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

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Article

Klein, Bjarke Mirner⁶  Arce, Joan-Cartes⁸  Iournaye, Herman⁹  De Sutter, Petra¹⁰  Decleer, Wim¹¹  Petracco, Alvaro¹²  Borges, Edson¹³  Barbosa, Caio Parente¹⁴  Havelock, Jon¹⁵  Claman, Paul¹⁶  Yuzpe, Albert^5,17  Visnova, Hana^4,18  Ventruba, Pavel¹⁹  Uher, Petr²⁰  Vary, Karlovy²¹  Mrazek, Milan²¹  Andersen, Anders Nyboe²²  Knudsen, Ulla Breth²³  Dewailly, Didier²⁴  Leveque, Anne Guivarc'h²⁵  La Marca, Antonio²⁶  Papaleo, Enrico²⁷  Kuczynski, Waldemar²⁸  Koziol, Katarzyna²⁹  Anshina, Margarita³⁰  Zazerskaya, Irina³¹  Gzgzyan, Alexander³²  Bulychova, Elena³³  Verdu, Victoria³⁴  Barri, Pedro³⁵  Antonio Garcia-Velasco, Juan³⁶  Fernandez-Sanchez, Manuel^1,2,3,37  Sanchez Martin, Fernando³⁸  Bosch, Ernesto³⁹  Serna, Jose⁴⁰  Castillon, Gemma⁴¹  Bernabeu, Rafael⁴²  Ferrando, Marcos⁴³  Lavery, Stuart⁴⁴  Gaudoin, Marco⁴⁵  Nelson, Scott M.⁴⁶  Fauser, Bart C. J. M.⁴⁷  Klein, Bjarke M.⁴⁸  Helmgaard, Lisbeth⁴⁹  Breinholt, Vibeke⁴⁹  Mannaerts, Bernadette^7,49  Arce, Joan-Carles⁴⁹ 

[1] IVI RMA Seville, Avda RepUbl Argentina 58, ES-41011 Seville, Spain

[2] Univ Seville, Dept Cirugia, Avda Sanchez Pizjuan S-N, ES-41009 Seville, Spain

[3] Univ Pablo Olavide, Dept Biol Mol & Ingn Bioquim, ES-41013 Seville, Spain

[4] IVF CUBE SE, Prague 16000, Czech Republic

[5] Olive Fertil Ctr, Vancouver, BC V5Z 3X7, Canada

[6] Ferring Pharmaceut, Global Biometr, DK-2300 Copenhagen, Denmark

[7] Ferring Pharmaceut, Sci & Med, DK-2300 Copenhagen, Denmark

[8] US Dev, Ferring Pharmaceut, Parsippany, NJ 07054 USA

[9] UZ Brussel, Jette, Belgium

[10] UZ Gent, Ghent, Belgium

[11] AZ Jan Palfijn AV, Ghent, Belgium

[12] Ctr Med Reprod, Porto Alegre, RS, Brazil

[13] Ctr Fertilizacao Assistida, Fertil, Sao Paulo, Brazil

[14] Inst Ideia Fertil Saude Reprod, Sao Paulo, Brazil

[15] Pacific Ctr Reprod Med, Burnaby, BC, Canada

[16] Ottawa Fertil Ctr, Ottawa, ON, Canada

[17] Olive Fertil Ctr, Vancouver, BC, Canada

[18] IVF CUBE SE, Prague, Czech Republic

[19] Ctr Assisted Reprod, Brno, Czech Republic

[20] Inst Reprod Med & Genet, Karlovy Vary, Czech Republic

[21] GYNEM, Prague, Czech Republic

[22] Copenhagen Univ Hosp, Fertil Clin, Copenhagen, Denmark

[23] Aarhus Univ Hosp, Fertil Clin, Skejby, Denmark

[24] Hop Jeanne Flandre, Dept Endocrine Gynaecol & Reprod Med, Lille, France

[25] Clin Mutualiste La Sagesse, Rennes, France

[26] Univ Modena & Reggio Emilia, Modena, Italy

[27] Ctr Natalita San Raffaele, Milan, Italy

[28] Kriobank, Bialystok, Poland

[29] nOvum Fertil Clin, Warsaw, Poland

[30] Ctr Reprod & Genet LLC, Moscow, Russia

[31] Minist Hlth Russian Federat, Fed Ctr Heart Blood & Endocrinol, Fed State Budgetary Inst, St Petersburg, Russia

[32] Inst Russian Acad Med Sci, Sci Res Inst Gynaecol & Obstet, North West Dept RAMS, St Petersburg, Russia

[33] Moscow Reg Sci Res Inst Obstet & Gynaecol, State Budgetary Hlth Inst Moscow Reg, St Petersburg, Russia

[34] Genefiv, Madrid, Spain

[35] Hosp Univ Quiron Dexeus, Barcelona, Spain

[36] IVI Madrid, Madrid, Spain

[37] IVI Sevilla, Seville, Spain

[38] Ginemed, Seville, Spain

[39] IVI Valencia, Valencia, Spain

[40] IVI Zaragoza, Zaragoza, Spain

[41] IVI Barcelona, Barcelona, Spain

[42] Inst Bernabeu, Alicante, Spain

[43] IVI Bilbao, Bilbao, Spain

[44] Boston Pl Clin, London, England

[45] Glasgow Ctr Reprod Med, Glasgow, Lanark, Scotland

[46] Univ Glasgow, Sch Med, Glasgow, Lanark, Scotland

[47] Univ Med Ctr Utrecht, Div Woman & Baby, Utrecht, Netherlands

[48] Ferring Pharmaceut AS, Global Clin & Nonclin R&D, Biometr, Copenhagen, Denmark

[49] Ferring Pharmaceut AS, Reprod Hlth, Global Clin & Nonclin R&D, Copenhagen, Denmark

关键词: Anti-Mullerian hormone;    Follitropin delta;    GnRH agonist triggering;    OHSS;    Ovarian stimulation;    Preventive interventions;   

DOI  :  10.1016/j.rbmo.2018.12.032

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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