ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03134690
Recruitment Status : Recruiting
First Posted : May 1, 2017
Last Update Posted : May 1, 2017
Sponsor:
Information provided by (Responsible Party):
Royan Institute

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).

Condition or disease Intervention/treatment Phase
Infertility, Female Procedure: delayed start Procedure: Conventional Not Applicable

Detailed Description:

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 antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of hCG. When at least two follicles greater than 17 to 18 mm is seen, two pre-filled syringes of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered. The patients will undergo puncture operation 32-34 hours after hCG injection.

In the control group (B), as conventional antagonist procedure, 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 on the 2th or 3th day of the menstrual cycle. 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 antagonist injection (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) will be started again to prevent premature LH surge and continues until the prescription of rhCG. 32-34 hours after the rhCG injection, the ovum pick up will be performed and subsequently intracytoplasmic sperm injection (ICSI) /in-vitro fertilization (IVF) will be done for all the patients.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of a Novel " Delayed Start" Protocol With Gonadotropin-releasing Hormone Antagonist in Poor Responders: A Randomized Clinical Trial Phase 3
Study Start Date : January 2016
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: delayed start antagonist
30 women with f poor ovarian responses undergo ovarian stimulation with delayed start antagonist.
Procedure: delayed start
In this protocol, ovarian stimulation will be started from ninth day of menstrual cycle .

Experimental: conventional antagonist
30 women with diagnose of poor ovarian response will have undergone ovarian stimulation with conventional antagonist protocol.
Procedure: Conventional
In this protocol, ovarian stimulation will be started from the 2th or 3th day of the menstrual cycle.




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Total number of retrieved oocytes [ Time Frame: 32-34 hours after rhCG injection ]
    Total number of retrieved oocytes 32-34 hours after rhCG injection .

  2. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • a history of ovarian surgery;
  • previous treatment using conventional protocols that yielded less than three oocytes;
  • antral follicle count of less than 5 on menstrual cycle day 2-3; and basal serum FSH concentration between 10 and 19 IU/l.

Exclusion Criteria:

  • ovarian failure including basal FSH above 20 IU/l or no antral follicle by ultrasound examination;
  • Endometriosis grade 3 or higher;
  • Any contraindications to ovarian stimulation treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03134690


Contacts
Contact: Nasser Aghdami, MD,PhD (+98)2123562000 ext 516 nasser.aghdami@royaninstitute.org
Contact: Leila Arab, MD (+98)23562000 ext 414 Leara91@gmail.com

Locations
Iran, Islamic Republic of
Royan Institute Recruiting
Tehran, Iran, Islamic Republic of
Contact: Nasser Aghdami, MD,PhD    (+98)23562000 ext 516    nasser.aghdami@royaninstitute.org   
Contact: Leila Arab, MD    (+98)23562000 ext 414    Leara91@gmail.com   
Sub-Investigator: Azar Yahyaei, M.Sc         
Sub-Investigator: Zahra Zolfaghary, M.Sc         
Sponsors and Collaborators
Royan Institute
Investigators
Study Chair: Hamid Gourabi, PhD Head of Royan Institute
Study Director: Mahnaz Ashrafi, MD Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Principal Investigator: Mandana Hemmat, MD Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Principal Investigator: Arezoo Arabipour, MSc Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Responsible Party: Royan Institute
ClinicalTrials.gov Identifier: NCT03134690     History of Changes
Other Study ID Numbers: Royan-Emb-028
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: May 1, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Royan Institute:
Poor ovarian response gonadotropins antagonist

Additional relevant MeSH terms:
Infertility
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female