How does being compliant with your treatment plan impact the outcome of your treatment?

Senior Physician, PhD, MPG Kathrine Birch Petersen

TFP Stork Fertility/Gynaecologists Birch and Eriksen

In the medical world, we use terms like compliance and adherence. Can you explain a bit more about what this means?

These are words used to explain how good patients are at following the treatment a doctor has prescribed them. It describes how good you are at taking medication but also how you treat yourself. For example, diabetes patients - how do they manage their diet in addition to their medication? If you have had a new knee or hip operation, how good are you at sticking to your rehabilitation plan? For fertility patients, it describes how good you are at taking your fertility medication at the correct times and in the right dose. So everything is related to the treatment of specific conditions.

So how do you make sure patients are compliant?

You have everything explained at the clinic, but often things go wrong anyway.

It's not easy to understand everything, and you have to deal with a lot of information in 10 minutes. Also, in terms of starting to take a new medication, you don't know how to mix it, how to take it, you haven't tried to inject yourself in the stomach before, and for many people to have to inject themselves in the stomach is a difficult step that has to be taken. That's why it's essential that you also have written instructions when undergoing fertility treatment.

What does it mean if a patient is not compliant with treatment?

It can get a bit technical, so hang on.

In fertility treatment, part of the medication is something you take via injection, and for many, this is a high dose. This is because when you need more follicles per ovary, some little receptors sit on the ovaries that have a threshold. You need to go above that threshold for the ovary to produce more follicles.

We observe that if the patient does not take her medication at the same time every day, the level of medication in her body drops below the threshold and then there is a risk that the patient does not get the maximum benefit of the medication.

Imagine a level in your body - that needs to be constant - you ensure this by being compliant with the medication treatment.

Another reason is that timing is generally important in IVF treatment. A good example is egg retrieval. It has to be timed very precisely. If you miss the time window for your ovulation shot, it affects when the eggs mature and when the clinic can take them out of the ovarian follicle.

That's because the egg (the little oocyte) sits in a little mound of cells in the ovary and is surrounded by cells that ensure it holds on really well to this egg. The ovipositor loosens these cells. So when we apply the needle, it creates negative pressure, enabling us to get the egg out. But if the patient is 2-3 hours late with their ovulation syringe, we have to reschedule the egg retrieval.

Another good example is the injection taken after a few days of stimulation. It is a shot that helps to prevent you from ovulating prematurely. It should also preferably be taken at the same time. Because if too much oestrogen is produced, it triggers the brain to start ovulating. That's exactly what the injection you take here is meant to suppress. If you miss it by a few hours, you risk the body continuing and ovulating.

Are there any statistics on what adherence means for treatment outcomes? If I take my medication 15-20 minutes late once or a couple of times, does that mean I have ruined my chance of succeeding with this treatment?

One of the best studies is from Human Reproduction Update (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576003/). It's a Dutch study that's from 2013 and sees almost 15,000 patients. The study shows that, generally, fertility patients are good at being compliant. About 78% follow their treatment over three cycles on average.

But the study also shows that after the 1st cycle of failure, the ability to be compliant drops. The more treatments you have, the worse you become at complying with medications and instructions.

In relation to whether it matters for the chances of getting pregnant, the study shows that if you take your medication as you should, you have a 15% higher chance of getting pregnant than if you do not follow your treatment plan exactly.

What categories/medications should be taken on the second (and why), and what can you be a little looser without ruining your treatment?

You can be relatively more relaxed with Progesterone, which you take when you have eggs. You can be a little loose on timings here because you typically have to take it three times in one day, so it's easier to meet the threshold.

Anything else that's important to point out?

What's important to include is that if you're receiving instructions before starting the fertility treatment journey, it is absolutely essential to ask any questions you may have or about anything you are unsure about. This is where using apps as a tool to remember your medication and how to take it can be helpful.