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Hum. Reprod. Advance Access originally published online on March 8, 2007
Human Reproduction 2007 22(6):1540-1546; doi:10.1093/humrep/dem033
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development

Trifon G. Lainas1, George K. Petsas1, Ioannis Z. Zorzovilis1, George S. Iliadis1, George T. Lainas1, Haris E. Cazlaris2 and Efstratios M. Kolibianakis3,4

1 Eugonia - Iatriki Erevna - IVF unit, Athens, Greece 2 University of Thessaly, Medical School, Histology-Embryology Department, Larissa, Greece 3 Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece

4 To whom correspondence should be addressed at: Unit for Human Reproduction, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Skoufa 5 Street, Pilea, Thessaliniki 55535, Greece. E-mail: stratis.kolibianakis{at}irg.gr

BACKGROUND: The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol.

METHODS: Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E2 level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels.

RESULTS: Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E2) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E2 was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml–1, P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group.

CONCLUSIONS: In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.

Key words: antagonist luteinizing hormone/estradiol/follicular development/GnRH agonist/PCOS

Submitted on September 10, 2006; resubmitted on December 15, 2006; resubmitted on January 17, 2007; accepted on January 19, 2007.


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