The effect of delayed initiation of gonadotropin-releasing hormone antagonist in a flexible protocol on in vitro fertilization outcome

Delayed administration of GnRH antagonist in a flexible protocol is associated with an attenuated pattern of ovarian response to stimulation but has no effect on implantation and pregnancy rates.


Samer Tannus, M.D., Ariel Weissman, M.D., Mona Boaz, Ph.D., Eran Horowitz, M.D., Amir Ravhon, M.D., Abraham Golan, M.D., David Levran, M.D.

Volume 99, Issue 3, Pages 725-730, 1 March 2013



To determine the proportion of patients stimulated on a flexible GnRH antagonist regimen who meet the criteria for antagonist administration after stimulation day 6 (S6), and to compare their clinical characteristics and cycle outcome to patients who start the antagonist on S6 or earlier.


Retrospective study.


Tertiary university hospital.


Patients undergoing IVF (n=442) using a flexible GnRH antagonist protocol.


Ovarian stimulation was performed using gonadotropins and GnRH antagonists. Group A (n=323) patients met the criteria for antagonist administration (follicle size >12 mm, E2 >300 pg/mL) on S6 or earlier. Group B patients (n=119) started the antagonist later.

Main outcome measure:

Implantation rate.


Comparable implantation (30.4 vs. 33.7%), clinical (47.4 vs. 52.9%) and ongoing pregnancy rates (41.2 v. 47.9%) were observed in groups A and B, respectively. Group B patients had a significantly higher BMI, longer stimulation, increased gonadotropins dosage, fewer oocytes and 2pn oocytes, fewer frozen embryos and fewer cycles with embryo freezing. PCOS patients were more likely to be in group B.


A considerable proportion of patients on a flexible regimen begin GnRH antagonist administration later than S6. Despite different stimulation and laboratory characteristics, their reproductive outcome is not compromised as compared to patients with an earlier antagonist start.

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