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Bernadette Mannaerts - One of the best experts on this subject based on the ideXlab platform.

  • large comparative randomized double blind trial confirming noninferiority of pregnancy rates for Corifollitropin Alfa compared with recombinant follicle stimulating hormone in a gonadotropin releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization
    Fertility and Sterility, 2015
    Co-Authors: R Boostanfar, K Gordon, Bernadette Mannaerts, Barbara J Stegmann, Han Witjes, Jolanda Elbers, Bruce S Shapiro, Michael J Levy, Zev Rosenwaks, Larry I Barmat
    Abstract:

    Objective To compare Corifollitropin Alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF. Design Phase 3 randomized, double-blind, noninferiority trial. Setting Multicenter trial. Patient(s) A total of 1,390 women aged 35–42 years. Intervention(s) A single injection of 150 μg of Corifollitropin Alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach ≥17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3. Main Outcome Measure(s) Vital pregnancy rate (PR), number of oocytes, and live birth rate. Result(s) Vital PRs per started cycle were 23.9% in the Corifollitropin Alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (−7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the Corifollitropin Alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (−0.2 to 1.2). The live birth rates per started cycle were 21.3% in the Corifollitropin Alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) −2.3% (−6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the Corifollitropin Alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups. Conclusion(s) Treatment with Corifollitropin Alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. Clinical Trial Registration Number NCT01144416.

  • short follicular phase of stimulation following Corifollitropin Alfa or daily recombinant fsh treatment does not compromise clinical outcome a retrospective analysis of the engage trial
    Reproductive Biomedicine Online, 2014
    Co-Authors: Tonko Mardesic, Bernadette Mannaerts, Han Witjes, Michael J Levy, M Abuzeid, Bart C J M Fauser
    Abstract:

    Abstract To evaluate whether a short follicular phase of ovarian stimulation compromises the chance of pregnancy, subjects from a double-blind, randomized trial treated with a single dose of Corifollitropin Alfa (n=756) or daily recombinant FSH (n=750) were categorized as early responders if three follicles ⩾17mm were reached and human chorionic gonadotrophin (HCG) was administered prior to or on stimulation day 8, and as normal responders if three follicles ⩾17mm were reached and HCG was administered after stimulation day 8. In the Corifollitropin Alfa and recombinant FSH groups, 23.2% and 29.1%, respectively, were early responders (P=0.01). Regardless of the treatment group, the initial ovarian response was higher in early responders, but with two extra days of stimulation, the number and size of follicles on the day of HCG in the normal responders was similar to those of the early responders. The number of oocytes was similar in both response groups following Corifollitropin Alfa treatment (13.6 versus 14.5) and recombinant FSH treatment (12.8, both groups). The ongoing pregnancy rates were comparable for early and normal responders regardless of the treatment group, supporting successful outcome following a stimulation period of only 1week. During ovarian stimulation for assisted reproduction, some women respond earlier than others to treatment with follicle-stimulating agents and require fewer days of treatment. To evaluate whether such short stimulation jeopardizes the chance of pregnancy, clinical outcomes of early responders and normal responders were compared in women aged 18–36years treated with either a single dose of Corifollitropin Alfa (756 women) or daily recombinant FSH (750 women) for the first 7days of stimulation. On average, about 25% of the evaluated women were early responders. The initial ovarian response was higher in early responders than in normal responders but the number of eggs retrieved and the ongoing pregnancy rates in early and normal responders were similar regardless of the treatment group. This study shows that the chance of ongoing pregnancy was not compromised in women requiring only 1week of stimulation compared with women who required a longer duration of stimulation.

  • high ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in a gnrh antagonist protocol
    Human Reproduction, 2013
    Co-Authors: Human M Fatemi, Georg Griesinger, Han Witjes, Kevin Doody, Bernadette Mannaerts
    Abstract:

    Study question Is the ovarian response to controlled ovarian stimulation (COS) related to the ongoing pregnancy rate when taking into account the main covariates affecting the probabilities of pregnancy following fresh embryo transfer? Summary answer In patients treated with Corifollitropin Alfa or daily recombinant FSH (rFSH) in a GnRH-antagonist protocol, a high ovarian response did not compromise ongoing pregnancy rates and increased cumulative pregnancy rates following fresh and frozen-thawed embryo transfer. What is known and what this paper adds A strong association between the number of oocytes and pregnancy rates has been described but this is the first comprehensive analysis assessing important confounders that might affect pregnancy rates. Study design In a large, prospective, double-blind, randomized trial (Engage; n = 1506), patients were treated with either a single dose of 150 μg Corifollitropin Alfa or daily 200 IU rFSH for the first 7 days of COS in a GnRH-antagonist (ganirelix) protocol. In this retrospective analysis, patients were categorized into five groups according to the number of oocytes retrieved (0-5, 6-9, 10-13, 14-18 and >18 oocytes). The number of good-quality embryos obtained and transferred, as well as the ongoing pregnancy rates, live birth rates and cumulative ongoing pregnancy rates per started cycle by group were evaluated. Univariate analysis was performed to identify factors that predict the chance of ongoing pregnancy. Logistic regression analysis on the dependent variables ongoing pregnancy and cumulative ongoing pregnancy, respectively, including oocyte category as an independent factor in the model, was performed by treatment group (Corifollitropin Alfa and rFSH) and overall. The likelihood of ongoing pregnancy and cumulative ongoing pregnancy was then evaluated taking into account ovarian response as well as other identified significant predictors of success. Participants and setting In total, 1506 patients had been randomized in a ratio of 1:1 to either of the treatment groups. Patients were aged ≤ 36 years and had a body weight >60 kg. Main results and the role of chance The ongoing pregnancy rates per started cycle increased in the Corifollitropin Alfa and rFSH groups from 31.9 and 31.3%, respectively, in the lowest response group (0-5 oocytes) to 41.9 and 43.4% in the highest response group (>18 oocytes) with a significant linear trend (P = 0.04). The cumulative pregnancy rates taking frozen-thawed embryo transfers into account increased from 33.0 and 31.3% to 60.8 and 55.9% in the Corifollitropin Alfa and rFSH groups, respectively. Univariate logistic regression analyses of ongoing pregnancy showed significant effects for the following factors: embryo transfer (double or single, P 1.5 or ≤ 1.5 ng/ml, P Bias, confounding and other reasons for caution The number of covariates included in the final model was limited to five major factors and not all other potentially significant predictive factors were available for evaluation. Generalizability to other populations This analysis is limited to IVF patients with a regular menstrual cycle up to 36 years of age and a body weight >60 and ≤ 90 kg treated with a GnRH-antagonist protocol and cannot be extrapolated to other patient populations or treatment regimens.

  • prospective follow up of 838 fetuses conceived after ovarian stimulation with Corifollitropin Alfa comparative and overall neonatal outcome
    Human Reproduction, 2012
    Co-Authors: Maryse Bonduelle, Arthur Leader, Bernadette Mannaerts, Christina Bergh, Dorrie Passier, Paul Devroey
    Abstract:

    study question: Is treatment with Corifollitropin Alfa, a new recombinant gonadotrophin with sustained follicle-stimulating activity, safe in terms of perinatal complications and birth defects in infants conceived following Corifollitropin Alfa treatment for contolled ovarian stimulation (COS)? summary answer: In terms of neonatal outcome and risk of malformations, treatment with a single dose of Corifollitropin Alfa during COS is as safe as treatment with daily recombinant FSH (rFSH). what is known and what this paper adds: This is the first pooled analysis of individual safety data in terms of neonatal outcome and major and minor congenital malformations collected following intervention trials of Corifollitropin Alfa. design: Pregnancy and follow-up studies were conducted prospectively and data were collected from all Phase II and III trials with Corifollitropin Alfa intervention, including two comparative randomized controlled trials (RCTs) in which patients received either a single dose of Corifollitropin Alfa or daily rFSH for the first 7 days of COS. Patients with ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour and the health of the offspring was assessed up to 4– 12 weeks after birth. participants and setting: Following Corifollitropin Alfa treatment prior to IVF or ICSI, the health of 677 pregnant women, 838 fetuses and 806 live born infants was evaluated. main results and the role of chance: Among 440 fetuses in the Corifollitropin Alfa arm and 381 fetuses in the rFSH arm of the two RCTs, there were 424 (96.4%) and 370 (98.7%) live births, respectively. Neonatal characteristics, the frequency of premature births and the incidence of infant adverse events were similar in both treatment arms. The overall incidence of any congenital malformations in live born infants was 16.3 and 17.0%, with major malformation rates of 4.0 and 5.4% in the Corifollitropin Alfa and rFSH groups, respectively [odds ratio (OR) for major malformations, 0.71; 95% confidence interval, 0.36 –1.38]. From 838 fetuses assessed in all Corifollitropin Alfa intervention trials, there were 806 (96.2%) live births with a major malformation rate of 4.5% in live born infants. bias, confounding and other reasons for caution: Both RCTs had a double-blind and active-controlled design and the adjudication of congenital malformations was also performed in a blinded fashion. As the total number of major malformations was limited (37), the confidence interval around the OR was rather wide. generalisability to other populations: The similarity of Corifollitropin Alfa and rFSH with respect to the incidence of congenital malformations was consistent across the RCTs and pregnancy type (singleton, multiple). This suggests that this similarity could hold in general. Overall incidences, however, may depend on the definitions of malformations and rules to adjudicate these events as major or minor.

  • a comparison of live birth rates and cumulative ongoing pregnancy rates between europe and north america after ovarian stimulation with Corifollitropin Alfa or recombinant follicle stimulating hormone
    Fertility and Sterility, 2012
    Co-Authors: R Boostanfar, Bernadette Mannaerts, Manuel Fernandezsanchez, Han Witjes, Samuel Pang, Paul Devroey
    Abstract:

    Objective To compare live birth rates after fresh embryo transfer (ET) and cumulative ongoing pregnancy rates after fresh ET and frozen-thawed (ET) between continents and overall after one treatment cycle with Corifollitropin Alfa or recombinant FSH. Design Double-blind, multicenter, randomized controlled trial. Setting Fourteen centers in North America (NA); 20 in Europe (EU). Patient(s) 804 NA patients and 702 EU patients. Intervention(s) Patients >60 kg received a single dose of Corifollitropin Alfa or daily rFSH for the first 7 days of controlled ovarian stimulation. Main Outcome Measure(s) Live birth rates. Result(s) Within each continent no differences were noted between the two treatment groups; however, between continents, the cumulative ongoing pregnancy rate and live birth rate were considerably higher in NA than in EU. The live birth rate in NA was 39.2% in both treatment groups compared with 31.5% and 28.8% in EU after Corifollitropin Alfa and rFSH treatment, respectively. Considering the number of embryos transferred, the live birth rate per ET was still higher in NA than in EU (42.7% v.s 36.8% with Corifollitropin Alfa and 41.6% vs. 30.9% with rFSH). Overall live birth rates after fresh ET were 35.6% and 34.4% (estimated difference 1.1% [95% confidence interval −3.7–5.8]), and the estimated cumulative live birth rates were 43.4% and 41.3% with Corifollitropin Alfa and rFSH, respectively. Conclusion(s) Live birth rates and cumulative pregnancy rates were higher in NA than in EU after treatment with either Corifollitropin Alfa or daily rFSH; both treatment protocols provided equal success rates. ClinicalTrials.gov Identifiers NCT00703014 and NCT00702273.

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

  • the performance of the elecsys anti mullerian hormone assay in predicting extremes of ovarian response to Corifollitropin Alfa
    Reproductive Biomedicine Online, 2020
    Co-Authors: Ana Raquel Neves, Georg Griesinger, Christophe Blockeel, Herman Tournaye, Panagiotis Drakopoulos, Juan A Garciavelasco, I Rodriguez, Antonio La Marca, Manuel Alvarez, Nikolaus P Polyzos
    Abstract:

    Abstract Research question What is the performance of anti-Mullerian hormone (AMH) as measured by the Elecsys® AMH assay in predicting ovarian response in women treated with 150 µg Corifollitropin Alfa (CFA)? Design Multicentre, prospective study conducted between December 2015 and April 2018. Women were aged 18–43 years, had regular menstrual bleeding, a body mass index of 17–35 kg/m2 and weighed 60 kg or over. Exclusion criteria: previous oophorectomy, history of ovarian hyperstimulation syndrome, a previous IVF and intracytoplasmic sperm injection cycle producing over 30 follicles measuring 11 mm or wider, basal antral follicle count (AFC) over 20 or polycystic ovarian syndrome. All women were treated with 150 μg CFA followed by recombinant FSH (150–300 IU/day) in a fixed gonadotrophin releasing hormone antagonist protocol. Results Of the 219 patients enrolled, 22.8% had low ovarian response (three or fewer oocytes), 66.2% had normal response and 11% had high ovarian response (15 or more oocytes). The AMH and AFC presented an area under the curve of 0.883 (95% CI 0.830 to 0.936) and 0.879 (95% CI 0.826 to 0.930), respectively, for low ovarian response; and an AUC of 0.865 (95% CI 0.793 to 0.935) and 0.822 (95% CI 0.734 to 0.909) for high ovarian response. An AMH cut-off of 1.0 ng/ml provided a sensitivity of 92.0% and a specificity of 66.9% in the prediction of low ovarian response; a cut-off of 2.25 ng/ml predicted high ovarian response with a sensitivity of 54.2% and a specificity of 91.8%. Conclusions The automated Elecsys® AMH assay predicts ovarian response in a CFA antagonist protocol. The best predictors of ovarian response in CFA-treated patients were AMH and AFC.

  • pituitary suppression protocol among bologna poor responders undergoing ovarian stimulation using Corifollitropin Alfa does it play any role
    Reproductive Biomedicine Online, 2019
    Co-Authors: Panagiotis Drakopoulos, Alessia Romito, Joaquin Errazuriz, Neelke De Munck, David Pening, A Racca, Herman Tournaye
    Abstract:

    Abstract Research question Does the type of pituitary suppression protocol influence cumulative live birth rate (LBR) in Bologna poor responders treated with Corifollitropin Alfa (CFA)? Design Retrospective cohort analysis including poor responder patients fulfilling the Bologna criteria who underwent their first intracytoplasmic sperm injection cycle using a CFA-based ovarian stimulation protocol between 2011 and 2017. The starting dose of CFA was 150 µg. The primary outcome was cumulative LBR, defined as the first delivery of a live born resulting from the fresh and all the subsequent frozen embryo transfers. Results A total of 717 cycles were divided into three groups: A (gonadotrophin-releasing hormone [GnRH] antagonist protocol, n = 407), B (long GnRH agonist protocol, n = 224) and C (short GnRH agonist protocol, n = 86). Cumulative LBR did not significantly differ between groups (20.1% versus 17.4% versus 14.0%; P = 0.35). Significantly more patients in Group A had supernumerary embryos cryopreserved (28.3% versus 18.4% versus 11.6%; P  Conclusions Poor responders according to the Bologna criteria in whom CFA is used for ovarian stimulation had comparable cumulative LBR, irrespective of the type of pituitary suppression. An increase in number of oocytes retrieved is an independent variable related to cumulative LBR.

  • 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 highly purified hmg versus recombinant fsh in young poor ovarian responders a multicentre randomized controlled clinical trial
    Human Reproduction, 2017
    Co-Authors: Panagiotis Drakopoulos, Christophe Blockeel, Michel Camus, Peter Humaidan, Thi Ngoc Lan Vuong, Alberto Vaiarelli, Anh Tuan Lam, Arne Van De Vijver, Herman Tournaye
    Abstract:

    Study question Does administration of Corifollitropin Alfa followed by highly purified (hp) HMG result in higher ongoing pregnancy rates compared with daily recombinant FSH (rFSH) in young poor responders? Summary answer Corifollitropin Alfa followed by hp-HMG does not increase ongoing pregnancy rates compared with rFSH in young poor responders, although more supernumerary cryopreserved embryos were obtained with Corifollitropin Alfa and hp-HMG. What is known already Poor ovarian response remains one of the main therapeutic challenges in women undergoing ovarian stimulation, given that very low live birth rates of 6% have been reported in this particular group of infertile patients. Nevertheless, concerns have been raised that a degree of heterogeneity remains, as the prognostic effect of individual factors is still unclear, particularly for the young poor responder group. The rationale for conducting the current randomized trial was based on the results of a previous pilot study demonstrating promising results with the administration of hp-HMG following Corifollitropin alpha in women younger than 40 years of age, fulfilling the 'Bologna' criteria. Study design, size, duration A multicenter, phase III, superiority, randomized trial was conducted using a parallel two-arm design. The study included 152 patients younger than 40 years old and fulfilling the 'Bologna' criteria for poor ovarian response, from one tertiary referral centre in Europe and one tertiary referral centre in Asia. Enrolment was performed from March 2013 to May 2016. Participants/materials, setting, methods Eligible patients were randomized to either administration of 150 μg Corifollitropin Alfa followed by 300 IU hp-HMG (Group A) or to 300 IU of daily recombinant FSH (Group B) in a fixed GnRH antagonist protocol. The randomization sequence was created using a computer generated randomization list stratified by centre, using 1:1 allocation. The primary outcome was ongoing pregnancy rate (defined as the presence of an intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation). Secondary outcomes included embryo cryopreservation rates, clinical and biochemical pregnancy rates and number of oocytes retrieved. Main results and the role of chance Overall, 152 poor ovarian responders defined by the 'Bologna' criteria were included in the study. Using an intention-to treat analysis, the ongoing pregnancy rates did not differ significantly between Group A 11/77 (14.3%) and Group B 11/70 (15.7%), absolute difference: -0.4 (-11.5 to 10.8), OR = 0.9 (0.4-2.4). Biochemical and clinical pregnancy rates, live birth rates and the number of oocytes retrieved were also comparable between the two groups. Nevertheless, more patients in the Corifollitropin Alfa group had cryopreserved embryos compared to the rFSH group [22 (28.6%) versus 10 (14.3%), OR = 2.4 (1.01-5.5)]. Incidentally, Asian patients had significantly lower cancellation rates compared to European poor responders [2/64 (3.1%) versus 17/83 (20.4%), OR = 0.12 (0.03-0.5)]. This discrepancy could be explained by the fact that Asian women were better prognosis patients than European patients, with significantly lower FSH [9.8 (5.3) versus 11.5 (5.4), P = 0.017] and significantly higher AMH [1.1 (0.9) versus 0.4 (0.3), P-value Limitations, reasons for caution Ongoing pregnancy rates close to 14% for both treatment groups differ significantly from the hypothesized primary outcome rates used in the power calculation. Therefore, our randomized trial might have been underpowered to detect smaller differences. The use of multiple secondary outcomes and multiple comparisons could have increased a Type 1 error. Finally, although the chance of selection biases remains low given the nature of the infertile population, the open-label design could have been a limitation. Wider implications of the findings Poor ovarian response represents a challenge and although a specific protocol may have increased the number of cryopreserved embryos, no difference was observed in ongoing pregnancy rates. Our study, being one of the largest RCTs in 'Bologna' criteria poor responders, highlights that baseline characteristics may play a crucial role in clinical prognosis of this population. Given that ovarian stimulation using novel protocols does not seem to significantly increase pregnancy rates even in young women, we suggest that future clinical research should focus on increasing the number of recruitable follicles and on oocyte quality rather than evaluating different stimulation protocols. Study funding/competing interests No external funding was used for this study. P.D., N.L.V., N.A.V.H., A.V., M.T.H., M.C., A.T.L. and A.V.V. have no conflict of interest to report. C.B. has received unrestricted research grants from MSD and Ferring as well as honoraria for lectures from Abbott, MSD, Merck and Ferring. P.H has received unrestricted research grants from MSD, Merck and Ferring as well as honoraria for lectures from Merck, MSD and IBSA. H.T. has received unrestricted research grants from MSD, Merck, Ferring, Cook, Roche Diagnostics, Besins International and Goodlife as well as consultation fees for research project in female infertility from Merck Finox, Abbott and ObsEva. N.P.P. has received unrestricted research grants from MSD, Ferring, Roche Diagnostics and Besins International as well as honoraria for lectures from MSD, Merck and Ferring. Trial registration number The EUDRACT number of the trial was 2013-000583-29 and the study was registered at clinicaltrials.gov (NCT01816321). Trial registration date 19 February 2013. Date of first patient enrolment 28 February 2013.

  • ORIGINAL ARTICLE Infertility Addition of highly purified HMG after
    2016
    Co-Authors: N. P. Polyzos, M De Vos, R. Corona, V. Vloeberghs, C. Ortega-hrepich, D. Stoop, Herman Tournaye
    Abstract:

    Corifollitropin Alfa in antagonist-treated poor ovarian responders: a pilot stud

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

  • replacing hmg fsh by low dose hcg to complete Corifollitropin Alfa stimulation reduces cost per clinical pregnancy a randomized pragmatic trial
    Reproductive Biomedicine Online, 2020
    Co-Authors: W Decleer, K Osmanagaoglu, Frank Comhaire, Jonas Balduyck, Alice Ameye, Paul Devroey
    Abstract:

    Abstract Research question The cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after Corifollitropin Alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation. Design One hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections. Results The clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol. Conclusion This study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate.

  • Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin Alfa or rFSH in a GnRH Antagonist Protocol
    2016
    Co-Authors: Georg Griesinger, Davis Gates, Paul Devroey, 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

  • Corifollitropin stimulation in combination with GnRH-antagonists after estradiol valerate pre-treatment. A pilot study on patientfriendly IVF.
    Facts views & vision in ObGyn, 2015
    Co-Authors: W Decleer, K Verschueren, S Vandeginste, K Osmanagaoglu, Paul Devroey
    Abstract:

    OBJECTIVE To demonstrate the feasibility of scheduling an IVF cycle, without disadvantages, in the new patient friendly stimulation protocol using the long acting Corifollitropin Alfa, in combination with GnRH-antagonist protection and GnRH-agonist triggering. STUDY DESIGN Two groups of ten patients were admitted in the study. Both received the same stimulation protocol with Corifollitropin Alfa in combination with GnRH-antagonist protection. After ultrasound evaluation on day 7 individually dosed Menopur was added. For triggering final oocyte maturation GnRH-agonists were used. The only difference between the two groups was that in the study group, estradiol valerate 4 mg/day was given from day 25 of the preceding cycle for a period of 10 days, thus postponing the start of follicular growth. RESULTS Scheduling the IVF stimulation by the administration of estradiol valerate 4 mg/day did not influence the hormonal curves, nor the embryological results in comparison to patients with the same stimulation, starting their stimulation at the beginning of menstruation. In this pilot study four out of ten patients turned out to be pregnant, demonstrating an acceptable pregnancy rate. CONCLUSION The combination of estradiol valerate 4 mg/day pre-treatment with the novel combination of Corifollitropin Alfa stimulation with GnRH-antagonist protection, individually topped off with Menopur, and triggered with GnRH-agonist proved to be a safe, patient-friendly (limited number of injections in comparison to classical IVF) (Patil, 2014) and efficient alternative to classical IVF stimulation protocols, allowing patients - and doctors - to schedule the treatment cycle to their convenience.

  • a new approach for ovarian stimulation in ivf using Corifollitropin Alfa in combination with gnrh analogues to trigger final oocyte maturation a pilot study
    Facts views & vision in obgyn, 2014
    Co-Authors: W Decleer, K Osmanagaoglu, G Meganck, Paul Devroey
    Abstract:

    A pilot study of 10 patients undergoing IVF stimulation, using the new combination of Corifollitropin Alfa with highly purified hMG and GnRH antagonists has been performed, whereas final oocyte maturation was induced by GnRH analogues. The hormonal profiles were analyzed, as well as the clinical outcome. All patients were recruited between March 1st 2013 and June 30th 2013. They were all younger than 38 years, had a normal BMI (between 18,0 and 32,0) and did not have more than three previous IVF stimulations. The combination of long acting FSH with hphMG, and under protection of GnRH antagonists against spontaneous LH-surge, provided a normal hormonal profile for estradiol, progesterone, LH, and FSH. The average oocyte quality and embryo quality were excellent, which resulted in four pregnancies out of ten. We conclude that the described combination is a safe, efficient, and patient friendly alternative for the classical IVF stimulation.

  • Corifollitropin Alfa or rfsh treatment flexibility options for controlled ovarian stimulation a post hoc analysis of the engage trial
    Reproductive Biology and Endocrinology, 2013
    Co-Authors: Arthur Leader, Paul Devroey, Han Witjes, Keith Gordon
    Abstract:

    Background: We sought to determine the impact of treatment flexibility on clinical outcomes in either a Corifollitropin Alfa or recombinant follicle-stimulating hormone (rFSH) protocol. Methods: Post hoc analysis of a prospective, multicenter, randomized, double-blind, double-dummy non-inferiority clinical trial (Engage). Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3, patients who received rFSH step-down or fixed-dose rFSH, patients who received rFSH on the day of human chorionic gonadotropin (hCG) compared with those who did not, and patients who received hCG when the criterion was reached versus those with a 1-day delay. Results: The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant. The estimated difference (95% confidence interval) in ongoing pregnancy rate was -4.3% (-9.4%, 0.8%) for patients who started ovarian stimulation on cycle day 2 versus day 3, 1.8% (-4.1%, 7.6%) for patients who received hCG on the day the hCG criterion was met versus 1 day after, 3.2% (-2.1%, 8.6%) for patients who received rFSH on the day of hCG administration versus those who did not, and -5.8% (-13.0%, 1.4%) for patients who received a reduced versus fixed-dose of rFSH from day 8.

Barbara J Stegmann - One of the best experts on this subject based on the ideXlab platform.

  • an open label clinical trial to investigate the efficacy and safety of Corifollitropin Alfa combined with hcg in adult men with hypogonadotropic hypogonadism
    Reproductive Biology and Endocrinology, 2017
    Co-Authors: Eberhard Nieschlag, Christine Mccrary Sisk, Barbara J Stegmann, P M G Bouloux, Ravi R Shankar, Yanfen Guan, A Tzontcheva, Hermann M Behre
    Abstract:

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin Alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of Corifollitropin Alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of Corifollitropin Alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg Corifollitropin Alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 106/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-Corifollitropin Alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 106/mL. No subject developed confirmed anti-Corifollitropin Alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin Alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  • Corifollitropin Alfa versus recombinant follicle stimulating hormone an individual patient data meta analysis
    Reproductive Biomedicine Online, 2016
    Co-Authors: Georg Griesinger, Davis Gates, R Boostanfar, Keith Gordon, Christine Mccrary Sisk, Barbara J Stegmann
    Abstract:

    A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of Corifollitropin Alfa versus rFSH: Engage (150 µg Corifollitropin Alfa n = 756; 200 IU rFSH n = 750), Ensure (100 µg Corifollitropin Alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 µg Corifollitropin Alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or ≤60 kg (Ensure), or women aged 35-42 years and body weight ≥50 kg (Pursue), received a single injection (100 µg or 150 µg) of Corifollitropin Alfa (based on body weight and age) or daily rFSH. The difference (Corifollitropin Alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of Corifollitropin Alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH.

  • impact of patient characteristics on the pharmacokinetics of Corifollitropin Alfa during controlled ovarian stimulation
    British Journal of Clinical Pharmacology, 2016
    Co-Authors: Anthe S Zandvliet, Christine Mccrary Sisk, Marita Prohn, Rik De Greef, Frank Van Aarle, Barbara J Stegmann
    Abstract:

    Aim The aim of the present study was to characterize the pharmacokinetic profile of Corifollitropin Alfa and examine the relationships between dose, intrinsic factors [body weight, body mass index (BMI), age and race] and Corifollitropin Alfa pharmacokinetics. Methods Data from five phase II and III clinical trials of Corifollitropin Alfa were evaluated. All subjects included in the analysis received 60 – 180 μg Corifollitropin Alfa for controlled ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol followed by daily recombinant follicle stimulating hormone (rFSH) from day 8 onwards. Serum Corifollitropin Alfa levels (across the entire range of treatment) and total follicle stimulating hormone immunoreactivity levels (up to the start of rFSH treatment) were indicators of drug exposure. The analyses were performed using a nonlinear mixed-effects modelling approach. Results A total of 2630 subjects were treated with Corifollitropin Alfa, and 2557 subjects were evaluable for analysis. Body weight, BMI and race (Asian and Black vs. Caucasian) were significant determinants of Corifollitropin Alfa exposure. Dose-normalized Corifollitropin Alfa exposure was ~89% higher in women with a body weight of 50 kg vs. 90 kg (in subjects with a similar BMI of 24 kg m−2); 14% higher in women with a BMI of 18 kg m−2 vs. 32 kg m−2 (provided they were of similar body weight); and ~15.7% lower in Asian subjects and 13% higher in Black subjects vs. Caucasian subjects. Conclusions Body weight was the major determinant of Corifollitropin Alfa exposure; BMI and race (Asian and Black) were also determinants but to a lesser extent and without associated effects on clinical outcomes. Corifollitropin Alfa dose adjustment is indicated, based on body weight but not for BMI or race. These recommendations are consistent with the product label.

  • Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin Alfa or rFSH in a GnRH Antagonist Protocol
    2016
    Co-Authors: Georg Griesinger, Davis Gates, Paul Devroey, 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

  • predictive factors for ovarian response in a Corifollitropin Alfa gnrh antagonist protocol for controlled ovarian stimulation in ivf icsi cycles
    Reproductive Biology and Endocrinology, 2015
    Co-Authors: Sergio Oehninger, Scott M Nelson, Pierre Verweij, Barbara J Stegmann
    Abstract:

    Background This secondary analysis aimed to identify predictors of low ( 18 oocytes retrieved) in IVF patients undergoing controlled ovarian stimulation with Corifollitropin Alfa in a gonadotropin-releasing hormone (GnRH) antagonist protocol.

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  • short follicular phase of stimulation following Corifollitropin Alfa or daily recombinant fsh treatment does not compromise clinical outcome a retrospective analysis of the engage trial
    Reproductive Biomedicine Online, 2014
    Co-Authors: Tonko Mardesic, Bernadette Mannaerts, Han Witjes, Michael J Levy, M Abuzeid, Bart C J M Fauser
    Abstract:

    Abstract To evaluate whether a short follicular phase of ovarian stimulation compromises the chance of pregnancy, subjects from a double-blind, randomized trial treated with a single dose of Corifollitropin Alfa (n=756) or daily recombinant FSH (n=750) were categorized as early responders if three follicles ⩾17mm were reached and human chorionic gonadotrophin (HCG) was administered prior to or on stimulation day 8, and as normal responders if three follicles ⩾17mm were reached and HCG was administered after stimulation day 8. In the Corifollitropin Alfa and recombinant FSH groups, 23.2% and 29.1%, respectively, were early responders (P=0.01). Regardless of the treatment group, the initial ovarian response was higher in early responders, but with two extra days of stimulation, the number and size of follicles on the day of HCG in the normal responders was similar to those of the early responders. The number of oocytes was similar in both response groups following Corifollitropin Alfa treatment (13.6 versus 14.5) and recombinant FSH treatment (12.8, both groups). The ongoing pregnancy rates were comparable for early and normal responders regardless of the treatment group, supporting successful outcome following a stimulation period of only 1week. During ovarian stimulation for assisted reproduction, some women respond earlier than others to treatment with follicle-stimulating agents and require fewer days of treatment. To evaluate whether such short stimulation jeopardizes the chance of pregnancy, clinical outcomes of early responders and normal responders were compared in women aged 18–36years treated with either a single dose of Corifollitropin Alfa (756 women) or daily recombinant FSH (750 women) for the first 7days of stimulation. On average, about 25% of the evaluated women were early responders. The initial ovarian response was higher in early responders than in normal responders but the number of eggs retrieved and the ongoing pregnancy rates in early and normal responders were similar regardless of the treatment group. This study shows that the chance of ongoing pregnancy was not compromised in women requiring only 1week of stimulation compared with women who required a longer duration of stimulation.

  • Corifollitropin Alfa doses based on body weight clinical overview of drug exposure and ovarian response
    Reproductive Biomedicine Online, 2011
    Co-Authors: William J Ledger, Paul Devroey, Anthe S Zandvliet, Bart C J M Fauser, Bernadette Mannaerts
    Abstract:

    Corifollitropin Alfa is a new recombinant gonadotrophin with a different pharmacokinetic profile but similar pharmacodynamic properties to conventional recombinant FSH. A single dose of Corifollitropin Alfa sustains multiple follicular development during the first 7 days of ovarian stimulation. This review is based on results of phase II and III trials testing the selected dose of 150 μg Corifollitropin Alfa in subjects >60 kg and 100 μg in subjects ≤60 kg. Exposure to Corifollitropin Alfa is inversely related to bodyweight. The selected doses of 100 and 150 μg in subjects weighing ≤60 and >60 kg, respectively, provide, on average, equal drug exposure producing similar ovarian responses in terms of the number of growing follicles, serum oestradiol, inhibin B and number of oocytes retrieved. Clinicians treating IVF patients with Corifollitropin Alfa should alter their treatment paradigm as a lower or higher dose than recommended according to body weight does not affect the ovarian response, which depends mainly on the ovarian reserve. After decades of daily dosing with FSH preparations, Corifollitropin Alfa allows a simpler IVF treatment regime with fewer injections. Successful use of Corifollitropin Alfa requires assessment of patient suitability and dosing before the start of stimulation.

  • pharmacokinetics and follicular dynamics of Corifollitropin Alfa versus recombinant fsh during ovarian stimulation for ivf
    Reproductive Biomedicine Online, 2011
    Co-Authors: Bart C J M Fauser, Anthe S Zandvliet, William J Ledger, Michael M Alper, William B Schoolcraft, Bernadette Mannaerts
    Abstract:

    A single injection of Corifollitropin Alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150μg Corifollitropin Alfa versus daily 200IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with Corifollitropin Alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ⩾11mm was slightly higher after Corifollitropin Alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (CI) 0.5-1.8; P<0.01) and on the day of HCG injection (difference, 2.1; 95% CI 1.4-2.8; P<0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of Corifollitropin Alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar. A single injection of Corifollitropin Alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. The objective of this study was to compare the pharmacokinetics and pharmacodynamics of Corifollitropin Alfa versus daily rFSH. A total of 1509 patients were randomized in a double-blind, controlled trial to either a single injection of 150μg Corifollitropin Alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation. Serum levels of FSH immunoreactivity were analysed (pharmacokinetic analysis), together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response (pharmacodynamic analysis). Serum FSH immunoreactivity levels were higher up to stimulation day 5 for Corifollitropin Alfa compared with the daily rFSH regimen but were similar from day 8 onwards, when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached. Corifollitropin Alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH. It is concluded that the pharmacokinetics of Corifollitropin Alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar.

  • 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: Paul Devroey, Pieta C Ijzermanboon, Bernadette Mannaerts, R Boostanfar, N P Koper, Bart C J M 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.

  • advances in recombinant dna technology Corifollitropin Alfa a hybrid molecule with sustained follicle stimulating activity and reduced injection frequency
    Human Reproduction Update, 2009
    Co-Authors: Bart C J M Fauser, B. M. J. L. Mannaerts, Arthur Leader, P Devroey, Irving Boime, D T Baird
    Abstract:

    Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH beta-subunit and the C-terminal peptide of the hCG beta-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the alpha-subunit and the chimeric FSH beta-subunit produces a new recombinant molecule, named Corifollitropin Alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH. Medline searches by subject and additional searching by hand. Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that Corifollitropin Alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin Alfa regimens have been developed with dosages of 100 and 150 mu g, for patients with body weight 60 kg, respectively. Corifollitropin Alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of Corifollitropin Alfa is the first step towards a new generation of recombinant gonadotrophins.