E-ISSN: 2619-9467

Contents    Cover    Publication Date: 03 Nov 2021
Year 2021 - Volume 31 - Issue 3

Open Access

Peer Reviewed

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Dual Trigger with Gonadotropin-releasing Hormone Agonist and Human Chorionic Gonadotropin Improves Live Birth Rate for Women with Expected Normal Ovarian Response in Gonadotropin Releasing Hormone Antagonist Cycles: Retrospective Study

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JCOG. 2021;31(3):89-96
DOI: 10.5336/jcog.2021-86043
Article Language: EN
Copyright Ⓒ 2020 by Türkiye Klinikleri. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Objective: To evaluate and compare cycle outcomes following triggering final oocyte maturation with dual trigger of concomitant gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) administration versus hCG alone for women with expected normal ovarian response that underwent antagonist cycles with intracytoplasmic sperm injection (ICSI). Material and Methods: Women with expected normal ovarian response that underwent GnRH antagonist cycles with ICSI between January 2010 and April 2020 were evaluated in this retrospective cohort study. A total of 2,443 patients were included. Dual trigger was used for oocyte maturation in 637 cycles whereas hCG alone was used for triggering in 1,806 women. Cycles with dual trigger were assigned to study group and cycles with hCG alone are taken as controls. Results: Number of retrieved oocytes (14.08±3.58 vs. 13.15±3.61), number of metaphase 2 oocytes (9.77±3.08 vs. 8.06±3.14), fertilization rate (0.75±0.19 vs. 0.69±0.19), implantation rate (0.43±0.48 vs. 0.35±0.50) and clinical pregnancy rate (49.9% vs. 40.6%) were significantly higher in dual trigger group in comparison to hCG alone group. Higher number of good quality embryos were obtained in dual trigger group (85.7% vs. 76.3%). Live birth rate was significantly increased in dual trigger group in comparison to hCG only trigger group (45.1% vs. 36.7%). Multivariate logistic regression analysis showed dual trigger is a significant factor in predicting live birth deliveries (odds ratio 1.426, 95% confidence interval 1.185-1.716). Conclusion: Dual-triggering appears to improve embryo quality, increase implantation rates, clinical pregnancy rates and live birth rates in women with expected normal ovarian response that underwent GnRH antagonist cycles.
  1. Orvieto R. Triggering final follicular maturation--hCG, GnRH-agonist or both, when and to whom? J Ovarian Res. 2015;8:60. [Crossref]  [PubMed]  [PMC] 
  2. 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. [Crossref]  [PubMed] 
  3. 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(10): e46682. [Crossref]  [PubMed]  [PMC] 
  4. Kol S, Humaidan P. GnRH agonist triggering: recent developments. Reprod Biomed Online. 2013;26(3):226-30. [Crossref]  [PubMed] 
  5. 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. [Crossref]  [PubMed] 
  6. Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014;(10): CD008046. [Crossref]  [PubMed] 
  7. Guo S, Li Z, Yan L, Sun Y, Feng Y. GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity. Drug Des Devel Ther. 2018;12:1621-31. [Crossref]  [PubMed]  [PMC] 
  8. Tesarik J, Hazout A, Mendoza C. Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum Reprod. 2004;19(5): 1176-80. [Crossref]  [PubMed] 
  9. 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(2):405-9. [Crossref]  [PubMed] 
  10. Şükür YE, Ulubaşoğlu H, İlhan FC, Berker B, Sönmezer M, Atabekoğlu CS, et al. Dual trigger in normally-responding assisted reproductive technology patients increases the number of top-quality embryos. Clin Exp Reprod Med. 2020;47(4):300-5. [Crossref]  [PubMed]  [PMC] 
  11. Kim CH, Ahn JW, You RM, Kim SH, Chae HD, Kang BM. Combined administration of gonadotropin-releasing hormone agonist with human chorionic gonadotropin for final oocyte maturation in GnRH antagonist cycles for in vitro fertilization. J Reprod Med. 2014;59(1-2):63-8. [PubMed] 
  12. Benadiva C, Engmann L. Luteal phase support after gonadotropin-releasing hormone agonist triggering: does it still matter? Fertil Steril. 2018;109(5):763-7. [Crossref]  [PubMed] 
  13. 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. [Crossref]  [PubMed] 
  14. 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. [Crossref]  [PubMed] 
  15. Maged AM, Ragab MA, Shohayeb A, Saber W, Ekladious S, Hussein EA, et al. Comparative study between single versus dual trigger for poor responders in GnRH-antagonist ICSI cycles: A randomized controlled study. Int J Gynaecol Obstet. 2021;152(3):395-400. [Crossref]  [PubMed] 
  16. Lin MH, Wu FS, Hwu YM, Lee RK, Li RS, Li SH. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve. Reprod Biol Endocrinol. 2019;17(1):7. [Crossref]  [PubMed]  [PMC] 
  17. 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(4):203-9. [PubMed]  [PMC] 
  18. Chern CU, Li JY, Tsui KH, Wang PH, Wen ZH, Lin LT. Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: A retrospective cohort study. PLoS One. 2020;15(7):e023 5707. [Crossref]  [PubMed]  [PMC] 
  19. Li S, Zhou D, Yin T, Xu W, Xie Q, Cheng D, et al. Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols. Oncotarget. 2018;9(4):5337-43. [Crossref]  [PubMed]  [PMC] 
  20. Eser A, Devranoğlu B, Bostancı Ergen E, Yayla Abide Ç. Dual trigger with gonadotropin-releasing hormone and human chorionic gonadotropin for poor responders. J Turk Ger Gynecol Assoc. 2018;19(2):98-103. [Crossref]  [PubMed]  [PMC] 
  21. 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. [Crossref]  [PubMed] 
  22. Eftekhar M, Mohammadi B, Khani P, Lahijani MM. Dual stimulation in unexpected poor responder POSEIDON classification group 1, sub-group 2a: A cross-sectional study. Int J Reprod Biomed. 2020;18(6):465-70. [Crossref]  [PubMed]  [PMC] 
  23. Ali SS, Elsenosy E, Sayed GH, Farghaly TA, Youssef AA, Badran E, 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 Gynecol Obstet Hum Reprod. 2020;49(5):101728. [Crossref]  [PubMed] 
  24. Seval MM, Özmen B, Atabekoğlu C, Şükür YE, Şimşir C, Kan Ö, et al. 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. 2016;42(9): 1146-51. [Crossref]  [PubMed] 
  25. Zhou X, Guo P, Chen X, Ye D, Liu Y, Chen S. Comparison of dual trigger with combination GnRH agonist and hCG versus hCG alone trigger of oocyte maturation for normal ovarian responders. Int J Gynaecol Obstet. 2018;141(3):327-31. [Crossref]  [PubMed] 
  26. Ovarian Stimulation TEGGO, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI?. Hum Reprod Open. 2020;2020(2): hoaa009. Erratum in: Hum Reprod Open. 2020;2020(4):hoaa067. [Crossref]  [PubMed]  [PMC] 
  27. Humaidan P, Alviggi C, Fischer R, Esteves SC. The novel POSEIDON stratification of 'Low prognosis patients in Assisted Reproductive Technology' and its proposed marker of successful outcome. F1000Res. 2016;5: 2911. [Crossref]  [PubMed]  [PMC] 
  28. Racowsky C, Vernon M, Mayer J, Ball GD, Behr B, Pomeroy KO, et al. Standardization of grading embryo morphology. J Assist Reprod Genet. 2010;27(8):437-9. [Crossref]  [PubMed]  [PMC] 
  29. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108(3):393-406. [Crossref]  [PubMed] 
  30. Lamb JD, Shen S, McCulloch C, Jalalian L, Cedars MI, Rosen MP. Follicle-stimulating hormone administered at the time of human chorionic gonadotropin trigger improves oocyte developmental competence in in vitro fertilization cycles: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2011; 95(5):1655-60. [Crossref]  [PubMed] 
  31. Haas J, Ophir L, Barzilay E, Machtinger R, Yung Y, Orvieto R, et al. Standard human chorionic gonadotropin versus double trigger for final oocyte maturation results in different granulosa cells gene expressions: A pilot study. Fertil Steril. 2016;106(3):653-9.e1. [Crossref]  [PubMed] 
  32. Maggi R, Cariboni AM, Marelli MM, Moretti RM, Andrè V, Marzagalli M, et al. GnRH and GnRH receptors in the pathophysiology of the human female reproductive system. Hum Reprod Update. 2016;22(3):358-81. [Crossref]  [PubMed] 
  33. Schachter M, Friedler S, Ron-El R, Zimmerman AL, Strassburger D, Bern O, 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. Fertil Steril. 2008;90(4):1087-93. [Crossref]  [PubMed] 
  34. Rackow BW, Kliman HJ, Taylor HS. GnRH anagonists may affect endometrial receptivity. Fertil Steril. 2008;89(5):1234-9. [Crossref]  [PubMed]  [PMC] 
  35. Lan KC, Chen YC, Lin YC, Tsai YR. Gonadotrophin-releasing hormone agonist triggering may improve central oocyte granularity and embryo quality. Zygote. 2020;28(4):337-43. [Crossref]  [PubMed]