IVF protocols for drug and drug stimulation (2023)

  • To maximize success rates within-vitro-FertilisationWe want a good number of quality eggs from the female. We generally try to get around 10-18 eggsegg retrieval procedure.
  • IVF Success Ratescorrelate with the number ofeggs retrieved.
  • There are several drug ovarian stimulation protocols that are used to "pump up" the ovaries to produce enough follicles and eggs. In the absence of stimulant medication, the ovaries only produce and release 1 mature egg per menstrual cycle (month).
  • The commonly used stimulation regimens include injections of follicle stimulating hormone - FSH.

There are 3 very commonly used ovarian stimulation protocols for in vitro fertilization:

  1. Luteal LupronProtocol also called "Long Lupron" or agonist "Down Regulation".
  2. Antagonistic Protocolsinvolving the use of GnRH antagonist drugs
  3. Flare and micro-flare logs, also called short Lupron protocols or short protocols, are used in patients who are expected to have a poor response to ovarian stimulation

IVF protocols for drug and drug stimulation (1)

3D ultrasound view of follicles from the stimulated ovary
3D ultrasound image of multiple follicles in an ovary stimulated for IVF
Our 3D ultrasound machine calculates exact follicle sizes

IVF stimulation protocols in the US generally involve the use of 3 types of drugs:

  1. A drug used to suppress the LH surge and ovulation until the developing eggs are ready.
    There are 2 classes of drugs used for this:
    • GnRH agonist (gonadotropin-releasing hormone agonist) such as Lupron
    • GnRH antagonists such as Ganirelix or Cetrotide
  2. FSH product (follicle stimulating hormone) to stimulate the development of multiple oocytes
    • Gonal-F, Torheiten, Bravelle, Menopur
  3. HCG (human chorionic gonadotropin) to bring about the final maturation of the oocytes

The ovaries are stimulated with the injectable FSH drugs for about 7-12 days until several mature-sized follicles have developed.

What is the goal of good in vitro fertilization with ovarian stimulation?

In ovarian stimulation for in vitro fertilization, the goal is to obtain approximately 8 to 15 high-quality oocytes at egg retrieval.

(Video) IVF Protocols and Procedures - Kathleen Brennan, MD | UCLA OBGYN/Fertility Clinic

We don't want to have ovarian hyperstimulation, which can cause significant discomfort for the woman and, in rare cases, Ovarian Hyperstimulation Syndrome, OHSS.

In recent years we have used aLupron triggers to reduce or eliminate the risks of ovarian hyperstimulation syndrome
Our 2014 study of using Lupron triggers to maintain high success rates and reduce the risk of overstimulation
We also don't want the ovarian stimulation to be insufficient and only give us a few eggs when we could possibly have gained more with higher doses of drugs etc.

In vitro fertilization can be successful with a very small number of eggs retrieved, but success rates are significantly higher when more eggs are retrieved.

More about egg count and success rates of in vitro fertilization

In the case of ovarian stimulation, the task of the fertility doctor is:

  • Choose an appropriate medication protocol and dosing regimen
  • Monitor the patient's stimulation progress so that the drug dose can be properly adjusted
  • Trigger with hCG at the ideal time. Triggering too early or too late reduces success and can sometimes increase the risk of ovarian hyperstimulation (if triggered too late).

IVF protocols for drug and drug stimulation (2)

(Video) Ovarian stimulation - medications and protocols #IVFWEBINARS

Stimulated ovary for ivf
Ultrasound of multiple follicles (black areas) in a stimulated ovary
Yellow cursors outline a 15 mm diameter follicle
Most mature follicles (approx. 15-20 mm in diameter) will release mature oocytes upon collection

Using the latest 3D ultrasonic technology to get precise measurements

Quality control throughout the process is very important in in vitro fertilization. One of the ways we have improved quality control in our program is through the use of highly specialized ultrasound equipment.

We use a GE Voluson E8 ultrasound machine with a built-in computer that can chart and accurately measure the developing follicles.

We have found this method to be more accurate and reliable compared to the traditional method - which usually involves manual measurements in two dimensions.

The computer in the machine tracks the follicle borders (in three dimensions). It then calculates a volume for each. From the volume, it calculates an average diameter for each follicle (as if it were a sphere).

This technology gives us more accurate and reliable measurements than in the past.

(Video) Lunchtime Live: IVF Protocols

IVF protocols for drug and drug stimulation (3)

2D and 3D ultrasound images with all 3 planes in the stimulated ovary

The ultrasound image shows the three levels in a data volume from one ovary
This patient is nearing the end of stimulation - numerous follicles can be seen in the ovary
Top left = sagittal plane, top right = transverse plane, bottom left = coronal plane
Below right is a 3D view of the follicles (computer generated)
See below for close-ups of the same images

IVF protocols for drug and drug stimulation (4)

Close-up of transverse plane (from same image above)
Computer-generated traces of follicles have different colors
3D rendered ultrasound image of follicles in stimulated ovaries

IVF protocols for drug and drug stimulation (5)
Close up 3D view of multiple follicles in a stimulated ovary
A computer in the machine made the “rendered” image from a collected amount of data
It is obvious that follicles are not spherical

(Video) Best Ovarian Stimulation Protocols for IVF with guest Dr. Geoffrey Sher

How is in vitro fertilization stimulation monitored?

  • We try to stimulate the woman to get at least 4 follicles with sizes from 14-20mm in diameter.
  • Ideally there are at least 8 follicles between 13 and 20 mm.
  • The goal is to get a good number (around 8-15) of good quality eggs
  • Blood hormone levels and developing follicle sizes are monitored.
  • Ultrasound is used to measure the follicles (discussed at the top of this page)
  • Estrogen hormone levels in the blood are important. Estrogen (actually estradiol) levels are usually below 60 pg/mL at the beginning of the cycle and rise significantly as multiple follicles develop.
  • Maximum estradiol levels in IVF at the time of HCG are usually between 1000 and 4000 pg/ml.
  • The stimulation process usually takes about 8-10 days

IVF protocols for drug and drug stimulation (6)

Estrogen hormone levels in IVF cycle
Chart showing estrogen hormone levels during IVF stimulation
Estradiol starts out low and rises to 1000-4000 pg/mL by the time of HCG injection

  • The HCG injection is given when estrogen levels and follicle measurements look best for a successful outcome. The HCG shot is needed to initiate final oocyte maturation.
  • Theegg removalis scheduled for 34-35 hours after the HCG injection - just before the woman's body may start releasing the eggs (ovulation).

View a sample Lupron IVF calendar showing doctor visit schedules and procedures

How many follicles does it take to get pregnant with IVF?

It is usually not difficult to get enough follicles to develop. However, sometimes the ovarian response is poor – and a small number of growing follicles can be seen. The ability of the ovaries to stimulate well and give us numerous eggs can be predicted fairly well by an ultrasound test –the antral follicle count.

The minimum number of follicles required to perform an in vitro fertilization treatment depends on several factors, including their size, the woman's age, the results of previous stimulations, and the couple's (and doctor's) willingness to work with the follicle Continue egg retrieval whenever there is a low number of eggs retrieved.

(Video) Webinar - Geoffrey Sher, MD - IVF Stimulation Protocols

In our experience, IVF success rates are very low with fewer than 3 mature follicles.

Some doctors will say that you should have at least 5 measuring 14mm or larger, while others may perform egg retrieval with just one follicle. Most IVF programs in the US want at least 3-4 mature (or nearly mature) follicles.

Women who respond poorly to ovarian stimulation would be those who have a low antral count,those women who are olderthan about 37, women withincreased FSH levels, and women with other signs of reduced ovarian reserve.

Videos

1. Agonist, Antagonist or Mini stimulation protocol? How stimulation protocols may affect treatment?
(MyIVFanswers)
2. Optimizing IVF Stimulation Protocol: How to Find A Golden Egg
(Progenesis Academy)
3. Stimulation Protocols in IVF
(Shield Connect)
4. Webinar on “Ovarian Stimulation Protocols” | Medicover Fertility India
(Medicover Fertility)
5. 6 - IVF Stimulation Protocols
(Gannah Hospital Conference)
6. My Stimulation Protocol: So Many Medications/ IVF in Mexico
(The Adventures of Drew and Amanda)
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