Triggering final follicular maturation- hCG, GnRH-agonist or both, when and to whom?

Journal of Ovarian Research

Raoul Orvieto¹ 

[1] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

关键词: Oocyte quality;    Controlled ovarian hyperstimulation;    OHSS;    Trigger;    Ovulation;    GnRH agonist;    hCG;   

Others  :  1224697
DOI  :  10.1186/s13048-015-0187-6

 received in 2015-07-16, accepted in 2015-08-08,  发布年份 2015

【 摘 要 】

Controlled ovarian hyperstimulation (COH) which combines GnRH antagonist co-treatment and GnRH-agonist (GnRHa) trigger has become a common tool aiming to eliminate severe early OHSS and to support the concept of an OHSS-free clinic. However, due to the reported significantly reduced clinical, efforts have been made to improve reproductive outcome. One of the suggested optional strategies aiming to improve outcome was the addition of low-dose (1500 IU) HCG bolus, administered, concomitant, 35 h or 5 days after the triggering bolus of GnRHa. All these regimens were demonstrated to rescue the luteal phase, resulting in improved reproductive outcome in patients at risk to develop severe OHSS, compared to GnRHa trigger alone, however, with the questionable ability to eliminate severe OHSS.

Moreover, following the observations demonstrating comparable or even better oocyte\embryos quality following GnRHa, compared to hCG trigger, and the different effects of LH and hCG on the downstream signaling of the LH receptor, GnRHa is now offered concomitant to the standard hCG trigger dose to improve oocyte/embryo yield and quality. GnRHa and hCG may be offered either concomitantly, 35–37 h prior to oocyte retrieval (dual trigger), or 40 h and 34 h prior to oocyte retrieval, respectively (double trigger).

【 授权许可】

   
2015 Orvieto.

【 图 表 】

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【 参考文献 】

• [1]Itskovitz-Eldor J, Kol S, Mannaerts B. Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report: short communication. Hum Reprod. 2000; 15:1965-8.
• [2]Orvieto R. Can we eliminate severe ovarian hyperstimulation syndrome? Hum Reprod. 2005; 20:320-2.
• [3]Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011; 6:2593-7.
• [4]Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update. 2006; 12:159-168.
• [5]Orvieto R, Rabinson J, Meltzer S, Zohav E, Anteby E, Homburg R. Substituting HCG with GnRH agonist to trigger final follicular maturation–a retrospective comparison of three different ovarian stimulation protocols. Reprod Biomed Online. 2006; 13:198-201.
• [6]Humaidan P, Bungum L, Bungum M, Yding AC. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online. 2006; 13:173-8.
• [7]Humaidan P, Bredkjaer HE, Westergaard LG, Andersen CY. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin- releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study. Fertil Steril. 2010; 93:847-854.
• [8]Humaidan P, Papanikolaou EG, Kyrou D, Alsbjerg B, Polyzos NP, Devroey P et al.. The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod Biomed Online. 2012; 24:134-41.
• [9]Seyhan A, Ata B, Polat M, Son WY, Yarali H, Dahan MH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod. 2013; 28:2522-8.
• [10]Orvieto R, Ben-Rafael Z. Role of intravenous albumin in the prevention of severe ovarian hyperstimulation syndrome. Hum Reprod. 1998; 13:3306-9.
• [11]Shapiro BS, Daneshmand ST, Garner FC, Aguirr M, Thomas S. Gonadotropin-releasing hormone agonist combined with a reduced dose of human chorionic gonadotropin for final oocyte maturation in fresh autologous cycles of in vitro fertilization. Fertil Steril. 2008; 90:231-233.
• [12]Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Comparison of “triggers” using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. Fertil Steril. 2011; 95:2715-7.
• [13]Orvieto R. Ovarian hyperstimulation syndrome- an optimal solution for an unresolved enigma. J Ovarian Res. 2013; 6:77. BioMed Central Full Text
• [14]Haas J, Kedem A, Machtinger R, Dar S, Hourovitz A, Yerushalmi G et al.. HCG (1500IU) administration on day 3 after oocytes retrieval, following GnRH-agonist trigger for final follicular maturation, results in high sufficient mid luteal progesterone levels - a proof of concept. J Ovarian Res. 2014; 7:35. BioMed Central Full Text
• [15]Fritz MA, Speroff L. Regulation of the Menstrual Cycle. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott Williams & Wilkins, Philadelphia; 2011.
• [16]Ludwig M, Doody KJ, Doody KM. Use of recombinant human chorionic gonadotropin in ovulation induction. Fertil Steril. 2003; 79:1051-9.
• [17]Gonen Y, Balakier H, PowellW CRF. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab. 1990; 71:918-922.
• [18]Fauser BC, de Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J et al.. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab. 2002; 87:709-15.
• [19]Kolibianakis EM, Schultze-Mosgau A, Schroer A, Van Steirteghem A, Devroey P, Diedrich K et al.. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of hCG in patients undergoing IVF with GnRH antagonists. Hum Reprod. 2005; 20:2887-92.
• [20]Humaidan P, Ejdrup Bredkjær H, Bungum L, Bungum M, Grøndahl ML, Westergaard LG et al.. GnRH agonist (Buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005; 20:1213-20.
• [21]Acevedo B, Gomez-Palomares JL, Ricciarelli E, Hernandez ER. Triggering ovulation with gonadotropin-releasing hormone agonist does not compromise embryo implantation rates. Fertil Steril. 2006; 76:1682-7.
• [22]Erb TM, Vitek W, Wakim ANG. Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final oocyte maturation in an oocyte donor program. Fertil Steril. 2010; 93:374-8.
• [23]Casarini L, Lispi M, Longobardi S, Milosa F, La Marca A, Tagliasacchi D et al.. LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling. PLoS One. 2012; 7:e46682.
• [24]Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril. 2013; 100:1296-302.
• [25]Decleer W, Osmanagaoglu K, Seynhave B, Kolibianakis S, Tarlatzis B, Devroey P. Comparison of hCG triggering versus hCG in combination with a GnRH agonist: a prospective randomized controlled trial. Facts Views Vis Obgyn. 2014; 6:203-9.
• [26]Griffin D, Feinn R, Engmann L, Nulsen J, Budinetz T, Benadiva C. Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril. 2014; 102:405-9.
• [27]Beck-Fruchter R, Weiss A, Lavee M, Geslevich Y, Shalev E. Empty follicle syndrome: successful treatment in a recurrent case and review of the literature. Hum Reprod. 2012; 27:1357-67.
• [28]Wang W, Zhang XH, Wang WH, Liu YL, Zhao LH, Xue SL et al.. The time interval between hCG priming and oocyte retrieval in ART program: a meta-analysis. J Assist Reprod Genet. 2011; 28:901-10.
• [29]Haas J, Zilberberg E, Dar S, Kedem A, Machtinger R, Orvieto R. Co-administration of GnRH-agonist and hCG for final oocyte maturation (double trigger) in patients with low number of oocytes retrieved per number of preovulatory follicles-a preliminary report. Journal of Ovarian Research. 2014; 7:77. BioMed Central Full Text
• [30]Zilberberg E, Haas J, Dar S, Kedem A, Machtinger R, Orvieto R. Co-administration of GnRH-agonist and hCG for final oocyte maturation in patients with low proportion of mature oocytes. Gyn Endocrinol. 2015; 31:145-7.
• [31]Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L et al.. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011; 26:1616-24.
• [32]Martinez F, Barri PN, Coroleu B, Tur R, Sorsa-Leslie T, Harris WJ et al.. Women with poor response to IVF have lowered circulating gonadotrophin surge-attenuating factor (GnSAF) bioactivity during spontaneous and stimulated cycles. Hum Reprod. 2002; 17:634-40.
• [33]Ben-Rafael Z, Orvieto R, Feldberg D. The poor-responder patient in an in-vitro fertilization-embryo transfer (IVF-ET) program. Gynecol Endocrinol. 1994; 8:277-86.