Research progress of dual trigger in GnRH antagonist protocol

doi:10.3760/cma.j.cn441417-20241211-10007

Abstract

Abstract:

The trigger is a key step in the process of ovarian stimulation. It uses exogenous drugs to simulate or induce the endogenous luteinizing hormone surge, promoting the final maturation of oocytes, resumption of meiosis, and triggering ovulation. It determines the outcomes of in vitro fertilization/intracytoplasmic sperm injection. The dual trigger is to promote the final maturation of the oocyte using gonadotropin-releasing hormone agonist and human chorionic gonadotropin, and is mostly used in the GnRH antagonist protocol. Dual trigger can improve oocyte quality and clinical pregnancy rates in poor and normal ovarian response populations, also reduce the risk of moderate/severe ovarian hyperstimulation syndrome, and offer the possibility of fresh embryo transfer cycle in high ovarian response populations. This article reviews the role of the dual trigger in the GnRH antagonist protocol.

Key words: Assisted reproductive technology, , Dual trigger, , Antagonist, , Clinical pregnancy, , In vitro fertilization/intracytoplasmic sperm injection, , Progress

摘要：

扳机是促排卵过程中的关键步骤，利用外源性药物模拟或诱发内源性的黄体生成素峰，促进卵母细胞最终成熟、恢复减数分裂和触发排卵，决定体外受精/胞浆内单精子注射助孕的成败。双扳机作为新兴的扳机方案，同时使用促性腺激素释放激素激动剂和人绒毛膜促性腺激素，多用于拮抗剂方案。研究发现双扳机可以提高卵巢低反应和正常反应人群拮抗剂方案的卵母细胞质量，改善临床妊娠率；降低卵巢高反应人群中/重度卵巢过度刺激综合征风险，为新鲜周期胚胎移植提供可能。本文就双扳机在拮抗剂方案中的应用做一综述。

关键词: 辅助生殖技术, , , 双扳机, , , 拮抗剂, , , 临床妊娠, , , 体外受精/胞浆内单精子注射, , , 进展

Yu Hanxu, Fan Yanru, Zhu Mingqing, Liu Xuemei.

Research progress of dual trigger in GnRH antagonist protocol [J]. International Medicine and Health Guidance News, 2025, 31(10): 1620-1623.

于涵煦范艳茹朱明青刘雪梅. 双扳机在拮抗剂方案中的应用进展 [J]. 国际医药卫生导报, 2025, 31(10): 1620-1623.

References

[1]Zhou C, Yang X, Wang Y, et al. Ovulation triggering with hCG alone, GnRH agonist alone or in combination? A randomized controlled trial in advanced-age women undergoing IVF/ICSI cycles[J]. Hum Reprod, 2022,37(8):1795-1805. DOI: 10.1093/humrep/deac114.

[2]Castillo JC, Humaidan P, Bernabéu R. Pharmaceutical options for triggering of final oocyte maturation in ART[J]. Biomed Res Int, 2014,2014:580171. DOI: 10.1155/2014/580171.

[3]Gonen Y, Balakier H, Powell W, et al. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization[J]. J Clin Endocrinol Metab, 1990,71(4):918-922. DOI: 10.1210/jcem-71-4-918.

[4]Wiser A, Klement AH, Shavit T, et al. Repeated GnRH agonist doses for luteal support: a proof of concept[J]. Reprod Biomed Online, 2019,39(5):770-776. DOI: 10.1016/j.rbmo.2019.07.031.

[5]Humaidan P, Bredkjaer HE, Bungum L, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study[J]. Hum Reprod, 2005,20(5):1213-1220. DOI: 10.1093/humrep/deh765.

[6]Shapiro BS, Daneshmand ST, Garner FC, et al. 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[J]. Fertil Steril, 2008,90(1):231-233. DOI: 10.1016/j.fertnstert.2007.06.030.

[7]Sloth A, Kjølhede M, Sarmon KG, et al. Effect of dual trigger on reproductive outcome in low responders: a systematic PRISMA review and meta-analysis[J]. Gynecol Endocrinol, 2022,38(3):213-221. DOI: 10.1080/09513590.2021.2000962.

[8]Hsia LH, Lee TH, Lin YH, et al. Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials[J]. J Assist Reprod Genet, 2023,40(9):2063-2077. DOI: 10.1007/s10815-023-02888-8.

[9]He Y, Tang Y, Chen S, et al. Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study[J]. BMC Pregnancy Childbirth, 2022,22(1):172. DOI: 10.1186/s12884-022-04499-0.

[10]Wu X, Yang L, Tang H, et al. Safety and effectiveness of dual trigger (GnRH agonist + HCG) versus HCG alone in patients with high ovarian response[J]. Am J Transl Res, 2024,16(11):6668-6678. DOI: 10.62347/QKPV5157.

[11]陈巧云,张野,陈璐,等.波塞冬组4卵巢低反应患者促排卵策略研究进展[J].生殖医学杂志,2024,33(9):1268-1273. DOI:10.3969/j.issn.1004-3845.2024.09.023.

[12]Zhao X, Ma B, Mo S, et al. Improvement of pregnancy outcome by extending embryo culture in IVF-ET during clinical application[J]. J Assist Reprod Genet, 2018,35(2):321-329. DOI: 10.1007/s10815-017-1065-5.

[13]Zhang QL, Lei YL, Deng Y, et al. Treatment progress in diminished ovarian reserve: western and chinese medicine[J]. Chin J Integr Med, 2023,29(4):361-367. DOI: 10.1007/s11655-021-3353-2.

[14]孙妍,罗笑卿,隗伏冰,等.来曲唑联合拮抗剂方案在卵巢储备功能低下患者辅助生殖技术中的疗效观察[J].国际医药卫生导报,2022,28(2):208-211. DOI:10.3760/cma.j.issn.1007-1245.2022.02.015.

[15]Zhang J, Wang Y, Mao X, et al. Dual trigger of final oocyte maturation in poor ovarian responders undergoing IVF/ICSI cycles[J]. Reprod Biomed Online, 2017,35(6):701-707. DOI: 10.1016/j.rbmo.2017.09.002.

[16]Lin MH, Wu FS, Hwu YM, et al. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve[J]. Reprod Biol Endocrinol, 2019,17(1):7. DOI: 10.1186/s12958-018-0451-x.

[17]Maged AM, Ragab MA, Shohayeb A, et al. Comparative study between single versus dual trigger for poor responders in GnRH-antagonist ICSI cycles: a randomized controlled study[J]. Int J Gynaecol Obstet, 2021,152(3):395-400. DOI: 10.1002/ijgo.13405.

[18]Chern CU, Li JY, Tsui KH, et al. Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: a retrospective cohort Study[J]. PLoS One, 2020,15(7):e0235707. DOI: 10.1371/journal.pone.0235707.

[19]Tulek F, Kahraman A, Demirel LC. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin improves live birth rates in POSEIDON group 3 and 4 expected poor responders[J]. Gynecol Endocrinol, 2022,38(9):731-735. DOI: 10.1080/09513590.2022.2101635.

[20]He Z, Liu Y, Huang N, et al. Dual trigger versus human chorionic gonadotropin trigger for blastocyst quality and cumulative live birth[J]. J Assist Reprod Genet, 2024,41(12):3445-3453. DOI: 10.1007/s10815-024-03293-5.

[21]Humaidan P, Kol S, Papanikolaou EG, et al. GnRH agonist for triggering of final oocyte maturation: time for a change of practice?[J]. Hum Reprod Update, 2011,17(4):510-524. DOI: 10.1093/humupd/dmr008.

[22]王金玉,张啸龙,张杰平,等. GnRH-a联合HCG双扳机在高龄卵巢储备功能减退患者中的应用[J].生殖医学杂志,2022,31(9):1176-1181. DOI:10.3969/j.issn.1004-3845.2022. 09.003.

[23]Haas J, Bassil R, Samara N, et al. GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study[J]. Hum Reprod, 2020,35(7):1648-1654. DOI: 10.1093/humrep/deaa107.

[24]Ali SS, Elsenosy E, Sayed GH, et al. Dual trigger using recombinant HCG and gonadotropin-releasing hormone agonist improve oocyte maturity and embryo grading for normal responders in GnRH antagonist cycles: Randomized controlled trial[J]. J Gynecol Obstet Hum Reprod, 2020,49(5):101728. DOI: 10.1016/j.jogoh.2020.101728.

[25]Cevher Akdulum MF, Arık Sİ, Demirdağ E, et al. In vitro fertilization outcomes with a dual trigger in normoresponders in antagonist cycles[J]. Cureus, 202,15(9):e45623. DOI: 10.7759/cureus.45623.

[26]潘丹,杨杰,李娜,等. GnRH-a联合HCG双扳机对年轻患者IVF/ICSI妊娠结局的影响[J].生殖医学杂志,2023,32(4):481-486. DOI:10.3969/j.issn.1004-3845.2023.04.002.

[27]Lin MH, Wu FS, Lee RK, et al. 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[J]. Fertil Steril, 2013,100(5):1296-1302. DOI: 10.1016/j.fertnstert.2013.07.1976.

[28]Schachter M, Friedler S, Ron-El R, et al. Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study[J]. Fertil Steril, 2008,90(4):1087-1093. DOI: 10.1016/j.fertnstert.2007.07.1316.

[29]Ding N, Liu X, Jian Q, et al. Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: a systematic review and meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol, 2017,218:92-98. DOI: 10.1016/j.ejogrb.2017.09.004.

[30]Fabris AM, Cruz M, Legidos V, et al. Dual triggering with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin in patients with a high immature oocyte rate[J]. Reprod Sci, 2017,24(8):1221-1225. DOI: 10.1177/1933719116682873.

[31]Zhu H, Zhao C, Pan Y, et al. Dual trigger for final follicular maturation improves cumulative live-birth rate in ovarian stimulation for freeze-allin vitro fertilization/intracytoplasmic sperm injection cycles[J]. Front Endocrinol (Lausanne), 2021,12:708247. DOI: 10.3389/fendo.2021.708247.

[32]Zilberberg E, Haas J, Dar S, et al. Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes[J]. Gynecol Endocrinol, 2015,31(2):145-147. DOI: 10.3109/09513590.2014.978850.

[33]Yan MH, Sun ZG, Song JY. Dual trigger for final oocyte maturation in expected normal responders with a high immature oocyte rate: a randomized controlled trial[J]. Front Med (Lausanne), 2023,10:1254982. DOI: 10.3389/fmed.2023.1254982.

[34]覃慧斯,周红,舒金辉,等.比较hCG联合GnRH-a双扳机和hCG单扳机方案对卵巢高反应人群的影响[J].中国性科学,2024,33(2):57-61. DOI:10.3969/j.issn.1672-1993. 2024.02.015.

[35]Kuroda K, Nagai S, Ikemoto Y, et al. Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals[J]. Reprod Biomed Online, 2021,42(1):125-132. DOI: 10.1016/j.rbmo.2020.09.001.

[36]谢言信,庄广论.卵巢高反应与过度刺激[J].生殖医学杂志,2012,21(2):95-99. DOI:10.3969/j.issn.1004-3845. 2012.02.001.

[37]Shapiro BS, Daneshmand ST, Garner FC, et al. Comparison of "triggers" using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin[J]. Fertil Steril, 2011,95(8):2715-2717. DOI: 10.1016/j.fertnstert.2011.03.109.

[38]Griffin D, Benadiva C, Kummer N, et al. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders[J]. Fertil Steril, 2012,97(6):1316-1320. DOI: 10.1016/j.fertnstert. 2012.03.015.

[39]罗燕群,朱秀兰,黄莉,等.不同扳机方案对卵巢高反应人群胚胎质量的影响比较[J].实用医学杂志,2020,36(15):2108-2113. DOI:10.3969/j.issn.1006-5725.2020.15.017.

[40]Fernández-Sánchez M, Fatemi H, García-Velasco JA, et al. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach[J]. Gynecol Endocrinol, 2023,39(1):2205952. DOI: 10.1080/09513590.2023.2205952.

[41]Zhai J, Zhang J, He J, et al. Live birth outcomes for PCOS patients under the follicular-phase long-acting GnRH agonist protocol or antagonist protocol - a retrospective chinese cohort[J]. J Multidiscip Healthc, 2023,16:2781-2792. DOI: 10.2147/JMDH.S432936.