Recent clinical trials in Fertility and Sterility from the Asia Pacific region

Hello everybody, my name is Kurt Barnhart. I'm the Editor-in-Chief for Fertility and Sterility and it is my pleasure to travel here to be part of Aspire to introduce a fertility and sterility sponsored journal club global. We envisioned these journal club globals a few years ago to be able to highlight papers in fertility and sterility and highlight local authors and highlight the quality of the science that's done across the world and give our authors and experts a chance to talk about that.

So these journal club globals I enjoy because it's a combination of talking about the science but then a really good conversation about where it can take us and how we can collaborate together. This one I think I'm going to be very much enjoying because we're really not only talking about the science but we're really talking about what are the recent RCTs in the Asia-Pacific region, how do we improve the quality, which is hard because they're already good quality, and how do we use this as an example to increase the amount of really good evidence-based research out of this region and the region in general. So I'm going to hand it over to my co-chair Claire who I think it was wonderful putting this together and I look forward to this so thank you very much.

Thank you, it's a great honor. I'm going to introduce our live panel first. We have Professor Ben Moll from Australia and Professor Richard Paulson from USA and we have Dr Ho Man Tuong from Vietnam.

But we're going to begin with our virtual speaker and we're very grateful to you Professor Zijian Chen for giving some time to us and we have about, you probably can't see us Professor Chen, but we've got about 80 people in the room and of course this session is being recorded so the audience is potentially exponential. But I'd like to invite you first to speak about your recent publication and its underpinning publication, the recent publication in Fertility and Sterility and its underpinning primary publication in the New England Journal of Medicine. So could you please begin your presentation, welcome.

Okay thank you, can you hear me? Yes we can, yeah it's great we can hear you. Okay thank you, thank you for your invitation and thanks to the organization and thanks to the president of TCV. I'm happy to see you Professor Barnhart and also other professors, old friends, Ben Moll, Paulson and Ho.

So it's my pleasure to participate in this fabulous panel discussion. So we are going to discuss about the work of recent RCT in the Asia-Pacific region. Can I show, oh I'm sorry I cannot show my PPT, I'm sorry we need to Can you, are we using Zoom? Oh I'm sorry, are we using Zoom? Yeah can you just share your screen? I don't know what's wrong.

Maybe describe it for us Prof Chen, would that be okay? Yeah okay, I described, sorry. It's okay. I'm from a reproductive medical center from Shandong University in China.

So I would like to introduce the you know the two RCT and the secondary analysis from this RCT was published this year in the Pacific Sterility. We know in recent years single embryo transfer has been widely adopted in clinical practice. The best embryo for the first transfer has been widely sought.

Embryo aneuploidy is considered to be associated with the implantation failure at the miscarriage. So PGT for aneuploidy screen is commonly used in clinic. However compared with conventional IVF, whether PGTA could improve the pregnancy outcome especially in the terms of accumulating live birth rate is unclear before we conduct our RCT data.

So we conducted the micro center RCT in 14 reproductive centers in China. The total 1,212 fertile women aged between 20 and 37 years old. The primary outcome of this RCT was accumulated live birth rate that resulted from up to three embryo transfer.

So in PGT group the embryo was selected by the aneuploidy with the NGS. In IVF group we just use the common live morphology. Our results show that accumulate live birth rate was lower in PGTA group than the IVF group.

The risk of accumulate clinical pregnancy loss was significantly lower in PGTA group than the conventional IVF group. So it was conducted that conventional IVF treatment was inferior to PGTA and result in a higher accumulative live birth rate in women with a prognosis of live birth. So that's what published in the New England Journal in 2021.

And as a common editorial in the same issue we learned that for the PGTA trials was responsible innovation requires normal potential risk reproductive technology be the subject of careful research. After the publication of primary study we performed a secondary analysis to invest the variation in pregnancy outcome between PGTA and conventional IVF treatment across these key groups cataloged categorized by the oocyte cuts. Participants were divided into two subgroups based on the quantity of the number of the oocyte retriever.

Among each group the pregnancy outcome was compared with the PGT and the conventional IVF we did. We found that there was an interaction between whether the performer PGTA the oocyte number catalog on the accumulated clinical pregnancy loss. The PGTA group had a lower accumulated pregnancy of clinical pregnancy loss compared with the IVF group when the number of oocyte retriever was less than 15.

So it was conducted that one I mean by this secondary analysis we found that when the number of a retriever egg was less than 15 of the PGTA group existed a lower accumulated clinical pregnancy loss rate but no higher accumulated life birth rate compared with the conventional group. So this is the two actually the two publications. The first data published in the journal and the second that we published in the reality.

Thank you very much. Thank you very much for that synopsis. That was perfect.

That was terrific. Can I ask our panel to make comment on this paper? You've all had a chance to have a look at it. Tuong would you like to go first? The paper I saw that actually the study compared between the two screening method for selection embryo for transfer.

The first one is morphology and actually the second one is a combined method morphology and PGTA not one by one but one with two. So the PGTA group actually they already screen the embryos by morphology first and then they picked up the morphology base embryos and then they do PGT. So actually in the PGTA group this is the combined method of embryo selection and regarding to the number of eggs less than 15 maybe the group that have lower number of oocytes are the age more age group.

So they have higher risk of unemployment. That's why we find better results and lower loss with the PGTA. Thank you.

That was a good explanation because I wanted to make clear why there was a secondary analysis. So the first study basically showed the non-inferiority of the two groups or of the screening method but one of the questions that remained was are there groups of people where PGTA is going to be more beneficial or less beneficial and the surrogate marker that wasn't so clear was number of oocytes can result to the prognosis of the patient because many are making the argument that the lower the prognosis of the patient the more PGTA might be helpful. Does that make sense Rick? Did you want to comment on that? Yes, well thanks for that Kurt and I mean I think the most important thing is this group should be congratulated for actually conducting a randomized clinical trial which is so difficult to do in IVF and the data are really unique and they should be commended for that.

Trying to do a subgroup that is slightly less good prognosis in this particular study is challenging. This was an experiment that was done in a very extremely good prognosis group. There was less than 25% of the patients who had less than 15 oocytes.

I mean this was a great, great group. They had a follicle count of 22, the estradiol at the time of trigger was 5,900. I mean this was a very good prognosis group.

I would point out that the study asked the clinical question of non-inferiority and what they called a cumulative pregnancy rate but what they really meant was the probability of pregnancy, first pregnancy, in up to three embryo transfers. That's not the same question as saying what is the cumulative pregnancy rate of all of the different embryos that are there because if you became pregnant after the first embryo transfer of course you still had two more embryos left and we are not taking into consideration the implantation potential of those two remaining embryos. Without getting too much into the weeds, the bottom line was that the pregnancy rate was essentially the same in both groups.

It was a non-inferiority study but the one group, I think the PGTA, was 77% after all of the embryos were transferred and the standard group was 81.8 so very similar. I had a very hard time understanding how that was possible because of course PGTA cannot have that low a loss rate. There must be a greater degree of damage from false positives in the embryo biopsy and this is an artifact of a number, a mathematical artifact of trying to look at how many embryos you need to get to that first pregnancy.

This is not the same as the full implantation potential of the two groups which I think is less in the PGTA group. They just turned out that they happen to be equal. So those are the two points I wanted to make.

This was an extremely good prognosis group. The two groups were very similar in terms of outcome but remember that does not mean that there was not damage that took place to the embryos from pre-implantation genetic testing which there was and there was probably a loss rate of somewhere. I tried to go through the numbers of probably around 15 to 20 percent in the PGTA group of potential losses of implantation.

Ben, you want to make a comment? Yeah, thank you and first of all thanks for being a member of this panel. I'm really privileged to sit here and congratulations to Prof Chen and our team to do this type of studies. I've worked in Netherlands.

I did multi-center trials there. I looked at Germany then and I thought, are any Germans in the room by the way, I thought wow if we could get Germany to randomize we would be five times as strong but China doing this study is 50 times as strong. So that is so incredibly important to do.

That's the first thing I want to say and I want to encourage Professor Chen, she's doing that but I just want to underline keep on doing these big studies because we need them. Then to the study itself I think the strengths are the large sample size and the second strength is the cumulative life birth rate as compared to many studies that we have seen in this area that focus only on the first transfer and if you're going to do embryo selection of course your first transfer is going to be better and you think that the technique is actually better but the key outcome for all of us in reproductive medicine is the cumulative life birth rate. The pain of infertility is lifelong so we should really focus on getting the cumulative life birth rate as high as possible and then maybe do it as quickly as possible and reduce pregnancy loss and the pain of death but in that order.

That's also the reason that the authors correctly choose a non-inferiority study. I've seen superiority studies for PGTA but any type of embryo selection is never going to increase the pregnancy rate. We should realize that so superiority studies for embryo selection have a design issue in itself and that's not happening here.

Then I think it's very important to underline that if you read the New England conclusion and I wrote that down conventional IVF was non-inferior to PGTA so if you only looked at the last line you think there was no difference or it was comparable but it's not. It's 4.6 percent less so to say so that is really an important thing that we should consider in safety and non-inferiority studies are difficult to interpret. I have had my battles also with journals who wants you to write down these impossible non-inferiority sentences but we should basically say it is five percent less and then to the subgroup analysis in the fertility real paper it's always good to look into subgroup analysis but realize that because you go into subgroup analysis in four different groups you lose statistical power.

So the pregnancy loss in each of the subgroups is still there but it doesn't reach statistical significance and just by maybe coincidence maybe there is a mechanism the pregnancy loss rate is lower in one subgroup but I would be very careful in translating that to clinical conclusion. It's useful to look in this data. It's good to have been presented in fertility sterility but I would really go with the primary conclusion of the paper that PGTA is reducing pregnancy loss a little bit but it is doing harm also in my opinion and that is a very important conclusion that I have not seen from any study from the west.

That's my first comment. Thank you Ben. One of the advantages of the Journal Club Global is we get to talk to the author.

Apparently not at the very moment because the video cut out but I'll ask the panel this question because I really want to ask Dr. Chen. One of the criticisms of this paper that's acknowledged in both papers is that they only biopsy the three best embryos and not the whole cohort. So I'm curious your opinion and hopefully Dr. Chen's.

How do you think that changes the results or helps us interpret this? As I said the PGT group actually they apply the combined method of choice. Both morphology go to pick up the three best and then they do biopsy and PGT. That is a combined method.

The thing is that because they in the PGTA group they only use up three best embryos. So if there are aneuploidy or mosaic embryo they will lose some embryos. In the other group they can use up all three embryos beyond the morphology.

So the design will have bear some kind of unequal between the two groups. So let me ask the question slightly differently and let Rick and Ben decide too. How do we interpret this in that the practice usually would be to biopsy all embryos and have more available to you.

So should we look at this as we expected a smaller difference because we only had three embryos biopsied or we expected a larger difference or how should we interpret this when we compare to other studies? So from a pure study design perspective I thought the design was excellent. So you had to make sure before you randomized the patients that they had to have at least three blastocysts. So that's what they did.

So there's a side effect of that and that is that you've got this incredibly good prognosis group that is difficult to extrapolate the results from that to 40 plus year olds. But in terms of the study design I thought all of that was very well done. I want to comment on something that Ben said just a second ago and that was the final sentence of the New England Journal study which said that it was non-inferior and then he points out the difference that it's three or four percent different.

I really think that that hugely understates the degree of damage that PGTA does to embryos and it is a mathematical byproduct of calling this a cumulative pregnancy rate. It's not really the total pregnancy potential of that cohort of embryos. It is how long did it take you to get to the first pregnancy.

It ignores all of the embryos that are left over and and and that's actually that's my only beef with this study. My only beef with this study is is that it it underestimates the the cost that you pay to get the benefit of the of the decreased miscarriage rate and the and the higher implantation rates with PGTA. So I thought the study design was great.

So I'm going to direct this question at Ben which is this the same kind of question. I'm going to be the advocate of the devil here. Many of my colleagues say really all they want to achieve in an IVF cycle is getting to the first pregnancy as fast as they can and that is the ultimate goal and I know Ben you're going to say that's not the goal of the woman but but how do we reconcile this because our field wants to go towards the best earliest outcome which may not be in my opinion the best outcome.

So what was I going to say you said? So I would I thought you were going to disagree with that. Sorry? I thought you would disagree with the premise I'm setting up. It's not it's not what I think it's what our patients think and there is a very good study from the Netherlands actually in human reproduction that asks patients what do you think is more important the number of embryos the number of miscarriage the time to pregnancy or the cumulative life birth rate and the scale of that result is such that they can hardly print it in human reproduction right.

So so so the importance of cumulative life birth rate is completely left and all the other things are much less and the reason that we all say to ourselves no no it's about time to pregnancy and reducing recurrent that is bullshit of course right. It is the cumulative life birth rate and if you say something you probably have a conflict of interest with your own wallet. Let me be very clear right.

It is the cumulative life birth rate that counts. Let me give many of us if they're obstetricians they're also have been on a labor ward right. So if you're on a labor ward and and there is a multi-pair of women who has six or seven centimeters centimeters to close then she she says I want to deliver now do a cesarean etc but you know that this woman is going to deliver in 15 or 30 minutes from now.

So it's your professional obligation so to say to coach and mentor that women through it and similarly we have to say to infertile patients in their own interest it is about the cumulative life birth rate. So I'm sorry it might be a little bit longer. So I'm just going to summarize that very important discussion we just had is that there's there is a debate is I guess a kind word to what is the right outcome when you're using PGTA that a lot of the literature is pointing to first transfer success immediate time to pregnancy and Dr. Molen many of us are making an argument that perhaps that's the wrong outcome and this trial got closer to what is a patient-centered outcome which is it's not just the first encounter that I'm worried about it's the overall encounter and how many embryos I have.

So that's the point I wanted to make and I'm glad we made that both in the primary paper and also the secondary analysis and I'm now going to take the chair's prerogative and change a little bit because this topic was not only about this paper but about trials in the region and I really wanted to ask Dr. Teong you you've also your group has made some very significant contributions in this area and I would love for you to describe a little bit them and but also say how you were able to succeed and and conduct such well conducted important trials. Actually 10-15 years ago we decided to do clinical research as our kind of strategy because we found that it is the if we could do good clinical research this is a good way for us to learn and then we can have better practice when we do clinical good clinical research and also we can develop ourselves better with how we have strong background of clinical research so we decided to do and we was a very young group and we don't have that kind of strong academic background so we decided to ask for help so we go for collaboration with our friends and mentor who have a lot of experience with doing clinical trials and we learn a lot and that's how we can we can move quite rapidly during the past 10 years and we provide some good trials and publish so I think that we we should do clinical research and publish and we can get the assistance and the help of our colleges and our professors from all over the world to help us and I think in Asia we have Asia Pacific we have more IVF cycles in more than any other areas in the world so we should contribute something to the to the data and the evidence of in this field this is what we have done. Thank you you you mentioned that one of the barriers was expertise and you found that overseas were there any barriers in recruitment because as I understand it you don't have funded IVF in Vietnam is that right can you talk a little bit about that? Actually we we have Vietnam we have a lot of IVF cycles and we now have more IVF cycles than any other countries in Southeast Asia we can have but we can serve more patients IVF is expensive of course but we can serve more patients because we can control quite well the cost of treatment for our patients even they have to pay their own pocket so they will have more patients and when we have more patients the cost will be lower so and the patients they believe in us and we have more patients we have numbers and we have the expertise and patients rely on us our profession and then when the they ask them to join us for trial so many of them ready to join us and it is why we have good recruitment rate and we can provide good set of data from our practice.

As a clinician when I read these trials we have to make a decision about how extrapolatable the findings are to our own practices do you see any issues for that Tuong and Rick and Ben the extrapolate ability of the findings to clinical practice can you speak about that particularly for this paper that we're discussing today? Well I mean you're always going to have a problem in that the recruitment is going to be specific to your patient population and your geographic area or whatever the other demographics are which is why it's critical to have appropriate control and this was a randomized clinical trial that had randomization and they were able to demonstrate that in fact the two groups were similar so I your point is well taken how can we extrapolate from one ethnic group to another and there may very well be differences. I worry more in the case of for example PGTA and other fertility treatments is that we typically study the group that has the best possible outcome because that's what gives you maximum power it's a lot easier to demonstrate a difference between I don't know 40 and 60 percent than it is between five and and ten percent where that would actually be a doubling and and yet that's you're going to need many more numbers so we always look at the group that has the highest success rate in order to have study power and then we go and we extrapolate so I'm always worried to bring the conversation back to PGTA is that all of our data are in these excellent prognosis patients. We don't have any idea whether a 41 or a 42 year old patient for example can grow embryos to blastocyst in vitro and and how well those older blastocysts tolerate the biopsy procedure and whether in fact the data that we get from the trophectoderm biopsy can be extrapolated to the so I worry more about extrapolation from a good prognosis group to the poor prognosis groups to whom is being applied more so than I think within the different ethnic groups.

Yeah I think one of the points I bring out here is that there are very specific questions in our practice that faces the patient I'm facing in front of me the patients I see in Philadelphia the patients that are 39 to 41 years old the patients that I have trouble getting one or two blastocysts that's a very different question and I want to know the answer. I don't necessarily think I can get it from the experience in this but what I can get from the experience of this is the true efficacy of the intervention. It might not tell me how to peak trace an A but it'll tell me that PGTA is or is not a benefit in general and that I think is the benefit of the science not only this question but the other questions you've done on ICSI or no ICSI or fresh versus frozen those are still techniques that are can be evaluated across the world and whatever the population is and even the next question.

I want to shift gears a little bit to say the value of doing a randomized trial though because look what this spun off right not only is a randomized trial giving us the best most unbiased answer to that specific question but it spun off secondary analysis in areas. It spun off collaborations with epigenetics between our colleagues. It spun off many other great collaborative science and that's the kind of science we need for our field and I want to again congratulate the studies have been done in the Asia-Pacific region because they're very difficult to do in the United States and Europe now.

Ben you gave me an anecdote earlier today about and you mentioned it a little bit today how difficult it is to randomize trial in some of the more developed areas where I can't enroll people in a randomized trial and you said you were having trouble yourself. Yeah I mean that's a reality the amount of paperwork that you have to do to do trials in the settings where I work in Australia and also what I mean the Netherlands where I left 10 years ago has had much more bureaucracy introduced also. That's a reality that luckily is not that stringent in Asia and so if I talk to colleagues from Vietnam or China they say to me oh we have a protocol and now we have to go to ethics and that's going to take a long time right and then you see them worrying and my goodness so how long it's going to take and then they say six weeks right.

I said listen in our setting we take six months right plus and I honestly don't know how this study are actually done in terms of the budget also there is there is no comparison in how efficient you do the studies because you integrate them with your clinical care, you motivate your whole team to do that, you collect the data within your database, there are all kinds of factors that make these studies feasible and in the west we should really reconsider what we try to achieve with all our all our bureaucracy to keep the research as good and safe as possible. Dr. Chiang I was going to ask you and also Dr. Chen who unfortunately we've lost how can you give us a little example of how you were able to recruit so efficiently and so successfully it would be we could all learn from that. Yeah usually we prepare we prepare very carefully the protocol very in details and we discuss in a group we train a group of people we have some good recruiter who can talk with patient who can discuss and who can convince and who can explain to our patient we have that group of people in our centers so we discuss together very carefully before we start to recruitment and actually we we have a privilege that because we are the quite a British group in Vietnam and most of patients know that we are the best in in in Vietnam for that kind of treatment and we have a prestigious of professional activities and we have names and that it that make it easier for us to recruit patient and patient rely to what we have done.

Professor Chen it's lovely to have you back again can you hear us yes we just like to ask ask you the same question that we've just asked Dr. Tuong and that is can you tell us about the barriers to recruitment how do you how do you manage to recruit such a large number of subjects can you take us through that please. Okay thank you thank you also thank you Dr. Ben-Mos comments yeah we actually the similar like Vietnam colleagues there in China we are big population and also we we did several I did several trials on the big sample size I think this very significant and for the clinical for change practice in I think the RCT is very important for all practice in the clinic and in China we have some benefit that we have big population we have a lot of big centers for IVF centers so when they organize this RCT I based on our international colleagues you know some friends help we have an international DSP committee letter committee yeah and the DSP data safety safety committee and we have a proposal committee we have a in a steering committee this big committee and we have some international professors and experts involved and at the beginning now when we started to do our research we train center by center face by face how to recruit a patient how to do our do our research the patient concern form and formation form and also we use the the third independent database the center in China we have all all you know statistic data centers so that is in the past more than 10 years we actually we completed more than six big you know trials this all of them is micro centers at the beginning we are difficult but getting better and better you know our doctors many many doctors or more and more centers are interested in the clinical trial right now because they realize how important the trials the clinical studies to to help us to improve our clinical practice and how important for our made our guidelines of clinical you know consensus thank you so that's a very important message we're I'm talking to two of the largest centers and most successful centers in Asia with these trials I'm I'm in awe at how you can do these so well but there are many people listening in this audience and and when they see this broadcast that might be interested in clinical trials I want to ask you both you said training was important but what what advice do you have for the centers that want to start doing trials that was the most surprising to you or the most paramount to keep this data so the integrity of this data so good and the quality so high what can you share to the smaller clinics that are interested in doing trials I try understand I cannot hear clearly clearly from you yeah we do we you know yeah I force one by one you know and we have class and each center we have you know some doctors we have a group for study from you know primary doctor clinical doctors nurses assistant and and you know they get together and even then learn how to do case by case from beginning how to talk with the case from beginning you know we have a center we have a different committees to do the quality quality control and also we do inside inspection one center by one center beginning then yeah I'm sorry because I cannot get you all what's cannot hear you clean no that answered it wonderfully Dr. Tiang what do you think was the largest barrier to your staff to do a randomized trial was it accepting the concept was it the idea of randomization what needed to be overcome I think we the thing is the most important thing is that all people all staff in our clinic in our hospital have to agree that we have to do it the right way so if someone some people some department they are not how they do not have interest in that and they don't want to do it like that we will fail so the most important thing that we have to agree in our it's it's one of our culture that we have to do research and we have to do the right way actually we we had a lot of mistake at the beginning when we start and Ben was with us at the from very beginning and and we learn we improve from time to time if the whole team decided to to do and decided to improve we will get there with the good help of our friends from experienced friends from many part of the world and maybe add to that the importance and the opportunity of this meeting is that it's actually 10 years ago that we were introduced to each other by Rob Norman at the meeting in Brisbane and I would encourage everyone to to reach out to people with expertise because we're going to go to a setting where the expertise doesn't have to come from abroad or outside Asia anymore it's just widely I mean you having done all these studies um uh the work of Professor Chen other people in the room I see doing the studies the expertise is here also so so if that could expand to other standards and they're gonna with that with that statistical power bring that quality that would be great one other comment about interpretation of the studies and the fact that it's not applicable to your population let us not forget that the first law of medicine is first do no harm so the obligation to show that something works is with every doctor that does these interventions and I don't think that we have the luxury to say we deny the finding that PGTA potentially harms or that ICSI is less than IVF and therefore I continue to do my practice if you say that you have to do the study in your own setting and and and if you're not doing that you're potentially in conflict with Hippocrates chew a little bit on that so I wanted to summarize I asked two world experts here and conducting wonderful clinical trials in reproductive medicine and they both told me the hardest part was to get the doctors to agree that a randomized trial was the right thing to do I didn't hear that you had trouble just talking to the patients is that is that true the patients adopt if if your staff agreed it was the right thing to do your patients agreed uh we have uh an advantage that all most of our doctors they came to us as fresh and they are trained under the same roof so we are very we quite easily to work together and to start something so we we mostly have no problem to have a kind of consensus of doing something and as I said that we have a group of assistants who help because doctors sometimes we don't have enough time to discuss to explain to our patients so after we have a consensus between our doctors and we working with that group of assistants now we will discuss what we're going to tell our patient and they what our assistant will tell to the patient and when they come to doctors so what we're going to add on that to explain and to convince our patient that they they had they should join us to in this trial so we work together as I said that the most important thing that is a culture of the group so they we decided to do it and we do it together. We're a little bit short on time so I'm going to ask everybody to give a final comment and I'm going to start with Dr. Chen.

Dr. Chen congratulations again on all of your studies are you finding it harder or easier and do you have any comment about this trial in general you want to share with us? Oh thank you I don't I don't think it's easier it's still hard if you want to get you know high quality trials you can't keep that it's not easy we have to you know work hard with one cases and the one complete one call and we need we need to negotiate with patients we need to got more trust for our patient and also we need a good team you know train the team to learn how to put quality trials thank you. Why don't we go around the panel just looking at the end Ben why don't you give us a summary of what you think you learned from this session and some advice you can give about trials in in this area? Well what I learned from this session is that that it's very clear that these large RCTs where in many areas of the world people say these studies are not possible they are possible and they're done here so I would encourage everyone to feel inspired by the leadership that we have seen from Vietnam and China here see if you can achieve that the same and I want to congratulate but at the same time challenge aspire being being a host of this to to to endorse this and to create a platform where these studies can continue to happen. So my parting words will be to again congratulate Dr. Chen on her study and to tell you that I'm absolutely in awe of your database and of your ability to complete a study like this and if I could try to convince you to go back and try to analyze the data to even a greater extent so you answered the basic question of the cumulative pregnancy rate but for those I spent a lot of time going through that study trying to reverse engineer what the implantation rates were and how it must have been and how many transfers were in one group and how many transfers were in the other group can you reveal that can you go back and and maybe publish another paper or two and and extract it and say this is what the implantation rate was in the first transfer this is what the implantation rate was in the second and in the third and how many transfers were there in the PGTA group given the fact that the euploidy rate was about 68 or 69 percent.

So please satisfy some of us super curious math nerds who can't get enough of this kind of data and congratulations again. Thank you for the suggestion. We we so after more than 15 years doing this we we think that the one who benefit the most from our clinical trial is our patient who who trust in it who give trusted us and our staff who can learn and do it the right way the better way for our patients.

We're going to have to close this session we're actually over time but it has been very stimulating I'm sure all of the audience will agree and of course there's going to be a virtual audience which is probably going to be enormous but I think 60 percent of the world's population live in Asia-Pacific and to see talented leaders like you harness that potential to study the medical intervention you are absolutely wonderful and again congratulations and let us thank all our presenters the investigators and our panelists and of course visiting editor-in-chief from fertility and sterility thank you my pleasure and I just want to again say thank you for attending a journal club global by fertility and sterility this will be catalogued online both at the fertility and sterility website as well as I hope aspire as well so please share the information and I hope I'll see you again at another menu