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J Reprod Med. 2001 May;46(5):485-9.

Clinical pregnancy rates in an IVF program. Use of the flare-up protocol after failure with long regimens of GnRH-a.

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Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, International Hospital-Istanbul, Istanbul Cad. No: 82, 34800 Ye┼čilkoy, Istanbul, Turkey.



To examine the efficacy of flare-up protocols in patients who failed to respond to a long protocol using gonadotropin-releasing hormone agonist (GnRH-a).


In this retrospective study, a total of 144 patients who underwent an in vitro fertilization/embryo transfer cycle with the flare-up protocol were analyzed. Of these, 111 patients (group I) had not responded well to ovulation induction with long-term down-regulation with GnRH-a (long protocol), and 33 (group II) had responded to ovulation induction with at least four follicles but failed to conceive after embryo transfer. The average age of the patients were 37.3 +/- 3.9 years (range, 28-43) and 36.5 +/- 3.7 (range, 24-44), respectively. All patients underwent a flare-up protocol with GnRH-a (leuprolide acetate, 0.5 mg/d) on day 2 and at least 6 ampules of gonadotropins on day 3 within 6 months following failure with the long protocol. Unresponsiveness was defined as having fewer than three developing follicles on day 7, with an estradiol level < 200 pg/mL. Patients with a cycle day 2 follicle stimulating hormone (FSH) level > 15 mIU/mL before initiating GnRH-a were not included in the flare-up protocol. The average day 2 FSH levels of the patients on the flare-up protocol cycles were 9.1 +/- 3.0 in group I and 7.1 +/- 2.0 in group II.


In group I, 44 of 111 (39.6%) patients did not respond to the flare-up protocol even with an increased dose of gonadotropins. In 67 patients, an average of 7.2 +/- 2.3 oocytes were obtained. Embryo transfer was performed on 64 patients with an average of 3.2 +/- 0.6 embryos. Fertilization did not occur in three patients. Eleven women conceived, eight of them miscarried, and three delivered. The pregnancy rate per cycle initiated was 9.9% (11/111) and live birth rate per cycle initiated, 2.5% (3/111). In group II, 3 of 33 patients were cancelled. The reasons were inadequate ovarian response, risk of hyperstimulation and absence of oocytes after aspiration. In 28 patients the average number of oocytes obtained was 6.9 +/- 3.9, and the average number of embryos replaced was 2.7 +/- 1.0. Six patients conceived, and all miscarried. The pregnancy rate per cycle initiated was 6/33 (18.1%), and no live births were achieved.


Although the flare-up protocol after an unsuccessful luteal phase long protocol increases the pregnancy rate per cycle slightly, the live birth rate is not improved in poor responders.

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