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Chapter 7 - Role of GnRH Antagonist in Assisted Reproduction

from Section 2 - Ovarian Hyperstimulation for IVF

Published online by Cambridge University Press:  14 April 2022

By
Mohamed Aboulghar
Edited by
Mohamed Aboulghar  and
Botros Rizk
Mohamed Aboulghar
Affiliation:
University of Cairo IVF Centre
Botros Rizk
Affiliation:
University of South Alabama
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Summary

Induction of ovulation is one of the major advances in the treatment of subfertility in the last decades. One aspect of ovulation induction that required attention is the occurrence of a premature luteinizing hormone (LH) surge before the leading follicle reaches the optimum diameter for triggering ovulation by human chorionic gonadotrophin (hCG). It was reported that premature LH surge occurs in a significant number of patients undergoing ovulation induction [1]. Such premature LH surge prevents effective induction of multiple follicular maturation for in vitro fertilization (IVF) and resulted in a significant cancellation of IVF cycles [2].

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Ovarian Stimulation , pp. 65 - 78
Publisher: Cambridge University Press
Print publication year: 2022

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References

Porter, RN, Smith, W, Craft, IL, Abdulwahid, NA, Jacobs, HS. Induction of ovulation for in-vitro fertilization using buserelin and gonadotrophins. Lancet 1984;2:1284–1285.CrossRefGoogle Scholar
Diedrich, K, Diedrich, C, Santos, E, et al. Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist cetrorelix during ovarian stimulation. Hum Reprod 1994;9(5):788–791.Google Scholar
Ron-El, R, Raziel, A, Schachter, M, et al. Induction of ovulation after GnRH antagonists. Hum Reprod Update 2000;6(4):318–321.Google Scholar
Gordon, K, Williams, RF, Danforth, DR, Hodgen, GD. The combined use of GnRH antagonists with gonadotrophins or pulsatile GnRH in ovulation induction. In: Bouchard, P, Caraty, A, Coelingh-Bennink, HJT, Pavlou, SN, eds. GnRH-analogs, Gonadotrophins and Gonadal Peptides. London, UK Parthenon Publishing Group; 1992:239 pp.Google Scholar
Hughes, EG, Fedorkow, DM, Daya, S, et al. The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials. Fertil Steril 1992;58(5):888–896.CrossRefGoogle ScholarPubMed
Clayton, RN, Catt, KJ. Gonadotrophin-releasing hormone receptors: characterization, physiological regulation, and relationship to reproductive function. Endocr Rev 1981;2:186–209.CrossRefGoogle ScholarPubMed
Clayton, RN, Catt, KJ. Receptor-binding affinity of gonadotropin-releasing hormone analogs: analysis by radioligand-receptor assay. Endocrinology 1980;106(4):1154–1159.Google Scholar
Coy, DH, Labrie, F, Savary, M, Coy, EJ, Schally, AV. LH-releasing activity of potent LH-RH analogs in vitro. Biochem Biophys Res Commun 1975;67(2):576–582.Google Scholar
Ditkoff, EC, Cassidenti, DL, Paulson, RJ, et al. The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women. Am J Obstet Gynecol 1991;165:1811–1817Google Scholar
Kenigsberg, D, Hodgen, GD. Ovulation inhibition by administration of weekly gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab 1986;62(4):734–738.CrossRefGoogle ScholarPubMed
Matikainen, T, Ding, YQ, Vergara, M, et al. Differing responses of plasma bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone to gonadotropin-releasing hormone antagonist and agonist treatments in postmenopausal women. J Clin Endocrinol Metab 1992;75(3):820–825.Google Scholar
Bouchard, PG, Charbonnel, B, Caraty, A, et al. The role of LHRH during the periovulatory period: a basis for the use of LHRH antagonists in ovulation induction. In: Filicori, M, Flamigni, C, eds. Ovulation: Basic Science and Clinical Advances. Elsevier Science BV International Congress series 1046. 1994.Google Scholar
The ganirelix dose-finding study group. A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). Hum Reprod 1998;13(11):3023–3031.CrossRefGoogle Scholar
Olivennes, F, Alvarez, S, Bouchard, P, et al. The use of a GnRH antagonist (cetrorelix) in a single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg. Hum Reprod 1998;13(9):2411–2414.CrossRefGoogle Scholar
Olivennes, F. Cunha-Filho, JS, Fanchin, R, Bouchard, P, Frydman, R. The use of GnRH antagonists in ovarian stimulation. Hum Reprod Update 2002;8:279–290.Google Scholar
Al-Inany, H, Aboulghar, M. Gonadotrophin-releasing hormone antagonist for assisted conception. Cochrane Database Syst Rev 2001;4:CD001750.Google Scholar
Kolibianakis, EM, Collins, J, Tarlatzis, BC, et al. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update 2006;12(6):651–671.Google Scholar
Al-Inany, HG, Abou-Setta, AM, Aboulghar, M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev 2006;3:CD001750.Google Scholar
Al-Inany, HG, Youssef, MA, Ayeleke, RO, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2016;4:CD001750.Google ScholarPubMed
Lambalk, BC, Banga, FR, Huirne, JA, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update 2017;23(5):560–579.CrossRefGoogle ScholarPubMed
Sunkara, SK, Coomarasamy, A, Faris, R, Braude, P, Khalaf, Y. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial. Fertil Steril 2014;101(1):147–153.Google Scholar
Toftager, M, Bogstad, J, Løssl, K, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod 2017;32(3):556–567.Google Scholar
Ludwig, M, Riethmüller-Winzen, H, Felberbaum, RE, et al. Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix. Fertil Steril 2001;75(1):18–22.CrossRefGoogle ScholarPubMed
Ludwig, M, Katalinic, A, Banz, C, et al. Tailoring the GnRH antagonist cetrorelix acetate to individual patients’ needs in ovarian stimulation for IVF: results of a prospective, randomized study. Hum Reprod 2002;17(11):2842–2845.Google Scholar
Mansour, RT, Aboulghar, MA, Serour, GI, et al. The use of gonadotropin-releasing hormone antagonist in a flexible protocol: a pilot study. Am J Obstet Gynecol 2003;189(2):444–446.CrossRefGoogle Scholar
Lainas, T, Zorzovilis, J, Petsas, G, et al. In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH antagonist is associated with increased pregnancy rates in IVF. Hum Reprod 2005;20(9):2426–2433.CrossRefGoogle Scholar
Al-Inany, H, Aboulghar, MA, Mansour, RT, Serour, GI. Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol. Reprod Biomed Online 2005;10(5):567–570.Google Scholar
Messinis, IE, Loutradis, D, Domali, E, et al. Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment. Hum Reprod 2005;20(11):3192–3197.Google Scholar
Aboulghar, MA, Mansour, RT, Serour, GI, et al. Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist administration: randomized controlled trial. Reprod Biomed Online 2004;8(5):524–527.CrossRefGoogle ScholarPubMed
Propst, AM, Bates, GW, Robinson, RD, et al. A randomized controlled trial of increasing recombinant follicle-stimulating hormone after initiating a gonadotropin-releasing hormone antagonist for in vitro fertilization-embryo transfer. Fertil Steril 2006;86(1):58–63.Google Scholar
Engel, JB, Ludwig, M, Felberbaum, R, et al. Use of cetrorelix in combination with clomiphene citrate and gonadotrophins: a suitable approach to ‘friendly IVF’? Hum Reprod 2002;17(8):2022–2026.Google Scholar
Mansour, R, Aboulghar, M, Serour, GI, et al. The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol. Acta Obstet Gynecol Scand 2003;82(1):48–52.Google Scholar
Barmat, LI, Chantilis, SJ, Hurst, BS, Dickey, RP. A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization. Fertil Steril 2005;83(2):321–330.CrossRefGoogle ScholarPubMed
Bendikson, K, Milki, AA, Speck-Zulak, A, Westphal, LM. Comparison of GnRH antagonist cycles with and without oral contraceptive pretreatment in potential poor prognosis patients. Clin Exp Obstet Gynecol 2006;33(3):145–147.Google ScholarPubMed
Pinkas, H, Sapir, O, Avrech, OM, et al. The effect of oral contraceptive pill for cycle scheduling prior to GnRH-antagonist protocol on IVF cycle parameters and pregnancy outcome. J Assist Reprod Genet 2008;25(1):29–33.Google Scholar
Kim, CH, Jeon, GH, Cheon, YP, et al. Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection. Fertil Steril 2009;92(5):1758–1760.CrossRefGoogle ScholarPubMed
Huirne, JA, van Loenen, AC, Donnez, J, et al. Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a ranmdomized study. Reprod Biomed Online 2006;13:235–245.CrossRefGoogle ScholarPubMed
Kolibianakis, EM, Papanikolaou, EG, Camus, M, et al. Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial. Hum Reprod 2006;21(2):352–357.Google Scholar
Griesinger, G, Venetis, CA, Marx, T, et al. Oral contraceptive pill pretreatment in ovarian stimulation with GnRH antagonists for IVF: a systematic review and meta-analysis. Fertil Steril 2008;90(4):1055–1063.Google Scholar
Farquhar, C, Rombauts, L, Kremer, JA, Lethaby, A, Ayeleke, RO. Oral contraceptive pill, progestogen or oestrogen pretreatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 2017;5:CD006109.Google Scholar
Cavagna, M, Louzada Maldonado, LG, de Souza Bonetti, TC, et al. Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone for intracytoplasmic sperm injection cycles using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression. Fertil Steril 2010;94(1):167–172.Google Scholar
Griesinger, G, Schultze-Mosgau, A, Dafopoulos, K, et al. Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol. Hum Reprod 2005;20(5):1200–1206.Google Scholar
Cédrin-Durnerin, I, Grange-Dujardin, D, Laffy, A, et al. Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study. Hum Reprod 2004;19(9):1979–1984.CrossRefGoogle ScholarPubMed
Rongières-Bertrand, C, Olivennes, F, Righini, C, et al. Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (cetrorelix): a pilot study with minimal stimulation. Hum Reprod 1999;14(3):683–688.Google Scholar
Pelinck, MJ, Vogel, NE, Arts, EG, et al. Cumulative pregnancy rates after a maximum of nine cycles of modified natural cycle IVF and analysis of patient drop-out: a cohort study. Hum Reprod 2007;22(9):2463–2470.Google Scholar
Humaidan, P, Kol, S, Papanikolaou, EG. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update 2011;17(4):510–524.Google Scholar
Humaidan, P, Papanikolaou, EG, Kyrou, D, et al. The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod Biomed Online 2012;24(2):134–141.Google Scholar
Fauser, BC, de Jong, D, Olivennes, F, et al. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab 2002;87(2):709–715.Google Scholar
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):159–168.Google Scholar
Humaidan, P, Bungum, L, Bungum, M, Yding Andersen, C. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study. Reprod Biomed Online 2006;13(2):173–178.CrossRefGoogle ScholarPubMed
Youssef, MA, Van der Veen, F, Al-Inany, HG, et al. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev 2014;10:CD008046.Google Scholar
Leth-Moller, K, Hammer Jagd, S, Humaidan, P. The luteal phase after GnRHa trigger-understanding an enigma. Int J Fertil Steril 2014;8(3):227–234.Google Scholar
Elgindy, EA, Sibai, H, Mostafa, MI, et al. Towards an optimal luteal support modality in agonist triggered cycles: a randomized clinical trial. Hum Reprod 2018;33(6):1079–1086.Google Scholar
Franco, JG Jr., Baruffi, RL, Mauri, AL, et al. GnRH agonist versus GnRH antagonist in poor ovarian responders: a meta-analysis. Reprod Biomed Online 2006;13(5):618–627.Google Scholar
Ozmen, B, Sönmezer, M, Atabekoglu, CS, Olmus, H. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online 2009;19(4):478–485.Google Scholar
Baruffi, RL, Mauri, AL, Petersen, CG, et al. Recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-antagonist protocol: a meta-analysis. Reprod Biomed Online 2007;14(1):14–25.CrossRefGoogle ScholarPubMed
König, TE, van der Houwen, LE, Overbeek, A, et al. Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study. Hum Reprod 2013;28(10):2804–2812.Google Scholar
Tavaniotou, A, Albano, C, Van Steirteghem, A, Devroey, P. The impact of LH serum concentration on the clinical outcome of IVF cycles in patients receiving two regimens of clomiphene citrate/gonadotrophin/0.25 mg cetrorelix. Reprod Biomed Online 2003;6(4):421–426.Google Scholar
Lin, YH, Seow, KM, Chen, HJ, et al. Effect of cetrorelix dose on premature LH surge during ovarian stimulation. Reprod Biomed Online 2008;16(6):772–777.Google Scholar
Messinis, IE, Templeton, A. Effect of high dose exogenous oestrogen on midcycle luteinizing hormone surge in human spontaneous cycles. Clin Endocrinol (Oxf) 1987;27(4):453–459.CrossRefGoogle ScholarPubMed
Glasier, A, Thatcher, SS, Wickings, EJ, Hillier, SG, Baird, DT. Superovulation with exogenous gonadotropins does not inhibit the luteinizing hormone surge. Fertil Steril 1988;49(1):81–85.Google Scholar
Messinis, IE, Templeton, A, Baird, DT. Endogenous luteinizing hormone surge during superovulation induction with sequential use of clomiphene citrate and pulsatile human menopausal gonadotropin. J Clin Endocrinol Metab 1985;61(6):1076–1080.CrossRefGoogle ScholarPubMed
Kolibianakis, EM, Bourgain, C, Papanikolaou, EG, et al. Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles. Hum Reprod 2005;20(9):2453–2456.Google Scholar
Aboulghar, MA, Mansour, RT, Amin, YM, et al. A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS. Reprod Biomed Online 2007;15(3):271–279.CrossRefGoogle ScholarPubMed
Lainas, TG, Sfontouris, IA, Zorzovilis, IZ, et al. Management of severe OHSS using GnRH antagonist and blastocyst cryopreservation in PCOS patients treated with long protocol. Reprod Biomed Online 2009;18(1):15–20.Google Scholar
Bonilla-Musoles, FM, Raga, F, Castillo, JC, et al. High doses of GnRH antagonists are efficient in the management of severe ovarian hyperstimulation syndrome. Clin Exp Obstet Gynecol 2009;36(2):78–81.Google ScholarPubMed
Wang, R, Lin, S, Wang, Y, Qian, W, Zhou, L. Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: a systematic review and meta-analysis. PLoS One 2017;12(4):e0175985.Google Scholar
Demirol, A, Gurgan, T. Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study. Fertil Steril 2009;92(2):481–485.Google Scholar
Toftager, M, Sylvest, R, Schmidt, L, et al. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril 2018;109(1):154–164.Google Scholar
Devroey, P, Aboulghar, M, Garcia-Velasco, J, et al. Improving the patient’s experience of IVF/ICSI: a proposal for an ovarian stimulation protocol with GnRH antagonist co-treatment. Hum Reprod 2009;24(4):764–774.CrossRefGoogle ScholarPubMed
Fauser, BC, Devroey, P, Yen, SS, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999;14:2681–2686.Google Scholar
Ledger, WL. Favourable outcomes from “mild” in-vitro fertilization. Lancet 2007;369:717–718.Google Scholar
Nargund, G, Fauser, BC, Macklon, NS, et al. The ISMAAR proposal on terminology for ovarian stimulation for IVF. Hum Reprod 2007;22:2801–2804.Google Scholar
Lambalk, CB, Leader, A, Olivennes, F, et al. Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial. Hum Reprod 2006;21(3):632–639.Google Scholar
Qublan, HS, Amarin, Z, Tahat, YA, Smadi, AZ, Kilani, M. Ovarian cyst formation following GnRH agonist administration in IVF cycles: incidence and impact. Hum Reprod 2006;21:640–644.Google Scholar
Al-Inany, H, Aboulghar, M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod 2002;17(4):874–885.Google Scholar

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