Delayed Start to Ovarian Stimulation

Phase 4

Terminated

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.

Recruitment & Eligibility

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).

Arm && Interventions

Group	Intervention	Description
Delayed Start	Ganirelix acetate	Study subjects will receive 7 days of pre-treatment with a GnRH antagonist (Delayed Start) before standard ovarian stimulation with FSH/LH.
Conventional Start	Ganirelix acetate	Ovarian stimulation with standard antagonist protocols (no delay).

Primary Outcome Measures

Name	Time	Method
Fertilization Proportions	8 to 24 hours after in vitro fertilization, oocytes will be checked for fertilization	Developmental competence (fertilization of oocytes) through standard in vitro fertilization (estimated time frame to be between 8-24 hours following IVF). This percentage will be calculated as the number of fertilized eggs ( 2PN stage) per total number of eggs collected from the egg retrieval.
Number of Oocytes Retrieved	up to 1 hour after oocytes retrieved	The egg retrieval procedure will be performed 36 hours after the ovulation trigger. The procedure is estimated to take up to 1 hour at study visit as part of routine care. The number of retrieved eggs will be counted

Secondary Outcome Measures

Name	Time	Method
Pregnancy Rates	2 to 3 weeks following embryo transfer	Beta HCG levels will be assessed at 2 weeks and 3 weeks after embryo transfer. A positive pregnancy is defined as two positive beta HCG levels (a value \> 5 mIU/ml ) observed over the time frame.
Stages of Oocyte Nuclear Maturation	average of 1 to 2 hours on the Day of Retrieval	Quality of oocytes will be assessed for developmental stages (Germinal Vesicles, Meiosis I, or Meiosis II)
Number of Mature Follicles	up to 1 hour (during the Transvaginal Ultrasound before Retrieval of Oocytes)	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	up to 1 hours after oocyte retrieval	The number of oocytes recovered at the time of oocyte retrieval following ovarian stimulation.
Embryo Quality	One hour on day 2 or 3 (following IVF procedure)	Embryo quality will be assessed by the embryologist on days 2 or 3 (Cleavage stage) following IVF using standard embryo grading criteria. Embryos grading is based on three criteria: the number of blastomere cells present in the embryo, the degree of observed cell fragmentation and the degree of observed symmetry of the cells.

Locations (1): UCSF Center for Reproductive Health
🇺🇸
San Francisco, California, United States