Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Dual Trigger with Gonadotropin Releasing Hormone Agonist and Human Chorionic Gonadotropin of Fresh Autologous Cycles in High Responders: A Systematic Review

Authors
Andreas A Vyrides 1
Essam El Mahdi 2
Demetris Lamnisos 3
Konstantinos Giannakou 3
1 Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
2 Department of Obstetrics and Gynaecology, Newham University Hospital NHS Trust, London, United Kingdom
3 Department of Health Sciences, School of Sciences, European University of Cyprus, Nicosia, Cyprus
10.18502/jri.v23i1.8446
Abstract
Background: The purpose of the current study was to investigate the effect of coadministration of human chorionic gonadotropin (hCG) with gonadotropin releasing hormone agonist (GnRH-a) trigger (dual trigger) in high responders for fresh autologous cycles in order to investigate the pregnancy outcomes and rates of ovarian hyperstimulation syndrome (OHSS) in comparison to GnRH-a trigger alone. Methods: A systematic search was performed in PubMed and Ovid MEDLINE from inception through February 2020. The included materials were case-control, cohort and, cross-sectional studies as well as clinical trials in which the outcomes of dual trigger with GnRH-a were compared for final oocyte maturation in high responders undergoing GnRH-ant cycles. Results: Five retrospective studies were included for this review. Three of the studies showed that the use of dual trigger versus GnRH-a trigger resulted in no statistically significant difference in rates of OHSS while achieving a statistically significant difference in favor of the dual trigger group in ongoing pregnancy rates, early pregnancy loss, and fertilization rates. Conclusion: Currently, there is insufficient evidence to support improved clinical pregnancy rate, fertilization rate, live birth rate, and early pregnancy loss rate by the use of dual trigger versus GnRH-a trigger. Larger double-blind clinical studies are required to properly evaluate the efficacy of this protocol for use in high responders.
Keywords
Dual trigger
Fresh autologous cycles
Gonadotropin releasing hormone (GnRH)
Ovarian hyperstimulation syndrome (OHSS)
Systematic review
Tobler KJ, Zhao Y, Weissman A, Majumdar A, Leong M, Shoham Z. Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques. Arch Gynecol Obstet. 2014;290(3):561-8.
Albano C, Riethmüller-Winzen H, Smitz J, Van Steirteghem A, Camus M, Devroey P. Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation. Fertil Steril. 1997;67(5):917-22.
Borm G, Mannaerts B. Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. Hum Reprod. 2000;15(7):1490-8.
Itskovitz-Eldor J, Kol S, Mannaerts B, Bennink HC. First established pregnancy after controlled ovarian hyperstimulation with recombinant follicle stimulating hormone and the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462). Hum Reprod. 1998;13(2):294-5.
Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: Prevention and treatment. Fertil Steril. 1992;58(2):249-61.
Mathur RS, Akande AV, Keay SD, Hunt LP, Jenkins JM. Distinction between early and late ovarian hyperstimulation syndrome. Fertil Steril. 2000;73(5):901-7.
Dourron NE, Williams DB. Prevention and treatment of ovarian hyperstimulation syndrome. Semin Reprod Endocrinol. 1996;14(4):355-65.
Papanikolaou EG, Pozzobon C, Kolibianakis EM, Camus M, Tournaye H, Fatemi HM, et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil Steril. 2006;85(1):112-20.
Golan A, Weissman A. Symposium: update on prediction and management of OHSS-A modern classification of OHSS. Reprod Biomed Online. 2009;19(1):28-32.
Humaidan P, Nelson SM, Devroey P, Coddington CC, Schwartz LB, Gordon K, et al. Ovarian hyperstimulation syndrome: Reviewand new classification criteria for reporting in clinical trials. Hum Reprod. 2016;31(9):1997-2004.
Delvigne A, Kostyla K, Murillo D, Van Hoeck J, Rozenberg S. Oocyte quality and IVF outcome after coasting to prevent ovarian hyperstimulation syndrome. Int J Fertil Womens Med. 2003;48(1):25-31.
De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: results generated from European registries by ESHRE: the European IVF-monitoring Consortium (EIM) for the European society of human reproduction and embryology (ESHRE). Hum Reprod. 2018;33(9):1586-601.
De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(1):hoz038.
Wyns C, Bergh C, Calhaz-Jorge C, De Geyter Ch, Kupka MS, Motrenko T, et al. ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(3):hoaa032.
Shanbhag S, Bhattacharya S. Current management of ovarian hyperstimulation syndrome. Hosp Med. 2002;63(9):528-32.
Kol S. Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome. Fertil Steril. 2004;81(1):1-5.
Kol S, Itskovitz-Eldor J. Severe OHSS: yes, there is a strategy to prevent it! Hum Reprod. 2000;15(11):2266-7.
Orvieto R. Can we eliminate severe ovarian hyperstimulation syndrome? Hum Reprod. 2005;20(2):320-2.
Humaidan P, Bredkjær HE, Bungum L, Bungum M, Grøndahl ML, Westergaard L, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20(5):1213-20.
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(10):2887-92.
Vlaisavljević V, Kovačič B, Knez J. Cumulative live birth rate after GnRH agonist trigger and elective cryopreservation of all embryos in high responders. Reprod Biomed Online. 2017;35(1):42-8.
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(5):1296-302.
Haas J, Bassil R, Samara N, Zilberberg E, Mehta C, Orvieto R, et al. GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study. Hum Reprod. 2020;35(7):1648-54.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006-12.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5.
O’Neill KE, Senapati S, Maina I, Gracia C, Dokras A. GnRH agonist with low-dose hCG (dual trigger) is associated with higher risk of severe ovarian hyperstimulation syndrome compared to GnRH agonist alone. J Assist Reprod Genet. 2016;33(9):1175-84.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre 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(1):231-3.
Griffin D, Benadiva C, Kummer N, Budinetz T, Nulsen J, Engmann L. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril. 2012;97(6):1316-20.
Huang CY, Shieh ML, Li HY. The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles. J Chin Med Assoc. 2016;79(7):387-93.
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(8):2715-7.
National institute for health and clinical excellence. Ectopic pregnancy and miscarriage: diagnosis and initial management. NICE Guideline NG126. 2019 [cited 2021 Jun 17]; (April 2019):1–34. Available from: www.nice.org.uk/guidance/ng126
Banker M, Patel J, Patel A, Banker J, Gupte-Shah A. Miscarriage: biochemical and clinical. In: Skinner M, editor. Encyclopedia of reproduction. US: Academic Press; 2018. p. 317-23.
Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989;44(6):430-40.
Gonen Y, Balakier H, Powell W, Casper RF. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab. 1990;71(4):918-22.
Itskovitz J, Boldes R, Levron J, Erlik Y, Kahana L, Brandes JM. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril. 1991;56(2):213-20.
Kolibianakis EM, Bourgain C, Platteau P, Albano C, Van Steirteghem AC, Devroey P. Abnormal endometrial development occurs during the luteal phase of nonsupplemented donor cycles treated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil Steril. 2003;80(2):464-6.
Beckers NGM, Macklon NS, Eijkemans MJ, Ludwig M, Felberbaum RE, Diedrich K, et al. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilizatio. J Clin Endocrinol Metab. 2003;88(9):4186-92.
Albano C, Grimbizis G, Smitz J, Riethmüller-Winzen H, Reissmann T, Van Steirteghem A, et al. The luteal phase of nonsupplemented cycles after ovarian superovulation with human menopausal gonadotropin and the gonadotropin-releasing hormone antagonist Cetrorelix. Fertil Steril. 1998;70(2):357-9.
Soliman S, Daya S, Collins J, Hughes EG. The role of luteal phase support in infertility treatment: A meta-analysis of randomized trials. Fertil Steril. 1994;61(6):1068-76.
Pritts EA, Atwood AK. Luteal phase support in infertility treatment: A meta-analysis of the randomized trials. Hum Reprod. 2002;17(9):2287-99.
Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002;78(5):1025-9.
Daya S, Gunby JL. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;3:CD004830.
Hoff JD, Quigley ME, Yen SSC. Hormonal dynamics at midcycle: A reevaluation. J Clin Endocrinol Metab. 1983;57(4):792-6.
Filicori M, Santoro N, Merriam GR, Crowley WF. Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual Cycle. J Clin Endocrinol Metab. 1986;62(6):1136-44.
Casper RF, Yen SS. Induction of luteolysis in the human with a long-acting analog of luteinizing hormone-releasing factor. Science. 1979;205(4404):408-10.
Rao C V. Multiple novel roles of luteinizing hormone. Fertil Steril. 2001;76(6):1097-100.
Sugino N, Kashida S, Takiguchi S, Karube A, Kato H. Expression of vascular endothelial growth factor and its receptors in the human corpus luteum during the menstrual cycle and in early pregnancy. J Clin Endocrinol Metab. 2000;85(10):3919-24.
Tesarik J, Hazout A, Mendoza C. Luteinizing hormone affects uterine receptivity independently of ovarian function. Reprod Biomed Online. 2003;7(1):59-64.
Licht P, Russu V, Lehmeyer S, Wildt L. Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo. Reprod Biol. 2001;1(1):10-9.
Licht P, Russu V, Wildt L. On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: Implications for differentiation and implantation. Semin Reprod Med. 2001;19(1):37-47.
Fatemi HM. The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online. 2009;19 Suppl 4:4331.
Fauser BCJM, Devroey P. Reproductive biology and IVF: Ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003;14(5):236-42.
Tavaniotou A, Devroey P. Effect of human chorionic gonadotropin on luteal luteinizing hormone concentrations in natural cycles. Fertil Steril. 2003;80(3):654-5.
Tavaniotou A, Albano C, Smitz J, Devroey P. Comparison of LH concentrations in the early and mid-luteal phase in IVF cycles after treatment with HMG alone or in association with the GnRH antagonist Cetrorelix. Hum Reprod. 2001;16(4):663-7.
Engmann LL, Maslow BS, Kaye LA, Griffin DW, Diluigi AJ, Schmidt DW, et al. Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35 h later in women at high risk of developing ovarian hyperstimulation syndrome - a prospective randomized double-blind clinical tri. J Ovarian Res. 2019;12(1):8.
Martazanova B, Mishieva N, Vtorushina V, Vedikhina I, Levkov L, Korneeva I, et al. Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients. Am J Reprod Immunol. 2021;85(6):e13381.
Chen SU, Chou CH, Lin CW, Lee H, Wu JC, Lu HF, et al. Signal mechanisms of vascular endothelial growth factor and interleukin-8 in ovarian hyperstimulation syndrome: Dopamine targets their common pathways. Hum Reprod. 2010;25(3):757-67.
Kaye L, Griffin D, Thorne J, Neuber E, Nulsen J, Benadiva C, et al. Independent serum markers of corpora lutea function after gonadotropin-releasing hormone agonist trigger and adjuvant low dose human chorionic gonadotropin in in vitro fertilization. Fertil Steril. 2019;112(3):534-44.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfers in high responders. Fertil Steril. 2011;96(2):516-8.
Kummer N, Benadiva C, Feinn R, Mann J, Nulsen J, Engmann L. Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist. Fertil Steril. 2011;96(1):63-8.
Delvinge A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review. Hum Reprod Update. 2002;8(6):559-77.
Tarlatzis BC, Bosdou J, Kolibianakis S. Elimination of OHSS by GnRH agonist and freezing embryos. In: Rizk J, editor. Complications and outcomes of assisted reproduction. Cambridge: Cambridge University Press; 2017. p. 149-63.
Bosdou JK, Venetis CA, Tarlatzis BC, Grimbizis GF, Kolibianakis EM. Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: a meta-analysis. Hum Reprod. 2019;34(3):491-505.
Giannakou K. Perinatal epidemiology: issues, challenges, and potential solutions. Obstet Med. 2021;14(2):77-82.
de Geyter C, Wyns C, Calhaz-Jorge C, de Mouzon J, Ferraretti AP, Kupka M, et al. 20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions. Hum Reprod. 2020;35(12):2832-49.
Royal College of Obstetricians & Gynaecologists. The management of ovarian hyperstimulation syndrome. Green-top Guidline No. 5. 2016. 22 p.
Journal of Reproduction & Infertility
Volume 23, Issue 1
Winter 2022
Pages 3-17