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Ovarian Stimulation Protocols for IVF
In order to maximize success rates with in vitro fertilization we want a good number of high quality eggs from the woman. We generally want to get about 8-15 eggs at the egg retrieval procedure.
IVF success rates correlate with the number of eggs retrieved with IVF.
There are several ovarian stimulation medication protocols that are used to "pump up" the ovaries to make sufficient follicles and eggs. Without stimulating medications, the ovaries will only produce one follicle and mature egg per menstrual cycle (month).
3D ultrasound view of multiple follicles in an ovary stimulated for IVF
A computer in our 3D ultrasound machine calculates accurate follicle sizes
A larger version of this image is shown below
All of the commonly used IVF regimens include injections of a medication containing follicle stimulating hormone - FSH. Injectable FSH products are sometimes referred to as "gonadotropins", or Human Menopausal Gonadotropins, HMG.
The most commonly used ovarian stimulation protocols for IVF are:
- Luteal Lupron protocol also called "long Lupron", or agonist "down regulation"
- Antagonist protocols that involve use of of the GnRH antagonist medications
- Flare and micro-flare protocols, also called short Lupron protocols, or short protocols are used for patients expected to have a low response to ovarian stimulation
IVF stimulation protocols in the US generally involve the use of 3 types of drugs:
- A medication to suppress the LH surge and ovulation until the follicles are mature.
There are 2 classes of drug used for this: - GnRH-agonist (gonadotropin releasing hormone agonist) such as Lupron
- GnRH-antagonist such as Ganirelix or Cetrotide
- FSH product (follicle stimulating hormone) to stimulate development of multiple follicles
- Follistim, Gonal-F, Bravelle, Menopur
- HCG (human chorionic gonadotropin) to cause final maturation of the eggs
The woman is stimulated with the injectable FSH medications for about 8-12 days until multiple mature size follicles have developed.
What is the goal of a good IVF ovarian stimulation?
With ovarian stimulation for in vitro fertilization, the goal is to produce approximately 8 to 15 follicles that will give quality eggs at the egg retrieval procedure.
We do not want to have overstimulation of the ovaries which can lead to significant discomfort for the woman and in rare cases can result in ovarian hyperstimulation syndrome, OHSS.
We also do not want the ovarian stimulation to be insufficient and only give us a few eggs if we might have been able to obtain more by using higher medication doses, etc.
IVF can be successful with a very low number of eggs retrieved, but success rates are substantially higher when more than a few eggs are recovered.
Learn more about the number of eggs at retrieval and IVF success rates
With the ovarian stimulation, the job of the infertility specialist doctor is to:
Ultrasound of multiple follicles (black areas) in a stimulated ovary
Yellow cursors outline a 15 mm diameter follicle
Most mature sized follicles (about 15-20 mm diameter)
will give mature eggs at retrieval
Using the latest 3D ultrasound technology to obtain precise follicle measurements
Quality control throughout the entire process is very important with in vitro fertilization. One of the ways that we have improved quality control in our program is by using highly specialized ultrasound equipment.
We use a GE Voluson E8 ultrasound machine with a computer built-in that can outline and accurately measure the developing follicles.
We have found that this method is more precise and reliable as compared to the traditional method - which is usually manual measurements in two dimensions.
The computer in the machine traces the borders of the follicles (in three dimensions). It then calculates a volume for each follicle. From the volume it calculates an average diameter for each follicle - as if the follicle was a sphere.
This technology gives us more accurate and reliable measurements of the follicles than we had in the past.
Ultrasound picture shows the three planes in a volume of data from one ovary
This patient is near the end of IVF stimulation - numerous follicles seen in the ovary
Upper left = sagittal plane, upper right = transverse plane, lower left = coronal plane
At lower right is a 3-D view of the follicles (generated by the computer)
See below for close up views of the same images
Close-up view of the transverse plane (from the same image above)
Computer generated tracings of follicles are different colors
Close-up of the 3D view of the follicles (from the same image above)
The computer in the machine created this "rendered" image from a captured volume of data
How is the monitoring of the IVF stimulation done?
Graph showing estrogen hormone levels during an IVF stimulation
Estradiol starts low and rises to 1000 to 4000 pg/ml by the time of the HCG injection
See a sample calendar that shows timing of office visits and IVF procedures
How many follicles do you need in order to get pregnant with IVF?
Usually, it is not difficult to get enough follicles to develop. However, sometimes the response of the ovaries is poor - and a low number of growing follicles are seen. The ability of the ovaries to stimulate well and make numerous follicles can be predicted fairly well by an ultrasound test - the antral follicle count.
The minimum number of follicles needed to proceed with IVF treatment depends on several factors, including follicle sizes, age of the woman, results of previous IVF stimulations and the willingness of the couple (and the doctor) to proceed with egg retrieval when there will be a low number of eggs obtained.
Some IVF doctors will say that you should have at least 5 follicles of 14mm or greater while others might do the egg retrieval with only one follicle. Most IVF programs in the US want a minimum of about 3-4 mature (or close to mature) follicles.
Women that are more likely to be low responders to ovarian stimulation would be those that have low antral follicle counts, those women who are older than about 37, women with elevated FSH levels, and women with other signs of reduced ovarian reserve.
Details about the long Lupron protocol - also called down regulation, or mid-luteal Lupron
Details about antagonist IVF protocols - using Ganirelix or Cetrotide
Details about Lupron flare protocols - also called microflare
Details about subcutaneous injections and intramuscular injections used for IVF
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