Understanding the IVF Antagonist Protocol and Other Uses for GnRH Antagonist Injections
Many treatment approaches exist for patients who need in vitro fertilization (IVF). Although there are several ways to approach each one, most involve using a gonadotropin-releasing hormone (GnRH) antagonist to prevent early ovulation.
The IVF antagonist protocol is mainly intended for patients who are relatively young (under age 35), have unexplained infertility, have not had prior injectable ovarian stimulation cycles and have had a fair or good response to ovarian stimulation using an estrogen receptor modulator (clomiphene) or an aromatase inhibitor (letrozole).
How an Antagonist Protocol Works
This IVF protocol typically begins in the prior luteal phase with combination oral contraceptives (which contain both estrogen and progesterone) to suppress oocyte production. This suppresses or "quiets" the ovaries to hopefully ensure synchronous oocyte size at the beginning of ovarian stimulation.
However, for patients who have poor-quality or reduced-quantity oocytes, a natural start might be the best choice due to the increased chance of oversuppression.
In an ordinary menstrual cycle, both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increase prior to ovulation — FSH faster than LH. Between two and three days before ovulation, FSH dips and LH dramatically increases. At the time of ovulation, FSH increases once again and LH reaches its peak. Applying exogenous hormones mimics this process but aims to produce many follicles rather than one.
The ovarian stimulation portion of the IVF antagonist protocol typically involves FSH (follitropin) and human menopausal gonadotropin (hMG) (menotropin). Some reproductive endocrinologists prefer to start at high doses of both to prompt a quicker initial ovarian response and then reduce the dose as the cycle progresses. Others start at low doses and increase over time.
Once the lead follicles reach 11-12 mm, according to research published in the Middle East Fertility Society Journal, physicians introduce GnRH antagonist injections (cetrorelix or ganirelix) to release a combination of FSH and LH.
Finally, when most follicles reach at least 17 mm, the GnRH antagonist injections cease, and a trigger shot of human chorionic gonadotropin (hCG) and/or a GnRH agonist (such as leuprolide) tells the body to release LH and trigger an LH surge. Approximately 36 hours later, reproductive endocrinologists conclude the IVF antagonist protocol by retrieving the oocytes.
Alternatives: The Schoyer Protocol
The Schoyer protocol is a priming protocol that starts in the patient's luteal phase prior to follicular phase ovarian stimulation. It suppresses FSH by maintaining high estrogen levels. A few days after beginning estrogen supplements — either pills or patches — patients introduce a GnRH antagonist, according to research published in Reproductive Biology and Endocrinology. These medications continue simultaneously until the patient's menstrual period starts, at which point the GnRH antagonist ceases.
This protocol is mainly indicated for patients who cannot take birth control pills for these reasons:
- A history of blood clots, migraines or ovarian cysts
- Having poor-quality and/or reduced-quantity oocytes
- Prior poor response to ovarian stimulation
- High FSH levels
Other Uses for GnRH Antagonist Injections
Because GnRH antagonists slow down a patient's LH surge, they can be used in any IVF protocol as long as the patient is not also taking a GnRH agonist (such as leuprolide).
GnRH agonists lower estrogen levels by triggering the release of FSH and LH from the pituitary gland. This inhibits the pituitary gland's ability to control the ovary and thus prevents premature ovulation. In other words, patients do not need both a GnRH antagonist and GnRH agonist at the same time — they perform the same function in a different way. Ongoing pregnancy rates are approximately the same with both approaches, according to research published in PLoS One.
It is important that reproductive endocrinologists explain the various protocol options that may be indicated, the function of each medication and the approximate timeline to patients. Patients should be encouraged to ask questions until they fully understand and can make informed decisions about their fertility treatment plan.
