What is the recommended protocol for an IVF (In Vitro Fertilization) antagonist protocol, including dosing and administration of medications such as cetrorelix (Cetrotide) or ganirelix (Antagon) and FSH (Follicle-Stimulating Hormone), e.g. follitropin alpha (Gonal-F) or beta (Follistim)?

From the Guidelines

The recommended IVF antagonist protocol involves FSH stimulation with follitropin alpha (Gonal-F) or follitropin beta (Follistim) at doses of 150-300 IU daily, combined with GnRH antagonists such as cetrorelix (Cetrotide) 0.25 mg or ganirelix (Antagon) 0.25 mg, to prevent premature LH surge and ovulation, as supported by recent clinical guidelines 1.

When implementing the IVF antagonist protocol, several key considerations must be taken into account:

• FSH stimulation typically commences on day 2-3 of the menstrual cycle, with doses adjusted based on patient characteristics like age, AMH levels, and antral follicle count.
• GnRH antagonists are introduced daily once the lead follicle reaches 12-14 mm in diameter or by stimulation day 5-6, and continue until trigger day, to prevent premature LH surge and ovulation.
• Follicular development is closely monitored via transvaginal ultrasound and estradiol levels every 2-3 days, with medication adjustments made accordingly to optimize outcomes.
• When at least 2-3 follicles reach 17-18 mm, final oocyte maturation is triggered with hCG (5,000-10,000 IU) or GnRH agonist (0.2-0.4 mg), and egg retrieval occurs 34-36 hours post-trigger, as outlined in recent clinical guidelines 1.

The advantages of the antagonist protocol include its shorter duration, lower risk of ovarian hyperstimulation syndrome, and flexibility for cycle scheduling, while still providing good pregnancy outcomes, making it a preferred choice for many patients undergoing IVF, as noted in recent studies 1. Individual protocols may vary based on patient-specific factors and clinic preferences, highlighting the importance of personalized care in IVF treatment.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Induction of Ovulation (2.2) Initial starting dose of the first cycle: 75 International Units of GONAL-F RFF per day for 14 days, administered subcutaneously Individualize doses after 14 days Do not administer doses greater than 300 International Units per day Development of Multiple Follicles in Assisted Reproductive Technology (ART) (2.3) Initial starting dose of the first cycle: 150 International Units per day, administered subcutaneously Dosage adjustments after 3 to 5 days and by 75 to 150 International Units at each adjustment Do not administer doses greater than 450 International Units per day

The recommended protocol for an IVF antagonist protocol includes:

• Initial starting dose: 150 International Units of FSH (e.g. follitropin alpha) per day, administered subcutaneously
• Dosage adjustments: after 3 to 5 days, adjust the dose by 75 to 150 International Units at each adjustment
• Maximum dose: do not administer doses greater than 450 International Units per day
• Administration of antagonist: the drug labels do not provide information on the administration of cetrorelix (Cetrotide) or ganirelix (Antagon), therefore no conclusion can be drawn about the dosing and administration of these medications in an IVF antagonist protocol 2 2

From the Research

IVF Antagonist Protocol

The IVF antagonist protocol is a type of ovarian stimulation protocol used in in vitro fertilization (IVF) cycles. This protocol involves the use of gonadotropin-releasing hormone (GnRH) antagonists, such as cetrorelix (Cetrotide) or ganirelix (Antagon), to prevent premature luteinizing hormone (LH) surges.

Medications and Dosing

The medications used in the IVF antagonist protocol include:

• GnRH antagonists: cetrorelix (Cetrotide) or ganirelix (Antagon)
• Follicle-stimulating hormone (FSH): follitropin alpha (Gonal-F) or beta (Follistim) The dosing of these medications may vary depending on the individual patient's needs and response to treatment. According to a study 3, a single injection of cetrorelix (3 mg) or daily dose of ganirelix (0.25 mg) can be effective in preventing premature LH surges.

Administration of Medications

The administration of medications in the IVF antagonist protocol typically involves:

• Starting GnRH antagonist when the lead follicle reaches a certain size (e.g. 14-15.9 mm) or when the estrogen level reaches a certain threshold (e.g. 500-599 pg/mL) 4
• Administering FSH (e.g. follitropin alpha or beta) to stimulate follicular growth
• Continuing GnRH antagonist administration until the day of human chorionic gonadotropin (hCG) triggering

Key Considerations

Some key considerations when using the IVF antagonist protocol include:

• The choice of GnRH antagonist (cetrorelix or ganirelix) may depend on the individual patient's needs and response to treatment 3, 5
• The dosing and administration of FSH and GnRH antagonist may need to be adjusted based on the patient's response to treatment 6
• The timing of GnRH antagonist start is critical, as starting too early or too late may reduce the odds of clinical pregnancy 4

Benefits and Drawbacks

The benefits of the IVF antagonist protocol include:

• Reduced risk of premature LH surges
• Improved control over ovarian stimulation
• Potential for improved pregnancy rates However, the drawbacks of this protocol include:
• Increased complexity and cost compared to other ovarian stimulation protocols
• Potential for reduced pregnancy rates if the GnRH antagonist is started too early or too late 4