Course / Ovarian Stimulation Protocols
The primary goal of ovarian stimulation in an IVF cycle, particularly within a surrogacy arrangement, is to maximize the chances of creating a viable embryo for your surrogate to carry.
In a natural menstrual cycle, the body selects a single dominant follicle to mature and release one egg. While this is efficient for natural conception, it is suboptimal for IVF where the aim is to retrieve multiple eggs. This is because:
Not all eggs are mature: Only about 70-80% of retrieved eggs are typically mature (MII).
Not all mature eggs fertilize: Even with ICSI, fertilization rates are not 100%.
Not all fertilized eggs become blastocysts: A significant portion of fertilized eggs (zygotes) will arrest in development before day 5-6.
Not all blastocysts are genetically normal: Especially for older intended parents, a percentage of blastocysts may have chromosomal abnormalities (aneuploidy) and cannot result in a successful pregnancy.
By using injectable hormones called gonadotropins, we can rescue a cohort of follicles that would otherwise be lost that month, allowing multiple eggs to mature simultaneously. This increases the number of eggs retrieved, fertilized, and developed into blastocysts, thereby increasing the statistical probability of having at least one, and often multiple, high-quality, euploid (chromosomally normal) embryos for transfer—either fresh or frozen for future sibling journeys.
The gonadotropin dose is not a one-size-fits-all prescription; it is a carefully calculated decision based on the individual female’s profile. The objective is to find the “Goldilocks Zone” – a dose that is high enough to stimulate a robust cohort of follicles but low enough to minimize the risk of Ovarian Hyperstimulation Syndrome (OHSS) and produce high-quality eggs.
Key factors influencing the starting dose include:
Antral Follicle Count (AFC): A baseline ultrasound count of small, resting follicles. A higher AFC often correlates with a better response and may allow for a moderate dose.
Anti-Müllerian Hormone (AMH): A blood test that is a strong predictor of ovarian reserve. High AMH may indicate a strong response, requiring a conservative dose to prevent OHSS, while low AMH may necessitate a higher dose.
Age: Younger patients typically have better quality eggs and may require different dosing strategies than older patients, even with similar AMH/AFC.
Body Mass Index (BMI): Higher BMI can sometimes require higher doses of medication to achieve the desired response.
Previous Response to Stimulation: If a patient has undergone a previous IVF cycle, their response is the single most valuable data point for protocol and dose adjustment.
Typical starting doses range from 150 IU to 450 IU of gonadotropins per day. The response is closely monitored through serial ultrasounds and estrogen (E2) blood tests, allowing for dose adjustments throughout the cycle.
The “protocol” refers to the specific sequence and timing of medications used to control the menstrual cycle and stimulate the ovaries. The choice of protocol is tailored to the patient’s unique profile and goals.
Common Ovarian Stimulation Protocols:
Antagonist Protocol (Most Common):
Description: This is the contemporary workhorse of IVF clinics. It involves starting gonadotropins early in the cycle (Day 2-3) and adding a GnRH Antagonist mid-cycle (typically when the lead follicle is ~13-14mm or E2 reaches a certain level) to prevent a premature LH surge.
Best For: Most patient types, especially high responders and those at risk for OHSS. It offers a shorter treatment duration and a significantly lower risk of OHSS.
Key Advantage: Flexibility and excellent safety profile.
Long Agonist Protocol (Down-Regulation):
Description: This classic protocol begins with a GnRH Agonist (e.g., Lupron) in the luteal phase of the preceding cycle (one week after ovulation) to “shut down” the pituitary gland. After confirmation of down-regulation (with a period), gonadotropin stimulation begins.
Best For: Typically younger, high-responder patients with a good ovarian reserve where precise cycle control is desired. It can also be used in certain cases of endometriosis.
Key Advantage: Prevents a premature LH surge very effectively. Can sometimes lead to a very synchronized cohort of follicles.
Microdose Flare Protocol:
Description: A variation of the agonist protocol where a small, “micro” dose of Lupron is used at the start of the cycle to stimulate a brief flare of the body’s own FSH/LH before adding gonadotropins.
Best For: Often used for “poor responders” or patients with diminished ovarian reserve (DOR) where the goal is to recruit as many follicles as possible by leveraging the initial endogenous hormone flare.
Mini-IVF / Gentle Stimulation:
Description: Uses lower doses of oral medications (like Clomid or Letrozole) with or without low-dose injectable gonadotropins.
Best For: Patients who are sensitive to high doses of medication, those with a very low ovarian reserve where quality may be prioritized over quantity, or for those wishing to minimize medication exposure and cost. The goal is often to produce a smaller number of high-quality eggs.
Understanding the different classes of medications is key to understanding your protocol.
| Drug Class | Purpose | Brand Name Examples |
|---|---|---|
| Gonadotropins | To stimulate the ovaries to develop multiple follicles. These are recombinant or purified forms of FSH and LH. | Gonal-F, Follistim (recombinant FSH) Menopur (purified urinary FSH & LH) |
| GnRH Agonists | To initially stimulate, then suppress, the pituitary gland to prevent ovulation. Used in “Long” protocols. | Lupron (leuprolide) |
| GnRH Antagonists | To provide an immediate block of the pituitary gland to prevent a premature LH surge. Used in “Antagonist” protocols. | Ganirelix, Cetrotide (cetrorelix) |
| hCG / Triggers | A single, large dose to finalize egg maturation and trigger ovulation ~36 hours before egg retrieval. | Novarel, Pregnyl, Ovidrel |
| Adjuvant Medications | Used to support the stimulation process or prepare the uterus. | Letrozole, Clomid, Growth Hormone |
A visual timeline is highly recommended here. Below is a descriptive breakdown.
Antagonist Protocol Timeline:
Cycle Day 1: Patient calls clinic with menses onset.
Cycle Day 2/3: Baseline ultrasound and bloodwork. If clear, begin daily Gonadotropin injections.
~Stimulation Day 5-7: Monitoring appointment. Based on follicle size and E2 levels, begin daily GnRH Antagonist injections.
Stimulation Days 8-12: Continued monitoring every 1-2 days.
When follicles are ready: Administer hCG or Lupron “trigger” shot.
36 hours post-trigger: Egg Retrieval procedure.
Long Agonist Protocol Timeline:
Luteal Phase (~1 week post-ovulation): Begin daily Lupron injections.
~10-14 days later: Confirm down-regulation with ultrasound and bloodwork (patient will get a period).
Cycle Day 2/3: Begin daily Gonadotropin injections. Reduce Lupron dose to a “micro” level.
Stimulation Days 8-12: Monitoring.
When follicles are ready: Administer hCG trigger shot.
36 hours post-trigger: Egg Retrieval.
Adjuvants are supplemental medications or treatments proposed to potentially improve outcomes in specific scenarios. It is crucial to discuss the evidence-based rationale for any add-on with your physician.
Growth Hormone (GH):
Purpose: Hypothesized to improve egg quality, particularly in poor responders or patients with previous poor embryo development.
Evidence: Growing but still considered for specific cases. It is not a standard for all patients.
Testosterone / DHEA Pre-treatment:
Purpose: Androgens are thought to increase the number of FSH receptors on follicles, potentially leading to a better response in low-prognosis patients.
Evidence: Controversial. Should only be used under strict medical supervision due to potential side effects.
Coenzyme Q10 (CoQ10):
Purpose: An antioxidant that supports mitochondrial function in the egg. Mitochondria are the energy powerhouses crucial for cell division.
Evidence: Generally considered safe. Many clinicians recommend it for both female and male partners for 2-3 months prior to an IVF cycle to potentially improve gamete quality.
Aspirin:
Purpose: Sometimes used to improve blood flow to the ovaries and uterus.
Evidence: Routine use is not supported by strong evidence. It is typically reserved for patients with specific medical indications (e.g., blood clotting disorders).
Intralipid Therapy:
Purpose: Proposed to modulate the immune system and improve implantation in cases of suspected immune dysfunction or recurrent implantation failure.
Evidence: Highly controversial and not supported by robust clinical trials. It is not a standard of care in most clinics.
Conclusion:
A successful ovarian stimulation is the critical first step in building your family through surrogacy. At Surrogacy4All, we work with top-tier fertility partners who specialize in creating personalized, evidence-based protocols to maximize your chances of retrieving healthy eggs and creating the embryos that will make your dream of parenthood a reality.
Disclaimer: This information is for educational purposes only and does not constitute medical advice. All treatment decisions must be made in consultation with a qualified fertility specialist.
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