Season 1, Episode 76
Make it Count – Diminished Ovarian Reserve Cycles with Dr. Lyndon Chang
In this insightful episode, Dr. Lyndon Chang delves into the innovative world of minimal stimulation IVF, commonly known as mini IVF. He discusses its benefits for patients with diminished ovarian reserve or advanced maternal age. Dr. Chang explains how using lower doses of medication can result in more efficient and targeted cycles, potentially optimizing both the quality and quantity of eggs retrieved that make it to blastocyst as normal embryos.
Beyond the medical aspects, he emphasizes the importance of a holistic approach to fertility, considering factors like stress management and overall health. Additionally, Dr. Chang addresses the controversy and skepticism surrounding minimal stimulation IVF, highlighting the need for more comprehensive research to validate its efficacy. Tune in to gain a deeper understanding of mini IVF and its role in modern fertility treatments.
Key takeaways:
- Mini IVF uses lower medication doses to stimulate egg production, leading to more efficient cycles.
- It optimizes egg quality and quantity, especially for those with diminished ovarian reserve or advanced maternal age.
- Minimal stimulation aims to avoid ovarian overstimulation, enhancing the chances of success.
- Comparable success rates to traditional IVF, but more research is needed for definitive evidence.
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Read This Episode Transcript
Lorne Brown:
By listening to the Conscious Fertility Podcast, you agree to not use this podcast as medical advice to treat any medical condition in either yourself or others. Consult your own physician or healthcare provider for any medical issues that you may be having. This entire disclaimer also applies to any guest or contributors to the podcast. Welcome to Conscious Fertility, the show that listens to all of your fertility questions so that you can move from fear and suffering to peace of mind and joy. My name is Lorne Brown. I’m a doctor of traditional Chinese medicine and a clinical hypnotherapist. I’m on a mission to explore all the paths to peak fertility and joyful living. It’s time to learn how to be and receive so that you can create life on purpose.
Want to welcome you to another episode of the Conscious Fertility Podcast, and this one is one of those fertility focused ones. I’m with Dr. Lyndon Chang. He’s the medical director of Hanabusa IVF in San Diego, and he’s a pioneer in the field of minimal stimulation, also the mini IVF in the states. And he specializes in a holistic approach, which we’re going to find out what that means to him when it comes to fertility using low stimulation IVF protocols. And I invited Dr. Chang to have this discussion on our podcast because a large part of our population had been diagnosed with diminished ovarian reserve or advanced maternal age. And when I started asking my patients and asking my colleagues, they said, you got to talk to Dr. Chang because he’s helped facilitate live births with a lot of patients ranging between the ages of 45 to 49. He’s had live births with patients with FSH between 20 and 166 conceiving through IVF using their own eggs. So Dr. Chang, welcome to the Conscious Fertility Podcast.
Lyndon Chang:
Good afternoon. Thank you for having me.
Lorne Brown:
And I think it’s Mark Sklar, my acupuncture colleague that I also put you on the radar for me. So you mentioned that you kind of have a little bit of a holistic approach. Is Mark Sklar part of your holistic approach? Tell me what that means for you and then we’ll jump into mini IVF and more. But what is a holistic approach from your perspective?
Lyndon Chang:
The holistic approach to it is looking at each patient as a total person as opposed to just focusing on this whole fertility, because so much of what happens outside can impact what’s happening inside your body. So just an example, a woman under a great deal of stress, studying a lot, working a lot, it’s going to suppress that pituitary of theirs. They’re not going to make enough FSH follicle stimulating hormone. Their eggs are not going to grow well if their eggs don’t grow well, they’re not going to produce good eggs to fertilize, they’re not going to ovulate very well, they’re not going to get pregnant. So you can’t just focus on, we’re just going to get the eggs out, we’re going to get the sperm to the egg. There are many, many aspects to this and this is where when I think of holistic, I think of, I guess it’s more in my situation of individualizing the case person to person as opposed to lumping them into this one group of patients who are having difficulty getting pregnant.
Lorne Brown:
Well, it’s nice to hear you say this because you basically are sharing the principles of Chinese medicine where they say that we don’t treat the disease so infertility, we treat the individual and that each individual you got to look at in a unique way. So it’s refreshing to hear somebody who’s practicing an IVF clinic, a reproductive endocrinologist, has this approach and we’re seeing more and more of the data coming out about how stress can interfere with your fertility, how diet and the microbiome can affect your fertility. So it’s nice that you have a systemic holistic approach. Now, I really wanted to hear more about this patient population, like the women in their late thirties and forties or those who have been diagnosed or have diminished ovarian reserve. And I hear this term mini IVF thrown around a lot and talking to colleagues, they directed me to you because they said not all mini IVFs are the same and that this is kind of one of the things that you’re, I would say you specialize in or you have a focus in. So maybe we can start with differentiating or what is mini IVF and how is it different from what we would call traditional IVF?
Lyndon Chang:
I guess you have to kind of clarify the terms a little bit. I think if you’re going to contrast it to traditional IVF, you should use the term minimal stimulation. And minimal stimulation is exactly what it sounds like. You’re using less stimulation, you’re using less stimulation medication opposed to a traditional high stimulation protocol. And that’s what we really should be thinking about when we’re talking about traditional IVF. This is a high stimulation protocol. You’re using hundreds, thousands of units of these injections of FSH that are being produced and you’re trying to stimulate the eggs as many eggs as possible and then you’re crossing your fingers and praying that one of those eggs is ideal in minimal stimulation. One of the fundamental principles of minimal stimulation is that the natural egg that your body produces every month is the ideal egg that’s been recruited by your body now.
And that would be a natural type, a natural cycle. We do have natural IVFs where you do nothing but you just wait for that egg to come out and try to capture it with our retrieval needle with minimal stimulation. Well, with IVF in general, the idea would be for women at certain stages of their life, you can make the process more efficient. Instead of one egg being one baby, women in certain stages of her life can actually have multiple eggs resulting in more than one baby. And could you make the whole process a little bit more efficient? A woman in her twenties, I’ve seen 10, 12, 15 eggs result in totally normal healthy, well not babies, but embryos that potentially could be healthy Babies after testing a woman in her forties will rarely ever make more than one healthy embryo. So what you do when minimal stimulation, the concept behind it is when you are stimulating the first egg that you produce is the best second egg is second best and you can stimulate to the point where you can optimize a patient cycle where in a patient who’s in her forties, you know that there’s only going to be one ideal egg in any given cycle.
There’s no need to try to stimulate for 13, 14, 15 eggs. If you want a hedge, you can stimulate for three or four eggs and that should be all the eggs that are necessary to optimize your chances for that cycle. So with minimal stimulation, it’s literally just using less medications to try to accomplish the same results in a certain situation. When you’re talking about mini IVF, you’re talking about a very specific protocol that came out of the KATO Ladies clinic in Tokyo, Japan. This is where a lot of this work came from. And with mini IVF, it’s a protocol that involves reducing the amount of injections to something pretty much every other day. And how you’re going about doing this is you’re using an oral medication called Clomid to stimulate the pituitary to have your body help stimulate along with this. C Clomid itself will probably produce maybe two, sometimes three eggs to grow, although it’s not unusual, it can even be more.
I’ve had one patient that came to me relatively long. She was in her mid thirties, failed multiple Ivfs high stimulation cycles in Massachusetts, moved, came to me. I did a protocol where it was just oral medications. He produced six eggs and three of them ended up being perfectly healthy normal embryos and she had a baby. And we still have two more that we’re going to be hopefully transferring in the near future, but many IDF is this particular protocol, oral medication and using injections to try to accomplish the same thing with higher doses, but it is a minimal stimulation protocol but a particular minimal stimulation protocol.
Lorne Brown:
And the reason behind that, then like so many clinics, if somebody comes in with diminished reserve or in their forties, they tend to want to give them a high dose to try and get as many eggs for that retrieval. So why not do it that way? Why are you suggesting let’s just go and try and get one or two or three with a minimal stimulation? What happens when we really are aggressive and give high doses of meds? Does it impact the egg quality?
Lyndon Chang:
What’s going to happen when most women age? And also we talk about those women whose ovaries prematurely age, the diminished bearing reserve is the number of eggs that are available for recruitment every month decreases. And with this lower amount of eggs, you have a smaller amount of eggs consuming that stimulation that FSH that’s being used. And what we need to think about in this whole process is FSH is what is making the eggs grow. It is the water, the fertilizer to your plants, it’s the food for your eggs. We know that plants need a certain degree of water and fertilizer, but we also know that after killing manning plants, if you give plants too much water and fertilizer, you will actually harm them. You will destroy them from a more microscopic perspective. There’s receptors on these eggs that respond to FSH, but if you flood these eggs with too much FSH, they will just shut down.
All those receptors will prevent the FSH from coming in so they don’t become desensitized. It’s a very common situation where you see women, you’ll hear patients, they’re going with all these follicles and then they get these high stimulation protocols and everything shuts down and they’re called non-responders. In this case, they’re most likely overstimulated by the amount of medication. So another thing that we do and with minimal stimulation, we avoid the overstimulation scenario. Now what we like to do here, we like to think of it as optimizing your FSH, trying to optimize the amount of water and fertilizer that’s kind of feeding your plants, your garden. And we do that by measuring the hormones specifically we measure a hormone called FSH to try to optimize FSH. So we can not only optimize the quality, but we are hoping we can also optimize the quantity of eggs in the cycle and that will allow us to hedge you a little bit in certain situations.
But once again, when we talk about women in their forties and women with very high FSH, there are a lot of good studies from 15, 20 years ago that show that there’s really not any difference between a high stimulation cycle and no medication at all. The success rates are very, very similar. If anything, the natural cycles tend to start to have higher success rates because once again, many of these patients are just getting overstimulated by the treatments. I just had a patient come in earlier who unfortunately circumstances she gets pregnant, but unfortunately Lou lost the baby in the process. There’s no infertility here. So in a case like this, she’s in her forties, we’re trying to help her get pregnant. Our job is not to mess up her eggs, which naturally she would get pregnant with. And that’s what I think is a problem with a lot of IVF centers. They are actually ruining the eggs by their protocols as opposed to helping them.
Lorne Brown:
Do you have data then, because you’re saying or suggesting high stimulation for these older women or those that have fewer eggs are having poor results, as you said, it could be negatively impacting that egg quality, therefore not getting those blasts. Is the data showing better results When you do them minimal stimulation, then
Lyndon Chang:
What happens? If you notice with any studies with IVF, actually IVF is not evidence-based, there’s usually not enough power. There are not enough patients going through the process. Although it seems like a lot of patients, there’s not enough patients to say that certain protocols work. There’s just the numbers, but there is data to show that many IVF is comparable to high stimulation IVF. There are some studies that are showing higher levels of success from lower stimulation in these cases. Unfortunately because the numbers are small, these are not thousands that we can compare in a randomized blind and control study. We can’t say it’s definitive, but you’ll hear multiple anecdotal cases, observational studies that show, hey look, women who are failing traditional IBF succeeding with low stimulation protocols in these cases of diminished ovarian reserve or the older patients.
Lorne Brown:
I had questions I wanted to go back to that And then I want to ask more about your testing, what you do, the monitoring, but just talking about the data, I’m just thinking about patients listening that are 41, 42 maybe have had failed IVS, you mentioned that you’ve helped people 45 to 49, so oftentimes they’re encouraged to do donor eggs if they want a parent because they’ve had unsuccessful IVFs and because of the age factor. Just what are you seeing though in your practice if somebody comes at 44, is it one out of a thousand or one out of 10? I’m just wondering how much hope we can put into the minimal stem or are you still recommending that this population donor egg is really the route to go? Or do you feel that there’s still a worthy type of IVF because you can still get pregnant with your own eggs from your clinical experience?
Lyndon Chang:
Yeah, good question. It doesn’t guarantee anything because there’s actually so many variables involved. Sperm quality, mechanical issues associated with the body. So minimal stimulation doesn’t guarantee anything. But when I look at the cycle, when I think of a person going to donor IVF, I’m thinking, well this is a person that has exhausted all the options available to them. And what I find is that many patients are getting pushed in that direction without exploring other options other than this one high stimulation protocol. At this one IVF center example, a patient who just graduated from our program was from Washington actually she was not that old. She was only 30 at the time, 30 9:00 AM H 0.7. Her baseline FSH is 27. She goes to IVF center standard protocol, 300 plus units of injections daily, no response. And the doctor says, Hey look, it looks like you need to get egg donors.
I mean this was one cycle from one IVF center with one protocol and this was very premature. She comes to our center, we optimize her cycle. We didn’t do a full-blown very mini, it was more of a modern stimulation. But based on our FSH, we realized this person was getting too much medication. Every cycle blast assist, multiple euploid embryos transferred her first she became pregnant, is on her way to having a baby. We have a couple other embryos frozen. So before going into egg donation, we should be thinking of egg donation as a last resort, we should be thinking, look, what is it 70-year-old woman in Uganda two years ago yet last year just had a baby from egg donation. What is the rush into doing egg donation? There’s a financial factor, there’s a time and money factor in all this. And yes, there are going to be situations where you’re exploring more IVF versus the cost of egg donation. It may make more sense to go egg donation because if you use up your resources for your autologous and you’re not successful, you may not have anything for egg donation. But then again, from an egg donation standpoint, look, once again, 70-year-old woman in Uganda, 74-year-old woman in India, you have time to explore those options.
Lorne Brown:
I don’t know if I want to be raising a child, a baby at 70. So when you say you could do it, you’re 70. I also think about the child too, right?
Lyndon Chang:
But everybody’s situation is,
Lorne Brown:
But I see what you’re saying is there’s an opportunity for some to have a baby with their own eggs, what everybody’s first choice is, and just from the donor egg cycle, we have an episode on this and I just want to share because we’ve brought up the donor egg is there’s many ways to parent and I will share that I’ve been doing this for at the time of this recording 24 years and I’ve never had a patient regret doing donor eggs. Donor regret she has had is that she waited so long to donate eggs to meet this child. So there’s many ways to do it and a donor egg is definitely an option. There’s a time and place like you said, holistically individually what’s your circumstances? But there are people that just mentally, spiritually, culturally are not going to do donor eggs. So here’s another option. Like you said, you can’t guarantee another option. And so
Lyndon Chang:
When you talk about, like you said, cultures, the Middle Eastern culture, the muss Islamic culture, egg donation is not acceptable within the religion. They only have this option and if a doctor’s saying, look, we’re not going to treat you unless you do egg donation, they have no options there.
Lorne Brown:
Yeah, so it’s another option. And the minimal stim, you talked about testing and you talked about it’s often done with oral medications. So one of the ovulation drugs you mentioned is Clomid. Letrozole. Would you guys use letrozole as well or is it always Clomid for a minimal stim?
Lyndon Chang:
No, we use Letrozole as well. If anything I like to mix up. I do worry that when you use one medication too long too often you’ll have negative effects with it. We know with Clomid, even though it stimulates the ovaries pretty well, it can have negative effects on the uterine lining. The environment doesn’t develop very well. So you can argue, well, I’m not going to do a fresh transfer. But at the same time these metabolites do linger in the system. It’s been found that some of the CLO metabolites can linger for 6, 7, 8 months and if you’re planning to do a transfer three or four months later, you may still have negative effects with these medications. So I like to kind of change things up. Letrozole has its downside as well. Letrozole, how does it work? It artificially lowers your estradiol levels, a type of estrogen that we measure, but that is the estrogen that we measure to determine egg quality as well.
So it’s very hard, especially when I have these patients who are in their forties and we do worry about egg quality if they’re on letrozole. It’s very hard for me to determine whether or not this is an egg worthwhile going forward with an egg retrieval because I’m in a situation in my practice where many times I have these patients who they only have one or two eggs for retrieval. I don’t want to do an egg retrieval unless it’s really worth their while that we have an opportunity on Letrozole makes it very, very difficult. Although it doesn’t have that impact on negative lining on creating a negative lining, which might be beneficial for someone who’s thinking about doing a fresh embryo transfer or a transfer sooner than later.
Lorne Brown:
So you can use either or, but it sounds like your preference often is CH clomid and it depends on lining issues and then you’re testing. So most of the clinics I’ve experienced, they’re looking at the kind of tracking the estradiols on their labs and ultrasound for size and quantity, how many follicles, and you said you’re testing FSH. So would your protocol change based on that woman that had FSH? I think you shared one of your case studies in her twenties, her FSH was already elevated in the twenties. Do you do anything to try and lower the FSH before you start a stem because your protocol is going to increase the FSH by giving them CH clomid and you’re going to give them exogenous FSH by injecting it. So just curious what you’re looking for and why it’s important to be monitoring FSH and how it changes your approach while they’re stimming.
Lyndon Chang:
So like I said, the FSH is your water, well think of it like water on your soil and you’re just trying to make sure you’re not overwatering the soil. So a couple of things you bring up with a gram reserve high FSH suppressing the FSH beforehand because if the FSH is too high beforehand, the eggs are not going to grow and that’s an important thing to suppress and bring it down to a level that is more ideal for egg development. That’s going to be somewhere in the 10 20, 10 30 range. Anything in between eggs tends to grow better.
Lorne Brown:
Can you repeat that? Your FSH number was between what
Lyndon Chang:
You’ll hear 10, 20, 10, 25, 10 30. Once you get clearly over 30, the eggs really don’t grow well. And at that point I have what’s called a suppression stimulation where we’re actually literally giving medications to suppress at FSH, we’re giving birth control pills, estrogen progesterone antagonists to suppress the hormones which will actually allow the eggs to grow. Oddly enough.
Lorne Brown:
Would a priming do that as well if you just give them the AndroGel and tric and
Lyndon Chang:
That is the purpose of priming in that situation to try to bring that FSH down. Now what will happen though is many times after the prime is done, the doctors will immediately start stimulating at that particular point, but there’s going to be a slight rebound in the patient’s FSH once you stop that prime. So that’s where a lot of times the doctors are very too aggressive at the beginning when they start stimulating. What we do is we are looking at the hormonal response and we’re looking also at the follicular response. Until those follicles start growing and producing estrogen that FSH is, it’s going to start going up. And if you are stimulating that point, it’s going to force the FSH to a level that it’s going to overstimulate the eggs and everything shuts down. But one of the fundamental things that we do is essentially priming the second part.
There is always a time between stopping the prime and starting the stimulation where you kind of let nature, trying to equilibrate things, see what the follicles are doing until those follicles are present. Your FSH is going to continue to go up. The follicles have to be present. You can’t just stimulate blindly like that. And then what you’re doing along the way is you’re testing the FSH to make sure that FSH is not going to go overly high or overly low. We’re talking about being overly high in most cases, but when you deal with patients with polycystic ovarian syndrome, you can actually see very low Fs hs in these situations and people do get over suppressed by a lot of the medications.
Lorne Brown:
So going back to this, if you prime or you’re doing before the IVF, you’re artificially suppressing the FSH by giving them things like birth control or estrogens. When they stop that prime often, like you said, there’s a rebound that it’s going to start up again and the brain’s going to start producing lots of FSH if that was their history. So what happens if, because that’s going to be common for a lot of them. Some of them they’re still quiet and then you wait so much and then you start to stimulate. And I’m asking if that’s one scenario, if the scenario, how long until you wait because eventually it’s going to come back online and they’re going to produce their own FSH. If it starts to produce and you’re seeing this high FSH, do you go again to suppress it? You have to keep suppressing until you get a low FSH.
Lyndon Chang:
You keep suppressing until you start to see the estrogen elevate, the follicles start to grow once the estrogen elevates, we know that FSH starts decreasing but
Lorne Brown:
Won’t the FSH be the FSH is going to tell the follicles to grow, which is going to produce the estrogen. So aren’t you going to have some elevated FSH then because you need the FSH to tell the ovaries to grow.
Lyndon Chang:
That’s what you have to worry about over suppression at the starting of the cycle, which is a problem as well with a lot of centers, they arbitrarily start suppressing priming and they oversuppress their patients. And with that over suppression, nothing is growing, nothing is responding. Even with suppression, as long as the initial FSH is within kind of a normal-ish range, eggs will grow, eggs will grow on birth control pills. People do get pregnant on birth control pills, not because they missed the birth control pills, but because they tend to have high FSH and the birth control pills lower that FSH two levels that are more ideal for egg development. One protocol that I found was kind of interesting, they do it in CHR, Dr Glacier Center in New York. They actually keep the patients on estrogen and stimulate on top of that. And it’s kind of like driving with your parking brakes on, you’re slamming your foot on the accelerator, but you have the parking brakes on, so everything is going smoothly. My thought would be, is there really a need to have the parking brakes on? Why don’t you just reduce the stimulation in a situation like that? But that’s a way they get away with being able to do a high stimulation protocol in a situation like this.
Lorne Brown:
And when you’re testing the FSH because you’re giving them, say in this case Ched and you’re giving them injectables, FSH derivatives, won’t you have a high FSH when you do the blood test?
Lyndon Chang:
Well, we may not be able to do both. And in some situations, what you’re aiming for is that window of FSH that you’re comfortable with, whether or not it’s 15, 20, 25, somewhere in that ballpark. I know that I believe UCSF, a lot of times their goal was somewhere in the 25-30 range. So the idea once again is you’re just giving enough medication to get yourself into that range. Let’s just say a person. And a lot of this has to do with antral follicle count as well. How many eggs are there and how much FSH are they going to be able to use? I see a patient with four follicles at the beginning of the cycle. I know that I can’t give probably much more than 25 50, well, 50 units of Clomid, that’s probably max what I could do or a hundred fifty, two hundred twenty five units of injections. I may not even be able to do both.
And then in a situation like that, do you really need to do both? But really the primary thing of mini IVF is a cost issue. Can we use oral medications to reduce the amount of injections that we need to do? Typically, I don’t actually do a lot of mini IVF where we do this combination of oral and injections because I want to be able to control the FSHA a little bit better. And if I use an oral medication and depend on nature, responding to nature a lot is unpredictable. Sometimes I know that if I give a certain amount of injections, I can see a certain increase in FSH, but if I give a pill, it could be sometimes unpredictable.
Lorne Brown:
So in your practice, if you can describe how you’re doing, how you’re dealing with diminished over and reserving your success, because we talked about the minimal STEM compared to traditional is the minimal stim was oral medication like Clate letrozole with some stim.
Lyndon Chang:
That’s mini IVF, that’s mini IVF,
Lorne Brown:
Mini IVF. And then I think I heard that you kind of prefer for yourself not the oral, but just giving them still minimal stimulation injectables so you have a better sense to read how much FSH they’re getting to the ovaries.
Lyndon Chang:
Exactly, exactly. So it looks like a traditional IVF cycle in some ways, but the dosages are 75% less, 80, 90% less.
Lorne Brown:
And I’ve heard from other REI’s on the podcast, and I’m just seeing because if you subscribe to this and that there’s data for this that the high dose, and you talked about overwatering or if there’s four follicles, that’s a lot for them to consume. They were suggesting that it impacts the FSH receptors and basically you could have a good egg and this woman says at 42, but if I think I’ve heard them use the word pound, the ovaries with that much medication, you could take a good egg and make it not so good.
Lyndon Chang:
That’s my belief and my understanding. You’ll see a lot of this in Asia and you’ll see a lot of this in Europe, this belief in this idea, not so much here in the United States, although they’re starting to get around it. There’s another center that opened up nearby in San Diego, part of the RMA network. They’re called Pearl Mini because of the fact that they do believe in this lower stimulation protocol and it’s slowly, I think people are going to accept, finally get around to understanding that this actually might be a better way of treating patients with IFSH.
Lorne Brown:
Why is it that this is not fully accepted then in your peers and your colleagues? Why is it for this group of advanced maternal age aid quality or AL Reserve that they’re still doing what we’re calling the conventional traditional IVF versus these mini IVFs?
Lyndon Chang:
Well, I think what happens is you have these doctors who are trained in this is all they’re trained in, and then what happens is that it works. Let’s just say it can work like 80% of the time for their general patient population. The doctors, well, there’s a big supply of demand issue as we realize that there’s a lot of patients who need fertility care, but there’s really not enough doctors. So the doctors are trying to do whatever is most efficient for them, what they know best and they’re really kind of not getting out of their comfort zone. Another thing is that there’s been a kind of a battle between the minimal stimulation and the high stimulation group in this diminished ovarian reserve realm. And there’ve been some very vocal people that are supporting the high stimulation protocols and they’re very anti-men. I think there’s a little bit of politics involved as well. So I think unfortunately there’s the supply demand, there’s just not enough physicians, so it’s hard for them to kind of broaden their knowledge base and their understanding of this. And that unfortunately has limited the growth of other types of options in medicine. And
Lorne Brown:
Then clinically, your experience once we get into the diminished reserve in advanced control age, there’s only so many, like we say, good eggs that will turn into good blast that turn into babies. So clinically, what’s your experience since you’re going to do the minimal stimulation IVF or a mini IVF? Do they have to do a few to get to that? Because you’re not pulling out eight eggs sometimes you’re pulling out two. So do you find that they’re probably going to do a series of cycles to get to that good embryo?
Lyndon Chang:
If you’re talking about diminished overbearing reserve and women over 40, no. If anything, you may end up doing less cycles because you’re more successful in creating good embryos. The argument that I would make is that the high stimulation protocols are making things worse. You’re ruining the egg as opposed to helping the egg. So it’s not unusual that like a case that I presented earlier, one cycle, there was nothing. Every cycle we were producing embryos that potentially could have been pregnancies. How can we make things a little bit more efficient? How did in the past, what would we do? In my old center in New York, New Hope fertility, it was New Hope Fertility in New York City, Dr. John Zang basically brought Kato’s Ladies clinic, this idea of minimal stimulation to the United States while we were working to spread this open. What we did in those days, we would just collect bank embryos over and over again and the hope is that eventually one of those embryos would be successful.
But there have been situations where we go through, we run through all the embryos, nothing happens. One thing that has changed things in many IVF centers is PGT preimplantation genetic testing. How can we prevent ourselves from having to bank dozens and dozens of embryos? Well, we could do PGT, we can test the embryos, see if the embryos are more likely to be normal or less likely to be normal. If we get to the point we find an embryo more likely to be normal, we can stop there or we can plan a little bit. We know that two embryos guarantees one child, maybe the patient’s interest in having two kids, you bank your embryo enough to have two children. Another approach would be everybody’s been doing this freeze all nowadays, you take it the total opposite approach. Fresh embryo transfers transfer these embryos as day three, see if the patient gets pregnant and focus on making sure that everything else, cleaning out that uterus, everything else optimizes the chance that a good embryo will actually implant. You do increase the risk of miscarriages in those situations, but at the same time, the hope is that you’re going to be lucky enough that you’ve transferred an embryo that would result in a healthy motor baby.
Lorne Brown:
How wide did you say you would increase the chance of miscarriage?
Lyndon Chang:
Oh, because what happens is we know that as women get older, their risk of miscarriage increases because of chromosomally abnormal embryos. So every time you just randomly put an embryo into a woman’s body over the age of 40 and they should get pregnant 50% or more, that pregnancy is going to be abnormal. They’re going to miscarry.
Lorne Brown:
Well, this is if you’re not testing for,
Lyndon Chang:
If you’re doing fresh embryo transfer, I
Lorne Brown:
Thought it was day three versus day five for some reason I thought because you mentioned putting it in on a day three fresh, so I was wondering if that had anything to do with it.
Lyndon Chang:
No, I mean you could also do a fresh day five. I tend not to do fresh day five fresh blasts, transfers because many of my patients come from outside the area and logistically it makes it difficult because not all embryos are going to make it to blast assist five days, and you kind of don’t want to have a patient linger travel, stay around for an extra week and find out that there’s no embryo good enough to transfer situation like that.
Lorne Brown:
Can I ask this? I want to talk about that. Again. I used to be A CPA, so I have this auditor’s brain, so I’m thinking like, so here’s how, I’m just going to ask the question and then I want to hear if you have a different thought for this. So you had mentioned that you’ll often do a fresh day three because if they have to stay an extra two or three days to get it to blasis, so day five or six, it may not grow to blasis, so you have nothing to transfer and that’d be really disappointing, but we’re just putting in the day three, it’s still not going to give them a pregnancy. So at the end of the day, it’s still unsuccessful because it wouldn’t grow If your lab is good, and this is what I’ve heard, again, I’m the acupuncturist, not an IVF clinic, but if they can’t make it to day five, then the thought process is that day three that wouldn’t have made it day five wouldn’t have ended up as a live birth. So some people would like the idea of knowing versus having to take medicines for the next two weeks and waiting. So what’s your thought on that?
Lyndon Chang:
It’s an interesting point with the laboratory. Is the laboratory really as good as the uterus as an incubator? There was an old,
Lorne Brown:
Well, I would say yes, because on day three we’re putting the embryo in the uterus and the lab is mimicking the fallopian tube because on day three, the embryo wouldn’t be in the uterus, it would be in the fallopian tube. And so if the lab is mimicking the medium of the fallopian tube, then I would think it could be better than the uterus because the uterus shouldn’t have an embryo in it on day three.
Lyndon Chang:
Here’s another point, is the laboratory too good? We know a lot of these embryos are actually a mix of normal abnormal cells. As the embryo starts to split, mutations happen. These abnormal cells develop in the uterus. Is it a Darwinian environment? And then if that’s the case, the healthier cells tend to survive, the unhealthy cells tend to die away in a laboratory environment. If the laboratory perhaps is better than the human body, are you actually supporting these abnormal cells to develop and are you actually forcing these embryos to become abnormal as opposed to these mosaic embryos? We know that mosaic embryos can result in healthy normal babies, but are we perhaps forcing these abnormal cells and forcing these embryos into becoming amyloid cells as opposed to letting the abnormal cells die weight in the body and self-Correct.
Lorne Brown:
Right. That’s a good question. I don’t know if the embryo is self-correcting if it does it differently in the uterus versus a lab. I don’t know if that data exists,
Lyndon Chang:
But, and that’s where there’s a lot of controversy with PGT. How can we be completely confident with the results from PGT that an abnormal cell, I mean abnormal embryo has no chance of resulting in normal healthy babies. Obviously we saw with the first generation NGS, what is it, about seven, eight years ago, many embryos were not transferred. They were called abnormal, but we realized many of those embryos would have resulted in healthy normal babies.
Lorne Brown:
The results
Lyndon Chang:
Have gotten much better than that recently. But at the same time, we don’t have the data right now. The only paper that I’ve seen, we’re talking about maybe 150, 200 embryos that have been transferred in a case like that.
Lorne Brown:
And what you’re reminding our listeners is that we forget that this is technology and we’re advancing, but we’re not at the level of God energy that people have. The expectation, understandably, they want this to work so badly and there’s so much advancements, but at the end of the day, as you’re sharing, there’s just so many unknown factors still, but the technology has come a long way. It’s pretty amazing. And yet we don’t get a hundred percent success, unfortunately.
Lyndon Chang:
Right. We
Lorne Brown:
Kind of alluded to, talked about it a bit, but I thought maybe we just kind of explicitly say, I want to know who the candidates are, and I think I need clarification. I don’t know if I’m understanding the terms correctly, mini IVF and minimal stimulation. To me that sounds the same, but are those two different procedures or are they the same?
Lyndon Chang:
Mini IVF is one protocol. So you kind of say that you’ll hear what this thing called an antagonist protocol or a long protocol. IVF is a particular minimal stimulation protocol that applies to a combination of oral medications and injections. That’s many IVF
Lorne Brown:
And minimal stimulation could be without the oral medication could just be the injectables at a minimal level,
Lyndon Chang:
Yes, minimal stimulation could apply to natural IVFs as well. There’s
Lorne Brown:
No so natural or just
Lyndon Chang:
Minimal, no stimulation there. Yeah. Okay.
Lorne Brown:
Alright. So then we’re going to use the word minimal stimulation because it encompasses more, so it’s lower dose of the FSH type drugs or those lower drug, lower injectables plus oral ovulation drug clomid or letrozole or just a natural cycle where you go in and do a retrieval, minimal stimulation. Who are the candidates that you want to educate them and use this approach with? Who are those patients that you see that you see that they could benefit from this over the traditional IVF in general?
Lyndon Chang:
Well, let’s just take up a person who’s perfectly healthy. They don’t have an issue of age or diminished over reserve, but let’s have a person whose tubes are blocked. We know that the egg quality is probably fine. Tubal ligation, a person with a tubal ligation finds themselves in another relationship. Untying the tubes is not necessarily a hundred percent effective to reconnect those tubes. Again, minimal stimulation might be a good option where you just take some oral medication. We have something called a low complexity IVF cycle where you take some oral medications for five days, one or two days of injection, two or three, you get two or four eggs created. You create those embryos and then I usually just put them back as a fresh embryo transfer at some point, usually day two, day three. And that could be a candidate where they’re technically not fertile, infertile, they just have some sort of blockage in their tubes or maybe a lesbian couple, same sex couple. In a situation like that, the patients are not necessarily infertile. Maybe the iis have not been successful, then a low stimulation protocol might make a lot of sense in a situation like that.
Lorne Brown:
And can you clarify why? Because in these two groups, age or egg quality doesn’t seem to be an issue. So the question is why not do a traditional and get a lot of embryos because we’re not worried about the high FSH may be damaging their eggs and why put it in fresh on day two or three? Why not grow them out to blast for that group?
Lyndon Chang:
Well, medications, I guess you’re in Canada, but in the United States, medications can basically be the cost of the IDF cycle. You’re doubling the cost. We can reduce the cost of medication to $500 even less if you’re just doing oral medications. Another thing that you can do, which we routinely do here at our center, 80 to 90% of my egg retrievals are done under local anesthesia. If you have 20 or 30 eggs to retrieve, it could be done. I’ve retrieved 35-40 eggs under local anesthesia, but it’s difficult and the patients have to be very motivated. Two or three eggs, I mean that takes me no more than five minutes. These patients don’t have to starve themselves. They can drive to work if they want to right after the retrieval. There’s no cost for the anesthesia, there’s no anesthesia risk by the time the patients are asleep under sedation. I can be done with an egg retrieval by that time. So there’s cost benefits and efficiency benefits associated with it.
Lorne Brown:
So the efficiency and the cost. But are we sacrificing success? Because at the end of the day, if somebody’s going to have an increase in the live birth rate, a lot of them would be happier to have the inconvenience of not being able to drive or the expense versus not the success. So we
Lyndon Chang:
Then you talk about the embryos that you have left over, you’ve maybe five, six embryos. Your intention is to only have one child. First embryo transfer is successful. What do you do with those extra embryos?
Lorne Brown:
Right? There’s always those dilemmas, isn’t there? You’re right. And then sometimes people don’t get pregnant the first try, so they only have one and they don’t. So but
Lyndon Chang:
That’s where patient selection, you’re talking about patients who are not necessarily in their egg quality, fine sperm quality, fine. It’s a patient selection issue. Another scenario would be,
Lorne Brown:
I was just thinking, I was thinking that the candidate, I wasn’t expecting you to share the same sex group or somebody who had blocked tubes. I was wondering if your candidates are these people that are older, have a diagnosis of a diminished ovarian reserve, or they’ve been through multiple failed IVFs. I was thinking about how I would predict your population for this.
Lyndon Chang:
Yeah, my specific population, you’re right. My specific practice is diminished ovarian reserve high FSH patients who failed multiple IDF sets cycles doing it one way. The idea is to try it a different way. For my patients with the diminished ovarian reserve, typically I would want them to have a period on a regular basis. Once you start getting very irregular periods where you’re only cycling every other month, every third month, the diminished ovarian reserve, it’s getting into that POI, premature ovarian insufficiency, it can start getting very, very difficult at that point. But age makes a huge difference. If I have a patient who’s very irregular, the A MH is very, very poor, and my ovarian reserve is very poor. If they’re 33, I have a chance there. But if I have a patient with a very regular cycle and a poor FSH and they’re 43, the likelihood is very, very low. Even in a situation like that, I might discourage them from pursuing this, although I know that I can at least give them an opportunity. And for some patients, all they want is that one opportunity before they say, well, maybe we should give up and head over to a donation or adoption.
Lorne Brown:
So with this population that you’re seeing, then you mentioned you want them to be cycling regularly and you start to get into the age group of the forties. I’m curious if your clinic does this based on your, because it sounds like your patient population, a big focus is diminished ovarian reserve, multiple failed IVFs and over 40, are you also doing PRP and growth factors injections? That’s something you do in your clinic. I’m just curious because I’m just starting to hear more about that. And we’ve had a couple of podcast episodes on that.
Lyndon Chang:
Yes, it just makes sense in these situations. So we’re working with a Dr. Pantos from the Genesis clinic in Greece. They were kind of the ones who pioneered all this. So we’re working with them and we do state ridge plasma. I used to have to refer them all the way to my patients, all the way to Greece to do this, but it just made sense. A lot of my patients were asking about it. So we just started our own program and we decided to partner with the people who started it. So we do that. I will counsel my patients on some experimental procedures heading over to the ed clinic in Spain for bone marrow stem cell therapy or thinking about in vitro activation where you’re taking out portions of the ovary and treating those in various growth hormones in the culture media and then reimplant that overate ovarian tissue into the body. I don’t do them myself, but I think it’s my obligation from the patient population that I have to talk about these procedures.
Lorne Brown:
There’s so many things happening and it is nice that you let them know about those resources. And yeah, I’m just curious to see where it’s going to go next. Having observed it since early 2000, it’s been pretty an amazing ride to see how much the technology has advanced. Going back to this holistic approach and just in the integration, is this part of also what you look into? Do you work with other allied health professionals with respect to acupuncture supplements, meditation, Chinese herbal medicine? Is that something that you like for this population as well? Do you have experience with that?
Lyndon Chang:
Yeah, I think that probably in a portion of this population, there’s a lot of depletion of their natural energy or the natural minerals in this group. I think what you guys do is so extensive. There’s no way that I have any, I can be a professional in what you do because I’m already working too hard as it is. So this is where I’m working with, like your colleague, Dr. Mark Sklar. I work with a lot of acupuncturists. Instead of saying, oh, I’m going to have you take these nutrients, which I don’t know how much research I’ve done, I’d rather just send them to a professional, someone who really knows what they’re doing, go to the specialist. And that’s where I depend on you and your colleagues to try to make sure my patient is overall healthy, because that will have a dramatic impact on what I can do for them.
Lorne Brown:
Yeah, it’s nice that integration, and again, at the time of this recording, integration has really come a long way. When I started, it was really difficult to work with IVF clinics and through perseverance. Now we have this integration where we’re referring patients to the clinics for these workups and these procedures like you’re doing, and then they’re referring them to us for a stress reduction diet, the right supplements, acupuncture, herbal medicine. So it’s nice at this time that patients now have the left and right hand talking together. Before patients would keep it a secret. When they saw me, now they’re like, I’m doing this. Or you’re saying, yeah, do the acupuncture while we do this. So it’s nice.
Lyndon Chang:
And what’s nice in California, the scope of practice for acupuncturists or naturopaths is much bigger than a lot of other states or countries, which is nice. So the patients who are not quite ready to see an REI are not quite ready to bring it to talk about this with a western physician, which is basically, I have a little bladder irritation. It might be an early infection. You go into your doctor, they’re going to be doing these tests and cultures and immediately putting you on high dose antibiotics. There’s another step in the process. You can go to your acupuncturist, you can go to your naturopath. They might be able to find some more holistic approach, more natural approach, and may avoid having to go through a lot of extensive testing and very invasive procedures.
Lorne Brown:
And can people, if they’re from outside of the United States, and we have listeners from all over the world, so obviously in the states, but outside, can they contact you to do a consultation? Do you do those?
Lyndon Chang:
Yes. We actually have, I’ve treated patients, actually have a number of patients from Germany. I don’t know why Germany, but a group of patients, a lot of patients from Germany. I get patients from Canada all the time. A lot are from Asia, especially because of our connection with our mother center in Cobe, Japan. So patients do reach out with the diminished ovarian reserve. It is, especially the more difficult ones, where the patients who are not ovulating on a regular basis, it’s difficult when you’re more than three time zones away. So logistically, it just becomes so difficult to be a patient in that situation. It’s not as simple. I will give you treatment. I’m expecting in two weeks to do anrie. This is sometimes how I’m treating you. I’m trying to make sure that the hormones are ideal. I’m waiting for a response. This could be two months, three months, and then suddenly at the very last moment, oh, I need to have you fly here to the United States. So we could do an trie in 48 hours. It’s not ideal. I’d much rather train doctors and teach doctors this. But once again, there is a little bit of a blow back right now from the conventional REI’s about minimal stimulation.
Lorne Brown:
So if our listeners want to connect with you, they can go to your website, Hanabusaivf.com, and we’ll put that in the show notes. Thank you. There’s videos there, by the way, where they summarize their approach to the mini IVF, and they also have videos information on their diminished ovarian reserve and how it works with their mini IVF for those that are interested. And you can also follow the clinic on Facebook, Instagram, YouTube, and LinkedIn. And we’ll put all that in the show notes so people can find a way to connect with you and learn a little bit more about this approach to helping them have a baby with their own eggs for where they haven’t had success thus far. So thank you for your time, Dr. Chung. I really appreciate you letting me pepper you with questions and clarify things. I really appreciate your patience and coming on the show today.
Lyndon Chang:
Yeah, thank you for having me. This is very fun and I am very open to all these questions. It’s always interesting. And the most important thing is just educating the patient so they understand that there are options out there.
Lorne Brown:
Yeah, there’s options out there. Thank you very much.
Lyndon Chang:
Welcome.
Speaker:
If you’re looking for support to grow your family, contact Acubalance Wellness Center at Acubalance. They help you reach your peak fertility potential through their integrative approach using low level laser therapy, fertility, acupuncture, and naturopathic medicine. Download the Acubalance Fertility Diet and Dr. Brown’s video for mastering manifestation and clearing subconscious blocks. Go to acubalance.ca. That’s Acubalance.ca.
Lorne Brown:
Thank you so much for tuning into another episode of Conscious Fertility, the show that helps you receive life on purpose. Please take a moment to subscribe to the show and join the community of women and men on their path to peak fertility and choosing to live consciously on purpose. I would love to continue this conversation with you, so please direct message me on Instagram at Lorne Brown official. That’s Instagram, Lorne Brown official, or you can visit my websites, Lorne brown.com and Acubalance.ca. Until the next episode, stay curious and for a few moments, bring your awareness to your heart center and breathe.
Listen to the Podcast
Dr. Lyndon Chang Bio:
Dr. Lyndon Chang, Medical Director at Hanabusa IVF. Dr. Chang is a pioneer in the field of minimal stimulation (Mini IVF) in the United States. He specializes in a holistic approach to infertility and the use of low-stimulation IVF protocols.
Dr. Chang has helped facilitate live births with patients ranging between 45-49 years old. He has had live births with patients whose FSH (Follicle Stimulating Hormone) ranges from 20 – 166 ml and who successfully conceived through In-vitro fertilization using their own eggs.
Where To Find Dr. Lyndon Chang:
Links to our pages on Mini IVF and DOR
- Our Page on Mini IVF with a video and key points summarizing our approach
- Our page on Diminished Ovarian Reserve and how it works with Mini IVF –
- Diminished Ovarian Reserve: https://www.hanabusaivf.com/unique-approach/diminished-ovarian-reserve/
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