Ultrashort Flare GnRH Agonist with GnRH Antagonist (MDA/Ant) Protocol Compared with Clomiphene Citrate/ Gonadotropins (CC/GND) for Poor Responder Patients

Abstract

Background: The ultrashort flare GnRH agonist/ GnRH antagonist protocol (MDA/Ant) has recently been advocated as a useful option for poor ovarian response (POR). POR patients with repeated IVF failures were offered stimulation with MDA/Ant (Group 1) or clomiphene citrate/gonadotropins (CC/Gnd; Group 2).Objective: The aim of this study was to compare Group 1 versus Group 2 in a POR population, from January 1st, 2010 until October 1st, 2014. Design: Retrospective Cohort Analysis.Methods: A total of 116 IVF cycles were included in the study. Group 1 received 21 days of oral contraceptives (OCP's), and were then treated with leuprolide acetate 40 mcg twice a day for the first 3 days, followed by high dose gonadotropins with a flexible start Gonadotropin Releasing Hormone (GnRH) antagonist. Group 2 received CC 100mg x 5 days, and on CC day 4 rec-FSH 600 IU was added.Results: No differences were found in age, body mass index (BMI), day 3 follicle stimulating hormone (FSH), or previous number of failed cycles. There were no differences noted in clinical pregnancy rate or live birth rate. Group 2 required a significantly lower amount of total gonadotropins, but Group 1 had a significantly lower rate of cycle cancellation. Conclusions:Although a higher dose of gonadotropins was required, the significantly lower cancellation rate when compared with Group 2 suggests that the MDA/Ant regimen may be a useful alternative protocol for poor responder patients. In Group 1 (n=69), patients took OCPs for approximately 21 days (range 15-25 days). Three days after the last pill, patients began taking microdose leuprolide acetate 40 mcg twice a day (BID) for 3 days. The next day, patients stopped the microdose leuprolide administration, and started recombinant follicle stimulating hormone (FSH) (rec-FSH; Follistim, Organon Pharmaceuticals, West Orange, NJ; or Gonal-F, Serono Pharmaceuticals, Rockland, MA) with or without the addition of human menopausal gonadotropins (hMG) (Menopur, Ferring Pharmaceuticals, Tarrytown, NY) for a total gonadotropin dose of 450-600 IU/day, at physician discretion. The gonadotropin regimen was maintained daily and adjusted individually according to serum estradiol (E2) concentrations and ovarian response as noted by ultrasound. When follicles reached ≥14 mm in mean diameter and/or E2 ≥350 pg/ml, patients started ganirelix acetate (Ganirelix; Organon Pharmaceuticals, West Orange, NJ) 0.25 mg subcutaneous (SC) daily. When at least 2 leading follicles reached ≥17 mm in diameter, human chorionic gonadotropin (hCG) 5,000-10,000 IU was administered, and oocyte retrieval was performed 35 hr later.Stimulation in Group 2 (n=47) started on the second day of menses with CC 100 mg PO daily x 5 days. On the fourth day of CC, patients started rec-FSH with or without the addition of hMG for a total gonadotropin dose of 450-600 IU/day. Individual adjustments in dose were made in the same fashion as mentioned above. When follicles reached ≥14 mm in mean diameter and/or E2 ≥350 pg/ml, patients started ganirelix...