A simple overview of IVF medication protocols

A simple overview of IVF medication protocols
Fertility drugs are used in IVF to stimulate ovulation and prepare a patient for pregnancy. Here’s what you need to know about them before starting IVF treatment.
Written by Christina Ren, MS, CGC and Dave Gennert, PhD candidate
Medically reviewed by Cristina Vidal, RN
  • Cristina Vidal, RN, is the IVF-Donor-Surrogate nurse coordinator at Stanford Reproductive Endocrinology and Infertility with over 20 years of experience in the fertility and reproductive clinic.

Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. As part of our “Pregnancy and Fertility” series, we distill down the IVF process to help you navigate what’s really going on during fertility treatments.

What are the IVF medications for?

The primary goal of IVF stimulation medications is to increase the growth and development of eggs in the ovaries.

During a typical menstrual cycle, only one egg is released. In one round or “cycle” of IVF, the goal is to grow a larger number of follicles, each of which houses an egg, and collect the respective number of eggs. This collection happens during a procedure called “egg retrieval.” 

In general, there are two types of injectable medications used in IVF stimulation that serve different functions:

  1. Stimulate multiple follicles to develop. 
  2. Prevent ovulation from happening before egg retrieval 

You might ask, “why is the second type of drug even necessary? Isn’t the whole point to stimulate egg production, not to suppress it?” But this step is critical: if you ovulate before egg retrieval, your eggs can’t be found or used for IVF. It’s like pulling down the starting gate in a horse race too early.  

Think of it this way: stimulation is like the gas pedal. These hormones are known as “gonadotropins.” Preventing ovulation is like the brake pedal. These are medications known as “gonadotropin-releasing hormone (GnRH) analogs.” 

There’s a delicate balance between the two drugs: doctors don’t want to overstimulate the ovaries because that can cause discomfort and, in rare cases, ovarian hyperstimulation syndrome. They also don’t want to end up with only a few mature eggs retrieved when more could have been collected by using higher medication doses. 

The final type of medication triggers ovulation at the right time for egg retrieval. This is like the starting gate for all the mature eggs to be retrieved simultaneously and is known as the “trigger shot.”

Most IVF treatments involve a mix of these three types of medications (fertility clinics call them “medication protocols”). We’ll describe a bit more about the three most common protocols: 

  • Long protocol
  • Microdose flare protocol
  • Antagonist protocol

The long protocol

The long protocol, also called the GnRHagonist protocol, was the first of the modern protocols to be developed, and has been in use since the 1980s. It is used generally in patients who respond well to ovarian stimulation medications and are expected to have around 15-30 eggs retrieved.

It consists of three main phases:

  1. For the first 10 to 11 days, “step on the brakes” by using daily injectable GnRH agonists. This suppresses ovulation from happening too early. The daily GnRh agonists also often overlap with birth control pills to regulate the patient's menstrual cycle. 
  2. About 6 to 7 days after taking birth control pills, “step on the gas” by using injectable gonadotropins to stimulate as many follicles to mature as possible. These medications are biologically similar to hormones a woman naturally secretes — follicle stimulating hormone (FSH), luteinizing hormone (LH), or a combination of the two. On average, patients stay on the stimulation medications for 10 to 12 days.
  3. About 35 hours before egg retrieval, trigger the release of the mature eggs with an injection of human chorionic gonadotropin (hCG). hGC is a naturally occurring chemical produced during pregnancy that functions similar to LH. 

The microdose-Lupron protocol

The microdose-Lupron protocol, also called the flare or microdose-flare protocol, is a slight modification of the long protocol. It is used in patients who respond poorly to the stimulation medications — for example, those who have low numbers of maturing follicles.  

The main difference compared to the long protocol is that doctors “ease up on the brakes” in the beginning by prescribing a lower dose of GnRH agonists over a shorter period of time. This helps retrieve more eggs for those whose ovaries are less responsive to stimulation medications. 

What this often looks like for patients on the microdose flare protocol:

  1. Three days after the patient’s last birth control pill, GnRh agonist injections start daily and continue daily with the stimulation medication (one dose in the morning and one dose in the evening). 
  2. Two days after the GnRh agonists, stimulation medications are injected for around 10-12 days.  

The name of the game with this protocol is steady growth and development of eggs. 

The antagonist protocol

The antagonist protocol is more recently developed, becoming increasingly popular in the clinic within the last 10-12 years. This protocol is generally shorter and can be used on various types of medication responders.

GnRH antagonists are effective brakes because they can block the production of FSH and LH within several hours but can be quickly reversed. This means there is no need for pre-stimulation suppression.

What this typically looks like for patients: 

  • The patient stays on stimulation medications for the typical 10-12 days.
  • Then, the brakes are applied later on in the cycle using GnRH antagonists to prevent ovulation and allow the eggs to grow and mature together.

Because the effect of GnRH antagonists can be quickly revered, after egg retrieval, the stimulatory hormones typically return to normal levels sooner.  

Which protocol is right for you?

Each protocol has its advantages and disadvantages, and they will work differently in different patients. It is important to talk with your doctor about your medication options. The most appropriate choice will depend on your IVF and medical history, how you might over or under respond to the medications, and other health and lifestyle factors.

Resources on how to use injectable medications

Fertility treatment and reproductive medicine have come a long way since IVF was first introduced over 40 years ago. Today, advanced embryo testing is now available to couples who want their child to have the best shot of a healthy life. Explore how Orchid helps you conceive with confidence.

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