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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 6/2017

01-06-2017 | Assisted Reproduction Technologies

Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI cycle outcomes in patients with history of poor fertilization

Authors: Rony T. Elias, Nigel Pereira, Lisa Artusa, Amelia G. Kelly, Monica Pasternak, Jovana P. Lekovich, Gianpiero D. Palermo, Zev Rosenwaks

Published in: Journal of Assisted Reproduction and Genetics | Issue 6/2017

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Abstract

Purpose

The purpose of this study was to investigate the utility of a combined GnRH-agonist (GnRH-a) and human chorionic gonadotropin (hCG) trigger in improving ICSI cycle outcomes in patients with poor fertilization history after standard hCG trigger in prior ICSI cycles.

Methods

Retrospective cohort study. Patients with a fertilization rate of <20% in at least two prior ICSI cycles who subsequently underwent another ICSI cycle with hCG trigger were compared to those who underwent another ICSI cycle with a combined GnRH-a and hCG trigger. Oocyte maturity, fertilization, clinical pregnancy, and live birth rates were compared. A multiple linear regression model was used to explore the association between combined GnRH-a and hCG trigger (vs hCG trigger alone) and fertilization rate.

Results

A total of 427 patients with mean age of 37.3 ± 1.94 years and mean baseline fertilization rate of 17.9 ± 2.03% were included, of which 318 (74.5%) and 109 (25.5%) patients underwent a subsequent ICSI cycle with hCG and combined GnRH-a and hCG trigger, respectively. The baseline parameters of the male and female partner were similar. The mean fertilization rate in the combined trigger group was 16.4% (95% CI: 7.58–25.2%) higher than the hCG trigger group, even after adjustment for confounders. Patients in the combined trigger group had higher oocyte maturity (82.1 vs 69.8%), higher clinical pregnancy (27.5 vs 5.67%), and higher live birth rates (20.2 vs 3.46%) compared to the hCG trigger group.

Conclusions

Combined GnRH-a and hCG trigger in ICSI cycles increase oocyte maturity, fertilization, clinical pregnancy, and live birth rates in patients with a history of poor fertilization after standard hCG trigger alone.
Appendix
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Literature
1.
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.CrossRefPubMed
2.
Youssef MA, Van der Veen F, Al-Inany HG, Griesinger G, Mochtar MH, Aboulfoutouh I, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst Rev. 2011;1:CD008046.
3.
Fatemi HM, Garcia-Velasco J. Avoiding ovarian hyperstimulation syndrome with the use of gonadotropin-releasing hormone agonist trigger. Fertil Steril. 2015;103(4):870–3.CrossRefPubMed
4.
Humaidan P, Papanikolaou EG, Tarlatzis BC. GnRHa to trigger final oocyte maturation: a time to reconsider. Hum Reprod. 2009;24(10):2389–94.CrossRefPubMed
5.
Casper RF. Reducing the risk of OHSS by GnRH agonist triggering. J Clin Endocrinol Metab. 2015;100(12):4396–8.CrossRefPubMed
6.
Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update. 2006;12(2):159–68.CrossRefPubMed
7.
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.CrossRefPubMed
8.
Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. 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. 2008;89(1):84–91.CrossRefPubMed
9.
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;97:1316–20.CrossRefPubMed
10.
Pabuccu EG, Pabuccu R, Caglar GS, Yılmaz B, Yarcı A. Different gonadotropin releasing hormone agonist doses for the final oocyte maturation in high-responder patients undergoing in vitro fertilization/intra-cytoplasmic sperm injection. J Hum Reprod Sci. 2015;8(1):25–9.CrossRefPubMedPubMedCentral
11.
Shapiro BS, Andersen CY. Major drawbacks and additional benefits of agonist trigger--not ovarian hyperstimulation syndrome related. Fertil Steril. 2015;103(4):874–8.CrossRefPubMed
12.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Ross R. Comparison of human chorionic gonadotropin and gonadotropin-releasing hormone agonist for final oocyte maturation in oocyte donor cycles. Fertil Steril. 2007;88(1):237–9.CrossRefPubMed
13.
Oktay K, Türkçüoğlu I, Rodriguez-Wallberg KA. GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. Reprod BioMed Online. 2010;20(6):783–8.CrossRefPubMedPubMedCentral
14.
Reddy J, Turan V, Bedoschi G, Moy F, Oktay K. Triggering final oocyte maturation with gonadotropin-releasing hormone agonist (GnRHa) versus human chorionic gonadotropin (hCG) in breast cancer patients undergoing fertility preservation: an extended experience. J Assist Reprod Genet. 2014;31(7):927–32.CrossRefPubMedPubMedCentral
15.
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.CrossRefPubMed
16.
Humaidan P, Bredkjaer 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.CrossRefPubMed
17.
Werner MD, Forman EJ, Hong KH, Franasiak JM, Neal SA, Scott Jr RT. Dual trigger with GnRH agonist (GnRHa) and varying doses of hCG increases the blastulation rate amongst high responders. Fertil Steril. 2014;102(3):Supplement e220–1.CrossRef
18.
Casper RF. Basic understanding of gonadotropin-releasing hormone-agonist triggering. Fertil Steril. 2015;103(4):867–9.CrossRefPubMed
19.
Pereira N, Elias RT, Neri QV, Gerber RS, Lekovich JP, Palermo GD, et al. Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity. Reprod BioMed Online. 2016;33(5):568–74.CrossRefPubMed
20.
21.
Pereira N, Reichman DE, Goldschlag DE, Lekovich JP, Rosenwaks Z. Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles. J Assist Reprod Genet. 2015;32(4):527–32.CrossRefPubMedPubMedCentral
22.
Palermo GD, Neri QV, Schlegel PN, Rosenwaks Z. Intracytoplasmic sperm injection (ICSI) in extreme cases of male infertility. PLoS One. 2014;9(12):e113671.CrossRefPubMedPubMedCentral
23.
Palermo GD, Cohen J, Alikani M, Adler A, Rosenwaks Z. Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility. Fertil Steril. 1995;63(6):1231–40.CrossRefPubMed
24.
25.
World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press, World Health Organization; 2010.
26.
Palermo GD, Kocent J, Monahan D, Neri QV, Rosenwaks Z. Treatment of male infertility. Methods Mol Biol. 2014;1154:385–405.CrossRefPubMed
27.
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.CrossRefPubMed
28.
El-Hayek S, Clarke HJ. Follicle-stimulating hormone increases gap Junctional communication between somatic and germ-line follicular compartments during murine oogenesis. Biol Reprod. 2015;93(2):47.CrossRefPubMed
29.
Carabatsos MJ, Sellitto C, Goodenough DA, Albertini DF. Oocyte-granulosa cell heterologous gap junctions are required for the coordination of nuclear and cytoplasmic meiotic competence. Dev Biol. 2000;226(2):167–79.CrossRefPubMed
30.
Sundström P, Nilsson BO. Meiotic and cytoplasmic maturation of oocytes collected in stimulated cycles is asynchronous. Hum Reprod. 1988;3(5):613–9.CrossRefPubMed
31.
Pereira N, Neri QV, Lekovich JP, Palermo GD, Rosenwaks Z. The role of in-vivo and in-vitro maturation time on ooplasmic dysmaturity. Reprod BioMed Online. 2016;32(4):401–6.CrossRefPubMed
32.
Rawe VY, Olmedo SB, Nodar FN, Doncel GD, Acosta AA, Vitullo AD. Cytoskeletal organization defects and abortive activation in human oocytes after IVF and ICSI failure. Mol Hum Reprod. 2000;6:510–6.CrossRefPubMed
33.
Hyun CS, Cha JH, Son WY, Yoon SH, Kim KA, Lim JH. Optimal ICSI timing after the first polar body extrusion in in vitro matured human oocytes. Hum Reprod. 2007;22(7):1991–5.CrossRefPubMed
34.
Vermeiden JP, Roseboom TJ, Goverde AJ, Suchartwatnachai C, Schoute E, Braat DD, et al. An artificially induced follicle stimulating hormone surge at the time of human chorionic gonadotrophin administration in controlled ovarian stimulation cycles has no effect on cumulus expansion, fertilization rate, embryo quality and implantation rate. Hum Reprod. 1997;12(7):1399–402.CrossRefPubMed
35.
Juneau CR, Morin SJ, Franasiak JM, Landis JN, Molinaro TA, Scott RT. A ‘follicle-stimulating hormone boost’ administered at the time of human chorionic gonadotropin trigger does not affect IVF cycle outcomes. Fertil Steril. 2016;106(3):Supplement e189–90.CrossRef
36.
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. e1CrossRefPubMed
37.
Park JY, Su YQ, Ariga M, Law E, Jin SL, Conti M. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science. 2004;303(5658):682–4.CrossRefPubMed
38.
Ben-Ami I, Komsky A, Bern O, Kasterstein E, Komarovsky D, Ron-El R. In vitro maturation of human germinal vesicle-stage oocytes: role of epidermal growth factor-like growth factors in the culture medium. Hum Reprod. 2011;26:76–81.CrossRefPubMed
39.
Hasegawa J, Yanaihara A, Iwasaki S, Mitsukawa K, Negishi M, Okai T. Reduction of connexin 43 in human cumulus cells yields good embryo competence during ICSI. J Assist Reprod Genet. 2007;24(10):463–6.CrossRefPubMedPubMedCentral
40.
Swain JE, Pool TB. ART failure: oocyte contributions to unsuccessful fertilization. Hum Reprod Update. 2008;14(5):431–46.CrossRefPubMed
41.
Esfandiari N, Javed MH, Gotlieb L, Casper RF. Complete failed fertilization after intracytoplasmic sperm injection--analysis of 10 years’ data. Int J Fertil Womens Med. 2005;50(4):187–92.PubMed
42.
Petersen CG, Oliveira JB, Mauri AL, Massaro FC, Baruffi RL, Pontes A, et al. Relationship between visualization of meiotic spindle in human oocytes and ICSI outcomes: a meta-analysis. Reprod BioMed Online. 2009;18(2):235–43.CrossRefPubMed
Metadata
Title
Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI cycle outcomes in patients with history of poor fertilization
Authors
Rony T. Elias
Nigel Pereira
Lisa Artusa
Amelia G. Kelly
Monica Pasternak
Jovana P. Lekovich
Gianpiero D. Palermo
Zev Rosenwaks
Publication date
01-06-2017
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 6/2017
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-017-0917-3

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