What is Mini-STEM or Minimal Stimulation IVF and should you be considering it? When it comes to Mini-STEM, Modified, Mini-IVF, Minimal STEM, Low-Cost, Low-Complexity, there’s a lot of different words people will throw out there.
In order to understand IVF and in order to understand Mini-STEM you have to understand the concept of ovarian reserve. If you imagine a vault inside your ovary where all your eggs are kept. When you’re born, that vault is full and throughout your life, eggs exit the vault. And when the vault is empty, now you’re in menopause. What actually happens is each month, an entire group of eggs each comes out of the vault. Each egg grows inside a follicle. Your brain in a normal month would send out follicle stimulating hormone, a well-named hormone, to stimulate one of these follicles to grow. The egg matures and ovulate and the rest of them die. And the next month, another group is released.
Now what is interesting is the more eggs you have in the vault, the more that come out every month and the fewer eggs that you have remaining, the fewer come out every month. And so, evaluating the eggs outside the vault is called evaluating your ovarian reserve. This can be done with an ultrasound measurement of counting the follicles.
You can actually see those on ultrasound. And that’s called an enteral follicle count or an AFC, or with a blood test called AMH or anti-mullerian hormone. Why this is important is that if we try to simplify any type of stimulation, IVF in a nutshell, all I can do is get all of the eggs that are outside the vault to grow.
And those are the ones we are taking out of the body with the egg retrieval, fertilising them with sperm, and then making embryos and either transferring or freezing or doing genetic testing. So that part is in vitro fertilisation. All types of IVF require eggs coming out of the body with an egg retrieval and being combined with sperm in some form or fashion to make embryos.
Now, depending on your age, your medical history, and your ovarian reserve, there’s different protocols or combination of medications that we use to get the eggs outside the vault to grow. Meaning if you have more eggs, you need to do something different than if you have less. And that makes sense.
If I’m trying to get 30 eggs to grow, I’m going to do something different than if I’m trying to get three to grow. So truly the idea of a minimal stimulation protocol is that I can stimulate you with less medication, less total dose, and still get eggs to grow. So, in my mind, in the perfect world, it is one of your protocols that as an IVF doctor, you would utilise and not a selling or a marketing point.
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So, types of mini or modified, you might hear it, minimal dose, minimal stimulation, mini IVF, modified IVF. There are a few different words that people use.
In general, you are going to be requiring less medication if you have fewer eggs. Makes sense because there’s only so many FSH receptors. So, if you don’t have 30 eggs, you only have three.
Can I get away with using less because I’m only trying to get three to grow? That’s the hypothesis. Now, how do we do it? Well, there’s a true natural cycle, which is just following the one egg that you have and we take it to retrieval.
That is an option. If you are not going to be able to stimulate and get more than one, then there’s many STEM, which can mean a lot of different things. But in most studies, it means using either a pure gonadotropin dose of less than 150 units or using just letrozole or just so oral agents that increase the release of FSH or a combination of both of them, but still a lower dose of gonadotropin every day.
And that’s in contrast to conventional IVF, where you’re using FSH plus typically an FSH LH combination or a higher dose gonadotropin total. Most conventional stimulation protocols started those closer to 300 total units a day versus mini-STEM at 150 or less units a day.
There are places that are telling you that minimal stimulation IVF is giving you better quality eggs. There is zero evidence to support that because the eggs are the same as they’ve been exposed to your same environment.
The only thing that’s different is the small dose of medication over less than two weeks of time. And that is not changing their quality. Quality is related to genetics. Genetics are related to age. So, it couldn’t save you money potentially.
Is it making your eggs better quality? Absolutely not. So that is a marketing play where people will say mini-STEM is better for you. It’s more natural.
You have better eggs and there’s zero evidence to support that. There is evidence to support the fact that for patients who are poor responders doing a minimal stimulation protocol likely yields you the same number of eggs and the same amount of elasticity as a conventional stimulation protocol. It’s typically a Clomid FSH overlap.
And the important thing to remember here is that studies have not shown that minimal stimulation is beneficial unless you’re a poor responder, meaning I don’t need as much dose if you don’t have as many eggs. So, they’re equal for the stimulation. Many STEM doesn’t have a higher chance of giving me a baby, doesn’t have a higher chance of giving me better eggs.
But if you have a higher egg count number, and now I am skimping on your stimulation, you’re going to walk out of there with fewer total eggs, fewer embryos, because you purposefully under-stimulated somebody. Now there are times when you choose to do this with proper counselling, and a really good example is InvoCell. InvoCell is a small device that some clinics use with a minimal stimulation protocol. With the InvoCell, you still go through the medications, the hormone shots, and you still do the egg retrieval. But then you put egg and sperm together in this device and incubate it inside the vagina, and then pull it out five days later, take an embryo and transfer it and freeze if there’s any others. The reason why InvoCell is combined with many STEM is one, to save money, but two, the device only holds eight to 10 eggs, so I don’t need 20 eggs.
If you have unexplained infertility, if you have male factor infertility, if you’re older and you need genetic testing, or you’ve had recurrent pregnancy loss, we don’t want InvoCell for that. It’s really fabulous for a PCOS patient who’s not responding to oral medication alone, and it can be really great for somebody with tubal disease who is younger.
Even if conventional IVF is costing more money, it is yielding them with more embryos and therefore more opportunities to grow their family. Well, the cost analysis, because the pregnancy rate is lower if you’re getting fewer eggs, is that mini-stem doesn’t save you money. It might save you a per cost basis, but the rate of success per cycle is so much lower that it doesn’t save you money overall.
We believe with my mini-stem protocols and patients who are older, 35 and older, that we should be doing genetic testing of embryos. We want to get you to that highest success rate possible, which is a genetically normal embryo. And if you’re older, your age is a barrier that we need to acknowledge.
The clinic’s getting money because you’re doing lots of cycles and lots of transfers. You as a patient are getting opportunities to get pregnant with the transfers, but this is not a yes, no situation. Meaning if you’re not pregnant and you can turn around the next month and do it again, fantastic. But what we find is you might get pregnant and miscarry 3-4 months later. And now you’re out of trying for a substantial period of time.
So, we are more quickly banking cycles to try to get you to your child goal versus waiting on these potential miscarriages in between transfers. One is that it was set up not to reflect modern practise, meaning people who went through conventional IVF had a double embryo transfer and people who went through mini-IVF had a single embryo transfer. The primary outcome was like birth rate after treatment. And so, when the conventional IVF group under that double embryo transfer, not genetically tested arm, the cumulative live birth rate was 63%.
The mini stimulation group, the cumulative live birth rate was 49%. These were both relatively good birth rates for IVF. However, it was significantly higher in the conventional IVF group. And so, the take-home message here is this. On a per cycle basis, mini-stem IVF might save you money.
It does not result in the same pregnancy rates as conventional IVF. It potentially is a protocol strategy your team may use. It should be proceeded with caution in anybody with normal or high ovarian reserve.
You need to be discussing expected embryo yield per cycle based on the protocol and the marketing strategies that promote better egg quality with less gonadotropin exposure is false. There’s no evidence to support that. There has been prior evidence that high gonadotropin dose may be associated with a lower live birth rate and a fresh transfer cycle, which we know.
And that’s why we do a lot of freeze all cycles. But when we’re talking about does that negatively impact the eggs? No, it impacts the endometrium negatively. And further higher gonadotropin dose has not been associated with differences in rates of euploidy or genetically normal embryos when you do IVF.
So if your team is saying conventional dose IVF is the right thing for you based on your ovarian reserve, that’s what you should do because the success rate of IVF is going to be higher. The more eggs that you can get.
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