Early Gonadotropin-releasing Hormone Antagonist Start Improves Follicular Synchronization and Pregnancy Outcome As Compared to the Conventional Antagonist Protocol

Overview

Journal Clin Exp Reprod Med

Date 2015 Jan 20

PMID 25599038

Citations 3

Authors

Chan Woo Park

Yu Im Hwang

Hwa Seon Koo

Inn Soo Kang

Kwang Moon Yang

In Ok Song

Affiliations

Soon will be listed here.

Abstract

Objective: To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR).

Methods: A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol.

Results: The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%).

Conclusion: The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

Citing Articles

Efficacy of the delayed start antagonist protocol for controlled ovarian stimulation in Bologna poor ovarian responders: a systematic review and meta-analysis.

Yang S, Liu N, Li Y, Zhang L, Yue R Arch Gynecol Obstet. 2020; 303(2):347-362.

PMID: 33236173 DOI: 10.1007/s00404-020-05894-8.

Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial.

Shin J, Park K, Choi Y, Kim H, Choi D, Lee W Clin Exp Reprod Med. 2018; 45(3):135-142.

PMID: 30202744 PMC: 6125151. DOI: 10.5653/cerm.2018.45.3.135.

Clinical analyses of successful and previously failed intracytoplasmic sperm injection cycle parameters in patients with poor ovarian reserve.

Kutlu T, Ozkaya E, Kumru P, Ayvaci H, Devranoglu B, Sanverdi I Turk J Obstet Gynecol. 2017; 14(1):58-63.

PMID: 28913136 PMC: 5558319. DOI: 10.4274/tjod.04382.

References

Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R . Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003; 18(12):2698-703. DOI: 10.1093/humrep/deg516. View

Ziebe S, Lundin K, Janssens R, Helmgaard L, Arce J . Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF. Hum Reprod. 2007; 22(9):2404-13. DOI: 10.1093/humrep/dem221. View

Kolibianakis E, Papanikolaou E, Camus M, Tournaye H, Van Steirteghem A, Devroey P . 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. 2005; 21(2):352-7. DOI: 10.1093/humrep/dei348. View

Le Nestour E, Marraoui J, Lahlou N, Roger M, De Ziegler D, Bouchard P . Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition. J Clin Endocrinol Metab. 1993; 77(2):439-42. DOI: 10.1210/jcem.77.2.8345049. View

Kolibianakis E, Zikopoulos K, Smitz J, Camus M, Tournaye H, Van Steirteghem A . Administration of gonadotropin-releasing hormone antagonist from day 1 of stimulation in in vitro fertilization. Fertil Steril. 2004; 82(1):223-6. DOI: 10.1016/j.fertnstert.2003.12.027. View

Depalo R, Lorusso F, Palmisano M, Bassi E, Totaro I, Vacca M . Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer. Gynecol Endocrinol. 2009; 25(5):328-34. DOI: 10.1080/09513590802617762. View

Smitz J, Andersen A, Devroey P, Arce J . Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod. 2006; 22(3):676-87. DOI: 10.1093/humrep/del445. View

Huirne J, van Loenen A, Donnez J, Pirard C, Homburg R, Schats R . Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study. Reprod Biomed Online. 2006; 13(2):235-45. DOI: 10.1016/s1472-6483(10)60621-9. View

De Ziegler D, Bijaoui G, Chapron C . Pre-hCG elevation of plasma progesterone: good, bad or otherwise. Hum Reprod Update. 2008; 14(4):393. DOI: 10.1093/humupd/dmn020. View

10.

Bukulmez O, Rehman K, Langley M, Carr B, Nackley A, Doody K . Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation. Reprod Biomed Online. 2006; 13(4):465-75. DOI: 10.1016/s1472-6483(10)60632-3. View

11.

Al-Inany H, Aboulghar M, Mansour R, Serour G . Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol. Reprod Biomed Online. 2005; 10(5):567-70. DOI: 10.1016/s1472-6483(10)61661-6. View

12.

Younis J, Soltsman S, Izhaki I, Radin O, Bar-Ami S, Ben-Ami M . Early and short follicular gonadotropin-releasing hormone antagonist supplementation improves the meiotic status and competence of retrieved oocytes in in vitro fertilization-embryo transfer cycles. Fertil Steril. 2009; 94(4):1350-1355. DOI: 10.1016/j.fertnstert.2009.08.033. View

13.

Roseff S, Bangah M, Kettel L, Vale W, Rivier J, Burger H . Dynamic changes in circulating inhibin levels during the luteal-follicular transition of the human menstrual cycle. J Clin Endocrinol Metab. 1989; 69(5):1033-9. DOI: 10.1210/jcem-69-5-1033. View

14.

Erb K, Klipping C, Duijkers I, Pechstein B, Schueler A, Hermann R . Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women. Fertil Steril. 2001; 75(2):316-23. DOI: 10.1016/s0015-0282(00)01702-7. View

15.

Kolibianakis E, Albano C, Kahn J, Camus M, Tournaye H, Van Steirteghem A . Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy. Fertil Steril. 2003; 79(4):873-80. DOI: 10.1016/s0015-0282(02)04920-8. View

16.

Rabinovici J, Rothman P, MONROE S, Nerenberg C, Jaffe R . Endocrine effects and pharmacokinetic characteristics of a potent new gonadotropin-releasing hormone antagonist (Ganirelix) with minimal histamine-releasing properties: studies in postmenopausal women. J Clin Endocrinol Metab. 1992; 75(5):1220-5. DOI: 10.1210/jcem.75.5.1385467. View

17.

Kolibianakis E, Albano C, Camus M, Tournaye H, Van Steirteghem A, Devroey P . Relationship between LH and oestradiol in IVF cycles before GnRH antagonist initiation. Reprod Biomed Online. 2003; 7(2):190-3. DOI: 10.1016/s1472-6483(10)61750-6. View

18.

Kolibianakis E, Collins J, Tarlatzis B, Devroey P, Diedrich K, Griesinger G . 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):651-71. DOI: 10.1093/humupd/dml038. View

19.

Wolfenson C, Groisman J, Couto A, Hedenfalk M, Cortvrindt R, Smitz J . Batch-to-batch consistency of human-derived gonadotrophin preparations compared with recombinant preparations. Reprod Biomed Online. 2005; 10(4):442-54. DOI: 10.1016/s1472-6483(10)60819-x. View

20.

Hall J, Schoenfeld D, Martin K, Crowley Jr W . Hypothalamic gonadotropin-releasing hormone secretion and follicle-stimulating hormone dynamics during the luteal-follicular transition. J Clin Endocrinol Metab. 1992; 74(3):600-7. DOI: 10.1210/jcem.74.3.1740493. View