During an in vitro fertilization (IVF) cycle, doctors use medications to calibrate a woman's menstrual cycle in a way that allows more control over the outcome of the procedure. These injections are part of the protocol needed to prepare the body for treatment.

Here we cover what stimulation protocols are, why they are used, and we dive into a few variations of protocols that may be used.

Why are stimulation protocols used for IVF?

The most critical aspect of the IVF process is to have good-quality embryos to transfer back to a uterus. Because a dramatic reduction in the number of viable eggs and/or embryos from the time of the egg retrieval to an eventual embryo transfer is a common occurrence, a larger number of eggs is beneficial in an IVF cycle.

In a typical menstrual cycle most women produce multiple egg follicles, but only one follicle will become dominant and mature into an egg that is released through the process of ovulation. IVF stimulation protocols use medications to stimulate a woman's ovaries in a process known as superovulation, which causes the production of multiple follicles at once.

Logically, more follicles should translate to more eggs, which should translate to more embryos, which hopefully translates to high-quality embryos for transfer, which means better odds for achieving pregnancy.

Variation in Stimulation Protocols

There are different ways medications are used to stimulate the ovaries during an IVF cycle and these are called IVF protocols. When you hear about injections of medication for IVF, a protocol is generally what is being referred to. Protocols differ depending on personal circumstances that can include a specific diagnosis or age.

The following are examples of three common protocols. These are examples only. Always adhere to your own doctor’s instructions for your cycle.

Long Lupron (Overlap) Protocol for IVF

Lupron (also known as leuprolide), is a medication that acts to temporarily overstimulate the body's production of fertility hormones, but afterwards causes the body to temporarily stop producing these hormones. Lupron ultimately blocks the pathway between the ovaries and the control centers in the brain, giving the doctors more control over the treatment cycle.

Birth Control Pills to Regulate Hormones

This protocol — also called standard or overlap protocol — usually starts with birth control pills, which are used to regulate the body’s hormones and synchronize the timing of the other drugs.

Another advantage of using birth control pills to overlap the Lupron is that the pills suppress the formation of ovarian cysts that sometimes form when Lupron is taken.

Lupron Starts

On Day 21 of your cycle (or after 21 days of active pills) you begin taking Lupron. This drug acts on the parts of the brain that communicate with the ovaries. The body’s initial response to Lupron is to produce a surge of hormones that stimulate the ovaries. This is followed by suppression of the ovary with continuing Lupron.

Have hormones been sufficiently suppressed?

It takes around 10 days of Lupron to fully reduce the body’s natural hormones to a very low level. When the hormone levels are sufficiently low, you are said to be suppressed or down-regulated. This suppression helps the ovaries to recruit multiple follicles instead of the single follicle, which would usually be recruited during a natural cycle.

Stimulation Phase

The birth control pill is eventually discontinued and Lupron continues during the stimulation phase of the cycle. This phase involves the injection of follicle-stimulating hormone (FSH) fertility drugs that stimulate the follicles to grow in the ovaries. During this time, you have various ultrasounds and blood tests to monitor the developing follicles, and the dose of drugs can be altered accordingly.

Because the growing follicles produce and secrete estrogen into the blood stream, the circulating levels of estrogen are monitored closely during the stimulation phase. This level, coupled with ultrasound counts and measurements of the follicles, allows the doctors to accurately measure the body’s response to the drugs.

Trigger Shot to Mature Eggs

After approximately 10 days of stimulation, when the biggest follicles are around 18 to 22 millimeters (about 2/3 to 5/6 inch) in diameter, you discontinue the stimulation medication and the Lupron. At this point, you take a human chorionic gonadotrophin (hCG) injection, which matures the eggs and releases them from the walls of the follicles in preparation for the egg retrieval (hCG acts in exactly the same way as luteinizing hormone would naturally).

Progesterone and Estrogen Supplementation

One to two days following the egg retrieval if you are having a fresh embryo transfer, you begin progesterone supplementation, which is very important for maintaining the lining of the uterus and keeping open a window of receptivity to embryo implantation. Estrogen is often taken following the egg retrieval to maintain the right balance of hormones in the body because egg collection can remove estrogen-producing cells that are important to the process.

To summarize, a long Lupron protocol is likely to include the following steps:

  • Birth control pills (overlap with Lupron)
  • Lupron (overlaps with stimulation medication)
  • Suppression check to see if hormones have been sufficiently down-regulated.
  • Stimulation medication (along with frequent ultrasound and blood tests for about 10 days)
  • HCG trigger shot
  • Egg retrieval
  • Progesterone and estrogen supplementation
  • Embryo transfer
  • Continued progesterone supplementation

Types of IVF Stimulation Protocols

Short Lupron (Microdose or Flare) Protocol for IVF

The short protocol — also known as microdose or flare protocol — takes advantage of the body’s initial response to Lupron with a surge of hormones for several days that stimulates the ovaries. During a short protocol, the Lupron is first introduced during the stimulation phase. This gives the ovaries an extra dose of natural follicle-stimulating hormone (FSH) on top of the high doses being injected.

A short protocol is used when a woman probably won't respond well to the long protocol based on the baseline fertility testing done before the IVF cycle starts. It’s one of the most potent protocols available and can help women with low ovarian reserves to get as many eggs as possible.

To summarize, a short Lupron protocol is likely to include the following steps:

  • Birth control pills
  • Mini-doses of Lupron started three days after the last pill and continued until the day of hCG (Continued Lupron prevents premature ovulation.)
  • Ovarian stimulation started shortly after Lupron and overlaps it
  • hCG trigger shot
  • Egg retrieval
  • Progesterone and estrogen supplementation
  • Embryo transfer
  • Continued progesterone supplementation

Types of IVF Stimulation Protocols

Antagonist Protocol for IVF

The antagonist drug (Ganirelix or Cetrotide) is similar to Lupron in its suppressive phase and prevents premature ovulation. The antagonist is taken during the stimulation phase of the treatment cycle when the follicles are around 14 millimeters (about 3/5 inch) in diameter and is continued until the hCG injection.

An advantage of the antagonist protocol is that the drug takes only one day to suppress the natural hormones that might interfere with the cycle. In addition, there are fewer injections and there may be a better response in women with a low ovarian reserve because the ovaries are not subjected to prolonged suppression before the stimulation phase. Antagonist protocols are good for almost everyone, but your doctor will decide which protocol is best for you to get the highest and safest response to the fertility drugs.

To summarize, an antagonist protocol is likely to include the following steps:

  • Birth control pills
  • Ovarian stimulation started at the end of the pill cycle
  • Antagonist (Cetrotide or Ganirelix) started four to five days after the stimulation medication; continued until the day of hCG trigger shot
  • hCG trigger shot
  • Egg retrieval
  • Progesterone and estrogen supplementation
  • Embryo transfer
  • Continued progesterone supplementation

Types of IVF Stimulation Protocols

Finding the Right Stimulation Protocol

There are many possible stimulation protocols. It may take multiple cycles of fertility drugs to develop the proper response in terms of the number and size of follicles that develop. It might even be necessary to cancel a cycle after you have started the fertility medications and restart on a different protocol. Although this may be a disappointing result, remember that you are starting over with a better understanding of your body.