Ovarian Stimulation

1.1 Why Stimulate the Ovaries?
In a natural menstrual cycle, a single dominant follicle is selected to ovulate one egg. For IVF, the goal is to override this natural selection process to obtain multiple eggs. This is because:

• Not all eggs are mature at the time of retrieval.
• Not all mature eggs will fertilize.
• Not all fertilized eggs (zygotes) will develop into viable blastocysts.
  Having multiple embryos allows for genetic testing (PGT-A) and the selection of the single most viable embryo for transfer, dramatically increasing the likelihood of a successful pregnancy, especially in a surrogacy scenario where the uterine environment is optimal.

1.2 The Key Hormones Involved

• FSH (Follicle-Stimulating Hormone): The primary driver of follicular growth and recruitment.
• LH (Luteinizing Hormone): Works synergistically with FSH in the final stages of follicular maturation and triggers ovulation.
• hCG (Human Chorionic Gonadotropin): Used as a “trigger shot” due to its structural similarity to LH, it initiates the final oocyte maturation process before retrieval.

Stimulation Protocols – A Tailored Approach

Identify the different stimulation protocols and the patient profiles for which they are best suited.

There is no one-size-fits-all protocol. The choice is based on the patient’s age, ovarian reserve (AMH, AFC), diagnosis, and previous cycle response.

2.1 The Antagonist Protocol (Most Common)
This is the contemporary gold standard for most patients due to its simplicity, safety, and efficacy.

• Process: Exogenous FSH injections begin on cycle day 2 or 3. A GnRH antagonist is introduced mid-cycle (typically when the lead follicle is ~13-14mm or as per E2 levels) to prevent a premature LH surge and ovulation.
• Advantages: Shorter duration, lower risk of Ovarian Hyperstimulation Syndrome (OHSS), and flexibility in the trigger shot choice.

2.2 The Agonist (Long Lupron) Protocol
One of the original protocols, still used in specific cases, such as patients with a high risk of premature ovulation or certain endometriosis cases.

• Process: A GnRH agonist (e.g., Lupron) is started in the luteal phase of the preceding cycle to achieve pituitary suppression. Once suppression is confirmed, FSH injections begin.
• Advantages: Excellent cycle control, very low risk of premature surge.

2.3 Other Specialized Protocols

• Microdose Flare Protocol: For patients with a poor ovarian response. Uses small doses of a GnRH agonist to “flare” or stimulate the release of the body’s own FSH/LH at the cycle’s start.
• Natural Cycle / Minimal Stimulation: For patients who cannot or choose not to use high doses of medication, often yielding fewer eggs per cycle.

The Medication Arsenal

Differentiate between the types of medications used and their specific roles.

3.1 Gonadotropins (FSH and LH Activity)

• Recombinant FSH (e.g., Gonal-f, Follistim): Pure FSH, produced in a lab. Offers precise dosing and consistency.
• Menotropins (e.g., Menopur): Contain both FSH and LH, derived from the urine of postmenopausal women. Often used in combination with recombinant FSH to provide LH activity, which can be beneficial for certain patients.
• hMG (e.g., Repronex): Similar to Menotropins.

3.2 Adjuvant Medications

• Clomiphene Citrate or Letrozole: Oral medications sometimes used in conjunction with gonadotropins to enhance response, particularly in poor responders.
• Growth Hormone (e.g., Omnitrope): May be used in select cases of poor ovarian response to potentially improve egg quality.

The Stimulation Cycle – From Start to Trigger

Outline the step-by-step process of monitoring and adjusting a stimulation cycle.

4.1 Baseline Assessment

• Timing: Cycle Day 2 or 3.
• Procedures: Transvaginal Ultrasound to count Antral Follicle Count (AFC) and measure endometrial lining. Blood work to check Estradiol (E2) levels.
• Purpose: To ensure the ovaries are quiet (no cysts) and confirm the start of stimulation.

4.2 Active Stimulation & Monitoring

• Duration: Typically 8-12 days.
• Process: The patient administers daily gonadotropin injections. Monitoring occurs every 2-3 days via:
  • Ultrasound: To track the number and size of growing follicles. We aim for a cohort of follicles growing in a synchronous manner.
  • Blood Work: To measure Estradiol (E2) levels, which rise as the follicles develop. Progesterone (P4) is also monitored to ensure it remains low.
• Dosage Adjustments: Medication doses are carefully adjusted based on this monitoring data to optimize growth and minimize risks.

4.3 The Trigger Shot

• Timing: Administered precisely when the majority of lead follicles have reached an optimal size (typically 16-20mm).
• Types of Triggers:
  • hCG Trigger: The traditional choice. Carries a higher risk of OHSS.
  • GnRH Agonist Trigger (e.g., Lupron trigger): Used in antagonist cycles. Virtually eliminates the risk of OHSS but may require additional luteal phase support.
  • Dual Trigger: A combination of both, often used to optimize maturity in certain cases.
• Egg Retrieval: Is scheduled for 34-36 hours after the trigger shot.

Managing Risks and Optimizing Outcomes

Recognize the potential risks of ovarian stimulation and the strategies to mitigate them.

5.1 Ovarian Hyperstimulation Syndrome (OHSS)

• What it is: A serious condition where the ovaries become overly enlarged and fluid leaks into the abdomen.
• Prevention Strategies: Using a GnRH antagonist protocol, GnRH agonist trigger, “freezing all” embryos to avoid a fresh transfer, and careful dosing based on patient profile.

5.2 Optimizing for Egg Quality
While egg quantity is largely predetermined, quality can be influenced. We advise:

• Pre-cycle Supplementation: 3 months of CoQ10, Vitamin D, and prenatal vitamins.
• Lifestyle Modifications: Maintaining a healthy BMI, smoking cessation, and reducing alcohol intake.