Ovulation & Progesterone Metabolite: The Role They Play in Your Fertility

Podcast


Transcript


Fempower Health founder, Georgie Kovacs, interviewed Amy Beckley, CEO and founder of Proov.

Proov is the at-home PdG test to confirm ovulation.


Georgie: Amy, tell us about yourself.


Amy: I have a PhD in pharmacology. I love science and have studied hormone signaling and drug and vaccine development. It wasn’t until I had a personal battle with fertility that I started paying attention to reproductive endocrinology and hormones. In 2006, my husband and I wanted to try to conceive. I did all of the tracking, LH tests, thermometer, all of the things.


I could tell my body wasn’t working right. I wasn’t getting the beautiful patterns that everyone was posting. It looked like I was ovulating but just not very well. I would call the doctor and be armed with this information. I was told that I hadn’t tried long enough and it was typical to struggle. I felt very lost. I knew something was wrong and couldn’t put my finger on it and no one was there to help me.


That’s where my passion started. I believe we deserve better. If there are answers, women deserve them. We have to advocate for ourselves, though. After about six months, we did get pregnant and I lost it about a week into the pregnancy which is very devastating. At least, though, I thought now I have an “in” to be treated by a doctor. I was amazed to discover that I was still considered “normal.” This was just “something that happens” and I should “keep trying,” which made me feel even more defeated.


After 12 months, some magical thing was triggered and a doctor would see me. I paid out of pocket to have a doctor look me in the eye and say, “we have absolutely no idea what’s wrong with you.” I was given two options: try naturally and have a 10% chance or do IVF. My diagnosis was “unexplained infertility,” which felt like a slap in the face. We did IVF. Two cycles. Second cycle, I conceived my son who is now almost ten. So, a happy ending on that.


But anyone who’s done IVF knows how hard it is to do. It’s financially very expensive, physically draining, you have to miss a lot of work and go to appointments. You get tons of hormones that make you off-balance. It was hard on my marriage. I decided I wouldn’t do IVF again, even though I wanted to have another child.


I took my background in hormone imbalancing and used myself as a guinea pig. I had symptoms: my temp didn’t stay up very long and I was spotting all of the time. Obviously, I was getting pregnant but losing it. There was an egg but my body wasn’t conducive to supporting conception and I wanted to know why. I had conversations with my physician and talked about all the things it could be. I made it clear I wasn’t going to do IVF.


We went through the diagnostics: bloodwork = fine, ultrasound = fine, day 21 blood work (which looks for progesterone) = fine. What was interesting was that the day 21 blood work showed that my progesterone was okay and I was ovulating, but a day or two after that, I would start spotting and then get my period. That is called luteal phase defect. That is one of the biggest problems with ovulation. You ovulate and have good progesterone levels but it causes you to drop too quickly.


If you think about ovulation and conception, the time from when your egg leaves the ovary and gets to the uterus is 7-10 days. The role of progesterone is to prepare the uterus to receive that embryo.


You need progesterone to stay high from when you ovulate to ten days after ovulation. This gives it enough time for the egg to go down the fallopian tube before the progesterone falls. The theory was that I was ovulating, just not very well. I asked my doctor for a simple supplement: I wanted more progesterone. My doctor agreed and within a couple cycles I was pregnant with my daughter, who is now six. That was my “aha!” moment. If we could help women understand if they were ovulating properly or having weak ovulatory events, it could empower women with more information so they can reach their goals faster.


Georgie: that context helps so much. For me, it was unexplained fertility, too, which does feel like a slap. Sometimes, the doctor isn’t investigating enough and other times there hasn’t been enough research.


Talk to me about the Proov test and what it does and how it works.


Amy: the Proov test is the first and only FDA cleared at-home ovulation confirmation kit. Basically, we are testing for PdG (Pregnanediol Glucuronide), which is a progesterone metabolite. At the doctor, you can get a cycle 21 blood draw to measure your progesterone levels at one point in time. You have to go to a lab and get a blood draw and get a little piece of information about your ovulation.


What we did is made a non-invasive product. Instead of measuring progesterone, we measure the metabolite. This naturally cycles through the body and comes out through your urine. Proov measures the PdG in urine. You can measure your levels of this critical hormone through the entire 7-10 days when it should be the highest to see if you’re successfully ovulating. You’re getting more data points for a longer period of time. That is very useful information to take back to a doctor and move your journey forward.


If you think about my situation, my cycle day 21 blood draw was great. It showed I ovulated and had progesterone but it wasn’t the full picture. I was still dropping too soon and there wasn’t a good diagnostic testing system out there to understand the complete picture of ovulation. I was just getting one little point in time and missing this problem.


So, we’ve created a system where it’s a more complete picture because you have more data points. It helps you understand: do I have a healthy ovulatory event? Not just yes or no, “did I ovulate?” But, is it healthy and successful?


In my opinion, the Proov kit is 3-4 steps ahead of a blood draw. You don’t have to go to the lab. You can buy our test on Amazon without a prescription. We make it very accessible for women to have this information. Once they have the results, they can be more empowered. They can say, “I’m ovulating in a healthy way and it isn’t a barrier for me to conceive.” OR they can know, “I didn’t get the results I wanted to get. Let me talk to my doctor and have a specific conversation.” This is a stepping off point to have a better conversation.


For my story, I had nothing to say to my doctor. And he had nothing to say to me, except, “do IVF.” The second time around I had data to say, here’s our stepping off point. I got to the outcome faster, with less stress and significantly cheaper.


Georgie: it is true that a lot of doctors will test on day 21. Even I didn’t know - after 10 years into my fertility journey - that the PdG can change over time. That’s the story that you need to understand around the luteal phase defect. This is almost like the next level of detail from the ovulation tracking charts. I know that people will track temperature and cervical fluid but this is an additional data point for more effective conversations.


Amy: yes, so true. Doctors are very busy. They do the best to treat you. It’s in the interest of everyone’s time to have as much information as possible. To go in armed with some answers at least is going to help you guide the conversation and help doctors do their jobs better. That benefits everyone involved.


Georgie: even when I look at groups on FB for fertility tracking apps, I see how the conversation is literally just, “did I ovulate?” It’s frustrating that women aren’t aware that there’s so much more to it than that. Ovulation is fine but do you have enough metabolites to support through a future pregnancy?


So, someone takes the Proov test and it’s clear that they need to supplement with progesterone. Is there any issue with translating this to the medical community and receiving supplements from your doctor?


Amy: first, the question of whether someone should be put on supplemental progesterone. The answer is not always yes. If a woman isn’t ovulating at all, progesterone could harm instead of hurting. If you produce no egg, you have zero chance of conception. Taking a Proov test, doing progesterone blood draws, will help you determine whether you ovulated at all.


So, second, if you didn’t ovulate successfully, a progesterone supplement could help with that. The PROMISE trial out of the U.K. is the biggest study done on this. Women were or were not given progesterone during the first-trimester of pregnancy. Live birth rates were increased 2-3%.


Another study, women were given progesterone three days after ovulation and it increased birth rates by over 20%.


Progesterone prepares the uterus for the embryo. Without progesterone, the embryo won’t attach to the uterus. If it’s given too late, for instance at a positive pregnancy test, you’ve already passed the reason for which you needed it. Timing matters. Literature shows that starting it sooner than later is more beneficial.


Third, the form of progesterone matters. Progesterone injections can irritate some women. Oral progesterone passes through the digestive system, so by the time it reaches the uterus it’s not in the same form, which decreases its effectiveness. Creams are great for women who are going through menopause or perimenopause but studies show that it takes about 10 days for the progesterone to reach the uterus when taken through the skin. Women with fertility issues don’t have 10 days.


If you have a progesterone deficiency, you need to talk to a doctor and get something prescription level. Before you self-medicate, always talk to a doctor. If you have a slight deficiency, you can do things naturally. Many women who are using Proov find slightly subpar results, which can be resolved through diet or stress relief. Levels can be so effectively changed this way that we see women who continue to monitor through Proov go from inadequate levels to positive pregnancy tests.


Ovulation isn’t “yes” or “no” for everyone: it’s about a continuum of health.


Georgie: when you talk about diet changes to help with progesterone, what are some of the things you’ve seen in the community that seem to be working?


Amy: seed cycling seems to work amazingly well. This is when you eat different seeds at different phases in your cycle.


First part of your cycle when estrogen is dominant: flax and pumpkin seeds

Second part of your cycle when progesterone is dominant: sunflower and sesame seeds


It’s mind-blowing how something so simple could have such a profound effect, but we see it over and over in real women. Hormones are very tied to how we eat and treat our bodies. Stress, too, can impact women’s fertility and wellness.


The menstrual cycle is called the 5th Vital Sign. Your body is telling you if you’re healthy and ready to support life by a healthy menstrual cycle. If not, your body pulls resources from the menstrual cycle. Because progesterone is the last hormone that gets released, it will be a resource your body pulls away if it lacks health or balance elsewhere. It’s worth tracking if you want to be healthy.


Georgie: I appreciate that. While I’m sad that you had to go through two miscarriages, I’m grateful that you turned it into something like this. There’s an amazing rhythm to women’s bodies. There aren’t a lot of clinical trials to understand women’s bodies, either for reproductive health or other diseases.


In regards to seed cycling, I’ve talked to some specialists who admit that there isn’t a lot of data about that. But anecdotally, there are so many people who rave about it. We all have to do what we can and acknowledge that, even though there isn’t a clinical trial, as long as your doctor agrees, why not try it? These things may help a lot of people.


Amy: there are some IVF clinics that mandate acupuncture before and after retrievals and transfers. CCRM here in Colorado is a top location with high success rates and they mandate acupuncture.


Georgie: one of the things that is interesting about Proov is the two-week wait. I think we’ve talked about this before where you have your test for ovulation, you time intercourse and then you wait. For Proov, this is another resource or data point that you can investigate during the wait.


So, there are fertility tracking apps and devices. Another resource is the ovulation predictor kit. To make sure everyone is clear: what do those do versus Proov?


Amy: they measure different things that are produced at different times during the cycle. Ovulation predictor kits, measuring cervical mucus, basal body temperature are geared toward predicting ovulation. You are estimating fertility windows so you know when to have intercourse. Those measure a hormone called LH (luteinizing hormone) and some measure estrogen. These are produced during the first half of your cycle. When the follicle ruptures and your egg is released, you ovulate.


The kits tell you when you’re ovulating because an egg can only be fertilized less than 24 hours after it’s released, pinpointing when you should have intercourse.


To confirm that you have ovulated and are ready to receive the embryo, you need to measure progesterone. This can be done through the blood draw or through a test like Proov. Many women, especially with PCOS, will get a healthy LH number. Prediction is good but if you don’t confirm that you’ve had a healthy ovulatory event, through a progesterone test, you won’t know the full picture.


Knowing whether or not you are ovulating gives you the right insight into whether or not your body is working properly to conceive and carry a baby.


Georgie: we are an interesting time when it comes to fertility. 10 years ago it was private and people didn’t talk about it. Now, we have clinics that just focus on egg-freezing for “one day.” Celebrities talk about it and reproductive health is all over social media. I can imagine, with the noise of so many people talking about it, that introducing a new way of thinking can have its challenges.


What are some of the challenges that you face in educating the community and even clinicians around this additional data point?


Amy: the challenges that we’ve had have included doctors who see studies and trials where there’s a low increase in live birth rates after progesterone supplementation. Doctors are so busy, so they see that one line and dismiss progesterone entirely. You get dismissed until you’ve had three losses and qualify for treatments.


It’s not a doctor’s fault. Women do need to know as much about their bodies as we can. This empowers them to come in and have the right conversations. If a doctor won’t listen, of course, find another one.


This is challenging, though.


We designed Proov to look like a pregnancy test over an ovulation test. You can collect first morning urine, dip a strip, wait five minutes, read the lines. This doesn’t require equipment. You don’t need a lab or a prescription. But women see the test strip and think it’s an ovulation predictor kit.


So, we are working hard to educate people on the science and how powerful this information is. It’s challenging to look the same as an ovulation predictor kit but they’re not the same.


Georgie: sure, not understanding the nuance to realize it’s different. I do want to echo for being your own advocate. Recently, I went to a doctor’s office and they basically said, “there’s nothing we can do to test what’s going on with you.” I had to list out for my doctor the blood work I wanted done. She told me she didn’t think it would accomplish anything but I was armed with the knowledge of what I needed to be tested for. I felt like a bully but I was pushing for my own health. It’s hard!


In this journey of educating and building your company, what is your greatest hope for women’s health?


Amy: there are so many amazing people out there doing amazing innovations that get us closer and closer to understanding more about our bodies. I was reading someone’s blog who said, “what if IVF was the past and we didn’t have to do this anymore?” IVF is a big medical bandaid and the only go-to procedure. Of course it is amazing and I have a son from IVF. But I also know how stressful and time-consuming and expensive it can be.


What if we could get to a world where we didn’t need IVF and could fix everyone’s problems without it? There are so many smart people out there who are making amazing things. I have good hope for the future that we can fix this problem. Infertility rates are growing, not shrinking. Now there’s going to be more innovation to address that. I have good feelings for the future.


Georgie: it makes me think about the survey that we built at Fertility4Me. I’ve observed that women are the best source of information for other women. Doctors are using data to drive decision-making but, like you said, they’re very busy. It’s all about stakeholder management. When you look at women, we’re the ones who talk to each other outside of the doctor’s office to find out what’s working and what's not working.


That’s where so much of the information is. That’s why I built the survey. If I could crowdsource this data to identify trends, we could partner with people like yourself and merge all of the information to find the best path forward. I hope that data will be helpful. It can level the playing field of information. There is a lot going on in women’s health! It’s a great time to be a woman.


What inspires you on a day-to-day basis?


Amy: the women in our Facebook group. We pride ourselves in helping women become their own advocates and getting the information they need. Anyone who uses Proov, wants to learn about Proov, talk about ovulation/progesterone/LH can join the community. Seeing them come in with, “oh my gosh, I’m at the end of my rope” to returning with positive pregnancy tests after using Proov is the most powerful moment.


We just started tracking pregnancies that were a direct result of Proov and we’re up to 98. These people never would have gotten pregnant if it wasn’t for Proov.


Georgie: what I see, Amy, if I could be your business planner: once you get everyone educated on Proov continue with the diagnostics! There’s so much more we can better understand about how a woman's body works to inform what needs to be done before jumping to IVF. Many of us agree that we jump to that too quickly just because we don’t have the information. Congratulations and I appreciate you! Our heart goes out to you and everyone who’s struggling with fertility right now with COVID-19.


Amy: we’ve looked at the data and women are making a lot of decisions about trying to conceive during COVID-19. Doctors have suggested that women take this time, while fertility clinics are closed, to learn about their bodies. Instead of sitting around and getting frustrated, you can learn more by using a test like Proov. This isn’t wasted time. Until fertility clinics open again, we’re offering 30% off of our test. We want women to be prepared to have these conversations with their doctors once fertility treatments start up again.


Georgie: that’s amazing. I just published a blog about this. I made mistakes because I wouldn’t pause and listen to my body. I wished something would have forced me to stop and learn more. In the rush, I made bad decisions. This is a powerful opportunity for people to pause and assess many things in their lives, including their effort to conceive.


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Our content is for informational purposes only — it's not a substitute for medical advice, diagnosis, or treatment.

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