Follicle Size and Oocyte Development

Controlled ovarian hyperstimulation is critical to assisted reproduction because it increases the number of oocytes undergoing development. The medications, designed to override the selection of a single dominant follicle, drive multiple antral follicles into the growth phase. These follicles grow at different rates, and management is guided by their size rather than their competence. Human chorionic gonadotropin (hCG) is usually used as a surrogate LH surge to induce luteinization of the granulosa cells, final oocyte maturation and resumption of meiosis. This treatment is therefore based on an assumption that follicular size predicts the developmental competence of the oocyte. The outcome, is that only a portion of the oocytes will be competent for fertilization and development into viable embryos.

Studies have shown that the follicles greater in diameter was most likely to have a mature oocyte that was capable of fertilization and best suited for development into a high-quality embryo. Smaller follicles showed lower rates ( 60%).

Lately new triggering protocols have emerged aiming to improve the proportion of mature oocytes at the time of retrieval. Following the observations demonstrating comparable or even better oocyte\\embryos quality following GnRHa, compared to hCG trigger, and the different effects of LH and hCG on the downstream signaling of the LH receptor, GnRHa is now offered concomitant to the standard hCG trigger dose to improve oocyte/embryo yield and quality. To the best of our knowledge, no studies have been done comparing the effect of the dual triggering on the amount of larger follicles per cycle and its effect on oocyte maturation.

The aim of this study is to learn the effects of the dual triggering compared to the standard hCG triggering on the oocyte development and quality as a function of the follicle size

Material and Methods A prospective cohort study including all women on antagonist protocol for controlled ovarian hyper stimulation with triggering using Ovitrelle ( hCG 250 mcg) or dual triggering - Ovitrelle ( Hcg 250 mcg) + Decapeptyl ( GnRH Agonist 0.1 mg*2 ).

As practiced at the IVF clinic, individuals will be monitored with transvaginal ultrasound and blood samples for hormonal profile ( including Estradiol, Progesteron, FSH). The decision to administer hCG or Dual triggering will be based on physician judgment, and the timing will be based on the lead follicular cohort, usually with at least two follicles measuring 18 mm for maximal diameter. A transvaginal, ultrasound-guided follicular aspiration will be conducted 36 hours after triggering administration. At retrieval, each follicle will be measured before aspiration. Follicles will be divided into five arbitrary follicular groups according to their maximal dimensional size: >18 mm, 16 to 18 mm, 13 to 15 mm, 10 to 12 mm, and <10 mm. Following identification, the follicles will be aspirated. Microscopic examination of the follicular aspirates will be performed by the embryologist. Once the oocytes will be identified, they will be collected and organized according to follicle size. Oocytes will be fertilized using conventional insemination or intracytoplasmic sperm injection (ICSI) . Each embryo will be cultured and evaluated after 72 hours.

Day-3 embryo grading, based on cellular cleavage and fragmentation, will be recorded separately. Fragmentation will be scored by the degree of fragmentation proportional to the whole embryo volume: 1, no fragmentation; 2, <10%; 3, 10% to 25%; 4, 25% to 50%; 5, >50%. The information for each oocyte, starting from the follicular size, will be followed through all laboratory procedures including insemination, oocyte stripping for ICSI, ICSI, pronuclear assessment, embryo culture, and embryo transfer.

Data will be collected from the medical file of each patient.

Inclusion criteria

• Age- 18-45
• Antagonist protocol
• Triggering: A- with Ovitrelle ( HCG) 250 mcg B- with dual triggering - Ovitrelle ( HCG) 250 mcg + Decapeptyl ( GnRH Agonist ) 0.1 mg*2

Exclusion criteria

• Endometriosis
• Known mutation of Fragile X