OVARIAN REJUVENATION – How to Improve AMH levels

OVARIAN REJUVENATION – How to Improve AMH levels

About Samuel Wood, M.D, PH.D., M.A.,M.B.A., HCLD/CC(AAB), FACOG

He is a world-renowned fertility specialist as well as an expert in reproductive genetics with over 30 years of clinical experience

Positions:

• President and Medical Director of Gen 5 Fertility in San Diego
• Laboratory Director of Progenesis, a leading PGS/PGD company
• CEO of Stemagen, a stem cell company renowned for having been the first research facility to therapeutically clone adult human cells

Academic Background:

• Residency in Obstetrics and Gynecology at the University of North Carolina
• Fellowship in Reproductive Endocrinology and Infertility at UCSD
• Board Certified in both Obstetrics and Gynecology and Reproductive Endocrinology and Infertility
• M.A. in Psychology
• Ph.D. in Biochemistry and Molecular Biophysics
• M.B.A.

Selected Honor/Awards:

• The only fertility specialist in the U.S. who has the honor of being a longtime listee in three Marquis’ publications: “Who’s Who in America,” “Who’s Who in the World,” and “Who’s Who in Science & Technology.”
• A “Top Doctor” by U.S. News and World Report
• A “Super Doctor” by SuperDoctors.com
• One of the “50 People to Watch” by San Diego Magazine
• One of the 20 “Men who Impact San Diego” by San Diego Metropolitan Magazine.

Selected Media Experience:

• “New York Times”
• “Newsweek”
• “Vogue”
• “Cosmopolitan”
• “Dr. Oz”
• “The Doctors”
• “World News Tonight,”
• “NBC Nightly News”
• “Good Morning America”
• “The Today Show”
• “ABC’s World News Tonight”
• PBS’ “Frontline”
• BBC documentary

Transcription : 

Marc Sklar:

Hi everyone. Welcome to another episode of Fertility TV, I’m Dr. Marc Sklar, the fertility expert, and I’ve worked with couples from all over the world helping you get pregnant naturally. If you want more of my support then make sure you subscribe to my YouTube channel by just clicking the bell so that you can get notified when I put out another video for all of you.

Marc Sklar:

Today I am talking with a local reproductive endocrinologist and fertility specialist, Dr. Samuel Wood, who is the main physician and medical director at Gen 5 Fertility here in sunny San Diego. I’m bringing him to all of you because he does some interesting and unique techniques when it comes to IVF. And so we’re going to be discussing today PRP, ovarian rejuvenation and a new technique that he uses for trans vaginal ultrasounds for transfer. So if you want more information on these unique techniques, then keep watching

Marc Sklar:

All right. So today we are talking with Dr. Wood from Gen 5 Fertility right here in sunny San Diego and we’ve got an interesting topic for everybody, one that I get a lot of questions about and I’m hoping that we can get a lot of awesome answers today. So Dr. Wood, thank you so much for joining. I appreciate you taking the time out of your busy day.

Samuel Wood:

Well thank you for inviting me. I’m looking forward to it.

Marc Sklar:

Awesome. So PRP, ovarian rejuvenation, is something that we often get questions about and the public at large is confused about the value, the success rates, and the process as a whole. So I was hoping to get your information on it. I know you’ve written several papers on this exact topic and you’re doing this in the clinic and there’s not many clinics, at least from my understanding that are doing this, at least here in the States. So I wanted to get into some of those details today. Can you simply explain to those watching what PRP and ovarian rejuvenation is?

Samuel Wood:

Well, PRP stands for platelet rich plasma, and so it’s an extremely simple procedure, as long as you know how to do it, and how to do it well, and of course it’s taken a while to learn exactly how to do it. But PRP itself has been around for about 30 years and it’s very commonly used in several different areas of medicine, including orthopedic surgery and plastic surgery, cardiac surgery, even neurosurgery. And what it involves doing is using the growth factors that are released from platelets to enhance the effect of whatever the surgical procedure is. So it’s extremely common for any athlete who’s been injured to place PRP in the area of injury as well as whatever the rest of the treatments are. And it works extremely well. And so I think the concept of using it for ovarian rejuvenation, which means to take the ovary and actually rejuvenate it, take it back to a younger age, was very exciting to begin with. We didn’t know if it was going to work or not, and it’s actually worked much better than we thought that it would.

Marc Sklar:

Oh, that’s excellent. Initially when I’ve always thought about stem cell and PRP, it was always around a lot of orthopedic procedures and worked very well for my mother when she was dealing with her knee issues. And I thought it was a very logical next step in progression to take it to ovarian rejuvenation. So I was happy to see that that was being done.

Samuel Wood:

Let me add something. As you may know, I’ve done a lot of stem cell work in the past and so when I heard that people were using stem cells in an attempt to rejuvenate the ovary, it’s an interesting idea. However, it simply does not work. It’s extremely expensive and it doesn’t work. And the US government and many other organizations and agencies had pointed that out, that taking stem cells and injecting them into the blood and hoping that they get to the ovary and hoping that they differentiate into the correct cells to actually enhance fertility, it’s a crazy idea done right now, and it really bothers me. And the interesting thing to me about PRP is it’s actually based on the same idea. So when you inject PRP and the growth factors are released as a result, what happens is, the stem cells within the ovary actually begin to grow and differentiate much as they do when a person is injured and platelets go to the area to help heal the injury.

Samuel Wood:

So what we’re doing is stem cells right, in a sense, because we’re activating the ones that are already there. We’re not activating stem cells that have no particular appearance, nothing like that and hoping that they differentiate into what we want. We’re actually taking those stem cells and differentiating them according to what’s already there at the ratios that are already there. And I think that’s the reason it works so well.

Marc Sklar:

That’s a great differentiation and clarification because I think there’s many people who think that stem cell and PRP are one in the same and they’re not. Definitely different procedures and it’s a different process, although along the same thought process as you mentioned. So I thank you for that and hopefully everyone now understands that a little bit better. How long is the process for someone who wants to, let’s say they reach out to you saying that they want to start this process of ovarian rejuvenation and they want to incorporate PRP. What’s the timeframe that they have to go through and when should they actually think about reaching out so that they have enough time to put this into place?

Samuel Wood:

It’s a really good question. When we started, we didn’t know how long it would be effective. And what we do now to look at effectiveness is we look at AMH levels, Anti-Mullerian Hormone levels, in about 70% of women, those levels go up. Now AMH is made by follicles. The more follicles you have, the higher the AMH is going to be. And so when we looked over time at what happened to AMH, we saw that some women, it would only be elevated for one month or two months. The longest we’ve seen is in the range of six months.

Samuel Wood:

The time to do it is right before you plan on doing a treatment cycle. And so we actually have two different ways of doing it. We take care of many patients from other countries and they’re usually not able to come and stay for six to eight weeks. Instead, they’re only here for two weeks. And so we do pretreatment before they arrive and then when they arrive we do the PRP or the EnPlaf and we can discuss that more later if you like. And then we start the cycle immediately. So the PRP or EnPlaf is done roughly two weeks before the egg retrieval in an IVF cycle. If it’s someone who has more time or who is a domestic patient, what we generally do is the PRP or EnPlaf, then start pretreatment for four weeks and then do the stimulation for another two weeks. And so in that case, it’s six weeks from the time that we do the PRP until we do the egg retrieval.

Samuel Wood:

And the reason we do that is I don’t want to miss it. And in the past sometimes we would do that. We would see a very nice rise and then we would see it trail off. And by the time we knew it had trailed off, it was too late to actually do the IVF cycle. And so the patients didn’t gain all the benefit from it that they could. And so this particular strategy has worked very, very well. We’re now using generation two techniques and if you’d like, I’d be happy to discuss those later. And so we’re seeing, as I mentioned, 70% of women responding and I just had another patient on Friday who went from roughly 0.6 up to 1.7 AMH he space of four weeks. And so we’ve seen many dramatic results. Unfortunately it’s not a hundred percent, but things are going very well.

Marc Sklar:

I think 70% is a good percentage to have. I don’t expect anything to be a hundred percent so those are good results. So that’s interesting because I was thinking in my mind that they wanted several rounds of PRP to give them the better result. But what you’re seeing is actually immediate effect right after in that same cycle, which is excellent. That makes it a lot easier for patients.

Samuel Wood:

In the past we have had patients that did multiple cycles, but I think it was in part because of the way we were doing it. Now that we’re using the new technique, it’s much less common because we see very high response rates. At the beginning it was 30 to 50% of women would respond and when they didn’t respond, they’d come back and we’d do another injection of PRP or EnPlaf. And then in some cases we’d see a response then when we didn’t at the beginning. So I think it’s a lot of the benefits that we’re seeing now and the speed with which we see those benefits come from the new technique.

Marc Sklar:

That’s excellent. And so when you say the new technique, do you mean by the gen two process?

Samuel Wood:

Generation two. Now, let me tell you how it started. The first cases were done in Greece and the way they did it was to do a laparoscopy. And then they would reach in with a grasper and they lift the ovary up and they would inject the PRP into the ovary. The problem is that the ovary is white on the outside. You can’t see through it, it’s not transparent. And so many of the injections that they made into the ovaries were blind. Now we know exactly where the eggs are in an ovary. And so when we started doing it via ultrasound, which allows you to see throughout the ovary, now we’re able to place it precisely, exactly where the eggs are. So that was really generation one. Generation two is based on the same idea, but it’s a different way of doing it. And we started this roughly a year ago, and since then we’ve seen much, much better results and it’s proprietary exactly how we do it. But it does work much, much better.

Samuel Wood:

Now this technique is actually patented, the technique that we use, which involves ultrasound and requires no anesthesia. There are a few other fertility centers that offer this, but to my knowledge, no one else offers it the way we do it. In fact, there’s one in New York that puts people to sleep and then does the ultrasound guided transfer of the PRP. And so there’s no reason to do that, it’s a near painless procedure, that takes a very short period of time and so there are good ways of doing it, not so good ways of doing it and I think with this new gen two technique that we’re using, it’s very good.

Samuel Wood:

Have I given up? No. Do I plan on having a gen three? Absolutely I do, and I’m working on that concept because although 70% is very good, I’m not happy with it. I think if we could get 90%, I could probably be happy with that because some women are simply not going to respond. They come and they see you so late that there are no eggs there, there’s nothing left. Those a really, really tough patients and so I don’t think we’ll ever be very successful with them. But if we could get up to 90% that’d be outstanding.

Marc Sklar:

Well, hopefully it doesn’t take you to get to gen five as your fertility name implies to get to that 90%. Hopefully it’s just around the corner.

Samuel Wood:

By the way, that reminds me, the techniques that we’re using for ovarian rejuvenation are really generation four. Most of the world, virtually all fertility centers right now, they’re are generation three which involves using and doing genetic testing of embryos. But in my mind, gen four is ovarian rejuvenation and then gen five is on the way.

Marc Sklar:

Well then maybe we should be hopeful that it gets to your namesake and gets the gen five.

Samuel Wood:

I agree with you.

Marc Sklar:

Well that’s great. And so you’ve seen a 70% improvement and change and how have you seen that impact success rates in terms of IVF transfer rates?

Samuel Wood:

Great question. Now, PRP actually does two things and we published a paper about the second area I’ll discuss in a moment. The first is to increase the number of eggs. Because as I mentioned, when you see an increase in AMH that’s really of no value by itself. An increased AMH doesn’t help you. But if it’s reflective of an increased number of follicles, increased number of eggs, then it does. What’s the other way it helps? It increases the quality of the eggs and eventually the embryos. And so we’ve had patients, and we published a paper about this last year, where they failed many, many cycles. And the reason they failed is they got blastocyst, which are the stage of embryo in which implantation occurs. But when they were tested, they were abnormal.

Samuel Wood:

So cycle after cycle, they would make eggs, they’d make embryos, but they’d be abnormal. But when you do PRP first, the chance that you’re going to get a normal embryo is higher. And that’s really the key because when you transfer a normal blastocyst and you transfer it gently and you transfer it in an optimal way, pregnancy rates are extremely high, they’re around 90%. Very, very high. So it’s really getting to that stage where you have a normal embryo, a normal blastocyst. That’s really the key. And so all of our efforts, including ovarian rejuvenation are all around accomplishing that, because without that you have nothing.

Marc Sklar:

That’s great. That’s a huge shift. And I imagine then you’re also seeing that translate to less miscarriages.

Samuel Wood:

Absolutely. No doubt about it. Miscarriage rates are probably 20% or so if you don’t do PGS for example, then they dropped a 5% if you do. So we’ve had some patients that had miscarried repeatedly and then after doing PRP, they didn’t miscarry. These are not perfect studies because there’s no randomization, but at least apparently it helps in terms of that as well.

Marc Sklar:

Oh that’s excellent. So for everyone watching, this basically gives you an understanding of what PRP is and ovarian rejuvenation and really the benefit and also the differences that not all PRP is the same. And there are different iterations and evolutions to that process, which is where Dr. Wood and Gen 5 fertility are at right now.

Marc Sklar:

Before we started recording this, Dr. Wood and I were talking about another procedure that they do in the office that has also changed their success rates and shown some improvements in their transfer rates and so that’s trans vaginal guided ultrasound for transfer. Can you tell us a little bit more about that and why you started to incorporate this technique?

Samuel Wood:

Sure, but first, I think I should mention one other issue, because many patients that come in have heard of PRP, they’ve also heard of something called EnPlaf and EnPlaf is considered by many people to be super PRP. And there’s a big difference between the two. It’s not clear which is better, but I think it’s valuable to explain the difference.

Marc Sklar:

Sure, please go ahead.

Samuel Wood:

As I mentioned before, in order to to obtain PRP, you draw a patient’s blood. Usually you obtain nine to 10 milliliters or CCs of blood and then you isolate the platelets from the blood sample. You then activate the platelets and when you activate them, the platelets release these growth factors. At that stage you draw platelets and the growth factors and inject them into each ovary. EnPlaf is completely different. Once again, you do get the platelets but then you incubate them for a couple of hours and at that stage, most of the growth factors are released. They’re released into the fluid around the platelets.

Samuel Wood:

So we draw that fluid up, not the platelets, just the fluid that has the growth factors in it and we inject them into the ovaries. Now by doing this, the concentration of the growth factors is 10 to 20 times higher with EnPlaf than it is with PRP. And so when we have those patients I mentioned that are coming from another country and they need to get everything done in a couple of weeks, in that case we always do EnPlaf because the speed of the reaction is instantaneous.

Samuel Wood:

So you would think, why wouldn’t you always do EnPlaf? Well, the reason is that the full effect of the EnPlaf is over relatively quickly because you’re injecting growth factors and as soon as the body takes care of the growth factors, it’s gone. Whereas when you do PRP, you’re injecting the platelets and those platelets continue to release growth factors probably for three days. So you can see why you would think PRP would be better, and you can see why you would think that that EnPlaf would be better. We’re not sure. Maybe it’s certain patients versus other patients, we don’t know. But we are pulling the data together and we intend to publish the results later this year. It’d be very nice to know which one patients should choose and under what circumstances one or the other would be better.

Marc Sklar:

So are you actually giving patients the choice in some circumstances or are you making that decision just based on time and their availability?

Samuel Wood:

Well, I’m someone who believes the patient should always make the choices. And as physicians, we need to carry out what the patient wants the best it can be carried out and no doctor should be telling any patient what to do. It’s their absolute right to choose their future, to choose their healthcare. So yes, in the circumstance that someone comes from another country and they’re only here for a couple of weeks, we recommend EnPlaf. But if they choose PRP, that’s fine, doesn’t matter to us at all. So in general, it’s entirely the patient’s choice. And many patients always impress me. They come in and they know things well. They’ve read the papers, done so much, they say, “Now what about this paper? Didn’t it say that?” And I love that, I love well-informed patients making the right decision for themselves.

Marc Sklar:

That’s great. That’s really important and it’s great for everyone to know the difference between this so they can make a really informed decision as they’re moving forward with that process and deciding how they want to proceed with the procedure.

Samuel Wood:

Now going back to the question you asked me before I got on the EnPlaf topic. I think it’s a really important topic. I have seen so many IVF cycles with beautiful embryos, young patients, and yet they fail. Why do they fail? They fail generally because of the transfer. The transfer is so critically important. Years ago, I worked with a fertility specialist that’s now well known in Southern California, and this person could not do a transfer. Couldn’t do it. Without saying whether it was a he or she, this person went I think something like nine months and never got a single successful pregnancy, because the transfer technique that this person used was highly suboptimal. So I’ll never forget day that we were doing a embryo transfer using egg donor eggs. And when they placed the embryo, they hit the end of the uterus, and blood came pouring back out through the cervix, and of course she didn’t become pregnant.

Samuel Wood:

So on that day, my lab director said, “That’s it. That person will never do another transfer here.” And we let them go at the end of the year. I don’t think patients realize how critical skill in doing an embryo transfer is. Everything needs to be done extremely gently. You have to know where to put the embryo. There is a best place to put the embryo, and it varies according to the thickness and the length of the uterus and other factors. So it’s critical. And so one of the reasons that I’m extremely interested and very happy that we’re doing the vaginal ultrasound guided transfers is it lets you be really precise. When you’re doing an abdominal transfer and then doing a transfer, which is probably what 98% of the fertility specialists in the US do, you’re a long ways away from the catheter. You’re a long ways away from the uterus. You’re on the skin outside of the abdomen looking through there, looking through bowel, then finding the uterus. You can’t see very well. You can’t be very precise.

Samuel Wood:

When you do an endovaginal transfer, a ultrasound, during the transfer you’re right there. The end of the ultrasound probe is within a few millimeters of the uterus, so you can see everything very precisely. You see areas you don’t want to release the embryos. You see a very nice area and so you’re able to do a much better job doing it. Now, why doesn’t everyone do it? Because it’s not easy to do. Really not easy, it’s completely different than what people are used to, but once you get used to it and you’re good at it, then the pregnancy rates are higher and there are multiple scientific studies showing the pregnancy rates are higher, but only after you get good at it, not when you first start it.

Samuel Wood:

And so we now do near a hundred percent of our transfers using vaginal ultrasound and I’m absolutely thrilled by it. People that have failed many times before have been able to become pregnant. Just in the last year we had someone failed 18 times, 15 times, 14 times. By using endovaginal ultrasound as well as some of the other things that we’ve mentioned, they were able to get pregnant and have a baby or they’re pregnant now. So I think it’s a huge advance in field and I wish it were done more in more places. I think there’d be far fewer failed IVF cycles in that case.

Marc Sklar:

That alone is such a big change and we can discuss why more people don’t do it, but it would be something nice to see as a big shift throughout the industry, that’s for sure. And what really struck me is that you said, how you talk about the procedure itself and how much of an impact it can have on the success rate. And it’s often when I’m talking to patients afterwards and they’ve had failures and they’re all upset, they’re often blaming themselves for the failure. What could I have done differently? What could I have taken differently? How could I have acted differently? And just hearing this, it just shows that maybe there wasn’t anything that they specifically could have done. Maybe there was, but it’s a combination of things, and depending on obviously circumstances and the patient and their history, there’s lots of factors involved, but that’s not one that’s typically discussed. So it was interesting to hear you mention that.

Samuel Wood:

Well, I also think that it’s rarely the patient’s fault.

Marc Sklar:

You and I agree here.

Samuel Wood:

It used to be back before we tested embryos, then that was the most common reason for failure was unknowingly transferring an abnormal embryo. But now that we test them, I think it’s unusual, but doctors, they like to blame patients and they say, “No, how long were you on bed rest? Did you get up? Did you do this or that?” All those kinds of questions make the patient feel like you have to do everything exactly right or you don’t succeed and there’s really no truth in that.

Samuel Wood:

In Australia for example, after you do an embryo transfer, you get up and you go back to work and they have very good pregnancy rates. So I think it’s unusual that it’s the patient’s fault and it feels terrible to think that they’re sitting there thinking, “I did something wrong. What did I do wrong? What day did I do it wrong?” Instead of realizing that if the lab is having an off week. There’s so many things, literally thousands of things that are involved in a successful IVF cycle, and as a patient, you really have no idea which one of those things caused the negative test and you should virtually never blame yourself.

Marc Sklar:

This is something that I find myself repeating almost exactly the way you described it just now to my patients. And so it’s nice to hear those sentiments echoed by yourself. I appreciate that. And I want to say thank you for your time, I appreciate your time. I’m sure we can go on and on about all sorts of other topics and maybe we will at some point in the future, but I think these two key points and areas were the big ones that I wanted to make sure that everyone was able to hear and learn more about because I think these could have huge impacts on their success in their journey. So thank you so much Dr. Wood for taking the time and for teaching all of us about PRP and the new procedure that you’re doing with guided vaginal ultrasounds for transfer, so I appreciate that.

Samuel Wood:

Well thank you very much, it was great to talk to you.

Marc Sklar:

I want to thank all of you for watching this episode and thank Dr. Wood for taking the time out of his schedule to talk with me and to inform all of you about his interesting techniques, his unique way of working with patients. And hopefully you gained some interesting knowledge and some information that will change your fertility now and forever. If you found this interesting, please comment below, let me know. If you want more information like this or you want to know a little bit more about PRP and the new techniques that Dr. Wood is doing, then please comment below, let us know so that we can get back to you. And if you are not a subscriber to my YouTube channel, then you need to be, so make sure you do by clicking that bell so that you can get notified when I put out another video for you. Until the next video, stay fertile.