Clinical Trial: GnRh Antagonist Protocol With Delayed Start Stimulation in Patients With Poor Ovarian Response

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluation of a Novel " Delayed Start" Protocol With Gonadotropin-releasing Hormone Antagonist in Poor Responders: A Randomized Clinical Trial Phase 3

Brief Summary: The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG trigger and the number of mature (MII) oocytes collected after conventional versus delayed-start ovarian stimulation protocol. Secondary outcome measures are including total number of oocytes retrieved, oocyte maturity rate (number of MII oocytes/total number of oocytes), oocyte yield (total number of oocytes retrieved/ antral follicle count [AFC]), mature oocyte yield (number of mature oocytes retrieved/AFC), total dosage of gonadotropin (recombinant FSH and/or highly purified hMG) needed, number of days needed for ovarian stimulation, quality of obtained embryos, fertilization rate (the proportion of total number of two-pronuclear [2PN] stage zygotes /per total injected MII oocytes), implantation rate (total number of observed gestational sac/ number of transferred embryos) and clinical pregnancy rate (presence of fetal heart beat by transvaginal ultrasound per embryo transfer).

Detailed Summary:

One of the principal steps to obtain the favorable success is still related to the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH analogues. In the patients with "poor ovarian response" diagnosis, the limited number of obtained oocytes remains the main obstacle in optimizing the live birth rates. The objective of present study is to evaluate a new procedure to increase a cohort of the growing antral follicles and consequently the number of retrieved oocytes after hormonal stimulation by gonadotropins in combination with GnRH antagonist. In present study, eligible patients with diagnosis poor ovarian responder based on the Bologna criteria are included. Ovarian stimulation procedure will be performed by antagonist protocol. All the patients will be received two tablets daily of Estradiol valerate (Estraval®, 2 mg, Aburaihan Co., Tehran, Iran) starting a week after LH surge until menses. The hormonal evaluation (serum LH and FSH) and basic vaginal ultrasound will be performed before the starting ovarian stimulation on the 2th or 3th day of the menstrual cycle. On this day, the block randomization method will be designed to randomize allocation of patients into groups with blocks of size 4.

In the Group A: treatment with GnRH antagonists (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started on the 2th or 3th day of the menstrual cycle and continues until the ninth day. Then, the ovarian stimulation with gonadotropin 300 IU recombinant FSH (Gonal - F®, Serono Laboratories Ltd, Geneva, Switzerland) and 150 IU of hMG (Menopur®; Ferring) will be started from ninth day of menstrual cycle until the day of hCG administration. The monitoring of ovarian stimulation will be done every other day by vaginal ultrasound and whenever at least 1 to 3 follicles larger than 13 mm are observed, the
Sponsor: Royan Institute

Current Primary Outcome:

  • number of dominant follicles (≥13 mm) [ Time Frame: 24h after rhCG injection ]
    The number of dominant follicles (≥13 mm) on the day of hCG trigger
  • Total number of oocytes [ Time Frame: 32-34 hours after rhCG ]
    the number of mature oocytes collected after conventional versus delayed-start ovarian stimulation protocol


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Total number of retrieved oocytes [ Time Frame: 32-34 hours after rhCG injection ]
    Total number of retrieved oocytes 32-34 hours after rhCG injection .
  • Quality of obtained embryos [ Time Frame: on the third day after oocyte retrieval ]
    we score embryo quality according to the following quality criteria: Excellent (Day 3: 6-8 even size blastomeres with ≤10% fragmentation), Good (Day 3: 6-8 even or uneven size blastomeres with 10%-20% fragmentation), Poor (Uneven and few blastomeres with >20% fragmentation)


Original Secondary Outcome: Same as current

Information By: Royan Institute

Dates:
Date Received: December 19, 2016
Date Started: January 2016
Date Completion: May 2017
Last Updated: April 26, 2017
Last Verified: December 2016