-releasing hormone (GnRH) antagonists activate the GnRH receptor are discussed. Most of the studies cited in support of this suggestion are in-vitro studies, testing supra-pharmacological doses of GnRH analogues in cancer cell lines, whereas GnRH antagonists, e.g. ganirelix or cetrorelix, do not affect the steroidogenesis of human granulosa cells in vitro. In patients treated with GnRH antagonists prior to IVF or intracytoplasmic sperm injection (ICSI), oocyte maturity and fertilization rates are equal to those achieved following a long protocol of GnRH agonists. Although there is a tendency towards a lower pregnancy rate (not statistically significant) in the initial trials using GnRH antagonist with either recombinant FSH or human menopausal gonadotrophin (HMG) for ovarian stimulation, this new treatment option of GnRH antagonists facilitates short and simple treatment and improves the convenience and safety for the patient. As with GnRH agonists in the past, the clinical outcome of GnRH antagonist treatment will improve with time as more clinical experience is gained (learning curve) and the treatment protocol is optimized. Moreover, a GnRH agonist instead of human chorionic gonadotrophin (HCG) may be used for triggering ovulation and will decrease the cancellation rate and minimize the risk for developing ovarian hyperstimulation syndrome (OHSS).

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovulation Induction; Pregnancy; Receptors, LHRH; Reproductive Techniques