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Joan-carles Arce - One of the best experts on this subject based on the ideXlab platform.
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Randomized, assessor-blind, antimüllerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with Follitropin delta.
Fertility and sterility, 2020Co-Authors: Osamu Ishihara, Bjarke Mirner Klein, Joan-carles ArceAbstract:Objective To establish the relationship between Follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimullerian hormone (AMH) levels. Design Randomized, controlled, assessor-blind, AMH-stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose-response trial. Setting Reproductive medicine clinics. Patient(s) A total of 158 Japanese women (20–39 years of age). Intervention(s) Controlled ovarian stimulation with 6, 9, or 12 μg/d of Follitropin delta or 150 IU/d Follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle. Main Outcome Measure(s) Number of oocytes retrieved. Result(s) Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d Follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with Follitropin delta. The vital pregnancy rate per started cycle with Follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with Follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. Conclusion(s) This trial establishes the dose-response relationship between Follitropin delta and ovarian response in Japanese women. Clinical Trial Registration Number NCT02309671.
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Establishing the Follitropin delta dose that provides a comparable ovarian response to 150 IU/day Follitropin alfa.
Reproductive biomedicine online, 2020Co-Authors: Joan-carles Arce, Per Larsson, Juan A. Garcia-velascoAbstract:Abstract Research question The objective of this investigation was to determine the daily Follitropin delta dose (µg) providing a similar ovarian response to 150 IU/day Follitropin alfa. Design The study was a post-hoc analysis of ovarian response in 1591 IVF/intracytoplasmic sperm injection (ICSI) patients undergoing ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol in two recent randomized, assessor-blind, controlled trials in the development programme for Follitropin delta: a phase II dose–response trial with a reference arm of a fixed daily dose of 150 IU Follitropin alfa throughout stimulation, and a phase III efficacy trial with a comparator arm of 150 IU/day Follitropin alfa as a starting dose. Results Daily Follitropin delta doses of 10.0 µg (95% confidence interval [CI] 7.9–12.8) and 10.3 µg (95% CI 9.7–10.8) yielded the same number of oocytes as 150 IU/day Follitropin alfa for all patients participating in the phase II and III trials, respectively. When analysing patients with either normal or high ovarian reserve (based on serum anti-Mullerian hormone ≥15 pmol/l) and no dose changes, the same number of oocytes was obtained with 150 IU/day Follitropin alfa and daily doses of Follitropin delta of 9.7 µg (95% CI 7.5–12.4) and 9.3 µg (95% CI 8.6–10.1) in the two trials. Daily Follitropin delta doses in the range 9.5–10.4 µg were consistently estimated to correspond to 150 IU/day Follitropin alfa for serum oestradiol concentration and number of follicles ≥12 mm at the end of stimulation across analysis populations in the phase III trial. Conclusions A daily Follitropin delta dose of 10 µg provides a similar ovarian response to 150 IU/day Follitropin alfa in IVF/ICSI patients.
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Individualization of the starting dose of Follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles.
Reproductive biomedicine online, 2018Co-Authors: Manuel Fernández-sánchez, Bjarke Mirner Klein, Bernadette Mannaerts, Hana Visnova, A. Albert Yuzpe, Joan-carles ArceAbstract:Abstract Research question Is individualization of dosing with Follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? Design A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18–40 years) randomized and treated with Follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. Results Individualized dosing with Follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with Follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Mullerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with Follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus Follitropin alfa. Conclusion An individualized Follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional Follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
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Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial
Reproductive biomedicine online, 2018Co-Authors: Ernesto Bosch, Bjarke Mirner Klein, Jon Havelock, Fernando Sánchez Martin, Birgitte Buur Rasmussen, Bernadette Mannaerts, Joan-carles ArceAbstract:Abstract Research question To evaluate the immunogenicity of Follitropin delta in repeated ovarian stimulation. Design Controlled, assessor-blind trial in IVF/intracytoplasmic sperm injection patients undergoing repeated cycles of ovarian stimulation (cycles 2 and 3), following initial stimulation with Follitropin delta or Follitropin alfa (cycle 1) in a preceding randomized trial. In cycles 2 and 3, 513 and 188 women, respectively, were treated as randomized in cycle 1, with dosing based on ovarian response in the previous cycle. Results The incidence of treatment-induced anti-FSH antibodies with Follitropin delta was 0.8% and 1.1% in cycles 2 and 3, respectively, which was similar to the incidence in cycle 1 (1.1%). No antibodies were of neutralizing capacity. Women with pre-existing anti-FSH antibodies were safely treated with Follitropin delta without boosting an immune response. Treatment with Follitropin delta and Follitropin alfa gave similar outcomes for mean number of oocytes retrieved (9.2 versus 8.6 [cycle 2]; 8.3 versus 8.9 [cycle 3]), ongoing pregnancy (27.8% versus 25.7%; 27.4% versus 28.0%) and live birth rates (27.4% versus 25.3%; 26.3% versus 26.9%). The presence of anti-FSH antibodies did not affect the ovarian response. Conclusions The trial demonstrated the low immunogenicity potential of Follitropin delta in repeated ovarian stimulation, and confirmed the appropriateness of the Follitropin delta dosing regimen in repeated cycles, with documented efficacy and safety.
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individualized versus conventional ovarian stimulation for in vitro fertilization a multicenter randomized controlled assessor blinded phase 3 noninferiority trial
Fertility and Sterility, 2017Co-Authors: Anders Nyboe Andersen, Bjarke Mirner Klein, Wim Decleer, Joan-carles Arce, Petra De Sutter, Bart C J M Fauser, Scott M Nelson, Herman Tournaye, Juan A Garciavelasco, Alvaro PetraccoAbstract:Objective To compare the efficacy and safety of Follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimullerian hormone (AMH) and body weight, with conventional Follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18–40 years). Intervention(s) Follitropin delta (AMH Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins −8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference −0.9% [95% confidence interval (CI) −5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; −0.6% [95% CI −6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; −0.9% [95% CI −5.8% to 4.0%]) rates were similar for individualized Follitropin delta and conventional Follitropin alfa. Individualized Follitropin delta resulted in more women with target response (8–14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110.
Bjarke Mirner Klein - One of the best experts on this subject based on the ideXlab platform.
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Randomized, assessor-blind, antimüllerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with Follitropin delta.
Fertility and sterility, 2020Co-Authors: Osamu Ishihara, Bjarke Mirner Klein, Joan-carles ArceAbstract:Objective To establish the relationship between Follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimullerian hormone (AMH) levels. Design Randomized, controlled, assessor-blind, AMH-stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose-response trial. Setting Reproductive medicine clinics. Patient(s) A total of 158 Japanese women (20–39 years of age). Intervention(s) Controlled ovarian stimulation with 6, 9, or 12 μg/d of Follitropin delta or 150 IU/d Follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle. Main Outcome Measure(s) Number of oocytes retrieved. Result(s) Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d Follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with Follitropin delta. The vital pregnancy rate per started cycle with Follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with Follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. Conclusion(s) This trial establishes the dose-response relationship between Follitropin delta and ovarian response in Japanese women. Clinical Trial Registration Number NCT02309671.
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randomized assessor blind antimullerian hormone stratified dose response trial in japanese in vitro fertilization intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with Follitropin delta
Fertility and Sterility, 2020Co-Authors: Osamu Ishihara, Bjarke Mirner Klein, J C ArceAbstract:Objective To establish the relationship between Follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimullerian hormone (AMH) levels. Design Randomized, controlled, assessor-blind, AMH-stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose-response trial. Setting Reproductive medicine clinics. Patient(s) A total of 158 Japanese women (20–39 years of age). Intervention(s) Controlled ovarian stimulation with 6, 9, or 12 μg/d of Follitropin delta or 150 IU/d Follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle. Main Outcome Measure(s) Number of oocytes retrieved. Result(s) Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d Follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with Follitropin delta. The vital pregnancy rate per started cycle with Follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with Follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. Conclusion(s) This trial establishes the dose-response relationship between Follitropin delta and ovarian response in Japanese women. Clinical Trial Registration Number NCT02309671.
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individualization of the starting dose of Follitropin delta reduces the overall ohss risk and or the need for additional preventive interventions cumulative data over three stimulation cycles
Reproductive Biomedicine Online, 2019Co-Authors: Bjarke Mirner Klein, Bernadette Mannaerts, Hana Visnova, A. Albert Yuzpe, M Fernandezsanchez, J C ArceAbstract:Abstract Research question Is individualization of dosing with Follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? Design A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18–40 years) randomized and treated with Follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. Results Individualized dosing with Follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with Follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Mullerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with Follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus Follitropin alfa. Conclusion An individualized Follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional Follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
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Individualization of the starting dose of Follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles.
Reproductive biomedicine online, 2018Co-Authors: Manuel Fernández-sánchez, Bjarke Mirner Klein, Bernadette Mannaerts, Hana Visnova, A. Albert Yuzpe, Joan-carles ArceAbstract:Abstract Research question Is individualization of dosing with Follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? Design A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18–40 years) randomized and treated with Follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. Results Individualized dosing with Follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with Follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Mullerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with Follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus Follitropin alfa. Conclusion An individualized Follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional Follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
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Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial
Reproductive biomedicine online, 2018Co-Authors: Ernesto Bosch, Bjarke Mirner Klein, Jon Havelock, Fernando Sánchez Martin, Birgitte Buur Rasmussen, Bernadette Mannaerts, Joan-carles ArceAbstract:Abstract Research question To evaluate the immunogenicity of Follitropin delta in repeated ovarian stimulation. Design Controlled, assessor-blind trial in IVF/intracytoplasmic sperm injection patients undergoing repeated cycles of ovarian stimulation (cycles 2 and 3), following initial stimulation with Follitropin delta or Follitropin alfa (cycle 1) in a preceding randomized trial. In cycles 2 and 3, 513 and 188 women, respectively, were treated as randomized in cycle 1, with dosing based on ovarian response in the previous cycle. Results The incidence of treatment-induced anti-FSH antibodies with Follitropin delta was 0.8% and 1.1% in cycles 2 and 3, respectively, which was similar to the incidence in cycle 1 (1.1%). No antibodies were of neutralizing capacity. Women with pre-existing anti-FSH antibodies were safely treated with Follitropin delta without boosting an immune response. Treatment with Follitropin delta and Follitropin alfa gave similar outcomes for mean number of oocytes retrieved (9.2 versus 8.6 [cycle 2]; 8.3 versus 8.9 [cycle 3]), ongoing pregnancy (27.8% versus 25.7%; 27.4% versus 28.0%) and live birth rates (27.4% versus 25.3%; 26.3% versus 26.9%). The presence of anti-FSH antibodies did not affect the ovarian response. Conclusions The trial demonstrated the low immunogenicity potential of Follitropin delta in repeated ovarian stimulation, and confirmed the appropriateness of the Follitropin delta dosing regimen in repeated cycles, with documented efficacy and safety.
R Driebergen - One of the best experts on this subject based on the ideXlab platform.
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Continued improvements in the quality and consistency of Follitropin alfa, recombinant human FSH
Reproductive biomedicine online, 2005Co-Authors: Rm Bassett, R DriebergenAbstract:The use of gonadotrophins for the treatment of infertility began in the 1930s following early work on the pituitary-ovarian axis and the discovery of FSH and LH. The technological development of pharmaceutical gonadotrophins over the last 40 years has shown improvements in specific activity, purity, degradation and impurities. Throughout these pharmaceutical developments the gonadotrophin content of both urinary and recombinant preparations has been assessed using an animal in-vivo bioassay. This paper reflects upon the manufacturing history of recombinant human FSH (r-hFSH) and Follitropin alfa filled by mass (FbM), and evaluates the impact of introducing a pharmaceutical product that is formulated and assayed by a physicochemical method for r-hFSH protein content. It also compares the analytical consistency of Follitropin alfa FbM with another commercially available r-hFSH, Follitropin beta.
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quantification of follicle stimulating hormone Follitropin alfa is in vivo bioassay still relevant in the recombinant age
Current Medical Research and Opinion, 2003Co-Authors: R Driebergen, G BaerAbstract:SummaryQuantification of follicle-stimulating hormone (FSH) for clinical use has traditionally involved the use of in vivo bioassays, particularly the Steelman–Pohley bioassay. This assay has limited precision, requires large numbers of laboratory animals and involves cumbersome procedures for data generation and interpretation. Recent advances in manufacturing procedures for recombinant human FSH (r-hFSH) have resulted in a preparation (Follitropin alfa; Gonal-F) that is highly consistent in both isoform profile and glycan species distribution. As a result, Follitropin alfa can be reliably quantified using an optimisedsize exclusion high-performance liquid chromat-ography (SE-HPLC) method, and vials can be filled by mass. Preliminary clinical studies suggest that the fill-by-mass process results in a product that delivers a more consistent clinical response and is more effective than Follitropin alfa vials filled by bioassay in women undergoing controlled ovarian stimulation. Non-bioassay methods such as...
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Quantification of follicle stimulating hormone (Follitropin alfa): is in vivo bioassay still relevant in the recombinant age?
Current medical research and opinion, 2003Co-Authors: R Driebergen, G BaerAbstract:Quantification of follicle-stimulating hormone (FSH) for clinical use has traditionally involved the use of in vivo bioassays, particularly the Steelman-Pohley bioassay. This assay has limited precision, requires large numbers of laboratory animals and involves cumbersome procedures for data generation and interpretation. Recent advances in manufacturing procedures for recombinant human FSH (r-hFSH) have resulted in a preparation (Follitropin alfa; Gonal-F) that is highly consistent in both isoform profile and glycan species distribution. As a result, Follitropin alfa can be reliably quantified using an optimised size exclusion high-performance liquid chromatography (SE-HPLC) method, and vials can be filled by mass. Preliminary clinical studies suggest that the fill-by-mass process results in a product that delivers a more consistent clinical response and is more effective than Follitropin alfa vials filled by bioassay in women undergoing controlled ovarian stimulation. Non-bioassay methods such as SE-HPLC are likely to become increasingly important for quality testing and regulatory purposes, provided that the manufacturing process is well controlled and produces a protein of highly consistent physico-chemical properties.
J C Arce - One of the best experts on this subject based on the ideXlab platform.
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randomized assessor blind antimullerian hormone stratified dose response trial in japanese in vitro fertilization intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with Follitropin delta
Fertility and Sterility, 2020Co-Authors: Osamu Ishihara, Bjarke Mirner Klein, J C ArceAbstract:Objective To establish the relationship between Follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimullerian hormone (AMH) levels. Design Randomized, controlled, assessor-blind, AMH-stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose-response trial. Setting Reproductive medicine clinics. Patient(s) A total of 158 Japanese women (20–39 years of age). Intervention(s) Controlled ovarian stimulation with 6, 9, or 12 μg/d of Follitropin delta or 150 IU/d Follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle. Main Outcome Measure(s) Number of oocytes retrieved. Result(s) Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d Follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with Follitropin delta. The vital pregnancy rate per started cycle with Follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with Follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. Conclusion(s) This trial establishes the dose-response relationship between Follitropin delta and ovarian response in Japanese women. Clinical Trial Registration Number NCT02309671.
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individualization of the starting dose of Follitropin delta reduces the overall ohss risk and or the need for additional preventive interventions cumulative data over three stimulation cycles
Reproductive Biomedicine Online, 2019Co-Authors: Bjarke Mirner Klein, Bernadette Mannaerts, Hana Visnova, A. Albert Yuzpe, M Fernandezsanchez, J C ArceAbstract:Abstract Research question Is individualization of dosing with Follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? Design A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18–40 years) randomized and treated with Follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. Results Individualized dosing with Follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with Follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Mullerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with Follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus Follitropin alfa. Conclusion An individualized Follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional Follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
G Baer - One of the best experts on this subject based on the ideXlab platform.
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quantification of follicle stimulating hormone Follitropin alfa is in vivo bioassay still relevant in the recombinant age
Current Medical Research and Opinion, 2003Co-Authors: R Driebergen, G BaerAbstract:SummaryQuantification of follicle-stimulating hormone (FSH) for clinical use has traditionally involved the use of in vivo bioassays, particularly the Steelman–Pohley bioassay. This assay has limited precision, requires large numbers of laboratory animals and involves cumbersome procedures for data generation and interpretation. Recent advances in manufacturing procedures for recombinant human FSH (r-hFSH) have resulted in a preparation (Follitropin alfa; Gonal-F) that is highly consistent in both isoform profile and glycan species distribution. As a result, Follitropin alfa can be reliably quantified using an optimisedsize exclusion high-performance liquid chromat-ography (SE-HPLC) method, and vials can be filled by mass. Preliminary clinical studies suggest that the fill-by-mass process results in a product that delivers a more consistent clinical response and is more effective than Follitropin alfa vials filled by bioassay in women undergoing controlled ovarian stimulation. Non-bioassay methods such as...
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Quantification of follicle stimulating hormone (Follitropin alfa): is in vivo bioassay still relevant in the recombinant age?
Current medical research and opinion, 2003Co-Authors: R Driebergen, G BaerAbstract:Quantification of follicle-stimulating hormone (FSH) for clinical use has traditionally involved the use of in vivo bioassays, particularly the Steelman-Pohley bioassay. This assay has limited precision, requires large numbers of laboratory animals and involves cumbersome procedures for data generation and interpretation. Recent advances in manufacturing procedures for recombinant human FSH (r-hFSH) have resulted in a preparation (Follitropin alfa; Gonal-F) that is highly consistent in both isoform profile and glycan species distribution. As a result, Follitropin alfa can be reliably quantified using an optimised size exclusion high-performance liquid chromatography (SE-HPLC) method, and vials can be filled by mass. Preliminary clinical studies suggest that the fill-by-mass process results in a product that delivers a more consistent clinical response and is more effective than Follitropin alfa vials filled by bioassay in women undergoing controlled ovarian stimulation. Non-bioassay methods such as SE-HPLC are likely to become increasingly important for quality testing and regulatory purposes, provided that the manufacturing process is well controlled and produces a protein of highly consistent physico-chemical properties.
