Podcast (Transcript Below)
Georgie Kovacs, founder of Fempower Health, interviews Sylvia Kang, biomedical engineer and co-founder/CEO of Mira.
Georgie: before the discussion we’re going to have about hormones, I thought we could start with your background and how you became interested in women’s health.
Sylvia Kang: I’m the co-founder of Mira. My background is a master’s in biomedical engineering from Columbia and a degree from Cornell. I have so many friends like me. We are women, have advanced careers and tend to pursue motherhood later in life. Because of our advanced maternal age, we encountered limited information about women’s bodies during this season. When you get to the point where you want to begin to have a child and see no results, even doctors may not give you answers about what’s wrong. Eventually, you end up doing IVF.
I look at this situation and see a gap. If we could have a tool to help us know our bodies better and be more aware, we can be more mindful about what’s going on and make important decisions. These decisions can be more educated and happen before it’s too late. This gives the woman much more control and helps monitor their expectations about how long it could take.
I work with partners and we responded to this opportunity.
Georgie: there are over 100 reproductive health apps out there. I’ve made the transition in that language (instead of a “fertility tracking app”). A lot of these track the fertile window. What might be helpful is to broaden this and educate women on the intricacies of how the body works.
I’d like to start with the baseline: a lot of people have the myth that it’s a “28-day cycle,” which it’s not. Maybe you can talk about that cycle, which hormones are present and what role they play throughout that cycle.
Sylvia: the 28-day cycle is definitely more a myth than a rule. This concept has been around for about 20 years, when we didn’t have a lot of stats or tools to track the cycle range. 28 was established as an average. However, every woman and every cycle is different.
Cycle length is just the tip of the iceberg to understanding what’s going on in your body.
At the beginning of the cycle is right after your period. This is where FSH (follicle stimulating hormone) is released from the hypothalamus in the brain, which regulates your pituitary system. The FSH stimulates the growth of the follicles in your ovary. Every month, you have many many follicles in your ovary. They are preparing to be mature. Not every follicle will mature. When FSH rises, it stimulates the growth of those follicles. The follicle grows to a certain point, at which time estrogen is released. This indicates you are in a fertile window. Estrogen tells you a lot of pathological information. Your OBGYN will look at your estrogen to assess a lot of things. This estrogen rises as the second hormone and triggers a luteinizing hormone (LH). Most ovulation predictor kits measure this hormone.
LH allows the egg to come out from the follicle. This occurs during a precise timeline but differs from woman to woman. Typically, the LH surge will happen 12-24 hours before ovulation. A lot of fertility testers use this hormone to indicate when ovulation is about to happen.
After the egg is released, the fourth important hormone is progesterone, or PDG. When PDG rises, it prepares the uterus for pregnancy. It thickens the uterus lining because the fertilized egg will need to attach to something. The function is to create a nice environment for the egg to grow.
If your egg is not fertilized, no egg attached to the uterus wall, the progesterone will start to drop. During this, the thickened uterus lining will shed. These tissues become the bleeding you see in your period, which is the start of your next cycle.
This sounds like a complicated process. There is something that we as women should understand. The cycle is composed of a lot of steps. Your body is working like a symphony. Every hormone you can think of as a musical instrument. They have to work together and with certain spacing between them. This happens in a beautiful, natural way. There is a pattern.
Many women have conditions that make it difficult to conceive, such as lifestyle considerations or age. Understanding the period will help you understand the cascade of events. You want to understand the hormones and their relationship with each other.
Georgie: so, we’ve broken down what the main hormones are. It’s clear that, like an orchestra, they have to play together.
Let’s talk about the impact if their interconnection is imbalanced.
Sylvia: the most common issue may be PCOS. There are many causes and symptoms of PCOS. One important matrix the doctor uses to diagnose PCOS is the ratio between LH and FSH. Many women who have PCOS will have elevated LH levels.
LH is not a straight line, it has a peak. The function of the LH surge or increase is to release the egg from the follicle. If you have a peak, you have a baseline. Your very low baseline may be between 5-10. If you have PCOS, your baseline may be more like 40. This ratio becomes bigger if you have PCOS. When your LH is higher, that will impact other hormone levels.
If your hormones are not in place, ovulation may not happen.
This is also why a lot of women who have PCOS use OPK testing. This marker may not be able to tell you how high your hormones are and how fertile you are. It’s a subjective threshold based on population averages.
Another interesting to look at is estrogen and LH. LH helps you understand when you are peaking, when ovulation is triggered. Once that increases, you may have an egg release within 24 hours. With that fresh egg, you have a high chance of getting pregnant when you have sex. But, estrogen is quite important too. The estrogen rise overlaps with your fertile window.
Estrogen rises 4-5 days before your ovulation. At that time, you are fertile. The key is that the sperm, if you have good quality of sperm and mucus, can live inside the woman’s body for four days. This means that you still have a chance during the early days before you even have an available egg. Your fertile window could be four days before ovulation until the 24 hours after ovulation itself. This is why tracking your hormone levels at home helps you understand your full fertile window or full infertile window.
Some publications say that after ovulation, you have lower and lower chances of getting pregnant. This is because the quality of the environment peaks and then quickly decreases. You need to know your ovulation before it happens. This is determined by the relationship between those two hormones.
Georgie: that’s a good clarification how, when these hormones are not in sync, a woman could be impacted.
I remember I used trackers and got the strangest phases-flashing, not flashing-and thinking that I wanted more data-driven information. According to the things I could test, it wasn’t enough. Clearly, tracking basal body temperature and cervical fluid and the position of your cervix are really helpful. Those charts can be difficult to interpret if you’re not an expert.
While there are a lot more resources, that can be a great way of forcing women to understand what’s happening in their bodies.
It may seem like it’s about fertility, but understanding these hormones addresses diseases, issues and conditions.
Because you have a biomedical background, help us understand how these different apps and devices measure information.
What are the benefits and potential concerns?
Sylvia: from my perspective, it’s a good thing that there are so many products on the market. We are seeing more awareness in this area. Many people are tracking different things and constantly trying to make it more accurate and more convenient. Those are the most two important things for any tracking tool.
The most familiar product type may be the app. An app tracks your period. You enter the date and average cycle. It will calculate based on population average. That’s good if you’re just tracking your cycle. For example, if you’re a teenager or if you want an alert for an irregular period. That doesn’t give you too much detail.
One scientific study says that for accuracy, you need to track your period for more than 12 months.
Thermometers are another kind of tracking tool. There are a few kinds. This is quite convenient. The problem is that your temperature rises after ovulation. If you are seriously trying to conceive and capture your fertile window, that will only tell you it may be too late. If you decide to measure temperature, which is a good thing and will bring awareness, you want to measure something that’s not being impacted by the environment. Skin or skin surface temperature is not a good reading. You need oral or vaginal readings.
For basal body temperature, you have to test at rest. You need to not move for four hours before testing. If you do it first thing in the morning, you shouldn’t go to the bathroom at night or take care of kids or move at all. Before any movement, you should test. That will eliminate some environmental factors.
The biggest category is the OPK. Most OPK only detect LH. That’s a good thing because that hormone controls almost everything in your cycle. You can see that it is a root cause for why your cycle happens. Temperature and mucus are the consequences. That’s your body responding to the hormone. It’s a good thing to detect. The drawback of OPK is the fixed threshold. That’s why you sometimes get confusing results. Sometimes it’s positive, sometimes it’s negative and it can be hard to see what’s really going on. When you’re above a certain threshold doesn’t necessarily mean it is ovulation to you. It’s ovulation for the population average.
We as the Mira team are trying to get you numeric hormone concentrations so you can see your hormone curve. The most important thing is the package: all of your numbers are relative. Surge has to be compared to a baseline. Seeing this is the most important thing.
Other categories of products include things like electrolyte testing and viewing samples under a microscope.
I wouldn’t solely rely on a tool to give me an ovulation window.
There are also people who are trying to observe ovulation naturally. They’re looking at cervical position change, mucus change and how weak or soft the cervix is. These make you pay attention to your body. A big move that has to happen to get women to conceive is to pay more attention to our bodies: knowing what we’re looking at and how we should understand it.
Georgie: I agree about tracking over time. In monitoring a lot of the women who are posting screenshots of results, some panic when they don’t know what’s going on with their body right away but it’s only their first month using their app or device. It takes a few months.
One question I wanted to touch on before we get into the algorithms is these apps that are using the “pee on the stick” method. When these sorts of things came out a few years ago, there was discussion from doctors about how they’re not as accurate as a blood draw.
Can you tell us about the value of that kind of at-home test versus a blood draw?
Sylvia: the first part is, are we really measuring the correct sample? That is measuring urine. At the lab, your doctor is doing blood work. These are different. The difference is not significant enough. Physiologically, most hormones exist in the blood and also metabolize in the urine. Most urine tests measure the hormone in the urine.
A lot of papers are published about the correlation between blood tests and urine tests. The accuracy really depends on what your goal is. What are you trying to understand? You can easily identify surges and patterns with home tests. You see changes and trends and that’s significant enough to detect ovulation and the fertile window.
From a scientific perspective, urine tests would be accurate enough to understand ovulation.
Second, the OPK. This tests the metabolized hormone products in urine. Personally, I don’t think it is accurate enough. Doctors won’t endorse it. They will only endorse blood work and ultrasounds. The biggest reason they won’t is that OPK is a binary product. If you assume that a hormone ranges from 0-100. At the baseline, you’re climbing up a mountain and get to ovulation and get to 50-60. Then, your hormone will come down. This is a bow-shaped curve. OPK won’t be able to tell you this. It will draw a line. You’ll get “about 10” and get positive, “about 20” and get positive, etc. For negative, it’s the same. Maybe your hormone levels are low, beneath their threshold, and you’ll think your window has passed.
When our eyes look at a picture, it’s very colorful and you see all of the detail. But when you translate this in black and white, you lose all of the perspective and resolution. That’s what an OPK does. Also, for an OPK to work, it has to have a fixed-number threshold. It’s not dynamic, flexible or adjustable. We know that population averages don’t apply to everyone.
OPK is a good option for you to get certain understanding through your cycle. But, the scientifically reliable data needs to come with numbers. Your numbers are relative and have meaning.
Georgie: I can’t tell you how many times I see someone post a pregnancy test with the question, “do you see a line? Is there a line?” Tell us about the faint pink lines versus the bright pink lines. How does all that work?
Sylvia: in an ovulation test, a really faint line probably means there’s no ovulation. You’ll have to follow the manufacturer instructions. To say it’s really ovulation, it needs to be at least as dark as the control line. Sometimes there’s a fluctuation. If you don’t have hormones in your urine, it could still show a little pink on your test.
If this comes to pregnancy, it may be a little different. Pregnancy is a very complicated process. There could be a really early pregnancy that got lost. You do have a fertilized egg but it gets lost at an early stage. The majority of the reasons for a biochemical pregnancy or miscarriage is genetic issues. This can happen more the older you are.
Georgie: it would be helpful to better understand the algorithms. I understand that the information is only as good as the data that’s being entered. How do we understand what the algorithms really mean? My sense is that, over time, the data gets better, but it’s still contingent on the data. Not every woman can look at the marketing and understand if one algorithm is better than another. As women evaluate what's right for them, how can they be more in-the-know?
Sylvia: there is a difference between evaluation and prediction. It needs baseline data. Where that comes from is important. How accurate your measurement is sets a foundation. It also depends on how well the algorithm is written.
Many apps claim to have great algorithms but the biggest gap is probably where the data comes from. As we talked earlier, it will only record your period. That’s a black box. What the algorithm can learn from that is minimal. It will get slightly more accurate over time.
What we really need at this moment is a good way to interpret data. The algorithm learns from positives and negatives and quantity of information. The learning will be more effective with better data input.
Georgie: sure, it’s so hard to pick between two companies making the same claim. From what I’m hearing you say, it’s really about inputting data, tracking over time and some of the AI behind these systems. Even though we may not understand, we know that the more information we share and the way things are being measured is different.
My takeaways from today are that there are a lot of great apps out there. Women are better assessing their bodies. When I was younger it was as basic as, “you get a period.” All of these apps and devices play a role but it depends on the information you’re trying to gather.
I’d like to close by asking: what drives you most with what you’re doing?
Sylvia: there should be more accurate, easy-to-use tools to help women understand what’s going on with their bodies. Many women lack awareness about their cycle. Women experience a lot of anxiety and doubts. I’m passionate about solving that. We need to find solutions. Even small solutions, but we need to gradually move in that direction.
We need more clarity. Once you have data, you know what’s going on and will become less anxious.
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