What are individualised IVF protocols? Antagonist, agonist and mild stimulation classes, adapting the plan to the response, and the limits of the evidence.
Individualised IVF protocols mean adapting the ovarian stimulation medicine plan to your characteristics and to the response you give to stimulation. Here, "individualisation" describes the plan being adjusted for you by the doctor; it is not a separate method that guarantees the outcome. The information below offers a general framework and does not replace a diagnosis or treatment recommendation specific to you.
What is an IVF protocol?
A protocol is not the name of a single medicine, but a plan made up of several parts. The medicine that stimulates the ovaries, the group of medicines that prevent early ovulation, the trigger that brings about the maturation of the eggs, and how the embryo transfer will be done are parts of this plan. Throughout the process you are monitored with ultrasound and, when needed, blood tests. The names, amounts and durations of the medicines differ from person to person and are determined by your doctor.
What does the antagonist protocol mean?
In this plan the medicine that prevents early ovulation comes into play later in the stimulation. According to current guidelines on this subject, the antagonist group is included, as a strong recommendation, for those in whom a strong response to stimulation is predicted; but the data supporting this recommendation are still very limited.
How are the long and short agonist protocols distinguished?
In these plans, the group of medicines that prevent early ovulation is of the agonist type. They are called long or short depending on how long before stimulation the medicine is started. Which type will be used in which person is determined according to your history, your previous response and your doctor's assessment.
What do mild stimulation and the natural cycle mean?
In mild stimulation a smaller number of eggs is aimed for by using less stimulation medicine. In a natural or modified natural cycle, the egg that develops in the person's own cycle is made use of, and stimulation is either not done at all or stays very limited. Your doctor decides which of these approaches is suitable.
By which indicators is the plan suited to you determined?
To estimate the response you will give to stimulation, the number of small follicles counted on ultrasound or the AMH level in the blood is looked at. Current guidelines on this subject recommend these two indicators, but the data they rest on are very limited. The same guidelines do not recommend using age, body mass index and some basal hormone measurements to predict the response. Although the follicle count and AMH describe the response of the ovary, they are not recommended for predicting pregnancy or live birth; that is, ovarian reserve shows the response, it does not determine the outcome. Your age and body mass index, on the other hand, are counted among the predictors of pregnancy and live birth. The response in a previous cycle is also important data that influences the plan.
How does a very strong or a limited response affect the plan?
Your ovaries responding very strongly to stimulation can increase the risk of ovarian hyperstimulation syndrome (OHSS). When the response remains more limited than expected, whether to continue the cycle is discussed with your doctor specifically for you; according to current guidelines on this subject, a low response is not on its own a reason to end the cycle. For those in whom a high response is predicted, a lower starting plan is probably recommended; for those in whom a normal response is predicted, changing the starting plan is probably not recommended.
Can your protocol change during treatment?
During monitoring, the ultrasound and hormone results show the course of the plan. According to your response, the medicine plan can be adjusted, the time or type of the trigger can be changed, and postponing the transfer can be considered. For this reason, even under the same protocol name, the process of two people can run differently.
What does the evidence say?
Most of the recommendations in the current guidelines on this subject rest on data of low or very low certainty. For this reason it is not possible to say that one class of protocol is better for everyone. Adapting the plan to you makes it possible to take the risks into account; but there is no strong evidence that this additionally increases the chance of pregnancy. Add-on medicines such as growth hormone and DHEA are also not recommended in people with a normal response in current guidelines.
How are the trigger and the time of transfer determined?
The type of trigger and the time of the transfer are also part of the protocol. On the type of trigger and the freezing of embryos, current guidelines recommend a combination for people at risk of OHSS. The details of this combination and who it will be applied to are discussed with your doctor; the freezing approach has not been recommended as the usual practice in current assessments.
What can you ask your doctor when discussing your protocol?
- Which indicators are being looked at to predict my response?
- If I have had previous cycles, how does this plan differ from them?
- Which findings during monitoring could change the plan?
- What is being considered to reduce my risk of excessive response?
- How will the time of the trigger and the transfer be determined?
What side effects and risks can there be during stimulation?
Bloating, headache and mood changes related to the stimulation medicines may be seen. OHSS in a high response, the cycle not being completed as planned in a low response, multiple pregnancy if more than one embryo is transferred, and clotting problems are important risks.
Frequently Asked Questions
Is a natural cycle recommended for a person with a low ovarian response?
According to current guidelines on this subject, a modified natural cycle is probably not recommended as the usual choice over classic stimulation in people with a low response; this is a conditional recommendation. But it can be used if your ovarian reserve is very low. Your doctor determines which approach suits you.
Do I need to bring the results of my previous cycle?
Yes, records showing your response in previous cycles are useful: the medicine plan, the monitoring ultrasounds, information on the eggs collected and embryos formed, and your history of overstimulation if you have had it. These help your doctor to structure the next plan.
In the agonist type, is long or short preferred?
Current guidelines on this subject recommend, if an agonist is to be used, that the long protocol be preferred to the short or very short protocol; this is a strong recommendation, but the data it rests on are limited. Whether to use an agonist or an antagonist is a separate decision and is determined with your doctor according to you.
Does an individualised protocol guarantee the outcome of pregnancy?
No. It is the adaptation of the plan to your characteristics and your response. There is no strong evidence that it additionally increases the chance of pregnancy.
Is a protocol made up of a single medicine?
No. The stimulation medicine, the group of medicines that prevent early ovulation, the trigger that brings about maturation and the transfer plan are dealt with together.
Does treatment proceed in the same way for everyone using the same protocol?
No. The plan can be adjusted according to your response as seen from ultrasound and hormone results. Even under the same protocol name, processes can differ.
Do AMH and the follicle count show my pregnancy outcome?
No. They are used in assessing the response of the ovary; they are not recommended for predicting pregnancy or live birth. That they show the response does not mean that they determine the outcome.
If my ovaries respond poorly, is the cycle necessarily ended?
No. A low response is not on its own a reason to end the cycle. The decision to continue is discussed with your doctor specifically for you.
If a high response is expected, can the starting plan be different?
Yes. A lower starting plan is probably recommended. For those in whom a normal response is expected, changing the starting plan is probably not recommended.
Is there a single protocol suitable for everyone?
No. Most of the recommendations rest on data of low or very low certainty. It cannot be said that one class of protocol is better for everyone.
Are the time of the trigger and the transfer also part of the protocol?
Yes. The type and time of the trigger and the postponement of the transfer can be assessed according to your response. The freezing approach is not recommended as the usual practice for everyone.
Is adding growth hormone or DHEA recommended in people with a normal response?
No. Current guidelines do not recommend these add-on medicines in people with a normal response.
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