The Most Common and Effective IVF Protocols
The IVF process involves various medications designed to stimulate the ovaries to produce multiple mature eggs for retrieval and fertilization in a laboratory. “IVF protocols” refers to the specific combinations and schedules of these medications.
This article will discuss the most common IVF protocols and give an overview of the alternative or add-on protocols that can be beneficial for specific issues.
Common Medications Used in IVF Protocols
IVF protocols generally involve the use of three types of medications:
Medications used to stimulate the development of multiple mature eggs. This almost always includes Follicle Stimulating Hormone (FSH) and may include luteinizing hormone (LH)
Common medications in this class include Gonal-F, Follistim, Bravelle, Menopur, and microdose hCG (which contains LH).
Medications that prevent ovulation until the majority of developing eggs are mature and ready for retrieval.
There are 2 classes of medications that prevent the surge in LH that would normally cause ovulation:
- GnRH-agonists (gonadotropin-releasing hormone agonists) such as Lupron and Provera.
Medications that “trigger” the final maturation of the eggs for retrieval. This may be Human Chorionic Gonadotropin (hCG) or Lupron.
Note that certain medications (like Lupron) can be used for different purposes – largely depending on their timing and dosage.
Now, let’s review how these medications are used in various IVF protocols.
Antagonist Protocol (Short Protocol)
The Antagonist Protocol (aka the Short Protocol) is the most common IVF protocol used today.
Here’s a standard antagonist protocol timeline (note that this is an average, and your specific timing and medications may differ):
- 10 days of FSH (and LH).
- Day 5-9, you will begin taking an antagonist medication (Ganirelix or Cetrotide) along with FSH
- Day 10-11, you will take either hCG, a high dose of Lupron, or a combination of both medications to trigger final oocyte maturation.
The antagonist protocol has become the most common IVF protocol, as antagonists are as effective as agonists at suppressing ovulation, but require less time, fewer injections (lower cost), and are easier to follow.
Ganirelix or Cetrotide stops the body from releasing LH (Luteinizing Hormone), thereby delaying ovulation. This allows the retrieval of eggs at the optimal moment when most eggs are fully matured.
Provera is another commonly used medication in an antagonist protocol. Provera prevents premature luteinizing hormone surges and has been found to be especially effective for women at high risk of ovarian hyperstimulation syndrome during ovarian stimulation.3
Though HCG and Lupron work equally well to trigger egg maturation, Lupron is better tolerated by some and can significantly decrease the risk of Ovarian Hyperstimulation Syndrome (OHSS).
Agonist Protocol (Long Protocol)
Though less common than the antagonist protocol, an agonist (long) or “down regulation” protocol uses Lupron to suppress the pituitary gland’s normal production of hormones, essentially preventing/delaying ovulation.4
Though comparatively as effective as the antagonist (short) protocol, the effects of Lupron at this dosage take 7-10 days to properly suppress LH and FSH hormones prior to initiating stimulation. This means that the agonist (long) protocol adds around a week of time and around two weeks of Lupron injections to the IVF cycle.
Here’s an example of a standard agonist protocol:
- Lupron is taken daily for 7-14 days before expected menstruation.
- Lupron and FSH are taken together for another 9-10 days, then stopped.
- On day 10 or 11 you take hCG to trigger the final maturation of eggs.
The Flare, or Microdose Lupron Flare Protocol
This IVF protocol utilizes the same medications as the Long Agonist Protocol but with some key differences:
- The GnRH agonist (Lupron) is administered at a lower “micro” dose, beginning on the first day of the cycle.
- One or two days later, gonadotropins are introduced.
- The GnRH agonist is used for a shorter duration than in the traditional Long Agonist Protocol, which is why this approach is sometimes called the “short agonist protocol.”
The rationale behind this protocol is that the GnRH agonist (Lupron) serves a dual purpose:
- In combination with gonadotropins, it stimulates follicle growth (known as the flare effect)
- Later in the cycle, it helps prevent premature ovulation.
This protocol may be recommended for women with low ovarian reserve or those who had a poor response (few eggs retrieved) in a previous IVF cycle or protocol. It is usually not used for women at high risk of ovarian hyperstimulation syndrome (OHSS).
Alternative and Additional Protocols
There are numerous variations and add-ons to a standard IVF protocol. Most are not standardized, and they can go by various names. Here’s a rundown of some common alternative and add-on protocols.
Mini/Micro IVF (antagonist)
Mini, or minimal stimulation IVF, is a non-standardized term that involves reduced medication dosages compared to standard dose antagonist IVF protocols. Other than the decreased dose of medications, it follows the same timeline and uses the same medications as the standard antagonist (short) protocol.
Mini, micro, or low stim/stimulation are used interchangeably. Mini IVF is a variant of traditional IVF without a uniform protocol.
At some clinics, this may only require oral medications like letrozole or clomid. At CNY, the mini protocol entails lower doses of injectable gonadotropins with the addition of letrozole for 5 days beginning with the start of FSH.
This protocol is classically recommended for individuals with a low ovarian reserve or those who, despite using high doses of gonadotropins in a previous cycle, retrieved only a small number of eggs. It can also be used for people with PCOS to avoid OHSS and retrieve the most amount of eggs safely.
In these cases, research suggests that a lower-dose approach can yield outcomes just as favorable as those achieved with higher doses.5 6
However, low-dose antagonist protocols have become increasingly popular due to their effectiveness in most populations and may be recommended for most patients.
Estrogen Priming Protocol
Estrogen priming involves taking a birth control pill, estrogen pills, or using an estrogen patch in the days or weeks before starting the IVF cycle. This practice, known as priming, is mainly used to control and schedule the timing of the IVF cycle.
This protocol is often helpful for women with Diminished Ovarian Reserve (DOR) or those with dyssynchronous follicle growth issues. It works by suppressing FSH and increasing the follicles’ sensitivity to FSH when it is eventually given in the form of an injection for IVF. It also helps to synchronize the stimulation of more follicles for retrieval.
Immune & Enhancement Protocols
Various immune and enhancement protocols can be used to improve egg quality, prepare the body for embryo transfer, and enhance the likelihood of successful implantation and healthy birth.
These protocols can be initiated at various stages of the IVF process and involve the use of numerous medications, including:
- Human Growth Hormone (HGH)
- Prednisolone
- Low-dose naltrexone
- Prograf
- Neupogen
- Intralipids
- IVIG
- Doxycycline
- ASA
- Lovenox
- Over the counter antihistamine like Claritin, Pepcid, and Benadryl
IVF Protocols: The Bottom Line
There are various IVF protocols that can be tailored to meet the unique needs of each individual. From common approaches like the antagonist protocol, to the less common agonist, and specialized options such as estrogen priming and immune protocols, there are numerous strategies to enhance the chances of success.
Schedule a consultation to learn more about the best options for you.
