Delayed Start to Ovarian Stimulation (DOS/DOR)

This study has been terminated.
(Slow enrollment resulted in withdraw of funding)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01614067
First received: May 2, 2012
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

In couples with infertility secondary to Diminished Ovarian Reserve, the investigators hypothesize that a delayed start (7 day) to ovarian stimulation with an GnRH antagonist (Ganirelix) will improve oocyte maturation and quality, and improve pregnancy outcomes.


Condition Intervention
Diminished Ovarian Reserve
Infertility
In Vitro Fertilization
Drug: GnRH antagonist

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Delayed Start to Ovarian Stimulation Improves Oocyte Maturation and Quality: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Fertilization Proportions [ Time Frame: 8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilzation ] [ Designated as safety issue: No ]
    Developmental competence (fertilization of oocytes) through standard in vitro fertilization(estimated time frame to be between 8-24 hours following IVF)

  • Number of Oocytes Retrieved [ Time Frame: up to 1 hour after oocytes retrieved ] [ Designated as safety issue: No ]
    The egg harvest will be performed 36 hours after the ovulation trigger. Harvest procedure estimated to take up to 1 hour at study visit.


Secondary Outcome Measures:
  • Embryo Quality [ Time Frame: One hour on day 2 or 3 (following IVF procedure) ] [ Designated as safety issue: No ]
    Embryo quality will be assessed by the embryologist on days 2 or 3 following IVF

  • Pregnancy Rates [ Time Frame: 2 to 3 weeks following embryo transfer ] [ Designated as safety issue: No ]
    Beta HCG levels will be assessed at 2 weeks and 3 weeks after embryo transfer.

  • Stages of Oocyte Nuclear Maturation [ Time Frame: average of 1 to 2 hours on the Day of Retrieval ] [ Designated as safety issue: No ]
    Quality of oocytes will be assessed for developmental stages (Germinal Vesicles, Meiosis I, or Meiosis II)

  • Number of Mature Follicles [ Time Frame: up to 1 hour (during the Transvaginal Ultrasound before Retrieval of Oocytes) ] [ Designated as safety issue: No ]
    Maturation of follicles will be assessed by measuring the size of follicles (mature > 13mm) prior to (or at the time of) oocytes retrieval.

  • Oocyte Recovery Rate [ Time Frame: up to 1 hours after oocyte retrieval ] [ Designated as safety issue: No ]
    The number of oocytes recovered at the time of oocyte retrieval following ovarian stimulation.


Enrollment: 26
Study Start Date: May 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Delayed Start
Study subjects will receive be randomized to receive 7 days of pre-treatment with a GnRH antagonist (Delayed Start) before standard ovarian stimulation with FSH/LH, or standard ovarian stimulation (Conventional Start) with no "pre-treatment".
Drug: GnRH antagonist
Subjects will receive 7 days of pre-treatment with the GnRH antagonist
Other Names:
  • Ganirelix
  • Ganirelix acetate
Active Comparator: Conventional Start
Ovarian stimulation with standard antagonist protocols (no delay).
Drug: GnRH antagonist
Subjects will receive 7 days of pre-treatment with the GnRH antagonist
Other Names:
  • Ganirelix
  • Ganirelix acetate

Detailed Description:

Over the past two decades, the success rate of assisted reproductive technology (ART) has dramatically increased. This increase is attributed to improvements in embryo culture, laboratory conditions, and optimization of ovarian stimulation protocols. Over the past years, there has been more interest in altering the ovarian stimulation protocol to improve outcomes. For example, recently our group found that a modification of ovulation trigger toward a more physiologic process improves oocyte quality and pregnancy outcomes. Others have suggested minimal stimulation improves in vitro fertilization (IVF) outcomes. The investigators propose to further investigate modifying the ovarian stimulation for women who have "decreased" ovarian reserve. The investigators propose that a delayed start to ovarian stimulation will improve oocyte maturation and quality and pregnancy outcomes. No published studies to date have evaluated if a delayed start to ovarian stimulation improves pregnancy outcomes. However, the investigators hypothesize that the use an antagonist for a delayed start of stimulation will work by one of two mechanisms:

I. The partial suppression of FSH will allow for further recruitment of early antral follicles.

II. The partial suppression of FSH will allow for further FSH responsiveness in existing follicles to synchronize the primary cohort, thereby increasing the total number of follicles.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Antral Follicle Count (AFC) less than or equal to 4 as measured by transvaginal ultrasound (TVUS), or
  • Cancellation of a prior IVF cycle due to poor ovarian response.
  • Patients will receive an antagonist stimulation protocol for IVF, or IVF with Intracytoplasmic Sperm Injection (ICSI).

Exclusion Criteria:

  • Severe male factor infertility requiring surgical intervention to obtain sperm
  • Major uterine abnormality,
  • Preimplantation genetic diagnostic (PGD) testing,
  • Planned cycles without embryo transfer (for example, freeze-all, donor, or surrogate cycles).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01614067

Locations
United States, California
UCSF Center for Reproductive Health
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mitchell Rosen, MD UCSF Center for Reproductive Health and Fertility Preservation
  More Information

Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01614067     History of Changes
Other Study ID Numbers: UCSF 11-07259
Study First Received: May 2, 2012
Last Updated: June 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
DOR
Infertility
IVF
ART
GnRHa
GnRH Antagonist Protocol
Ganirelix

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Ganirelix
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014