Clinical trial NCT01614067: Delayed Start to Ovarian Stimulation
Official title: Delayed Start to Ovarian Stimulation Improves Oocyte Maturation and Quality: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diminished Ovarian Reserve
Infertility
In Vitro Fertilization
Keywords: DOR
Infertility
IVF
ART
GnRHa
GnRH Antagonist Protocol
Ganirelix
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-06-07
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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).

Primary outcomes:
measure: Fertilization Proportions
timeFrame: 8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilization
measure: Number of Oocytes Retrieved
timeFrame: up to 1 hour after oocytes retrieved
Secondary outcomes:
measure: Embryo Quality
timeFrame: One hour on day 2 or 3 (following IVF procedure)
measure: Pregnancy Rates
timeFrame: 2 to 3 weeks following embryo transfer
measure: Stages of Oocyte Nuclear Maturation
timeFrame: average of 1 to 2 hours on the Day of Retrieval
measure: Number of Mature Follicles
timeFrame: up to 1 hour (during the Transvaginal Ultrasound before Retrieval of Oocytes)
measure: Oocyte Recovery Rate
timeFrame: up to 1 hours after oocyte retrieval
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Center for Reproductive Health
state: California
Study officials:
affiliation: UCSF Center for Reproductive Health and Fertility Preservation
name: Mitchell Rosen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blockeel C, Riva A, De Vos M, Haentjens P, Devroey P. Administration of a gonadotropin-releasing hormone antagonist during the 3 days before the initiation of the in vitro fertilization/intracytoplasmic sperm injection treatment cycle: impact on ovarian stimulation. A pilot study. Fertil Steril. 2011 Apr;95(5):1714-9.e1-2. doi: 10.1016/j.fertnstert.2011.01.028.