What Happens in an Embryology Lab and Why Patients Should Care

* Note this is an automatic transcription, please forgive the errors.

[00:00:00] Going to be talking with Dr. Marie Werner. She is a fellow in reproductive endocrinology and infertility at Rutgers and she’s at Reproductive Medicine Associates of New Jersey where she has completed an intensive six month embryology training program. She is also one of the lead investigators of the summit study. Those of you who are longtime listeners know that I really appreciate good well-designed research and one of the missions here at creating a family is to be the bridge between the research community and the patient community. It is really important to us to bring you research that will help you in a very practical way make decisions along your infertility path. Your infertility journey and the summit excuse me the summit study is one such study and we’re going to be discussing that today. Other guest is Dr. Michael Tucker. He has been working in the field of reproductive medicine and embryology for well probably close to 30 years now. He is well-known in the field. He was part of a team that was involved with the first successful baby born through the intracytoplasmic sperm injection as well as the team that was responsible for the birth of the baby from the first cryopreserved egg. You know we take all this for granted now. We assume that xey and frozen eggs are just a part or comma and they are common of course and a standard part of our practice. But Dr. Tucker was really innovative and part of the beginning at the end have been involved with some of that cutting edge research and developments in this field. He has also been a long time supporter of creating a family.

[00:01:51] In the past he has served on our board. He has been such a support and quite frankly an inspiration for me personally and because he’s just a really nice person and a fun person. So I think you’re really going to enjoy talking to him. He is the director of embryology at Shady Grove Fertility and at Georgia Reproductive Specialists. This is a real airing of a show that we did a couple of years ago. It is one of the best shows we’ve done on this topic and as you can tell I think this topic is a really important one. It has been very popular and we’re so happy to be able to bring it to you again. Enjoy. Welcome doctors Tucker and Warner to creating a family thank you. Thank you. Well we’ve got a real basic question to begin with it came in from Lisa. She is new with this process she says. I am confused about exactly the role that embryologist placed in my treatment versus the role with Dr. plays my r e will decide on the merits to stimulate my ovaries. And then she turns the X over to the embryologist to grow. Is that about right. P.S. I’m new to this so I have just guessing. So Doctor word are can you address Lisa’s question about the distinction between what exactly and or does it what exactly. An embryologist. Sure I’d love to tackle that question. I know our listeners are thinking that maybe this is a more basic question but really it can be complicated and it depends on the facility that you might be in.

[00:03:20] In general the reproductive endocrinologist does do the initial patient visit and lay out the treatment plan for what strategies might be used for the patient and that includes everything from medication the type of the type of those the sperm that we’re going to use if it’s going to be an artifice. Intracytoplasmic Sperm insemination or if it’s going to be a conventional insemination and then the way out plans for how many days to culture that embryo out in the lab whether it be 3 5 or 6 and whether or not those embryos can go back and are fresher frozen cycle. So the reproductive endocrinologist is laying out the groundwork so that we can determine what will actually happen in the lab. But once the embryo at those eggs are taken out of the patient embryologists really has the domain over what happens next. So the embryologist will follow the guidelines given by the clinician or the reproductive endocrinologist and carry out those plans until the embryos created and either ready for transfer potentially even for an embryo biopsy or for freezing at that point. And so I think it’s a complicated interplay between the endocrinologist and the embryologist and sometimes it can be altered depending on the facility that you’re in. But that’s the basic division of labor and could you just are talking about kind of basics here. What is the distinction between an embryo zygote and a fetus. Sure. Typically most people refer to the zygote as a very early embryo. So once an egg has been fertilized and probably until say one or two of development on day three you start seeing a more formed embryos that will be around eight cells or so.

[00:05:12] And then by age five or six that’s when we get an even greater volume to the embryo and many more cells. And that’s what we call a blastocyst. Once that embryo has been placed back into mom and starts to grow in implants and we see a documented heartbeat most people would call it a fetus at that point. So once you an embryo can zygote as a subsection of an embryo from a nomenclature standpoint and then once once the embryo has implanted and a Heartbeat has been found at that point it becomes a fetus I think that the definition varied widely among the population. But that’s how we see it from our OK good. I just I’m not really sure there’s that much confusion about it but I figure as long as we’re talking about basics we ought to get that one out. All right. You know we’ve been doing this show since 2007 and during that time we’ve seen a steady increase in success rate for IVF treatment in IVF free fertility treatment and IVF. What advances in embryology and embryology labs and well and in medicine in general have resulted in this increase of success rates. Dr. TUCKER Oh gosh that’s a very complex question.

[00:06:36] But when you add that the last the last ten years for sure have seen major steps forward and to put it into a nutshell it’s probably in the general sense it is really about drilling down on selection of embryos so that we’re so much more focused now on finding the single embryo which we can then transfer into the uterus and we hope we’ll have the highest potential to make a healthy Singleton baby so that’s where the focus in the industry has totally shifted in the last decade. For more now the Europeans were a little bit ahead of us on that in some regards but we finally sort of got the memo and that is the case in trying to focus much more carefully on selecting the best most potentially viable embryo. Those steps which have helped us get there were in the first instance focusing on the full quality of the first five or six days of development instead of putting embryos back at the early stages of development. On day two and day three which is still relatively common in many other countries and in some clinics even in the U.S. still see that there are even some reports going back to the 80s with people transferring zygotes just to pick up on that terminology and a zygote is the one cell fertilized egg stage that’s before it’s after fertilization. But it’s the point at which the embryos poised to begin dividing and developing for fear that we would actually mess things up in the lab through inappropriate culture conditions many people over the decades have actually explored putting embryos back very very early on even at the one cell zygote stage but it’s still relatively common day to day three of development when the embryos are somewhere between four and eight cells in composition. But in fact extended cultures throughout the full preimplantation period has been a key to helping us develop a much more routine transfer of single embryos. Now how we’ve done that and I’m sure we’ll touch on this through the summit’s study as development of better culture media systems.

[00:09:19] Additionally there’s been a great deal of focus on improvement of the actual incubation systems. We use the incubators we use no longer looked like big box ovens back in the day that we use for regular cell tissue culture from the labs that I grew up in. Now we’ve moved to much more miniaturised incubation systems which have much closer control on the environment that’s been extremely beneficial and also through the use of time lapse imagery we were able to follow the development of embryos through the first five or six days of development without actually getting us to embryologists involved. There are many of us embryologists which have access through our eye pads to view our patients embryos when we’re sitting in bed having a cup of coffee or even a glass of wine late at night. Now that’s not routine by any means but it certainly has been an enormous shift in the field that it has allowed us much greater access and recognition of what’s happening during that first five or six days of development. And that’s one big lesson and I’ll shut up after that. But one big lesson from that is certainly being that we recognize the lest lest we disturb the embryos by having a camera which does all the work for us. We’re not disturbing the embryos and upsetting their incubation environment. And we’ve learned if nothing else that the less we touch the embryos the healthier potentially more potentially viable they are at the later blastocyst stage which is the very last stage of development. The preimplantation stage that we can handle them in the lab before they have to be put back into the uterus to implant.

[00:11:10] So at this point has it developed such that once the egg and sperm has had have joined and has become fertilized you put it in the culture. Do you have to do. Can you watch it at that point you put it in your incubation system and you don’t ever have to open it up look at it do anything everything is done remotely from that point on. Or did I misunderstand you Dr. Tucker is that kind of hollow that that is one of the technologies which has been introduced in the last five or six years now. Not all my labs have access to that technology. But what it is told us is that actually you can just take your 1 day old one cell fertilized normally fertilized egg your zygote and put it back into culture and if you use a single step mana aphasic medium which is being more popular in recent years then you can actually put that embryo back into the incubator even if it’s a old fashioned big box incubator and not touch it for several days actually through until day five of development. So four days later and then and only thing go in and observe it. Now we grew up in us. Believe you me a embryologists lab rats are very anal we perhaps have historically looked at our embryos much more often than we should have done just because we’re so concerned and fascinated by observing every potential step along the way. But the problem with that is that you have to take the embryo or embryos out.

[00:12:55] Usually they come into a dish with a number all cluster together or even if they’re separated they’re in an individual short tray they have to come out of the incubator that upsets the incubator and upset the environment in the incubator of any other embryos which don’t come out and then they stay out of the incubator for several minutes or more as they get observed and during that time there’s potential for the the ph that’s the acidity alkalinity of the culture medium to drift and also the temperature to drift down. I would think when you have a negative impact. Yes. Well we do attempt to observe the embryos on heated stages and we certainly try and maintain a benign environment outside of the incubator as possible. Having the lab’s relatively warm. But we also do it as rapidly as possible but nevertheless it’s a step that we’re learning but we really don’t need to bother with. Because ultimately what we see at the endpoint on day five or six of development the blastocyst stage if an embryo forms to that point we can relatively easily select which is the most potentially viable. There are and I’m sure this will come up. There are now also additionally the potential for us to go in and biopsy the outer parts of those blastocysts from the affected arm and actually screen those embryos for their chromosomal status and check for their chromosome normality or otherwise. That’s a very popular gambit and it’s being pitched very strongly in the industry as a means to add to the selection potential for those embryos. No no no everyone’s going to have enough embryos potentially to justify that. There is the potential risk that even the biopsy process itself is not going to make the embryo better.

[00:15:02] So that if you have a marginal quality embryo there’s some argument against this process even if it is opening up the the the ladies that were on the question of whether that embryo is chromosomally normal or not. So I’m sure there’ll be more more discussion from on that topic as we go along here. But certainly that Croma thermal screening process called TGF or CCS complete chromosomal screening or preimplantation genetic screening the various acronyms that is being used much more routinely to add to the the and the screening of those late stage plasticizers before we even put them back. We did a research show last week. Yeah I think it was last week on exactly that. The whole discussion of the use of peaches yes our CCS. I wanted to shift now to a study that’s being done at RNA NewJersey it’s the title is summit study. And as I understand it one of the things I so appreciate so appreciate about in a New Jersey site is that they talk about the research which is something I’m very fascinated by and something that we hear at creating a family or are wanting to help disseminate information that the research community is finding to the patient community. Is a dearth of information for the patient community. Not everybody is interested but many are anyways. When I read about this study as I understand it it’s focusing on the conditions in the laboratory and the medium that’s being used to try to determine what’s optimal for embryo growth. Dr. Werner as one of the lead researchers or the lead researcher for this study and I know it hasn’t been published yet so I appreciate your willingness to tell us what you’re finding along the way.

[00:17:04] Are you comparing different types of media that are currently in use or are you. Is that is that what you’re doing. THE SUMMIT study Yeah that’s a good question. Dr. Tucker had referred to this a little that when he talked about monotheistic or single media and what we’re doing is we’ve determined in our lab that this culture will be embryologists and the clinician to select the highest quality and potentially the embryo that’s most likely to implant. So what we’re doing is comparing two different types of media formulations one of which is monotheistic or single that media some people even report in a global media against the more traditional sequential media. And so in development the embryo has two large phases. One is precon action and the other is post compaction and the requirements of the embryo as it transitions between those two stages is slightly different than a monotheistic or single media formulation have everything the embryo needs in relative quantities and it’s exposed to the whole time. Whereas in sequential media has one media developed for that pretty compaction state which is until day three of development and then a second media that the embryo gets placed into for the post compassion stage and that way can alter the level of amino acids glucose high Ruby to better accommodate or at least the thought is to better accommodate the physiologic requirements of what the embryo may need. Now let me out. Let me ask a question. How how do you transfer the embryo from one culture one dish to another one. Do you suck it up in a pipette and drop it over.

[00:18:59] I mean how I mean exactly how do you get it over to the to the to the second culture right. Well basically you have the right idea. So the embryo gets we use what we call stress tests and then you gently aspirate the embryo into a small channel and place it from one media and the other. Traditionally many. Well I would say a majority of labs and Dr. Tucker can correct me if I’m I’m on this defect but typically take the embryos out of the incubator on day three to take a look at them. And so when we transfer them because the embryo is already out of the incubator and it’s placed in usually an ice flat where the temperature environments are well controlled and they really move from that cleavage Change Media to the next stage which is to support BOCES development. And you’re right with a tiny little instrument and it’s in it’s it’s a very small channel material and it gets aspirated in and then placed back into the next media. This is the basic goal to try to emulate the conditions. The basic goal with media to try to emulate the conditions inside of a woman’s fallopian tubes. Dr. Yes exactly. So a lot of the initial research that sequential media formulations are based upon are are based on what the women’s reproductive tract is actually like so that early embryo the compassion embryo is exposed to the fallopian tube or they oviduct in there with these differing concentrations of materials such as glucose movie lactate oxygen and then once it becomes a later stage embryo that post compaction nearing day five days sex it’s going to be entering the uterus at that point where are those concentrations of substances are different.

[00:20:55] So that’s where that sequential media philosophy is based upon. OK. So because it inside of a woman’s body there are different cultures so to speak and because it’s in different places on the in the fallopian tube and then entering the uterus. So what are you find. I mean as I listen to you I can see the I can see the reasoning behind each of them. I mean it certainly makes sense to disturb as least as possible philosophically that kind of fits with my life philosophy. But on the other hand I can see the need for should understand why given that you’re trying to mimic a woman that would fight of a woman’s body. I could see the need for two different media. So what are you finding in your study comparing these to the single and the multistep media of course so that multistep media I think he phrased it very nicely a protest like a back to nature approach trying to emulate what happens in a woman’s reproductive strike and that single stop is we’re letting the embryo to sort of pick and choose what it means along the way. So the first portion of the study we completed last year where we looked at just how likely is the embryo to develop into a day five or six embryo or a blastocyst that would be suitable for embryo transfer. And is there a difference now the way that we designed the study I think is important to just briefly mention. So a lot of randomised control trials will start off with patients and randomised a single patient to one type of media in a single patient to another type of media.

[00:22:34] What we’ve done here is actually we’ve randomised the patients zygotes so after fertilization half the patients fertilized zygotes go into sequential media and half of the fertilized egg go into monotheistic moenia. So with the head to head comparison for each patient. And so I think that study design is very powerful and when we looked at this past year was that the difference in the number of embryos that got to each stage was not different for each patient. So if you place their embryos in the single media verses that used that media their embryos ultimately grew out in culture at the same rate. So that was reassuring because both of these types of media are FDA approved and widely utilized and last across the country. So it was good to know that both are acceptable alternatives to embryo culture. Yeah that’s fascinating partly I guess I’d be a little disappointed if the researcher could be look at this. I want to have I want to see an answer. I will ask you if you were disappointed that feels little perhaps unfair things for them. I think it is a fair question actually because I think the most important question are the most exciting question for me is how will these embryos do once they’re transferred back. So what are the pregnancy rates like for the women whose growth has been split. And I think that’s the most important question and that question unfortunately I don’t have any answer for you yet on because that’s a portion of the study that’s still ongoing. Are you transferring both embryos back into a woman or are you freezing one and transferring one how are you. First question.

[00:24:17] So again I think this is where the study becomes so powerful is where we’re choosing one embryo from the single fat media and one embryo from the two top media and putting those embryos back in. So every woman in this study as long as she has an embryo that’s grown out in each type of media and suitable for transfer is getting a double embryo transfer. So we can see which embryo is most likely to implant and create the baby. Well here’s a stupid question I suppose but how do you know what you insert what you transfer. How do you know which one is which. Right. So that’s good. Very good question. The way that we do here is we are chromosomally screening all of these embryos. But the technology Dr. Tucker mentioned CCS or comprehensive chromosomal screenings we take a small biopsy the outer layer of the embryo known as the affected term and before the embryos implanted and we run the genetic testing to make sure the embryos chromosomally normal. By doing that it also gives us sort of the genetic fingerprints of that embryo and using mom’s blood. And just taking a simple blood test from Mom at nine weeks we’ve been able to fingerprint which embryo it is that actually implants. We can also do it after delivery with instead of drying mom’s blood at about 9 weeks we can actually just swab the inner and outer layer of the cheek of the infant and do fingerprinting that way where we can match the genetic code of the baby to the genetic code of the embryo. Got you. OK. If all of that makes sense especially after birth if you would.

[00:25:59] Ultimately our goal is a healthy birth. So I understand that. Does it matter when you transfer two embryos or is each embryo the first one transfer the second or transfer just as likely to implant. Or is there some sequence where the first one has the greatest chance or are your chances equal. Not that good. This is to you Dr. Werner. It’s kind of talking about the summit just so you know in theory each embryo has its own potential for implantation and the ability of this teen pregnancy. So there are individual chances though your chance of having one embryo implanted chromosomally normal in our lab is about 60 percent and the chance of that second one to 60 percent as well. That doesn’t mean that if you have two embryos back that you’re definitely going to get an implantation. There is some bad out there that maybe having having a double embryo transfer may somehow increase the odds that that second one implanting if one implant before the other. I would say in general there are two separate events and each embryo has its own separate reproductive potential which why is why we think that that is a feasible one. Interesting. Let me stop here and take a moment to thank a few more of our Gold Sponsors and to remind you that it is through their generous support that we bring you this show as well as all the many resources you can find at our website.

[00:27:28] We have the law offices of James Fletcher Thompson they are a South Carolina firm committed to adoption and assisted reproductive law including providing a gestational surrogacy matching program as well as legal services for independent surrogacy. Egg donation and embryo donation matters and we have Nightlight Christian Adoptions. They are one of the pioneers in offering embryo donation and adoption services to clients throughout the world through their Snowflake’s Embryo Adoption Program. A couple of years ago at the American Society Society of Reproductive Medicine conference I attended a lecture on advances in air filtering for embryology Lapps that was resulting in increased success rates. But I really haven’t heard much about that since then. Dr. TUCKER What is the. It’s possible that I’m not hearing much because it’s not a real sexy thing to talk about you know air filtration is not exactly does it feel cutting edge or does it feel like significant advances. But what’s happening with the whole air filtration systems for embryology labs and has the research really panned out to show that it makes a difference in success rates yes it has in two ways the the. This this goes back many years really from the recognition that certain substitution substances in the atmosphere of a libertarian embryo lab can have a very negative toxic effect on the embryo development and these compounds that are sort of generally referred to are volatile organic compounds or VMOs these for short. There’s sort of another aspect to air quality which is a little more tangible in the sense that it is also the particular quality of the air in a laboratory. The number of particle counts per cubic metre is attempted to be as low as possible to what is referred to as a clean room.

[00:29:47] And the reason for this rather more obviously is to exclude particulate matter which may be contaminating the most common of which in traditional old school labs were a mold spore has particularly common this time of year here down in the south mould spores that get into your culture system just through airborne contamination and you end up getting mould growing in your lab dishes. So that’s one of the aspects of cleaning up the air using high efficiency particulates cleaning tools referred to as HEPA filtration systems. So by applying that technology as we’ve done very similar to operating room quality air standards we minimise the amount of Particulate content in the atmosphere in the lab that’s been going on for quite a while. But in the last 10 15 years the focus has shifted. War additionally has focused on adding potassium permanganate and carbon filtration systems to take out these volatile organic compounds they actually absorb the filter systems actually absorb those compounds and reduce enormously the potential risk in the lab from contamination of that sort. A very common illustration of this would be the lab back in the day that was knocking out pretty good reasonable results one day would find all its embryos arresting in development and somebody would discover that oh somebody had decided to come in and renew the bitumen in the carpark outside the clinic. And of course the air handling system was pulling in all the toxic fumes from the Richmond coming into the lab. So it’s a very classic example of how those kind of Votaw will go on it. Ganic compounds can impact the lead. So to say that this is not important would be absolutely untrue so many labs now have much higher quality air.

[00:32:12] And while you can apply certain bandaid systems bringing into old labs stand alone units to filter out the air both in terms of the particular but also the volatile organic compounds the seas sees many more nuclear facilities are having these h vac systems purpose built to deliver that quality of air. Now one last thing the approach to mini incubation systems which are using are avoiding the use of traditionally incubators drew from the atmosphere in the lab to get their air portion of of the gas to put into the incubator. In recent years the mini incubation systems now no longer tend to do that or if they do they do so in a highly filtered fashion. But what they do is they provide an extremely high quality air system within the mini incubators which in a sense positively displace even if you have relatively contaminated external air in the lab which is not too common but by applying many incubation systems you can actually keep your embryos buffered from that that potentially toxic outside air so not very sexy but very revealing in how we approach culture of embryos. You know I often think that so many of the advances in the biological sciences especially are in it and I realise this is not a simple thing but it’s something that it’s a more mundane thing that I mean it’s fascinating I guess I hadn’t really thought about how important that all of a sudden you would be having a well functioning lab and then something as simple as something that was happening outside that just slowly seeped even and probably very minute amounts seeped into the room and the rest of the developed all the embryos parts per million or even billion can have an impact certain of these compounds.

[00:34:30] Another classic example is the panic and in fact now all the clinics I work with and many others I’m sure actually have a policy before anybody from the the building maintenance consider repainting even a car or several floors the way we get a heads up on that just in case there is any way we can accommodate that or stop it or perhaps say look let’s let’s make sure we use Loevy Yossi or or virtually zero level sea paint which emulsion paints which allow reduction of any potential the contamination into the environment in that building. So it’s a lot to think about and just to come back to the the the single step versus the sequential medium approach I think to some extent the the seductive nature of the sequential media which fit theme with a very clear hypothesis of the needs of the embryos as they sit in vitro parallel that they would experience InVivo actually in the body doesn’t totally. All the issues because the sequential media still lack many of the fundamental growth factors that those embryos would experience in in vivo in the body. So that’s certainly a direction of approach addition in a very conservative way looking to adding growth factors into the culture media and the single step media which which had quite a lot to do with over the years there probably for commercial products out there as well as life global there’s GTL from breacher life. There’s a single step. Si Si C from Ervine and another one from Saige culture media. Everybody has gotten on that bandwagon because they recognize singles that media give you at least the potential to grow similar quality blastocyst as a sequential media.

[00:36:53] But there are two other key factors which are of great relevance there. One is it reduces labor in the lab. Now I’m not trying to say that we’re trying to be lazy or anything but anything to minimize the handling of the embryos. Also perhaps more importantly many of your eyes also reduce these risk. And Dr. Warner touched on it and you mentioned the moving the eggs and the embryos from one dish to another. That you know is routine and mundane as that may be that is still another step it’s a it’s another step to introduce a second or third day even that may not have been set up correctly. The more steps you add into this process the more you elevate the potential for risk. So the beauty of the single step media is certainly that in terms of risk reduction but it also just to bring it full circle. There’s a pretty famous reproductive physiologist out of England called Henry Leese who posited a quiet embryo hypothesis several years ago. Now that the quiet metabolizing whoops. Have we lost you. I think that’s what the single step approach certainly subscribes to. And you know that’s why we’ve tended to favor that approach and while not undertaking such an elegant study they are in a group with their double embryo transfers and then just you know fingerprinting of any subsequent implantation of any fetus. We did single embryo transfers of embryos randomly from the single step of the sequential This was four or five years ago now and happily proved to ourselves that we were getting least as good an outcome from the single step grown embryos.

[00:39:03] And if you think about it the in vitro environment that we generate in the IVF labs are in a sense totally unnatural. I mean heaven’s sakes. It is. It intrigues me when people want to minimize make as natural as possible what happens in the IVF process. And the realities are that we’re imposing a totally different set of standards than expectations on these embryos. In many respects. So the beauty of the single stat media is that it harks back to a process referred to as simplex optimisation where you basically take incredibly low level simple medium and just add in until just the point or the expected requirements in terms of nutrients are these embryos just to get them to a point where they’re optimized and adding no more and certainly just enough to to optimize the growth of the embryo. There’s still more to be done and certainly I think in the area of growth factor addition to get us there. But we’re dealing with an in vitro environment. So we may as well start from basics work up and optimize that system instead of talking to some sort of you know hypothetical what happens in nature. Let’s replicate that in the lab. Let me ask you a question. I think you blanked out just very briefly because I do want to move on to a totally different topic here that you blanked out when you were talking about the quiet embryo hypothesis and just in case somebody is curious about that. Just very briefly what was that.

[00:40:50] Well the quads embryo hypothesis is very simple terms it’s the embryo which metabolizes in a very quiet way has no extreme production of stress reaction and having to deal with metabolism basically when an embryo unless it’s focused on its development which had both. So in a relatively modest way if it has to deal with external stressors then it starts to have to metabolize as you say. OK yeah. Ok. Putting an embryo through a cross fit test or some brain. Yeah. It makes it fitter. But certainly for your average embryo is not going to enhance that. It may take out some of the less optimal embryos which would otherwise perhaps go into making a healthy baby. OK let me move now to to address Eleanors question. She said I’m going to read it she said. We found this podcast and creating a family because we are looking for a clinic. I had been working my way through the archives of old shows and they are a gold mine of information. So thank you. You’re welcome Eleanor. I was surprised to see the topic of today’s show because I had never really considered the last part of the clinic. I would like to hear you and your guests discuss what a prospective patient should ask about the lab. What should we be looking for in an embryology lab. Are they all alike so that we don’t really have to think about this when choosing. So Dr. Warner so I’d like to spend the rest of our time talking about what from a patient standpoint what should they be looking for when choosing and embryology lab. So let’s begin with that and you could start with the last question which are they all alike so she doesn’t have to worry about it. Sure.

[00:42:47] You know the great question by Ellen where she correctly identified something that not all patients really think about and is not widely discussed is what exactly can your lab offer you and is it different than other labs out there. You know I think that our philosophy here at Reproductive Medicine Associates of New Jersey is that the IVF Embryology Laboratory is really the heart of what we do and why we think you know our success rates are still high. I think as a patient coming in to a new practice for the first time something that you should make sure in our laboratory should have that sense that they are certified by KLIA which is basically like the National Governing Board to make sure that the embryology lab are following standard procedures and they should all have a certified high complexity lab director directing the workflow of the Embryology Laboratory in India different water. So I mean isn’t that require that they have a high complexity laughter Richter it is. It is a requirement and not the standard set forth by the American Society for Reproductive Medicine. So all of that. But I think one of the most important things is really just looking at the success rate which can be found and publicly available on the CDC’s Web site or on the Society for Assisted Reproductive Technology. So to really look at that ethic Sassen you can pick by age group and potentially the circumstance that each patient might be in to see which you know which places have the highest pregnancy rates and I think that’s very telling of what their laboratories are like.

[00:44:29] Well but there’s one issue though with and we’ve done a fair amount on shows on this the one issue with if you just look at success rates is what you don’t know is do the clinic except all patients are does the clinic weed out patients that are least likely or encourage strongly encourage or not except in patients older patients that won’t go to donor egg and that’s not clear necessarily on the when you’re looking at success rates. OK so what are the things you’ve mentioned being certified by KLIA having a high complexity lab. I’m screwing that up a certified high complexity lab director. What other things should from a patient standpoint and success rates. Because you’re right that’s that’s in Portland as well. Dr. TUCKER What other things can from a patient standpoint they ask before choosing a clinic if they’re concerned or if they want to consider the quality of the lab Well I would say. I always try and approach this from a much more global approach. And having worked all around the world in many different labs while there are differences in the quality that is brought to the embryology side of the equation which can have an impact on clinical success rates from lab to lab I would say in the U.S. in general the differences between labs has certainly narrowed in the last 10 years. So I think that that that’s one sort of big positives. Yet there are still differences in the quality of labs. But be assured that they’re nowhere near as wide apart as they used to be perhaps 10 15 years ago. The other thing I would say is it’s also very important if you’re discussing success rates the whole landscape of IVF and how you report your success rates or outcomes is changing enormously.

[00:46:41] Even in the last couple of years or more the probably the one key area that I would look at if I was a patient or a couple coming to this I would certainly look at the number of embryos transferred to achieve those outcomes because certainly as we recognized multiple pregnancies twins triplets or even worse are a complete train wreck that quickly and are rarely seen as much less a success than they used to be perhaps in prior decades. So that’s one thing. Check and you can you can actually pull up the individual clinic statistics and look at how many embryos across the age groups that they’re actually transferring to achieve the life born outcome. So that’s a really key one to look at. The other one is part and parcel whether or chromosomal screening is being used routinely for embryos prior to transfer in the clinic or not. But one of the great benefits the drivers of single embryo transfers whether fresh or otherwise is a clinic’s ability to freeze or more specifically the neurotechnology is specifically vitrification. If a clinic has a good bottom line in terms of its cryo embryo outcomes the frozen embryo transfer section of their outcomes then that’s a big plus because that’s the major adjunct to the move away from putting back more embryos fresh because if you count free and warm them up and get good viability survival implantation in the cryo program you’re not in the 21st century you’re certainly not in the second decade of the 21st century where vitrification is becoming so much more routine whether Folland chromosomal biopsy for chromosomal screening of your embryos or not.

[00:48:47] The realisation that transfer of embryos back into a frozen thaw cycle in a much more. If we’re talking natural IVF here in a much less disturbed endometrium in a relatively unstimulated or relatively manipulated natural cycle for the embryos for those implantation rates are actually higher than when we put more embryos in a fresh stimulated endometrium. So be assured that you can quote me in ten years from now the vast majority of all IVF will be undertaken following vitrification of human embryos. Yeah I think that’s a fascinating topic and we’ve talked about a fair amount that the move towards allowing vitrification has allowed that one of the questions that I chose not to ask but I was under the impression that the vast majority of embryology lab and infertility clinics in the U.S. do utilize vitrification. Dr. Werner Do you happen to know I might be wrong on that. I think that the majority of clinics to use vitrification the other method would be a method of freezing. But my impression is that a majority left out there do you have Stoli vitrification programs and pressure. Dr. TUCKER can also comment on that. But yeah. You know the hyperbole holdbacks not using vitrification I’d say there are maybe 10 to 15 percent of clinics are now hold but the transition to vitrification has occurred very rapidly in the last five or six years. So to some extent in fairness to those clinics that happened in our own clinic you have a lot of older sloe frozen embryos to work through. So those lesser outcomes from those Plouff frozen embryos will die Lou if you will your success rate moving forward until you’ve utilized them routinely in your clinic.

[00:50:57] One of the things that we’ve actually had patients request from us is to say well I’ve got 10 of those old Slowey frozen embryos that I want to pick through. What if we throw them out and then biopsy them screen them for chromosomal normality and then we can sort of cut it down to three or or so that we actually focus on. We read vitrified those and come back and have those then warmed again and we’ve done that actually a lot. And it’s surprising how well they go through the warming thawing the biopsy and the revision of the vitrification and then the warming again to give them healthy babies following chromosomal screaming. So that’s certainly a tactic that we’ve used. That’s just amazing. All right. So we’ve talked about the factors that from a patient standpoint how did they evaluate a lab. Because quite frankly you know you can. Other than the statistics people go for a number of different ways they choose a lab but not a lab clinic. But often it’s word of mouth. So if we’re taking it into the level of actually digging deeper to understand whether that the lab is one they want to use. We’ve talked about the certification we’ve talked about success rates. We’ve talked about the ability to use vitrification and also a number of embryos transferred although that’s perhaps less strict indication of a lab as it is a philosophy. Oh no not I disagree. Oh yeah. If you can call it the embryos you are happy to put back fewer of them.

[00:52:42] I mean we don’t want to be detrimental if you put back too many at once that if you’re transferring back that high quality embryos because you really get into some serious risk factors when you got even twins. But they’re only triplets or more higher order multiple pregnancies. OK. And so the number of embryos transferred is a good indicator of the quality of the lab because that’s telling you. OK. Exxon OK so that’s a that’s another factor. All right. Any other factors that patients can. Well I tell you what let me before we go any further let me read a question from Eric. We actually got two questions like this I’m going to read Eric’s and I’m going to shorten it just a bit. Eric says My wife and I are going to need donor sperm. We are very worried about getting the sperm to the right egg and getting the right embryo. What are the standard procedures to avoid mixing up eggs sperm and embryo. What question that we’ve got another one about this too. So it is a recurring concern even though it hasn’t been in the news lately. Every time there is a news report something like this happening in there there is about once a year it feels like it is heavily. It just sends a ripple effect through the patient community of fear and and it’s it’s very real. So let’s talk about what the standard practice for mailing chip in there. I mean yeah. Please don’t don’t Dr. Warner certainly mentioned the need for the laboratory to be certified. And part of that process is a recognition the very important recognition of verification steps in what is called Chain of custody.

[00:54:34] And in our case the chain of custody of gametes eggs and sperm and ultimately embryos. So in your high quality clinics and this is the case that RNA is every step of the way is verified whether it’s the accepting of the sperm in the laboratory whether it’s the excepting that the patient for the egg retrieval or somebody goes in the verifies the identity and ultimately from that point onwards once the eggs and the sperm are accepted in the lab there’s incredibly careful verification steps. Chain of custody is absolutely central to how operate in certain noble habes that I’m involved in just for the very reason that any mix ups just wouldn’t allow any of us to sleep at night. So I think that’s a very important question to ask of any clinic is can you give us an illustration of your standard operating procedures in terms of your chain of custody how you handle and how you verify each individual whether egg retrieval semen receipt or ultimately the embryo transfer and even to the point of you know how do you track in terms of identifying your frozen embryos and more increasingly frozen eggs in your system in your clinic. How do you make sure infertile get mixed up. So those are very important questions dwell if you can and should the clinic before you have anything to do with them. And what you’re looking for it sounds like is your standard operating procedure for the chain of custody before. And I’m glad you put in the frozen because what you’re asking for is both the gametes as well as the embryos and both fresh and frozen moment assume that the systems would be in place for both but it would be good too to ask Dr. Warner any other.

[00:56:44] Other than asking the chain of standard operating procedures for chain of custody. Anything else or anything else you can think of that would be directly relevant that a patient could ask to to know that they’re getting a clinic with a lab and not just the doctor that they feel comfortable with but a lab that they feel comfortable with and to give you the last word here. Sure. I think on that first new patient when you’re meeting the doctor for the first time the doctors are really going to be your interface but the rest of the practice whether it be embryology andrology is ask the doctor what their communication is like with the lab. The doctor should be able to answer every question about what happened here embryo in the lab and also be able to explain the procedures clearly to the patient as well and I think be if the patient being able to recognize that there is a clear and open communication between the clinical staff and the and more the reproductive endocrinologist and the embryology laboratory I think that’s really important because it’s not just the doctor and it’s not just the embryologists it’s really the appropriate communication between all sides that can that can have a successful outcome. So I think it’s a very important question for the patient and directly to the doctor. That’s a great idea and see how comfortable they are in talking about what happens in the lab and that gives you an idea of how good the communication is between Ariz and the embryologists. Yeah that’s a great idea.

• What is the role of the reproductive endocrinologist and the embryologist? How do their roles in IVF and fertility treatment differ?
• How does an embryo differ from a zygote and a fetus?
• What advancements in embryology, embryology labs, and in medicine have resulted in the increase of success rates for IVF?
• One of the greatest advances it seems to me is the ability to grow embryos to Day 5 and even Day 6. What has made this possible?
• Is the goal to replicate the conditions inside the fallopian tubes? How do you do that?
• Summit study being conducted at RMA NJ:
  • Focuses on conditions in the laboratory that affect ultimate outcome.
  • Designed to determine the optimal environment for embryo growth in the IVF laboratory.
  • Is comparing media to use for blastocyst culture (day 5 or day 6 embryos).
• Prior studies have shown that culturing embryos in single-step vs. multi-step media have the same outcomes. Both types of media are commercially available and FDA approved for clinical use. This study seeks to evaluate these two media with as regard to pregnancy outcome.
• What improvement have been made to embryo incubation systems in the last several years, and how have they affected IVF success and pregnancy rates?
• Time lapse imagery: how is it being used to improve selection of embryos for IVF?
• What developments have occurred in in air filtering for embryology labs, and why should patients care?Have there been any recent advances in cryopreservation?
• The emphasis has shifted in embryology to how to select the best embryo to transfer. How do you do that now?
• PGS or CCS?
• What should patients be looking for in an embryology lab? What questions should they ask to determine if their clinic’s lab is good enough to help them get pregnant?
• What types of qualifications are common for embryology labs that patients should look for?
• How can patients determine quality control at an embryology lab?
• What can patients and fertility clinics do to avoid the problem of mixed up embryos or egg or sperm? How can you minimize the risk of receiving the wrong embryos or egg or sperm?