A novel “delayed start” protocol with gonadotropin-releasing hormone antagonist improves outcomes in poor responders

Abstract

Objective To investigate whether delaying the start of ovarian stimulation with GnRH antagonist improves ovarian response in poor responders. Design Retrospective study Setting Academic medical center Patients Thirty patients, who responded poorly and did not get pregnant with conventional estrogen priming antagonist IVF protocol. Intervention(s) Delayed start antagonist protocol (estrogen priming followed by early follicular phase GnRH antagonist treatment for 7 days prior to ovarian stimulation) Main Outcome Measure(s) Number of dominant follicles and mature oocytes retrieved, mature oocyte yield and fertilization rate. Results The number of patients who met the criteria to proceed to oocyte retrieval was significantly higher in delayed start protocol [21/30 (70%)] compared to patient’s previous conventional estrogen priming antagonist cycle [11/30 (36.7%)]. The number of dominant follicles was significantly higher in delayed start (4.2 ± 2.7) compared with conventional protocol (2.4 ± 1.3). In patients, who had oocyte retrieval after both protocols (n=9), the delayed start resulted in shorter ovarian stimulation (9.4 ± 1.4 vs. 11.1 ± 2.0 days), higher number of mature oocytes retrieved (4.9 ± 2.0 vs. 2.2 ± 1.1) and trend toward increased fertilization rates with ICSI (86 ± 17% vs. 69 ± 21%) compared to conventional protocol. After delayed start, the average number of embryos transferred was 2.8 ± 1.4 with implantation rate of 9.8% and clinical pregnancy rate of 23.8%. Conclusions The delayed start protocol improves ovarian response in poor responders, by promoting and synchronizing follicle development without impairing oocyte developmental competence.

Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

“…Recently pretreatment E 2 and start of antagonist in early follicular phase from day 2-8 before gonadotropin therapy (double suppression) appears to improve ovarian response during COH and may result in more uniform follicular development. This protocol named delayed-start protocol ( 25 ). There is no sufficient research from efficiency of current protocol (delayed-start protocol), thus we planned a study about the effect of delayed-start protocol with GnRH antagonist in outcome of ART cycle in poor responders .…”

The Early Start of Gonadotropin-releasing Hormone Antagonist Versus Flexible Antagonist Ovarian Stimulation Protocol in Poor Responders: A Randomized Clinical Trial

“…Park et al in a retrospective study of normal responder women, concluded that the modi ed 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 requires to be studied further in prospective randomized controlled trials. Regarding to patients with POR diagnosis, the most of previous studies with early onset GnRH-ant protocol, estradiol pre-treatment (E 2 priming) was used in late luteal phase prior to the start of the antagonist protocol (7,8,16); hence, the results of the present study were not comparable to them. In whatever way regardless of how, most of the mentioned studies have shown evidence of improved ovarian stimulation outcomes (7,8,16,17) and pregnancy rates (8) after early onset GnRH-ant protocol with E 2 priming in POR patients.…”

“…Early follicular starting of GnRH-ant had been reported to decrease exposure to LH and estradiol during controlled ovarian stimulation which is negatively affecting the chance of pregnancy (4). Moreover, there is inhibition of increment of interphase peak of follicle-stimulating hormone (FSH) by administration of the antagonist at starting of the menstrual cycle leading to better synchronization of growing follicles cohort and consequently increasing the yield of oocytes (4,7,8).…”

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

“…Furthermore, delayed-start of antagonist protocol was proposed to result in favorable outcomes in terms of number of dominant follicles and mature oocytes retrieved, mature oocyte yield, and fertilization rates in poor responders. The authors concluded that this was the result of the promoting and synchronizing effect on follicle development without impairing oocyte developmental competence ( 15 ) . Besides a higher rate of fertilization, we also found significantly higher numbers of total, mature oocyte and earlier antagonist initiation in successful cycles.…”