辅助生殖技术中双扳机应用的研究进展

doi:10.12280/gjszjk.20240387

摘要/Abstract

摘要：

在辅助生殖技术（assisted reproductive technology，ART）的控制性超促排卵（controlled ovarian hyperstimulation，COH）过程中，适当扳机方式的选择至关重要。随着对人绒毛膜促性腺激素（human chorionic gonadotropin，hCG）扳机及促性腺激素释放激素激动剂（gonadotropin-releasing hormone agonist，GnRH-a）扳机利弊研究的不断深入，双扳机即GnRH-a联合hCG扳机被提出并应用于临床，以期减少卵巢过度刺激综合征（ovarian hyperstimulation syndrome，OHSS）发生率，改善ART结局。然而，由于不同患者在年龄、卵巢储备、体质量指数（body mass index，BMI）等方面存在异质性，双扳机应用于卵巢高反应、正常反应及低反应人群可能产生不同程度的效果。综述双扳机的最新研究进展，以期为临床不同卵巢反应患者扳机方式的选择提供参考，并探讨了双扳机需要继续深入研究的方向，如扳机药物剂量、取卵时机、个体化黄体支持方案及新扳机方式的探索。

关键词: 超排卵, 卵巢过度刺激综合征, 生殖技术, 辅助, 绒毛膜促性腺激素, 促性腺激素释放激素激动剂, 双扳机

Abstract:

The choice of appropriate trigger methods in the controlled ovarian hyperstimulation (COH) of assisted reproductive technology (ART) is crucial. With the in-depth study of the pros and cons of human chorionic gonadotropin (hCG) trigger and gonadotropin-releasing hormone agonist (GnRH-a) trigger, the dual trigger, defined as the combined trigger with GnRH-a and hCG, was proposed and applied in clinical practice in order to reduce the incidence of ovarian hyperstimulation syndrome (OHSS) and improve the outcome of ART. However, due to the heterogeneity of different patients in age, ovarian reserve, body mass index (BMI), etc., the application of dual trigger may produce varying degrees of effect, in the patients with high, normal and low ovarian response. This review summarizes the research progress of dual trigger, so as to provide a reference for the selection of trigger methods in the patients with different ovarian responses. We also discuss the directions for further research on the dual trigger, such as trigger doses, the timing of oocyte retrieval, the individualized luteal phase support, and new trigger methods.

Key words: Superovulation, Ovarian hyperstimulation syndrome, Reproductive techniques, assisted, Chorionic gonadotropin, Gonadotropin-releasing hormone agonist, Dual trigger

姚相宜, 刘培昊. 辅助生殖技术中双扳机应用的研究进展[J]. 国际生殖健康/计划生育杂志, 2025, 44(1): 36-40.

YAO Xiang-yi, LIU Pei-hao. Progress in the Application of Dual Trigger in Assisted Reproductive Technology[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(1): 36-40.

参考文献 29

[1]	Palomba S, Costanzi F, Nelson SM, et al. Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence[J]. Reprod Biol Endocrinol, 2023, 21(1):67. doi: 10.1186/ s12958-023-01113-6.
[2]	Humaidan P, Haahr T. GnRHa trigger-the story of the ugly duckling[J]. F S Rep, 2023, 4(Suppl 2):15-19. doi: 10.1016/j.xfre.2023.02.011.
[3]	Carosso AR, Canosa S, Gennarelli G, et al. Luteal Support with very Low Daily Dose of Human Chorionic Gonadotropin after Fresh Embryo Transfer as an Alternative to Cycle Segmentation for High Responders Patients Undergoing Gonadotropin-Releasing Hormone Agonist-Triggered IVF[J]. Pharmaceuticals(Basel), 2021, 14(3):228. doi: 10.3390/ph14030228.
[4]	Huang CY, Shieh ML, Li HY. The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles[J]. J Chin Med Assoc, 2016, 79(7):387-393. doi: 10.1016/j.jcma.2016.02.006.
[5]	林晓霞, 谭展虹, 蔡冰红, 等. PCOS患者拮抗剂方案双扳机与绒促性素扳机方案的临床应用[J]. 中国处方药, 2021, 19(2):108-109. doi: 10.3969/j.issn.1671-945X.2021.02.056.
[6]	O′Neill KE, Senapati S, Maina I, et al. GnRH agonist with low-dose hCG (dual trigger) is associated with higher risk of severe ovarian hyperstimulation syndrome compared to GnRH agonist alone[J]. J Assist Reprod Genet, 2016, 33(9):1175-1184. doi: 10.1007/s10815-016-0755-8.
[7]	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. pmid: 22480822
[8]	李蓉, 陈福锐, 陈诗琪, 等. 三种扳机方式在多囊卵巢综合征患者拮抗剂方案促排卵中的临床应用[J]. 生殖医学杂志, 2023, 32(11):1623-1629. doi: 10.3969/j.issn.1004-3845.2023.11.002.
[9]	Xu K, Wang J, Yang S, et al. Comparison of HCG Trigger versus Dual Trigger in Improving Pregnancy Outcomes in Patients with Different Ovarian Responses: A Retrospective Study[J]. Int J Endocrinol, 2024,2024:2507026. doi: 10.1155/2024/2507026.
[10]	沈秀珍, 沈新光, 王芳敏. 促性腺激素释放激素激动剂联合小剂量人绒毛膜促性腺激素双扳机在卵巢高反应患者拮抗剂促排卵周期中的应用效果[J]. 中国性科学, 2021, 30(6):84-87. doi: 10.3969/j.issn.1672-1993.2021.06.026.
[11]	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.
[12]	Wang Q, Wan Q, Li T, et al. Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study[J]. Arch Gynecol Obstet, 2024, 309(2):679-688. doi: 10.1007/s00404-023-07285-1. pmid: 38032411
[13]	He FF, Hu W, Yong L, et al. Triggering of ovulation for GnRH-antagonist cycles in normal and low ovarian responders undergoing IVF/ICSI: A systematic review and meta-analysis of randomized trials[J]. Eur J Obstet Gynecol Reprod Biol, 2023, 289:65-73. doi: 10.1016/j.ejogrb.2023.08.014.
[14]	Zhang Y, Guo X, Guo L, et al. Outcomes comparison of IVF/ICSI among different trigger methods for final oocyte maturation: A systematic review and meta-analysis[J]. FASEB J, 2021, 35(7):e21696. doi: 10.1096/fj.202100406R.
[15]	Gao F, Wang Y, Fu M, et al. Effect of a "Dual Trigger" Using a GnRH Agonist and hCG on the Cumulative Live-Birth Rate for Normal Responders in GnRH-Antagonist Cycles[J]. Front Med(Lausanne), 2021,8:683210. doi: 10.3389/fmed.2021.683210.
[16]	Guo D, Pang C, Wang K. Comparison of pregnancy outcomes in women with normal ovarian response to the gonadotropin-releasing hormone agonist protocol using different trigger methods: a single-center retrospective cohort study based on propensity score matching[J]. Arch Gynecol Obstet, 2024, 309(5):2153-2165. doi: 10.1007/s00404-024-07404-6. pmid: 38494512
[17]	Li Q, Li X, Li T, et al. Comparison of an HCG-only trigger versus dual trigger for final oocyte maturation in a progestin-primed ovarian stimulation protocol[J]. Reprod Biomed Online, 2022, 45(6):1176-1181. doi: 10.1016/j.rbmo.2022.08.101. pmid: 36207251
[18]	冼业星, 黄岩, 郭新宇. 空卵泡综合征研究进展[J]. 中国优生与遗传杂志, 2022, 30(10):1893-1898. doi: 10.13404/j.cnki.cjbhh.2022.10.015.
[19]	Turathum B, Gao EM, Chian RC. The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization[J]. Cells, 2021, 10(9):2292. doi: 10.3390/cells10092292.
[20]	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.
[21]	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.
[22]	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.
[23]	Kang MK, Kim MK, Kim TH, et al. Association between different dual trigger dosages and in vitro fertilization results in patients with patient-oriented strategies encompassing individualized oocyte number group Ⅳ[J]. Obstet Gynecol Sci, 2022, 65(2):215-222. doi: 10.5468/ogs.21317.
[24]	Gan R, Huang X, Zhao J, et al. Time interval between hCG administration and oocyte retrieval and ART outcomes: an updated systematic review and meta-analysis[J]. Reprod Biol Endocrinol, 2023, 21(1):61. doi: 10.1186/s12958-023-01110-9.
[25]	Ranit H, Shmuel H, Ahlad A, et al. Is there a preferred time interval between gonadotropin-releasing hormone (GnRH) agonist trigger and oocyte retrieval in GnRH antagonist cycles? A retrospective cohort of planned fertility preservation cycles[J]. J Assist Reprod Genet, 2024, 41(6):1531-1538. doi: 10.1007/s10815-024-03083-z.
[26]	Sharma B, Koysombat K, Comninos AN, et al. Use of kisspeptin to trigger oocyte maturation during in vitro fertilisation (IVF) treatment[J]. Front Endocrinol(Lausanne), 2022,13:972137. doi: 10.3389/fendo.2022.972137.
[27]	Abbara A, Clarke SA, Dhillo WS. Clinical Potential of Kisspeptin in Reproductive Health[J]. Trends Mol Med, 2021, 27(8):807-823. doi: 10.1016/j.molmed.2021.05.008. pmid: 34210598
[28]	Abbara A, Jayasena CN, Christopoulos G, et al. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy[J]. J Clin Endocrinol Metab, 2015, 100(9):3322-3331. doi: 10.1210/jc.2015-2332. pmid: 26192876
[29]	Abbara A, Islam R, Clarke SA, et al. Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment[J]. Clin Endocrinol(Oxf), 2018, 88(6):920-927. doi: 10.1111/cen.13569.