Georgie Kovacs, Fertility4Me: before we get into Pearl specifically, tell us about your background.
Leo: I am a scientist. I completed my PhD at the University of Cambridge in the UK working in biosensors and how we could bring photonics and light technology, or camera detection, into the biomedical field. So, that’s my background and where I come from. Then, I turned that into trying to find applications for it. One of them was fertility and measuring hormones with urine tests and that’s how Pearl actually developed. One has to use spectrometers in labs to measure substances on liquids and those machines are very expensive. I bought one of them. I was thinking, “that machine has everything you find in a smartphone except the light splitters and the prisms.” I got to work with programming built the first prototype of the Colorimetrix technology and that’s what I bring into fertility today.
Georgie: So, tell us in simple terms what Pearl does and what’s different about it.
Leo: Pearl is a mobile app that uses the current technology of transforming smartphones into measuring devices. Very simply, it takes pictures of hormone test strips. These tests change color when they’re exposed to certain hormones and concentration. Depending on the color, it indicates a change in concentration. These strips already exist, you can buy them in every pharmacy. What Pearl does differently is that it can measure the hormone levels in between the levels of coloration. Instead of having only positive, negative, happy face, sad face results, you can get a hormone level based on your relative, daily hormonal baseline. We teamed up with fertility specialists. We work close together with endocrinology centers here in Germany and clinics that help women with conception. This helps us understand and apply this science into the hormonal profiles for better understanding of the menstrual cycles.
Georgie: you mentioned that some of your female colleagues at Colormetrix were so excited at being able to understand their hormone levels and some patients who were able to associate, maybe, why they had a headache on a given day with a change in a hormone level. Maybe you can talk more about that and the types of hormones being measured.
Leo: we measure three hormones: FSH, LH, progesterone. We can measure them every day and how they change along the cycle. We have users and participants testing the app. They immediately started noticing how these changes were affecting them every day. You get comments, “you look happy today!” And they can say, “funny, I’m on my LH peak.” We found interesting science out there related to hormones and how they shape the day. There’s a study on opera singers. They started measuring the height of the notes (the pitch) and correlated that to the hormone levels. They found out that when they’re at the peak [LH], they could reach higher notes. That was mind-blowing. They really do affect everything! We kept researching and found that a lot of things related to emotions or physiology are also related to the hormone levels. Now, we have participants testing the app that see the correlation between hormones and their feelings. All of these little events in life are becoming explainable or at least relatable to something that is known that is happening physiologically [hormone fluctuations]. If you can see the hormone levels and how they’re changing and find for yourself your emotions and how they relate, it’s very personal. We try to provide this personal insight of what hormones look like for each user, who can then make their own conclusions. Of course we do proper research to find more correlations but correlation doesn’t mean causation.
Georgie: does this allow women to be able to know if they’re ovulating and/or pregnant?
Leo: definitely ovulation. It’s well known that after an LH peak, and plenty of research to back this up, that the egg is released 24 hours later in an ovulatory cycle. You can test with progesterone and confirm that after the LH peak there was, very likely, an ovulation. One thing that we also do very differently at Pearl is that we account for all of these instances where they cycle changes. We programmed in, for example, those 24-hours, AND the statistical variation of that prediction, to show the ovulation day. Sometimes it’s hard to explain to the lay user why [ovulation prediction] moves and changes. There are so many apps out there that count the cycle length and do averages. They compute ovulation based on those averages. The thing is, they are not communicating the actual variability of that observation. For a cycle length estimation, that could be up to 3.5 days. That means it could be 3.5 days off (or 4 days or 2 days, depending on the person). We included those factors in.
For pregnancy, we have an option to tell the app whether they are pregnant or not. We are working on a pregnancy mode. Once you tell the app you are pregnant, it transforms into a pregnancy guide. We don’t measure pregnancy tests. Not because we can’t but because you’re either pregnant or not. And to make the app certified to be able to confirm pregnancy is a long process that takes quite some regulatory steps.
Georgie: this is more than just an ovulation test. It’s informative to tell you what’s going on with your body and also help you understand when you’re ovulating.
Leo: another feature we have in the app is the FSH test. Not many people know, but the FSH starts changing far before ovulation. It’s more accurate than just calculating cycle length and can make a good prediction in advance of when the ovulation is going to come. This is important for women who are trying to conceive. The days 2nd, 3rd, and 4th (before ovulation have the highest chance of conception. Many studies agree that those are the days with the highest chance anyway. By knowing this in advance, couples can maximize their chance to get pregnant.
Georgie: I do get confused with so many apps predicting the fertile window. Some will say they give you more fertile days. To me, who’s been in this space for over 10 years and dealing with my own fertility, there’s a fertile window... period. I don’t think an app can cause you to have a longer fertile window. I’d love to get your perspective in terms of what women are being told about this and what you would like to correct about that.
Leo: that’s right. I find it hilarious. “We give you more fertile days,” but they don’t really explain what the fertile days are. There’s an agreement in the community that the fertile days are those with the highest chance of conceiving. But then we don’t agree on what is high or what is not high. From studies, we know that when the chances get higher than 5%, you have the best chance of conception, starting from day 6 or 7 before ovulation, there are 8, maybe 9 days. These are probabilities. These studies count how many women got pregnant after having intercourse during those days and correlate those days with the pregnancy information. Those are statistics, of course, The fertile days and the fertile windows are very particular for each woman independently of the studies. The truth is that the fertile window depends on the survival of the gametes, how long the ovule lives and how long the sperm can survive in the uterus. Of course that changes from individual to individual. Roughly, statistically, those are the 8 days of the fertile window. Pretty much every study finds that [8 days] but you can’t really extend those days.
Other products out there, for example, ovulation tests (LH or LH combined with estrogen), Interpret when they are positive, as high fertility. It doesn’t mean you are more fertile or are ovulating “more” those days, it means that the hormones have reached a certain high. That means, typically, that ovulation will come within 24-hours. You roughly know that you are probably one day before ovulation or 2. If you compare that to the fertile window extension, you are in a place along the cycle timeline where the chances are high, yes, but that doesn’t mean you have extended the fertile window. It just means that, statistically, you have a certain chance of getting pregnant.
Georgie: what would you say has been your greatest barrier on this journey?
Leo: the regulatory frameworks. We are based in Europe—in Munich, Germany—so we have to play under the European medical regulations. Funny enough, LH and FSH tests are regulated in Europe. So, we have to go through the hurdle of doing quality assessments, reporting statistics, performance, and safety very thoroughly, in order to get our certificate. This is the equivalent of having an FDA registered product in the US, but LH and FSH tests are exempt in the US. It was a big burden but we finally reached the end. Getting the commercial side has been a journey too. The app itself is also released and registered as a medical device because it reads the tests. It’s listed as a proceptive device, this means to help to get pregnant, it’s not subjected to direct enforcement (it’s listed as unclassified). And in Europe It’s probably the first app to be certified as a proceptive device . Now, we are trying to reach out to as many people as possible, continuing to conduct studies, and find out more information about how hormones influence our bodies and emotions. I observe and listen to my female colleagues' feedback to come up with better features.
Georgie: one challenge I might also bring up is not necessarily for Pearl fertility but for women. These hormone levels, when they see, “oh, I have a headache today because of this,” or, “I’m sad because of that,” is how much diet and exercise and toxins and stress all impact these hormone levels. I don’t think that medicine has caught up to these diagnostics. Even if women do find these changes in hormone levels, I think it would be very difficult to find a clinician who could then say, “because of this, you should try X-Y-Z.” I’m not saying they’re not out there but it’s not in their training. Certain specialties, like naturopaths or acupuncturists, may have more knowledge. The challenge is how to solve for what one finds.
Leo: that’s correct. Currently, Pearl doesn’t provide diagnostics but just information. We talked about the scientific principle of correlation and causation. There is a lot of misinformation and it’s a big challenge to fix that. Yet, having a tool such as Pearl that allows you to see hormone levels and allows everyone to take a step forward in understanding what impact these have is a step forward. One of the things we get asked about is PCOS. It’s known that two out of three different criteria must be diagnosed to have it. One of them is the follicle cysts in the ovary, that alter the natural hormone levels and ovulation. Because it’s hard to measure hormones every day in the lab, an app like Pearl could be effective with someone with this condition to regularly check the hormone levels. While we don’t claim laboratory precision with the app, it does give you trends over time for a better understanding of the cycle. This information can be a help for individuals and their doctors. It’s a step forward I think.
(Suffer from PCOS? Go here to learn more about that.)
Georgie: what inspires you and drives you to make this happen for women?
Leo: bringing knowledge to the world. I grew up around women. I understand some of the problems related to the cycle, even though I don’t experience them myself. But I get exposed to them very often. I want to listen and help and be there. My passion for knowledge brought me this topic. It’s natural for me to try and help to move it forward.
Georgie: I love talking to people who use an experience, whether it’s their expertise or a life experience, to make change happen. We need it. There’s so little data in women’s healthcare and yet there’s so much information that could be gathered. It’s going to take creativity, expertise and innovators like you to make this happen. I’m excited to watch Pearl be successful and see the changes it will make.
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