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

  • Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol
    2016
    Co-Authors: Georg Griesinger, P Devroey, Davis Gates, Keith Gordon, Barbara J Stegmann, Pierre J. M. Verweij, Basil C Tarlatzis
    Abstract:

    Study QuestionWhat is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels?Summary AnswerThe optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.What Is Known AlreadyIn comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH Antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH Antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1–2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-Antagonist protocol.Study Design, Size, DurationFrom the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.Participants/Materials, Setting, MethodsThe threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-Antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined.Main Results and the Role of ChanceThe optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS.Limitations, Reasons for CautionThis was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins.Wider Implications of the FindingsFor patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy.Trial RegistrationClinicalTrials.gov NCT00702845NCT00696800NCT00696878

  • severe ovarian hyperstimulation syndrome after gonadotropin releasing hormone GnRH agonist trigger and freeze all approach in GnRH Antagonist protocol
    Fertility and Sterility, 2014
    Co-Authors: Human M Fatemi, P Devroey, Peter Humaidan, Shahar Kol, Biljana Popovictodorovic, Manish Banker, Juan A Garciavelasco
    Abstract:

    Objective To report two cases with GnRH agonist triggering and a freeze-all approach in a GnRH Antagonist protocol resulting in the development of severe ovarian hyperstimulation syndrome (OHSS), requiring hospitalization and peritoneal drainage. Design Two case reports. Setting A tertiary referral center and an obstetrics and gynecology department of a hospital. Patient(s) Case 1 and case 2: severe OHSS with abdominal distension, ascites development, and hemoconcentration. Intervention(s) Case 1 and case 2: diagnosed by clinical, hematologic, and ultrasound findings. Hospitalization, IV infusion, and peritoneal drainage. Main Outcome Measure(s) Symptomatic treatment and prevention of further complication. Result(s) Complete recovery. Conclusion(s) Two cases of severe OHSS after GnRH agonist trigger in a GnRH Antagonist protocol without the administration of any hCG for luteal-phase support. Clinicians have to be aware that even the sequential approach to ovarian stimulation with a freeze-all attitude does not completely eliminate OHSS in all patients.

  • corifollitropin alfa followed by rfsh in a GnRH Antagonist protocol for poor ovarian responder patients an observational pilot study
    Fertility and Sterility, 2013
    Co-Authors: Nikolaos P Polyzos, P Devroey, Michel Devos, Peter Humaidan, Dominic Stoop, C Ortegahrepich, Herman Tournaye
    Abstract:

    Objective To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH Antagonist protocol. Design Retrospective pilot study. Setting University-based tertiary care center. Patient(s) Poor ovarian responders fulfilling the Bologna criteria developed by European Society for Human Reproduction and Embryology Consensus Group. Intervention(s) Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH Antagonist protocol. Main Outcome Measure(s) Endocrinologic profile and ongoing pregnancy rates. Result(s) Among 43 women treated with corifollitropin alfa, mean E 2 levels showed an increasing pattern during the follicular phase, reaching 825 ng/L on the day of hCG administration, whereas FSH values showed a marked increase during the first 5 days, reaching a mean value of 35 IU/L and remaining above 20 IU/L during the late follicular phase. Cycle cancellation rate was 32.6% and embryo transfer rate 53.3%. Five patients (11.7%) had a positive hCG test and three (7%) had an ongoing pregnancy. Ongoing pregnancy rates were 11.1% per oocyte retrieval and 13% per embryo transfer. Ongoing pregnancy rates per patient did not significantly differ compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). Conclusion(s) Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH Antagonist protocol results in low pregnancy rates, similarly to conventional stimulation with a short agonist protocol.

  • a randomized assessor blind trial comparing highly purified hmg and recombinant fsh in a GnRH Antagonist cycle with compulsory single blastocyst transfer
    Fertility and Sterility, 2012
    Co-Authors: P Devroey, Antonio Pellicer, Anders Nyboe Andersen
    Abstract:

    Objective To compare the efficacy and safety of highly purified menotropin (hphMG) and recombinant FSH (rFSH) for controlled ovarian stimulation in a GnRH Antagonist cycle with compulsory single-blastocyst transfer. Design Randomized, open-label, assessor-blind, parallel groups, multicenter, noninferiority trial. Setting Twenty-five infertility centers in seven countries. Patient(s) Seven hundred forty-nine women. Intervention(s) Controlled ovarian stimulation with hphMG or rFSH in a GnRH Antagonist cycle with compulsory single-blastocyst transfer on day 5 in one fresh or subsequent frozen blastocyst replacement in natural cycles initiated within 1 year of each patient's start of treatment. Main Outcome Measure(s) Ongoing pregnancy (primary end point) and live birth rates, as well as pharmacodynamic parameters. Result(s) The ongoing pregnancy rate after a fresh cycle was 30% with hphMG versus 27% with rFSH for the per-protocol (PP) population and 29% versus 27% for the intention-to-treat (ITT) population. Noninferiority of hphMG compared to rFSH was established. Considering frozen cycles initiated within 1 year, the cumulative live birth rate for a single stimulation cycle was 40% and 38% for women treated with hphMG and rFSH, respectively (both PP and ITT). Significant differences in pharmacodynamic end points were found between the two gonadotropin preparations. Conclusion(s) Highly purified hMG is at least as effective as rFSH in GnRH Antagonist cycles with compulsory single-blastocyst transfer. Clinical Trial Registration Number NCT00884221.

  • a double blind non inferiority rct comparing corifollitropin alfa and recombinant fsh during the first seven days of ovarian stimulation using a GnRH Antagonist protocol
    Human Reproduction, 2009
    Co-Authors: P Devroey, Bernadette Mannaerts, Pieta C Ijzermanboon, R Boostanfar, N P Koper, B C Fauser
    Abstract:

    background: Corifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation. methods: In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 mg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH Antagonist protocol. results: The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): 23.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus –oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P ¼ 0.15). conclusion: Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH Antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800.

Shee-uan Chen - One of the best experts on this subject based on the ideXlab platform.

  • Lower rate of early pregnancy loss in patients experiencing early-onset low LH in GnRH Antagonist cycles supplemented with menotropin
    'Elsevier BV', 2019
    Co-Authors: Po-kai Yang, Kuang-han Chao, Chin-hao Chang, Mei-jou Chen, Shee-uan Chen
    Abstract:

    Background/Purpose: The role of LH during controlled ovarian stimulation (COS) in the general population remains contentious. There is no consensus on the indications for LH supplementation during COS. The purpose of this study is to determine whether menotropin supplement is associated with decreases in early pregnancy loss rates in patients exhibiting low endogenous LH during COS. Method: This is a single-center, retrospective cohort from a university-affiliated hospital. Patients were enrolled from the in-vitro fertilization center from January, 2011 to December, 2014. Patients who experienced a LH level ≦ 0.8 mIU/mL during stimulation were identified, and patients that received menotropin supplementation were compared to those without menotropin supplementation. Outcome variables, including the number of oocytes retrieved, embryos obtained, implantation rates, pregnancy rates and early pregnancy loss rates, were compared. Results: Patients that experienced low LH during GnRH Antagonist protocol and were supplemented with menotropin were associated with lower early pregnancy loss when compared with patients without menotropin supplementation (26.7% vs. 11.5%, p = 0.045). More specifically, in patients who exhibited early-onset low LH, before the use of GnRH Antagonists, menotropin supplementation was associated with significantly lower early pregnancy loss compared with non-supplemented patients (3.3% vs. 29.0%, OR: 0.08, p = 0.012). Beneficial effects persisted after adjusting for confounders (aOR: 0.103, 95% CI: 0.011–0.933). Conclusion: Menotropin supplementation is associated with decreased early pregnancy loss in patient who exhibited low LH during GnRH Antagonist cycles. This effect is especially prominent in patients who experience low LH before the start of GnRH Antagonists. Keywords: Early pregnancy loss, GnRH Antagonist, Luteinizing hormone, Menotropins, Ovulation inductio

  • lower rate of early pregnancy loss in patients experiencing early onset low lh in GnRH Antagonist cycles supplemented with menotropin
    Journal of the Formosan Medical Association, 2019
    Co-Authors: Po-kai Yang, Kuang-han Chao, Chin-hao Chang, Mei-jou Chen, Shee-uan Chen
    Abstract:

    Background/Purpose The role of LH during controlled ovarian stimulation (COS) in the general population remains contentious. There is no consensus on the indications for LH supplementation during COS. The purpose of this study is to determine whether menotropin supplement is associated with decreases in early pregnancy loss rates in patients exhibiting low endogenous LH during COS. Method This is a single-center, retrospective cohort from a university-affiliated hospital. Patients were enrolled from the in-vitro fertilization center from January, 2011 to December, 2014. Patients who experienced a LH level ≦ 0.8 mIU/mL during stimulation were identified, and patients that received menotropin supplementation were compared to those without menotropin supplementation. Outcome variables, including the number of oocytes retrieved, embryos obtained, implantation rates, pregnancy rates and early pregnancy loss rates, were compared. Results Patients that experienced low LH during GnRH Antagonist protocol and were supplemented with menotropin were associated with lower early pregnancy loss when compared with patients without menotropin supplementation (26.7% vs. 11.5%, p  = 0.045). More specifically, in patients who exhibited early-onset low LH, before the use of GnRH Antagonists, menotropin supplementation was associated with significantly lower early pregnancy loss compared with non-supplemented patients (3.3% vs. 29.0%, OR: 0.08, p  = 0.012). Beneficial effects persisted after adjusting for confounders (aOR: 0.103, 95% CI: 0.011–0.933). Conclusion Menotropin supplementation is associated with decreased early pregnancy loss in patient who exhibited low LH during GnRH Antagonist cycles. This effect is especially prominent in patients who experience low LH before the start of GnRH Antagonists.

  • Protocols of corifollitropin alfa (CA) versus daily gonadotropin [human menopausal gonadotropin (hMG) or recombinant follicle-stimulating hormone (rFSH)] with the use of GnRH Antagonist through anti-Müllerian hormone (AMH) stratification.
    2018
    Co-Authors: Tsung-hsien Lee, Shee-uan Chen, Shu-ling Tzeng, Chun-i Lee, Hsiu-hui Chen, Chun-chia Huang, Maw-sheng Lee
    Abstract:

    The GnRH Antagonist was administered on sixth day of stimulation till the day of human chorionic gonadotropin (hCG) injection.

Herman Tournaye - One of the best experts on this subject based on the ideXlab platform.

  • Table_1_Cumulative Live Birth Rates Following Stimulation With Corifollitropin Alfa Compared With hp-hMG in a GnRH Antagonist Protocol in Poor Ovarian Responders.docx
    2019
    Co-Authors: Joaquin Errazuriz, Herman Tournaye, Panagiotis Drakopoulos, Alessia Romito, Michel De Vos, Billie Frederix, Analissa Racca, Neelke De Munck, Christophe Blockeel
    Abstract:

    Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly purified human menopausal gonadotrophin (hp-hMG).Objective: To compare cumulative LBRs in Bologna poor ovarian responders undergoing ovarian stimulation with CFA followed by hp-hMG vs. hp-hMG alone in a GnRH Antagonist protocol.Design: This is a retrospective cohort study. We included in total 917 poor responders fulfilling the Bologna criteria for poor ovarian response (POR) at a university-affiliated tertiary center from January 2011 until March 2017. Patients were administered either fixed daily doses of 300–450 IU of hp-hMG (group A) or a single dose of 150 μg of CFA followed by daily injections of ≥300 IU of hp-hMG from Day 8 of stimulation until the day of ovulation trigger (group B), in a fixed GnRH Antagonist protocol.Results: LBRs after fresh embryo transfer (ET) were similar in group A 71/510 (14%) and B 42/407 (10%). Cumulative LBR per cycle was significantly higher in group A (16.9%) compared to group B (11.8%); (P = 0.03). However, logistic regression analysis showed no association between the type of gonadotropin administered and cumulative LBR. Only age was significantly associated with cumulative LBR (OR = 0.93, P = 0.007).Conclusion: Cumulative LBRs are similar in Bologna poor responders stimulated with CFA followed by hp-hMG compared to hp-hMG monotreatment in an Antagonist protocol.

  • corifollitropin alfa followed by rfsh in a GnRH Antagonist protocol for poor ovarian responder patients an observational pilot study
    Fertility and Sterility, 2013
    Co-Authors: Nikolaos P Polyzos, P Devroey, Michel Devos, Peter Humaidan, Dominic Stoop, C Ortegahrepich, Herman Tournaye
    Abstract:

    Objective To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH Antagonist protocol. Design Retrospective pilot study. Setting University-based tertiary care center. Patient(s) Poor ovarian responders fulfilling the Bologna criteria developed by European Society for Human Reproduction and Embryology Consensus Group. Intervention(s) Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH Antagonist protocol. Main Outcome Measure(s) Endocrinologic profile and ongoing pregnancy rates. Result(s) Among 43 women treated with corifollitropin alfa, mean E 2 levels showed an increasing pattern during the follicular phase, reaching 825 ng/L on the day of hCG administration, whereas FSH values showed a marked increase during the first 5 days, reaching a mean value of 35 IU/L and remaining above 20 IU/L during the late follicular phase. Cycle cancellation rate was 32.6% and embryo transfer rate 53.3%. Five patients (11.7%) had a positive hCG test and three (7%) had an ongoing pregnancy. Ongoing pregnancy rates were 11.1% per oocyte retrieval and 13% per embryo transfer. Ongoing pregnancy rates per patient did not significantly differ compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). Conclusion(s) Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH Antagonist protocol results in low pregnancy rates, similarly to conventional stimulation with a short agonist protocol.

  • prolongation of follicular phase by delaying hcg administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH Antagonist cycles
    Human Reproduction, 2005
    Co-Authors: Efstratios M Kolibianakis, Herman Tournaye, Michel Camus, Andre C. Van Steirteghem, Claire Bourgain, Evangelos G Papanikolaou, P Devroey
    Abstract:

    Background: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. Methods: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH Antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as ≥3 follicles ≥17 mm were present on ultrasound (early-hCG group, n=5) or 2 days after this criterion was met (late-hCG group, n=5). Results: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). Conclusions: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH Antagonist cycles. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

  • profound lh suppression after GnRH Antagonist administration is associated with a significantly higher ongoing pregnancy rate in ivf
    Human Reproduction, 2004
    Co-Authors: Efstratios M Kolibianakis, Herman Tournaye, Michel Camus, Andre C. Van Steirteghem, Johan Smitz, Kostas A Zikopoulos, Johan Schiettecatte, P Devroey
    Abstract:

    Background: The significance of suppressed LH levels in GnRH Antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH Antagonist initiation in IVF cycles. Methods: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH Antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10 000 IU as soon as three follicles of ≥17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. Results: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation ≤0.5 IU/l. Conclusions: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further. © European Society of Human Reproduction and Embryology 2004; all rights reserved.

Anja Pinborg - One of the best experts on this subject based on the ideXlab platform.

  • quality of life and psychosocial and physical well being among 1 023 women during their first assisted reproductive technology treatment secondary outcome to a randomized controlled trial comparing gonadotropin releasing hormone GnRH Antagonist and GnRH agonist protocols
    Fertility and Sterility, 2018
    Co-Authors: M Toftager, Jeanette Bogstad, T Bryndorf, Kristine Lossl, Lisbeth Praetorius, Anne Zedeler, Randi Sylvest, Lone Schmidt, Anja Pinborg
    Abstract:

    Objective To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH Antagonist or long GnRH agonist protocol. Design Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Setting Fertility clinics at university hospitals. Patient(s) Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Intervention(s) Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH Antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Main Outcome Measure(s) Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Result(s) Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH Antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH Antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Conclusion(s) Women in a short GnRH Antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. Clinical Trial Registration Number NCT00756028.

  • cumulative live birth rates after one art cycle including all subsequent frozen thaw cycles in 1050 women secondary outcome of an rct comparing GnRH Antagonist and GnRH agonist protocols
    Human Reproduction, 2017
    Co-Authors: M Toftager, Jeanette Bogstad, T Bryndorf, Kristine Lossl, Lisbeth Praetorius, Anne Zedeler, L Nilas, Anja Pinborg
    Abstract:

    STUDY QUESTION: Are cumulative live birth rates (CLBRs) similar in GnRH-Antagonist and GnRH-agonist protocols for the first ART cycle including all subsequent frozen-thaw cycles from the same oocyte retrieval? SUMMARY ANSWER: The chances of at least one live birth following utilization of all fresh and frozen embryos after the first ART cycle are similar in GnRH-Antagonist and GnRH-agonist protocols. WHAT IS KNOWN ALREADY: Reproductive outcomes of ART treatment are traditionally reported as pregnancies per cycle or per embryo transfer. However, the primary concern is the overall chance of a live birth. After the first ART cycle with fresh embryo transfer, we found live birth rates (LBRs) of 22.8% and 23.8% (P = 0.70) for the GnRH-Antagonist and GnRH-agonist protocols, respectively. But with CLBRs including both fresh and frozen embryos from the first oocyte retrieval, chances of at least one live birth increases. There are no previous randomized controlled trials (RCTs) comparing CLBRs in GnRH-Antagonist versus GnRH-agonist protocols. Previous studies on CLBR are either retrospective cohort studies including multiple fresh cycles or RCTs comparing single embryo transfer (SET) with double embryo transfer (DET). STUDY DESIGN, SIZE, DURATION: CLBR was a secondary outcome in a Phase IV, dual-center, open-label, RCT including 1050 women allocated to a short GnRH-Antagonist or a long GnRH-agonist protocol in a 1:1 ratio over a 5-year period using a web-based concealed randomization code. The minimum follow-up time from the first IVF cycle was 2 years. The aim was to compare CLBR between the two groups following utilization of all fresh and frozen embryos from the first ART cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women referred for their first ART cycle at two public fertility clinics, 30 kg/m2), the CLBR was significantly higher in the GnRH-Antagonist group (P = 0.02). LIMITATIONS, REASONS FOR CAUTION: The duration of the trial is a possible limitation with introduction of new methods as 'Freeze all' and 'GnRH-agonist triggering', but as these treatments were used in only few women, a systematic bias is not likely. Blastocyst culture of surplus embryos for freezing was introduced to both groups simultaneously, thereby minimizing the risk of bias. Furthermore, with a minimum of 2-year follow-up, a minority (<1%) still had cryopreserved embryos and no live birth at the end of the trial. The post hoc prognostic covariate analyses with multiple strata should be interpreted with caution. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS: With the improvement of embryo culture, freezing and thawing methods as well as a strategy of elective SET, CLBR until first live birth provides an all-inclusive success rate for ART. When comparing GnRH-Antagonist and GnRH-agonist protocols, we find similar CLBRs, despite more oocytes being retrieved in the GnRH-agonist protocol. STUDY FUNDING/COMPETING INTERESTS: An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. TRIAL REGISTRATION DATE: 18 September 2008. DATE OF FIRST PATIENT'S ENROLLMENT: 14 January 2009.

  • risk of severe ovarian hyperstimulation syndrome in GnRH Antagonist versus GnRH agonist protocol rct including 1050 first ivf icsi cycles
    Human Reproduction, 2016
    Co-Authors: M Toftager, Jeanette Bogstad, T Bryndorf, Kristine Lossl, Janne Roskaer, T Holland, Lisbeth Praetorius, Anne Zedeler, L Nilas, Anja Pinborg
    Abstract:

    STUDY QUESTION Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH Antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?. SUMMARY ANSWER There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH Antagonist protocol. WHAT IS KNOWN ALREADY?: In the most recent Cochrane review, the GnRH Antagonist protocol was associated with a similar live birth rate (LBR), a similar on-going pregnancy rate (OPR), and a lower incidence of OHSS (odds ratio (OR) = 0.43 95% confidence interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta-analyses, no significant differences in LBR (OR = 0.86; 95% CI: 0.72-1.02) or in the incidence of severe OHSS were reported, while others found a lower LBR (OR = 0.82; 95% CI: 0.68-0.97) and a reduced risk of severe OHSS using the GnRH Antagonist protocol (OR = 0.60; 95% CI: 0.40-0.88). STUDY DESIGN, SIZE, DURATION Phase IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH Antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS, the primary outcome, between the two groups with a power of 80% and stratified for age, assisted reproductive technology (ART) clinic and planned fertilization procedure (IVF/ICSI). The secondary aims were to compare rates of mild and moderate OHSS, positive plasma (p)-hCG, on-going pregnancy and live birth between the two arms. None of the women had undergone previous ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total of 1099 subjects were randomized, including women with poor ovarian reserve, polycystic ovary syndrome and irregular cycles. A total of 49 women withdrew their consent, thus 1050 subjects were allocated to the GnRH Antagonist (n = 534) and agonist protocol (n = 516), respectively. In total 1023 women started recombinant human follitropin-β (rFSH) stimulation, 528 in the GnRH Antagonist group and 495 in the GnRH agonist group. All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or >36 years, with the option to adjust dose at stimulation day 6. Clinical OHSS parameters were collected at oocyte retrieval, and Days 3 and 14 post-transfer. On-going pregnancy was determined by transvaginal ultrasonography at gestational weeks 7-9. In the intention-to-treat (ITT) analysis for reproductive outcomes, 1050 subjects were included. For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77/495) (Δpp = -5.3pp; 95% CI: -9.6 to -1.0; P = 0.01) ] was significantly lower in the GnRH Antagonist group compared with the agonist group, respectively. In the GnRH Antagonist and agonist group, respectively, 4.7% (25/528) versus 8.5% (42/495) women were seen by a physician due to OHSS (P = 0.01), and 1.7% (9/528) versus 3.6% (18/495) were admitted to hospital due to OHSS (P = 0.06). No women had ascites-puncture in the GnRH Antagonist group versus 2.0% (10/495) in the GnRH agonist group (P < 0.01). LBRs were 22.8% (122/534) versus 23.8% (123/516) (Δpp = -1.0pp; 95% CI: -6.3 to 4.3; P = 0.70) and OPRs were 24.9% (133/528) versus 26.2% (135/516) (Δpp = -1.3pp; 95% CI: -6.7 to 4.2; P = 0.64) per randomized subject in the GnRH Antagonist versus agonist group, with a mean number of 1.1 versus 1.2 embryos transferred in the two groups. Pregnancy rates (PR) per randomized subject, per started gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve and thus predict risk of OHSS, were not performed. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS The short GnRH Antagonist protocol should be the protocol of choice for patients undergoing their first ART cycle in females <40 years of age including both low and high responders when an age-dependent initially fixed gonadotrophin dose is used, as an increased risk of severe OHSS and the associated complications is seen in the long GnRH agonist group and as PRs and LBRs are similar in the two groups. Patients at risk of OHSS particularly benefit from the short GnRH Antagonist treatment as GnRH agonist triggering can be used. STUDY FUNDING/COMPETING INTERESTS An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. Trial registration date: 18 September 2008. Date of first patient's enrolment: 14 January 2009.

Byungmoon Kang - One of the best experts on this subject based on the ideXlab platform.

  • effectiveness of GnRH Antagonist multiple dose protocol applied during early and late follicular phase compared with GnRH agonist long protocol in non obese and obese patients with polycystic ovary syndrome undergoing ivf icsi
    Clinical and Experimental Reproductive Medicine, 2012
    Co-Authors: Chunghoon Kim, Jeiwon Moon, Hyukjae Kang, Junwoo Ahn, Sunghoon Kim, Heedong Chae, Byungmoon Kang
    Abstract:

    �Objective: To evaluate the effectiveness of GnRH Antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF. Methods: Two hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH Antagonist MDP-EL (Antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups. Results: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antago nist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the Antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the Antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the Antagonist group. Similar findings were also observed in obese PCOS subgroup. Conclusion: GnRH Antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

  • minimal stimulation using gonadotropin releasing hormone GnRH Antagonist and recombinant human follicle stimulating hormone versus GnRH Antagonist multiple dose protocol in low responders undergoing in vitro fertilization intracytoplasmic sperm injection
    Fertility and Sterility, 2009
    Co-Authors: Chunghoon Kim, Sunghoon Kim, Heedong Chae, Sora Kim, Yongpil Cheon, Byungmoon Kang
    Abstract:

    This prospective randomized study was performed to investigate the effectiveness of minimal stimulation using recombinant human FSH (rhFSH) and GnRH Antagonist compared with GnRH Antagonist multiple-dose protocol (MDP) in low responders undergoing IVF/intracytoplasmic sperm injection. Our study demonstrated that minimal stimulation in natural cycles provides similar pregnancy rates to the GnRH Antagonist MDP with fewer dose and days of rhFSH used and thus can be a cost-effective alternative as a last chance before oocyte donation in low responders.

  • efficacy of controlled ovarian hyperstimulation using GnRH Antagonist in women with polycystic ovary syndrome undergoing ivf et
    Obstetrics & gynecology science, 2005
    Co-Authors: Jeong Won Choi, Chunghoon Kim, Sunghoon Kim, Heedong Chae, Hyang Ah Lee, Seok Ho Hong, Hee Young Nah, Young Jin Lee, Young Soo Son, Byungmoon Kang
    Abstract:

    목적: GnRH Antagonist가 최근 개발되어 과배란유도에 있어 새로운 치료책으로 제시되고 있다. 그러나 다낭성 난소증후군 환자들과 같이 기본 혈중 황체호르몬 농도가 상승되어 있는 환자들에서 GnRH Antagonist를 사용하는 것은 여러 문제점으로 인해 망설여져 왔다. 본 연구는 다낭성 난소증후군 환자들에서 체외수정시술을 위한 과배란유도 방법으로 GnRH Antagonist 다회투여법의 두 가지 방법과 표준화된 GnRH agonist장기요법을 비교 분석함으로써 효용성을 평가하기 위함이다. 연구 방법: 체외수정시술을 시행하는 24-38세 사이의 다낭성 난소증후군으로 진단받은 65명의 환자를 대상으로 하였다. 무작위적인 방법으로 초기와 후기 난포기에 GnRH Antagonist를 투여하는 다회투여법을 시행한 환자군 (GnRH-ant MDPEL, 1군)과 후기난포기에만 투여하는 다회투여법을 시행한 환자군 (GnRH-ant MDPL, 2군), 그리고 GnRH agonist 장기요법을 시행한 환자군 (GnRH-a luteal LP, 3군)으로 분류하였다. 모든 환자들은 단주기성의 경구용 피임제로 전처치를 시행하였다. 세 군간에 과배란유도에 대한 난소의 반응, 체외수정시술의 결과 그리고 임신율 등을 비교하였다. 결과: 각 군간에 환자의 나이, 체질량지수, 불임기간과 내분비적 호르몬 수치 및 당부하검사상 차이는 나타나지 않았다. hCG 투여일에 혈중 황체호르몬의 농도나 자궁내막두께는 세군간에 유의한 차이가 없었으나 혈중 estradiol 농도는 GnRH agonist를 사용한 3군에서 1, 2군에 비하여 유의하게 높았다 (P