Flexible GnRH antagonist versus flare-up GnRH agonist protocol in poor responders treated by IVF: a randomized controlled trial

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Although initial studies in poor responders using GnRH antagonists have reported encouraging results, they are limited in number, only a few of them are prospective, while the majority is characterized by limited power to detect a clinically important difference.


A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which five or less oocytes were retrieved, using ≥300 IU of gonadotrophins/day. Patients were randomized by computer-generated list and treated by either the flare-up GnRH agonist protocol (n=90) or a flexible GnRH antagonist protocol (n=180).


Ongoing pregnancy rate, the primary outcome measure, was significantly higher in the antagonist group compared with the agonist group (12.2 versus 4.4%, P< 0.048; difference 7.8%, 95% CI: 0.2 to 14.0). Estradiol levels on the day of hCG administration were lower in the antagonist protocol [median (interquartile range): 572 (325–839) versus 727 (439–1029) pg/ml, P=0.018]. Clinical and biochemical pregnancy rates, fertilization and implantation rates, as well as the number of oocytes retrieved, the number of mature oocytes present, the stimulation period and the gonadotrophin dosage were not significantly different between the two groups compared.


The flexible GnRH antagonist protocol is associated with significantly higher ongoing pregnancy rates compared with the flare-up GnRH agonist protocol in poor responders (www.clinicaltrials.gov; NCT00417066).

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