Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis
To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes.
A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation.
Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31–0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups.
Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.
KeywordsGnRH agonist plus hCG hCG In vitro fertilization Ovarian hyperstimulation syndrome
C-HuangC: project development and data analysis. CRT, PHW, WML, HYC, and HHC: Data collection and data analysis. C-HuiC: project development, data collection, data analysis, and manuscript writing.
Compliance with ethical standards
Conflict of interest
The authors declare they have no known conflicts of interest in this work.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Youssef MA, Van der Veen F, Al-Inany HG et al (2014) Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev 10:CD008046Google Scholar
- 2.Babayof R, Margalioth EJ, Huleihel M et al (2006) Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial. Hum Reprod 21:1260–1265CrossRefPubMedGoogle Scholar
- 5.Humaidan P, Ejdrup Bredkjaer H, Westergaard LG, Yding Andersen C (2010) 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 93:847–854CrossRefPubMedGoogle Scholar
- 6.Papanikolaou EG, Verpoest W, Fatemi H, Tarlatzis B, Devroey P, Tournaye H (2011) A novel method of luteal supplementation with recombinant luteinizing hormone when a gonadotropin-releasing hormone agonist is used instead of human chorionic gonadotropin for ovulation triggering: a randomized prospective proof of concept study. Fertil Steril 95:1174–1177CrossRefPubMedGoogle Scholar
- 7.Kasum M, Kurdija K, Orešković S, Čehić E, Pavičić-Baldani D, Škrgatić L (2016) Combined ovulation triggering with GnRH agonist and hCG in IVF patients. Gynecol Endocrinol 8:1–5Google Scholar
- 8.Fauser BC, de Jong D, Olivennes F et al (2002) 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 87:709–715CrossRefPubMedGoogle Scholar
- 11.Schachter M, Friedler S, Ron-El R, Zimmerman AL, Strassburger D, Bern O, Raziel A (2008) Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study. Fertil Steril 90:1087–1093CrossRefPubMedGoogle Scholar
- 12.Mahajan N, Sharma S, Arora PR, Gupta S, Rani K, Naidu P (2016) Evaluation of dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin in improving oocyte maturity rates: a prospective randomized study. J Hum Reprod Sci 9:101–106CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Iñarra MJ, Crisol L, Guembe MA (2015) Use of dual trigger with gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) to optimize oocyte recovery rates and IVF results. In: European Society of Reproduction and Embryology 2015 Annual Meeting; June 2015; Lisbon, PortugalGoogle Scholar
- 14.Cochrane Handbook for Systematic Reviews of interventions. Version 5.1.0. (updated March, 2011). The Cochrane Collaboration. http://training.cochrane.org/handbook
- 17.National Research Council (1992) Combing information: statistical issues and opportunities for research. National Academy Press, Washington, DCGoogle Scholar
- 22.Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM (2013) 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 100:1296–1302CrossRefPubMedGoogle Scholar
- 24.Seval MM, Özmen B, Atabekoğlu C et al (2016) Dual trigger with gonadotropin-releasing hormone agonist and recombinant human chorionic gonadotropin improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles. J Obstet Gynaecol Res 42:1146–1151CrossRefPubMedGoogle Scholar
- 29.Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C (2008) The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril 89:84–91CrossRefPubMedGoogle Scholar
- 33.Boothroyd C, Karia S, Andreadis N, Rombauts L, Johnson N, Chapman M, Australasian CREI Consensus Expert Panel on Trial evidence (ACCEPT) group (2015) Consensus statement on prevention and detection of ovarian hyperstimulation syndrome. Aust N Z J Obstet Gynaecol 55:523–534CrossRefPubMedGoogle Scholar