Delayed Start to Ovarian Stimulation (DOS/DOR)

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.

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.

Study subjects will receive 7 days of pre-treatment with a GnRH antagonist (Delayed Start) before standard ovarian stimulation with FSH/LH.

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.

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

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.

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.

Quality of oocytes will be assessed for developmental stages (Germinal Vesicles, Meiosis I, or Meiosis II)

Maturation of follicles will be assessed by measuring the size of follicles (mature > 13mm) prior to (or at the time of) oocytes retrieval.

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).

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.