The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Efstratios M Kolibianakis - One of the best experts on this subject based on the ideXlab platform.
-
significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH Antagonists and gonadotrophins a systematic review and meta analysis
Current Pharmaceutical Biotechnology, 2012Co-Authors: Efstratios M Kolibianakis, Christos A Venetis, J Bontis, Basil C TarlatzisAbstract:The current meta-analysis aimed to answer the following research question: is progesterone elevation on the day of hCG administration associated with the probability of clinical pregnancy in women undergoing ovarian stimulation for IVF using GnRH Antagonists? A literature search in MEDLINE, EMBASE and CENTRAL electronic databases followed by extensive hand-searching from two independent reviewers was performed to identify relevant studies. Eventually five eligible studies (n=585 patients) were identified. No significant differences were present between patients with and those without progesterone elevation regarding female age, duration of stimulation and total dose of gonadotrophins required. However, patients with progesterone elevation were characterized by higher serum estradiol levels on the day of hCG administration (+956 pg/ml, 95% +248 to +1664, random effects model, p=0.008) and more COCs retrieved (+2.9, 95% CI +1.5 to +4.4, fixed effects model, p < 0.001). Progesterone elevation on the day of hCG administration was associated with a significantly decreased probability of clinical pregnancy per cycle (-9%, 95% CI -17 to -2, fixed model effects, p). In conclusion, in patients treated with GnRH Antagonists and gonadotrophins, progesterone elevation on the day of hCG administration is significantly associated with a lower probability of clinical pregnancy.
-
is earlier administration of human chorionic gonadotropin hcg associated with the probability of pregnancy in cycles stimulated with recombinant follicle stimulating hormone and gonadotropin releasing hormone GnRH Antagonists a prospective randomized
Fertility and Sterility, 2011Co-Authors: D Kyrou, Efstratios M Kolibianakis, Herman Tournaye, Basil C Tarlatzis, Human M Fatemi, P DevroeyAbstract:Objective To evaluate the association of timing of hCG administration and probability of pregnancy in patients stimulated with recombinant FSH/GnRH Antagonists for IVF. Design Prospective randomized controlled clinical trial. Setting Dutch-speaking Free University of Brussels. Patient(s) One hundred twenty patients, aged Intervention(s) Ovarian stimulation was achieved using recombinant FSH starting on day 2 of the menstrual cycle at a fixed dose. To inhibit premature LH surge, daily GnRH antagonist was used from day 6 of stimulation. Triggering of final oocyte maturation was performed using 10,000 IU of hCG. Patients were randomized to receive hCG either as soon as three or more follicles of size ≥16 mm were present on ultrasonography (early-hCG group) or 1 day after the above criterion was met (late-hCG group). Main Outcome Measure(s) Ongoing pregnancy rate. Result(s) Significant differences were observed between the early-hCG and the late-hCG group regarding E 2 (1,388 ± 931 [mean ± SD] vs. 2,040 ± 1,231 pg/mL, respectively) and P (0.8 ± 0.3 vs. 1.1 ± 0.5 ng/mL, respectively) levels on the day of hCG administration and the number of metaphase II oocytes (9.2 ± 7.1 vs. 6.1 ± 4.9, respectively). No significant differences were observed between the early-hCG and the late-hCG group regarding positive hCG (46.2% vs. 50%, respectively) and ongoing pregnancy rates (34.6% vs. 40.7%, respectively). Conclusion(s) The current study provides evidence that earlier administration of hCG is not associated with the probability of pregnancy in cycles stimulated with recombinant FSH and GnRH Antagonists.
-
oral contraceptive pill pretreatment in ovarian stimulation with GnRH Antagonists for ivf a systematic review and meta analysis
Fertility and Sterility, 2008Co-Authors: G Griesinger, K Diedrich, Basil C Tarlatzis, Christos A Venetis, Tanja Marx, Efstratios M KolibianakisAbstract:Objective To assess the impact of oral contraceptive pill (OCP) pretreatment in ovarian stimulation for in vitro fertilization (IVF) using gonadotropin releasing hormone (GnRH) Antagonists. Design Systematic review and meta-analysis of randomized controlled trials (RTC). Setting University IVF center. Patient(s) Infertile patients (n = 847), treated in four trials. Intervention(s) Systematic literature search (MEDLINE, EMBASE, CENTRAL COCHRANE, conference proceedings, reference lists) for randomized trials on OCP treatment before stimulation with gonadotropins and GnRH antagonist for IVF. Meta-analysis of data yielding pooled odds ratios (OR) or weighted differences of the means (WMD) and 95% confidence intervals (CI). Main Outcome Measure(s) Ongoing pregnancy rate per randomized woman. Result(s) Ongoing pregnancy rate per randomized woman was not found to be significantly different between patients with and those without OCP pretreatment (OR: 0.74, 95% CI: 0.53 to 1.03). Duration of gonadotropin stimulation (WMD: +1.41 days, 95% CI: +1.13 to +1.68) and gonadotropin consumption (WMD: +542 IU, 95% CI: +127 to +956) were significantly increased after OCP pretreatment. No significant differences were observed regarding the number of cumulus–oocyte complexes (COCs) and the fertilization rates. Conclusion(s) A significant difference in ongoing pregnancy rates between patients who received OCP pretreatment and those who did not is currently not present, although further studies are necessary for more solid conclusions on pregnancy likelihood to be drawn.
-
GnRH Antagonists in ovarian stimulation for ivf
Human Reproduction Update, 2006Co-Authors: Basil C Tarlatzis, Klaus Diedrich, Efstratios M Kolibianakis, B C Fauser, Luk Rombauts, Paul DevroeyAbstract:The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) Antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH Antagonists. The role of GnRH Antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.
-
a lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of hcg in patients undergoing ivf with GnRH Antagonists
Human Reproduction, 2005Co-Authors: Efstratios M Kolibianakis, P Devroey, K Diedrich, A Schultzemosgau, A Van Steirteghem, A Schroer, G GriesingerAbstract:BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH Antagonists remains to be assessed. METHODS: 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. RESULTS: No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH Antagonists.
K Diedrich - One of the best experts on this subject based on the ideXlab platform.
-
EXPERIMENTAL STUDY Actions of gonadotropin-releasing hormone Antagonists on steroidogenesis in human granulosa lutein cells
2015Co-Authors: J. M. Weiss, Kerstin M. Oltmanns, S. Polack, R. Felberbaum, E M Gürke, F Eick, K Diedrich, O OrtmannAbstract:Objective: 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. Methods: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. Results: 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. Conclusions: 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. European Journal of Endocrinology 144 677–68
-
oral contraceptive pill pretreatment in ovarian stimulation with GnRH Antagonists for ivf a systematic review and meta analysis
Fertility and Sterility, 2008Co-Authors: G Griesinger, K Diedrich, Basil C Tarlatzis, Christos A Venetis, Tanja Marx, Efstratios M KolibianakisAbstract:Objective To assess the impact of oral contraceptive pill (OCP) pretreatment in ovarian stimulation for in vitro fertilization (IVF) using gonadotropin releasing hormone (GnRH) Antagonists. Design Systematic review and meta-analysis of randomized controlled trials (RTC). Setting University IVF center. Patient(s) Infertile patients (n = 847), treated in four trials. Intervention(s) Systematic literature search (MEDLINE, EMBASE, CENTRAL COCHRANE, conference proceedings, reference lists) for randomized trials on OCP treatment before stimulation with gonadotropins and GnRH antagonist for IVF. Meta-analysis of data yielding pooled odds ratios (OR) or weighted differences of the means (WMD) and 95% confidence intervals (CI). Main Outcome Measure(s) Ongoing pregnancy rate per randomized woman. Result(s) Ongoing pregnancy rate per randomized woman was not found to be significantly different between patients with and those without OCP pretreatment (OR: 0.74, 95% CI: 0.53 to 1.03). Duration of gonadotropin stimulation (WMD: +1.41 days, 95% CI: +1.13 to +1.68) and gonadotropin consumption (WMD: +542 IU, 95% CI: +127 to +956) were significantly increased after OCP pretreatment. No significant differences were observed regarding the number of cumulus–oocyte complexes (COCs) and the fertilization rates. Conclusion(s) A significant difference in ongoing pregnancy rates between patients who received OCP pretreatment and those who did not is currently not present, although further studies are necessary for more solid conclusions on pregnancy likelihood to be drawn.
-
cetrorelix in the treatment of female infertility and endometriosis
Expert Opinion on Pharmacotherapy, 2006Co-Authors: D Finas, K Diedrich, D Hornung, A SchultzemosgauAbstract:The use of cetrorelix within ovarian-stimulation protocols demonstrates several advantages compared with gonadotropin-releasing hormone (GnRH) agonist-containing protocols, which include, for example, significantly less time for analogue treatment and a reduction in the amount of gonadotropins needed. Furthermore, fewer side effects can be expected. There is no difference regarding endometrium quality and hormone profiles, and the results of assisted reproduction cycles are comparable. Cetrorelix also seems to be useful in the treatment of endometriosis which, in most cases, is an estrogen-dependent disease. Furthermore, fewer side effects occur with this agent (e.g., postmenopausal symptoms) and no estradiol add-back is needed. In the future, new nonpeptic GnRH Antagonists are expected to be available for oral administration. Although they are still under investigation, these agents have the potential to improve patients’ comfort and compliance.
-
GnRH agonists and Antagonists in assisted reproduction pregnancy rate
Reproductive Biomedicine Online, 2006Co-Authors: J Engel, R. Felberbaum, G Griesinger, A Schultzemosgau, K DiedrichAbstract:Although gonadotrophin-releasing hormone (GnRH) Antagonists offer many advantages when used in ovarian stimulation, their popularity is lower than expected. GnRH protocols are suspected to yield lower pregnancy rates compared with the long agonist protocol. In the current study, subgroup analyses from the German IVF registry (DIR) were performed to evaluate the hypothesis that GnRH Antagonists are often used as second-line medication in patients with difficult medical conditions, and thus pregnancy rates may be biased. Consequently, pregnancy rates in the first six stimulation cycles (low rank cycles) were more favourable in the group treated according to the long protocol, while in the patient group requiring more stimulation cycles (high rank cycles; 7, 9 and 10), numerically higher pregnancy rates were achieved with GnRH antagonist protocols. On the other hand, in a patient collective with equal demographic and clinical features (<35 years, tubal infertility), the long and the GnRH antagonist protocols resulted in similar pregnancy rates, supporting the hypothesis that both stimulation protocols lead to equal results.
-
a lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of hcg in patients undergoing ivf with GnRH Antagonists
Human Reproduction, 2005Co-Authors: Efstratios M Kolibianakis, P Devroey, K Diedrich, A Schultzemosgau, A Van Steirteghem, A Schroer, G GriesingerAbstract:BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH Antagonists remains to be assessed. METHODS: 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. RESULTS: No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH Antagonists.
Mark T Goulet - One of the best experts on this subject based on the ideXlab platform.
-
potent nonpeptide GnRH receptor Antagonists derived from substituted indole 5 carboxamides and acetamides bearing a pyridine side chain terminus
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Wallace T Ashton, Yi Tien Yang, Joel B Yudkovitz, George R Mount, Rena Ning Ren, Kang Cheng, Rosemary Sisco, Patrice H Gibbons, Bridget Butler, Mark T GouletAbstract:A pyridine side-chain terminus has been incorporated into the indole-5-carboxamide and indole-5-acetamide series of GnRH Antagonists. Potent activity was observed in binding and functional assays. Certain branched or cyclic tertiary amides were identified as preferred in each series. Alkylation of the side-chain secondary amine had generally unfavorable effects. Variations of the gem-dialkyl substituents in the indole-5-acetamide series were also investigated.
-
2-(3,5-Dimethylphenyl)tryptamine derivatives that bind to the GnRH receptor.
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Dominick Marino, Matthew J Wyvratt, Yi Tien Yang, Roy G Smith, Kang Cheng, Jane-ling Lo, Michael H. Fisher, Mark T GouletAbstract:A series of 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. Some para-substituents on the 4-phenylbutyl side chain attached to the tryptamine nitrogen led to compounds with potent GnRH receptor binding. The study has helped define structural requirements for GnRH receptor binding for the 2-aryltryptamine GnRH Antagonists.
-
Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor Antagonists.
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Mamta Parikh, Matthew J Wyvratt, Yi Tien Yang, Roy G Smith, Kang Cheng, Jane-ling Lo, Michael H. Fisher, Mark T GouletAbstract:Abstract A series of heterocyclic 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. The carbon tether length and heterocyclic ring attached to the amino group of 2-(3,5-dimethylphenyl)tryptamine were varied. Several of these derivatives were potent GnRH Antagonists with the most potent compound having an IC50 of 16 nM.
-
quinolones as gonadotropin releasing hormone GnRH Antagonists simultaneous optimization of the c 3 aryl and c 6 substituents
Bioorganic & Medicinal Chemistry Letters, 2000Co-Authors: Jonathan R Young, Song X Huang, Thomas F Walsh, Matthew J Wyvratt, Yi Tien Yang, Irene Chen, Robert J Devita, Mark T Goulet, Ning Ren, Joel B YudkovitzAbstract:A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) Antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal.
-
identification of phe313 of the gonadotropin releasing hormone GnRH receptor as a site critical for the binding of nonpeptide GnRH Antagonists
Molecular Endocrinology, 2000Co-Authors: Jisong Cui, Thomas F Walsh, George R Mount, Robert J Devita, Mark T Goulet, Roy G Smith, Suresh B Singh, James M Schaeffer, Kang ChengAbstract:The dog GnRH receptor was cloned to facilitate the identification and characterization of selective nonpeptide GnRH Antagonists. The dog receptor is 92% identical to the human GnRH receptor. Despite such high conservation, the quinolone-based nonpeptide GnRH Antagonists were clearly differentiated by each receptor species. By contrast, peptide antagonist binding and functional activity were not differentiated by the two receptors. The basis of the differences was investigated by preparing chimeric receptors followed by site-directed mutagenesis. Remarkably, a single substitution of Phe313 to Leu313 in the dog receptor explained the major differences in binding affinities and functional activities. The single amino acid replacement of Phe313 of the human receptor with Leu313 resulted in a 160-fold decrease of binding affinity of the nonpeptide antagonist compound 1. Conversely, the replacement of Leu313 of the dog receptor with Phe313 resulted in a 360-fold increase of affinity for this compound. These res...
Yi Tien Yang - One of the best experts on this subject based on the ideXlab platform.
-
modification of the pyridine moiety of non peptidyl indole GnRH receptor Antagonists
Bioorganic & Medicinal Chemistry Letters, 2002Co-Authors: Joseph P Simeone, Yi Tien Yang, Joel B Yudkovitz, Jisong Cui, George R Mount, Rena Ning Ren, Robert L Bugianesi, Mitree M Ponpipom, Mellissa Creighton, Anhua MaoAbstract:The synthesis of a number of indole GnRH Antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs.
-
2 arylindoles as gonadotropin releasing hormone GnRH Antagonists optimization of the tryptamine side chain
Bioorganic & Medicinal Chemistry Letters, 2002Co-Authors: Jonathan R Young, Song X Huang, Thomas F Walsh, Matthew J Wyvratt, Yi Tien Yang, Joel B Yudkovitz, Jisong Cui, George R Mount, Rena Ning Ren, Xiaolan ShenAbstract:A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) Antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents.
-
potent nonpeptide GnRH receptor Antagonists derived from substituted indole 5 carboxamides and acetamides bearing a pyridine side chain terminus
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Wallace T Ashton, Yi Tien Yang, Joel B Yudkovitz, George R Mount, Rena Ning Ren, Kang Cheng, Rosemary Sisco, Patrice H Gibbons, Bridget Butler, Mark T GouletAbstract:A pyridine side-chain terminus has been incorporated into the indole-5-carboxamide and indole-5-acetamide series of GnRH Antagonists. Potent activity was observed in binding and functional assays. Certain branched or cyclic tertiary amides were identified as preferred in each series. Alkylation of the side-chain secondary amine had generally unfavorable effects. Variations of the gem-dialkyl substituents in the indole-5-acetamide series were also investigated.
-
2-(3,5-Dimethylphenyl)tryptamine derivatives that bind to the GnRH receptor.
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Dominick Marino, Matthew J Wyvratt, Yi Tien Yang, Roy G Smith, Kang Cheng, Jane-ling Lo, Michael H. Fisher, Mark T GouletAbstract:A series of 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. Some para-substituents on the 4-phenylbutyl side chain attached to the tryptamine nitrogen led to compounds with potent GnRH receptor binding. The study has helped define structural requirements for GnRH receptor binding for the 2-aryltryptamine GnRH Antagonists.
-
Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor Antagonists.
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Mamta Parikh, Matthew J Wyvratt, Yi Tien Yang, Roy G Smith, Kang Cheng, Jane-ling Lo, Michael H. Fisher, Mark T GouletAbstract:Abstract A series of heterocyclic 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. The carbon tether length and heterocyclic ring attached to the amino group of 2-(3,5-dimethylphenyl)tryptamine were varied. Several of these derivatives were potent GnRH Antagonists with the most potent compound having an IC50 of 16 nM.
Basil C Tarlatzis - One of the best experts on this subject based on the ideXlab platform.
-
significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH Antagonists and gonadotrophins a systematic review and meta analysis
Current Pharmaceutical Biotechnology, 2012Co-Authors: Efstratios M Kolibianakis, Christos A Venetis, J Bontis, Basil C TarlatzisAbstract:The current meta-analysis aimed to answer the following research question: is progesterone elevation on the day of hCG administration associated with the probability of clinical pregnancy in women undergoing ovarian stimulation for IVF using GnRH Antagonists? A literature search in MEDLINE, EMBASE and CENTRAL electronic databases followed by extensive hand-searching from two independent reviewers was performed to identify relevant studies. Eventually five eligible studies (n=585 patients) were identified. No significant differences were present between patients with and those without progesterone elevation regarding female age, duration of stimulation and total dose of gonadotrophins required. However, patients with progesterone elevation were characterized by higher serum estradiol levels on the day of hCG administration (+956 pg/ml, 95% +248 to +1664, random effects model, p=0.008) and more COCs retrieved (+2.9, 95% CI +1.5 to +4.4, fixed effects model, p < 0.001). Progesterone elevation on the day of hCG administration was associated with a significantly decreased probability of clinical pregnancy per cycle (-9%, 95% CI -17 to -2, fixed model effects, p). In conclusion, in patients treated with GnRH Antagonists and gonadotrophins, progesterone elevation on the day of hCG administration is significantly associated with a lower probability of clinical pregnancy.
-
is earlier administration of human chorionic gonadotropin hcg associated with the probability of pregnancy in cycles stimulated with recombinant follicle stimulating hormone and gonadotropin releasing hormone GnRH Antagonists a prospective randomized
Fertility and Sterility, 2011Co-Authors: D Kyrou, Efstratios M Kolibianakis, Herman Tournaye, Basil C Tarlatzis, Human M Fatemi, P DevroeyAbstract:Objective To evaluate the association of timing of hCG administration and probability of pregnancy in patients stimulated with recombinant FSH/GnRH Antagonists for IVF. Design Prospective randomized controlled clinical trial. Setting Dutch-speaking Free University of Brussels. Patient(s) One hundred twenty patients, aged Intervention(s) Ovarian stimulation was achieved using recombinant FSH starting on day 2 of the menstrual cycle at a fixed dose. To inhibit premature LH surge, daily GnRH antagonist was used from day 6 of stimulation. Triggering of final oocyte maturation was performed using 10,000 IU of hCG. Patients were randomized to receive hCG either as soon as three or more follicles of size ≥16 mm were present on ultrasonography (early-hCG group) or 1 day after the above criterion was met (late-hCG group). Main Outcome Measure(s) Ongoing pregnancy rate. Result(s) Significant differences were observed between the early-hCG and the late-hCG group regarding E 2 (1,388 ± 931 [mean ± SD] vs. 2,040 ± 1,231 pg/mL, respectively) and P (0.8 ± 0.3 vs. 1.1 ± 0.5 ng/mL, respectively) levels on the day of hCG administration and the number of metaphase II oocytes (9.2 ± 7.1 vs. 6.1 ± 4.9, respectively). No significant differences were observed between the early-hCG and the late-hCG group regarding positive hCG (46.2% vs. 50%, respectively) and ongoing pregnancy rates (34.6% vs. 40.7%, respectively). Conclusion(s) The current study provides evidence that earlier administration of hCG is not associated with the probability of pregnancy in cycles stimulated with recombinant FSH and GnRH Antagonists.
-
oral contraceptive pill pretreatment in ovarian stimulation with GnRH Antagonists for ivf a systematic review and meta analysis
Fertility and Sterility, 2008Co-Authors: G Griesinger, K Diedrich, Basil C Tarlatzis, Christos A Venetis, Tanja Marx, Efstratios M KolibianakisAbstract:Objective To assess the impact of oral contraceptive pill (OCP) pretreatment in ovarian stimulation for in vitro fertilization (IVF) using gonadotropin releasing hormone (GnRH) Antagonists. Design Systematic review and meta-analysis of randomized controlled trials (RTC). Setting University IVF center. Patient(s) Infertile patients (n = 847), treated in four trials. Intervention(s) Systematic literature search (MEDLINE, EMBASE, CENTRAL COCHRANE, conference proceedings, reference lists) for randomized trials on OCP treatment before stimulation with gonadotropins and GnRH antagonist for IVF. Meta-analysis of data yielding pooled odds ratios (OR) or weighted differences of the means (WMD) and 95% confidence intervals (CI). Main Outcome Measure(s) Ongoing pregnancy rate per randomized woman. Result(s) Ongoing pregnancy rate per randomized woman was not found to be significantly different between patients with and those without OCP pretreatment (OR: 0.74, 95% CI: 0.53 to 1.03). Duration of gonadotropin stimulation (WMD: +1.41 days, 95% CI: +1.13 to +1.68) and gonadotropin consumption (WMD: +542 IU, 95% CI: +127 to +956) were significantly increased after OCP pretreatment. No significant differences were observed regarding the number of cumulus–oocyte complexes (COCs) and the fertilization rates. Conclusion(s) A significant difference in ongoing pregnancy rates between patients who received OCP pretreatment and those who did not is currently not present, although further studies are necessary for more solid conclusions on pregnancy likelihood to be drawn.
-
GnRH Antagonists in ovarian stimulation for ivf
Human Reproduction Update, 2006Co-Authors: Basil C Tarlatzis, Klaus Diedrich, Efstratios M Kolibianakis, B C Fauser, Luk Rombauts, Paul DevroeyAbstract:The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) Antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH Antagonists. The role of GnRH Antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.
-
GnRH Antagonists in ivf
Reproductive Biomedicine Online, 2005Co-Authors: Efstratios M Kolibianakis, Basil C Tarlatzis, Paul DevroeyAbstract:The present review summarizes existing knowledge on the use of gonadotropin releasing hormone (GnRH) Antagonists based on experience gathered after the completion of phase III comparative trials with GnRH agonists. Available data suggest that prolongation of the follicular phase significantly decreases the probability of pregnancy. Moreover, patients with elevated progesterone at initiation of stimulation have significantly fewer chances of achieving an ongoing pregnancy. Luteal support remains mandatory, while the replacement of human chorionic gonadotrophin by GnRH agonist does not appear to be feasible. Although not conclusive, existing data are not in favour of increasing the starting dose of gonadotrophins, of LH supplementation or of using a flexible antagonist protocol.