5 o'clock session in Hall A. This is something that a lot of you probably have shown up not knowing exactly what to expect. This is a new project that is part of IUGA's plan going forward to increase our knowledge, increase our ability to kind of cohort knowledge into a library on the IUGA website. And it is the International Urogynecology Consultation and like other consultations, we'll be fairly disease specific and the disease we're basically going to cover is pelvic organ prolapse. This stemmed out of an idea from Alex DeGesso and myself about four years ago. We took it to the IUGA board. We said there was no repository out there of the knowledge regarding pelvic organ prolapse and they agreed with us and they said if you guys can work with us to come up with a plan, we'll develop this consultation and that's sort of where it started. So we first identified a need and we felt there was a lack of a sort of a coordinated coverage of pelvic organ prolapse and so we thought we would set up a consultation by bringing together the experts and hopefully you'll agree that we've done a good job with that. The first thing we did is we decided we needed a good governance because as all big projects, you want to make sure that this is very transparent so myself and Dr. DeGesso met with the IUGA executive at the time and the first thing we did is we chose a steering committee and you can read the names here and the steering committee's job was then to select chairs for each of the subcommittees and you can see that we have five chairs for the first round of subcommittees. We developed a standard operating procedure which was sort of the terms of reference, what was expected of each chair, what was expected of each committee member. This is one of our last chairs and being on time was one of the things that we expected, close. So and then we basically had a document that we agreed to, it set up a timeline, it set up expectations and how we were going to get members to the different committees and that was agreed upon by all the parties. We then as a group, the steering committee, the board and the chairs, Dr. DeGesso and myself, we then selected the order in which we were going to look at things and I'll show you this is a three-year rotation and then we also selected the chairs. We then did an open call from the society at large and that was for members to participate in the various writing committees and that went out last year following the IUGA meeting in Vienna. We then developed those committees after we went through the applications, the committee chairs had last say on all the applications but certainly the executive and the consultation chairs, Dr. DeGesso and myself, helped the chairs select who we thought would be the best members for their committees. So the scope of the project, as I mentioned earlier, is basically it's a three-step or a three-year project. As opposed to trying to do one giant project and host it every three years, we felt it would probably be easiest on all involved if we did sort of a one-day project, have it part of the annual meeting. So the first part is this year which you'll be getting the initial findings on from our committee chairs and it was on basically defining pelvic organ prolapse, epidemiology, basic science. After this meeting, we'll be selecting, we've already selected some of the chairs for the next which will be the evaluation and we also will do non-surgical management. You'll be hearing from those folks next year. And then the final year will be on surgical treatment and outcomes. So for defining pelvic organ prolapse, we sort of came up with these five and we thought this was hopefully fairly inclusive concepts and one is the clinical definition. The second was sort of the epidemiology, prevalence, incidence, natural history. The third was the pathophysiology. So pregnant women get prolapse but what is it about pregnancy? The fourth one was patient's perception. We've seen a lot on this meeting about how sometimes we hit the mark, sometimes we don't. If you look at all the questionnaires out there, it's a bit of a hodgepodge of symptoms and so we kind of wanted to get patient's perception and there's a lot of body image stuff out there, et cetera. And then finally, we also wanted to sort of do a cataloging of what are the symptoms associated with pelvic organ prolapse. Is back pain truly associated with pelvic organ prolapse and at what incident and what's the literature that supports that, et cetera. So this is chapter two which will begin, we're currently selecting chairs for. That'll be the clinical evaluation requirements, radiologic evaluation, non-surgical management, disease-specific quality of life tools, and then investigations into associated symptoms such as obviously potential incontinence is one that gets a lot of play, but also defecography for defecating disorders, evacuation disorders, et cetera. And then the final will be treating pelvic organ prolapse. We've sort of dividing it up by obviously the three compartments we most think about, anterior, apical, and posterior. We're also going to have a section on sort of the new technologies, what's out there, what do we know, what do we don't know about them, and then obviously a section on assessing surgical outcomes because that's another thing we've learned over the last several days that we don't always hit the mark on. And can we get a better way of bringing together all of those associated things. So here's sort of the timeline. The first you get, it's a two-year project. A year is spent developing your committee and reviewing the literature. Once you review the literature, then you will build your subsections for your project. We met with all of the groups this year to kind of go through, you know, what we really want them to focus on. They've all done their literature search and then they'll spend the next year writing. They'll each write their section or chapter. That chapter will then appear on the iUGA website. A short summary of that chapter then will be submitted to the Blue Journal for publication. And as I've mentioned earlier, we're currently selecting the five chairs for the second. Following this, once we've identified our five chairs, then there will be an open call for members to submit applications to be on one of the five writing groups for Section 2 or Chapter 2. Chapter 3 then will be defining those chairs after next year's meeting. And the same thing, then we'll have an open call for the membership. Once we have our chapters, so this group today will be writing their chapters over the next year and hopefully published late next year, early 2021. So then in 19 or 2024, excuse me, I'm wrong century. 2024, we'll then assess what that knowledge is. We'll determine if we need to go back and sort of update those chapters. And that decision will then be made by the chairs in consultation, myself and Dr. Gigesu in consultation with the individual section chairs and the aUGA board. Are there any questions as we get started before I have the chairs come up individually and start to go through their subsections? Linda, can we turn on the microphone in the audience? There we go. That's better. First of all, why have you put non-surgical management in evaluation? We kind of looked at that and initially we didn't. We had it as part of the treatment. But because we figured the treatment was going to be a big giant section, most evaluation, most non-surgical treatment is sort of done in the office setting. We're kind of looking at this disease as the patient walks in your office, who is she? Once she's in your office, how do you evaluate her? And then the next step would be, what do you do to manage her? Surgical and non-surgical and non-surgical is more office space. So we kind of put it in there just to keep the sections fairly even. But it's going to bring in physiotherapy and electrical stimulation and all sorts of things that you might not be doing in your office that you might refer the patient on for. Exactly. And that's part of the new technologies as well. So that is going to be part of the treatment along with the surgical as well as surgical innovation. Okay. And the other thing I was going to raise is you haven't mentioned anything about cost or healthcare economics. You'll get that when we get to the patient's perception of disease, part of that subcategory or subgroup's charge was to look at the economics of prolapse and how it's affecting our population and the cost of the disease to the society. So we do have that in there. Yes. All right. Well, with that I'm going to have Sarah Collins. She's presenting for the clinical definition of prolapse group. Sarah. Okay. So I'm going to have Sarah Collins. She's presenting for the clinical definition of prolapse. Hello. Thanks for letting us present our progress so far on our section of the document. We were charged with beginning a document covering the clinical definition of pelvic organ prolapse. My name is Sarah Collins. I'm a urogynecologist from Chicago at Northwestern University. The remaining members of our team, they're all wonderful. Clara Sheck comes from Australia. We have Kim Van Delft from the Netherlands. There are some Americans. We have Michelle O'Shea who is at Duke University. Autumn Edenfield who's in South Carolina. Nicola Dykes who is actually, where is Nikki from? New Zealand. New Zealand. Thank you. And Olga Rahm from California. Our committee formed in about at the end of last year and we had our first few meetings in February of this year. We've been meeting on the phone pretty consistently. Our charge is defining the disease, specifically how symptoms and physical exam findings play a role in an accurate definition of the disease state of pelvic organ prolapse. We also aim to evaluate how radiologic studies fit into specifically defining the conditions. The committee should seek to develop a clinically useful definition of this disease based on what is known about normal support versus abnormal support and how the interaction of physical exam findings relate to pelvic organ prolapse specific symptoms. So to that end, we put together a pretty exhaustive list of search terms after several meetings. We were fortunate to work with a librarian who's very facile in all of the major search engines. Our initial search resulted in over 31,000 references, which together over a several month period of time we've whittled down to about 154 references which we'll be using. And this is very, very small. I'm sorry about that. But we will be initially in our introduction talking about basically the terms that we're choosing to use for pelvic organ prolapse in the most elementary portion of the document. We'll briefly touch on epidemiology, but we do know that that's actually part of another section of the project. We'll be talking about prolapse symptoms in general, the impact that prolapse has both physically for women and psychologically. We'll take another look at symptoms and specifically how they correlate with anatomy and physical exam findings. We'll talk about the ways in which pelvic organ prolapse is measured and reported, both the pelvic organ prolapse quantification system and the Baden-Walker system. We'll talk about flaws with both of those and areas in which there has been research on improvement of those scales. And we will be talking a little bit about imaging, anatomy and imaging. Again, a lot of those topics that are going to be doing most of the heavy lifting and the anatomy sections are going to be taken care of by a different section of the project. And lastly, and possibly most importantly, we will be talking about the patient important definitions of prolapse. So, you know, briefly touching on the very rare but clinically significant incidences in which prolapse can actually be dangerous, but also talking about the symptoms that most commonly women present with and what they aim to correct when they're seeking treatment for prolapse. That's our working outline now. And we hope to have our first drafts coming in the next months. And that's it. Any questions for the clinical definition section? Thank you. Thank you. I'm Lindsay Hayward. I'm on the steering committee for the epidemiology chapter. And I'm presenting on behalf of Heidi Brown, who gave birth to a baby boy on Tuesday, but still managed to join us two days post C-section on Thursday for our meeting. And I think that just shows the level of dedication that she has to the cause. So this is our committee members, Aparna Hegde from India, Bernard from Tanzania, Eliza from the USA, Irvin USA, Giselle Brazil, Hedwig Niels from Belgium, Marco from Brazil, and from Italy, Marcus from Switzerland, and Visha from the UK. So we tried very hard to get a truly international collaboration in this. And Robert Colo is the librarian who's been doing all the searches for us and has done a really fantastic job. So the goal that we were charged with was to assess the overall impact of pelvic organ prolapse, how many women are affected, the incidence and prevalence on a truly global perspective, what the lifetime risk might be of developing pelvic organ prolapse, and the natural history of pelvic organ prolapse only in untreated women, whether it progresses or regresses. We were not charged with looking at outcomes post surgery. The other thing that we're aiming to look at is the future needs for services, particularly what the burden of disease might do in terms of surgical care, given that in large areas of the world have an aging population. So we searched PubMed with a wide range of relevant keywords, which are included here. Interestingly, I saw the other search had 32,000 hits. Ours had 564 results, from which we narrowed it down to 213 abstracts. We screened those abstracts to see whether they looked promising, and from those we found 165 manuscripts that we reviewed in their full length and entirety. These were our criteria for inclusion. The prevalence incidence, natural history, future projections, or evaluation of need for services, with specific focus on POP. We also thought that it was okay to include the general population or specific populations of interest, such as post hysterectomy, obesity, or in the postpartum period. We had a number of exclusion criteria that included things that weren't directly relevant, such as rectal prolapse, neonatal prolapse, and so on. So we also excluded papers that focused on risk factors for POP, rather than pure prevalence and incidence. We used to go through our papers to try and be as consistent as we could, and we've put them on a spreadsheet that we've all handed in now. And then we're just in the process, having selected the full length papers, of going through the reference sections, cross-checking to make sure that there are no other papers that we might have missed in our initial screening. Once we've gone through that, we'll be ready probably in about four weeks' time to divide us up into sections for writing. And these are the following chapters that we've chosen. Prevalence and incidence. Prevalence and incidence in special populations, such as the obese. Natural history, future projections, and need for services, current and future. Our collaboration has been working extremely well, and I think we're all sticking to timeline, and hopefully we'll come up with something very interesting for you to read in about 12 months' time. And you're very welcome to ask any questions. There should have been a question slide in there, that's my fault. There should have been a question slide in there, that's my fault, before the next one. I'm sorry. I would like just to make a comment here. This isn't a Yuga project, even if this is our idea, this isn't a Yuga project. We are at the early stage, we are more than happy to hear any of the suggestions that might come from the Yuga member. So please do not hesitate to contact us, and if you are keen on being on board with us, just please do send an application through, and we will be very happy to continue working with you guys. We've got a young group, and some of our members are recently qualified and so on, so don't feel intimidated by this. It's a very guided process, and we do want truly international representation, so don't feel that you wouldn't be worthy to come forward. We're very interested in everybody applying. My name is Jan de Prest, I'm chairing the committee on the pathophysiology of pelvic organ prolapse. We were charged to find the cause of this disease, but we still have not found it. So this committee was charged to identify and report on the known mechanisms that predispose women to develop prolapse. Of those, a particular interest would have to be spent to the first inciting cause, which is pregnancy, labor, and the way women deliver. The second factor to look into would be the age, and we would try to look into the mechanisms that affect the structural support, both at the anatomical as well as the ultra-structural level, and how delivery contributes to this. Also, we have to look into known genetic factors, family history, predisposition, and we also took literally the advice that we should consult the membership, and I will come back to that at the end, because this is a consultation document. We have a committee that also is covering the entire world, so from the IUGA we have Maria Bortolini overseeing us, and Vivian Aguilar is from the United States, just as Christy Allen-Brady. Then from the United Kingdom, Rufus Cartwright, myself. Then moving to the other side of the world, Hans-Peter Dietz, as well as Yitima Manonay, again from Europe, Mariana Koch, and Dr. Oliveira Brito from Brazil again, and Adi in Israel. I would like to point to you that this is a gender equality in our committee, and we try to do our best to reach that in selecting our members. Recently, we have also extended an invitation to Dulce Oliveira from the group from Porto, who is an engineer who will actually summarize the computational models about delivery. This is what we thought that we should search into literature, looking into genetic factors, which is actually lumping together the literature that reports on family studies, twin studies that have been done, looking into potential genes responsible for prolapse or genetic variants is a more appropriate circumscription. In that section, we will also cover the literature that is showing in animal models how certain genes play a role. Under that category, we would also like to report on what is known on racial and ethnic factors contributing to prolapse. Then, in women with prolapse, what has been documented in terms of connective tissue changes as well as associated conditions that lead to connective tissue changes and put women at increased risk of prolapse, as well as certain congenital anomalies that lead to local structural changes that can lead to prolapse. The big chunk, of course, is anything that has to do with pregnancy, the birth process itself, the direct structural effects it may have on nerves, musculofacial structures. As well as the process of delivery itself, the more obstetrical factors, the management of labor, the mode of delivery, maternal factors such as body mass index, maternal age at the time of delivery, and fetal, what I call biometric factors like head circumference or birth weight. In the last chapter, we will cover what is known about the age of women contributing to prolapse as well as hormonal factors like menopause. We will include a section on animal models that study both age as well as simulated delivery as well as knockout models. What we did is we divided the work amongst four groups in the committee, and I will show in the next slide why that is, and we assigned people based on their expertise. So Rufus, Christy, and Mariana will be covering the section of genetics. Then Peter Dietz, Vivian Aguilar, and Luis Brito will cover pregnancy and delivery. We have added some young colleagues because we have been overwhelmed by the number of papers that we had to look at, age and hormones, also Dr. Brito, Weintraub, and Mananay, and then Maria and myself will cover the literature on animal models and, as I said, computational models, Dulce, Olivier. We took a same approach. Initially, we wanted to cover everything in a systematic way. We have defined our research questions in these four groups. The databases were section-specific. I will show in the next slide, but always PubMed included. And then after triage, abstract and title reading, of course, the data will be extracted in duplicates. Now, this is the section on genetics, which is, so to speak, completed. That was Rufus's group. As you see here, around 1,300 papers were initially selected to come up with a report, so around 66 papers that will be summarized, and that will be a systematic review methodologically, and they will report on multiple SNPs that have been identified. A lot of that work is from a very recent date, genome-wide association studies, and as well on selected genes that are candidate genes for a certain predisposition. So that hopefully will lead to some new insights, how genetic factors play a role into the metabolism of the extracellular matrix, the expression of certain hormone receptors, as well as potential new pathways. You don't have to try to read this slide, obviously, but look here. When we start to search for animal models, labor and delivery, and similarly for ancient hormones, we were overwhelmed by the number of hits. You see 7,000 in the last two columns, so therefore we became a little bit more pragmatical. For those, we will focus mainly on the last 10 years, on new literature on that. Of course, by selecting our papers or leaving out a certain section of the literature, it is possible that we will miss out on some literature, and the way we will try to compensate that is actually do a consultation when we have drafted our document with some experts who may identify gaps that we may have overseen, and we would also suggest to consult the membership, so when we have an interim version of each of these four sections, we would like to have it published on the website and then consult the membership who may identify gaps. This group is, as I said, worldwide. We consult each other every month on the progress, but as you see, living in so many different time zones, Yiti is the real victim because she has to wake up at 4 o'clock in the morning to participate in these teleconferences. The manuscript will be structured like this. We will be covering, as I said, the family history, the candidate genes, and racial differences. On connective tissue changes, we will cover the associated conditions, in particular, changes that have been identified in women with prolapse in certain genes, changes that have been identified in the extracellular matrix, so both changes in collagen, elastin, its metabolic factors, oxidative stress and inflammation, and then for pregnancy, labor and delivery, look to these specific factors that I just detailed before. Same for age and hormones. As you see, we will try to cover what is known on the effect of estrogens, progestins, and, if possible, dissection of the effect of age. What is not covered in here, and that was not our charge, is lifestyle factors, although that, I think, may need to be included in a future consultation document. We will try to take a bit of a quantitative approach for everything that is relating to labor and delivery. There we will try to give more a quantitative approach, but for the rest, we think we will end up with a quite narrative document. So this is the timeline. Everything should be ready by the Hague, just as we were charged, and as you see here, these are the time points that you may expect our documents for consultation, and we hope that you interact with us for anything that we would have overseen. Thank you very much. Can I ask a question? Yes. I'm concerned about the lack of those lifestyle issues. I think that's a mistake to leave that out. I also would ask you to consider the short oral number eight presented on Wednesday, talked about the issue of central sensitization, and I think that's a mistake to leave that out. I also would ask you to consider the short oral number eight presented on Wednesday, talked about the issue of central sensitization and, although it's not a mechanical mechanism, that is sometimes explaining why people have a tiny little prolapse and they feel a terrible bulge. So those are two issues I'd ask you to consider. The issue I think for the physical exam, sort of not matching up with the symptoms, will be covered in the group that's looking at the associated symptoms, which you'll hear from next. I agree, lifestyle. That is something that we sort of, I believe, have a little bit overlooked, and we'll address that. I agree with you. I think that's very important. And that's, again, why we're presenting it to a much larger audience, is we've now got hopefully three or 400 heads thinking about this versus six or seven, and then initially, and then another 20 on top of that. So thank you very much for your comments. Exactly. I mean, what we're showing today is what we think will be the best way to go forward. But we would like to present this project to you today, and we're looking forward to hear from your comments, suggestions. This is still the early stage, so please do not hesitate to stand up, take the microphone, and telling us what do you think we should do. One other question for clarification. Where will the mechanistic studies on the nature of prolapse be? Will that be in this committee or other committees? I wasn't clear whether the last line there was just biomechanical models of birth injury or whether that also include mechanistic studies of what prolapse is. I'm afraid I did not exactly understand the question over here. Could perhaps anybody? No, I couldn't hear it. We couldn't hear it. Where would the mechanisms of birth injury be discussed? Would it be in your chapter? Sorry, yes. So in the chapter on birth injury, we would like to cover that, what exact mechanisms are described. That's why we also included the computational models. But we will try to cover that. At least we consider that our task. And I would suggest it be its own heading if we're talking about prolapse. That we shouldn't only think about what leads to it, but we should also have equal emphasis on what it is. Just a suggestion to consider. John, a little bit of that will be covered as well in the definition when they're looking at the anatomy and how the anatomy of prolapse functions in the various radiographic. And I think that's probably where we'll see a little bit of that come in. But I'd love to hear your thoughts. And if you specifically have any references, please let us know. We'd love to hear them, because we'd like to incorporate that as well. Thank you. Great, thanks. Dudley? Thank you very much, Steve. And I'd like to thank Ayuga and the board for offering me the chance to chair this committee on patients' perceptions of disease and the burden of pelvic organ prolapse. I'm Dudley Robinson. For those of you who don't know me, I'm a urogynecologist from London in the UK. And we're being steered in the right direction by Chantal Dumoulin from Canada. So we have a truly international committee. From North America, we have Gerry Lauder and Kathy Helfish. From Europe, we have Maurizio Serrati, Svetlana Lozo. From the UK, we have Suzanne Hagen. I think we've just about counted Europe still at the moment. Chiara Getty, also from North America. Simferose Chan from Hong Kong. And Lisa Proliligad from the Philippines. So what we wanted was a global representation on our committee, which I hope we've got. So what are the aims of our committee, and what was our brief? Well, it's to look at women's perception of prolapse, so how women perceive their symptoms and how that affects them. Going on further than that, the relationship of their prolapse to their own body image, their own perception of their body image, and clearly their own health. The effect of prolapse on health and well-being and how that affects them on a daily basis, and the impact of those prolapse symptoms in terms of their general well-being. We're going to look at outcomes, so looking at treatment goals. The perception of treatment benefit and how that's measured, what we hope to happen following treatment. An evaluation of prolapse health-related quality of life measures. And also, we're going to have a look at some of the costs of urogenital prolapse to society. So we've done something slightly different to some of the other committees. We've broken it down by section, and then each of us have taken some sections in terms. So this is the section on impact on health and well-being. And as you can see, Svetlana's going to be looking at urinary symptoms. She's done an initial search using the search terms you see there, SUI, OAB, nocturia, voiding dysfunction, and urinary retention. She's identified 500 papers, and she's currently reviewing those to see how many should be selected. Simferosa is looking at bulge symptoms, so she's done a search using the search terms bulge and prolapse. She's identified 64 papers, and she's selected 10 so far for analysis. And Maurizio, he's going to be looking at sexual function and bowel function, and I understand his search is currently a work in progress. Perception of prolapse is being looked after by Jerry, Lisa, and Chiara. So Jerry's going to be looking at body image. So you can see he's searched for pelvic organ prolapse, found 136 articles, and selected 15. Urinary incontinence, 684. Bowel symptoms and fecal incontinence, 498. And sexual function, 869. Lisa's going to be looking at the overall patient perception of their prolapse condition, and also within that, looking at the effect of how that changes with age. So she's going to be looking at physical and psychological impact, the barriers that patients may have to seeking care, and also the motivation that they may have to seeking care as well. So those searches are ongoing. And Chiara's going to look at mood, which I think will be absolutely fascinating. So she's going to be looking at the association of prolapse with depression, anxiety, sleep, and just general patient mood overall. And she's done a search, and she's identified 158 papers, and she's currently selecting those which are pertinent to what we want to know. So in terms of cost and cost effectiveness, as Linda said, I think this is an incredibly important thing to look at. So this is being chaired up by Suzanne Hagen, with a little bit of help from me. And we're going to look at this in two different ways. We're looking at the cost to women of having prolapse in terms of their comorbidities, having to take time out of their comorbidities, and also in terms of sickness absence. And then we're going to expand that and look at it in a much bigger way, and look at the economic impact of prolapse in terms of society. So in terms of cost to health services, of treating prolapse, and also cost to society in terms of loss of productivity. What we're not going to do is look at individual costs of each operation, because I think that's probably going to come up in some more surgical chapters later on. So you can see Suzanne's started her search, looking at pelvic organ prolapse, sickness absence, economic productivity, and work are the search terms she's using. In terms of thinking about how we measure outcomes, so this is Cathy Hilfish, looking at patient treatment goals. So you can see Cathy's already done her search, looking at the search terms goals and pelvic organ prolapse goals. Pelvic floor expectations, pelvic organ prolapse, and expectations in pelvic floor. So she identifies 364 papers, 74 she's selected for further analysis, and she's used 33. And Cathy's streets ahead of the rest of us. She's already written an initial draft. In terms of prolapse quality of life, this is something that myself and Chantel are taking on. So we're now focusing on prolapse disease-specific health quality of life questionnaires. Both Chantel and myself also have a role with the International Consultation on Incontinence. So as one of our source documents, we're going to be using the searches we performed for the sixth report, which was performed in 2016. And then I've now updated that search from August, 2016 through to August, 2019. And you can see the search criteria. I've used questionnaire, pelvic organ prolapse, and quality of life. And all of those, I've found 262 papers of which I've retrieved 25 for further analysis. So when we're putting all of that together, this is the sections that we envisage in terms of our narrative review. So we'll have the impact on health and well-being, patient's perception of prolapse, the cost of that prolapse to society, treatment goals, and also a short review of health-related quality of life. In our section, this is gonna be relatively short because in the next chapter, if you like, chapter two, there's gonna be a much more in-depth look at prolapse quality of life questionnaires. We'll finish our narrative review, as I think all of our authors will, with looking at gaps in our knowledge, and of course, that's useful in terms of proposals for future research. So that's our plan, and hopefully this time next year, we'll be able to show you the fruits of our labors. And I'd like to finish by thanking all the incredibly hardworking members of my committee, and thank them for my support in what's an arduous process. And I'd like to take any questions if you have any. Thank you very much. Thank you, Dudley. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. 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Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank You don't have to try to read this slide, obviously, but look here, when we start to search for animal models, labor and delivery, and similarly for ancient hormones, we were overwhelmed by the number of hits. You see 7,000 in the last two columns. So therefore, we became a little bit more pragmatical. For those, we will focus mainly on the last 10 years, on new literature on that. Of course, by selecting our papers or leaving out a certain section of the literature, it is possible that we will miss out on some literature. And the way we will try to compensate that is actually do a consultation when we have drafted our document with some experts who may identify gaps that we may have overseen. And we would also suggest to consult the membership. So when we have an interim version of each of these four sections, we would like to have it published on the website and then consult the membership who may identify gaps. This group is, as I said, worldwide. We consult each other every month on the progress. But as you see, living in so many different time zones, Yiti is the real victim because she has to wake up at four o'clock in the morning to participate to these teleconferences. The manuscript will be structured like this. We will be covering, as I said, the family history, the candidate genes, and racial differences. On connective tissue changes, we will cover the associated conditions, in particular, changes that have been identified in women with prolapse in certain genes, changes that have been identified in the extracellular matrix, so both changes in collagen, elastin, its metabolite factors, oxidative stress and inflammation. And then for pregnancy, labor and delivery, look to these specific factors that I just detailed before. Same for age and hormones. As you see, we will try to cover what is known on the effect of estrogens, progestins, if possible, dissected out the effect of age. What is not covered in here is, and that was not our charge, is lifestyle factors, although that, I think, may need to be included in a future consultation document. We will try to take a bit of a quantitative approach for everything that is relating to labor and delivery. There, we will try to give more a quantitative approach, but for the rest, we think we will end up with a quite narrative document. So this is the timeline. Everything should be ready by the Hague, just as we were charged. And as you see here, these are the time points that you may expect our documents for consultation. And we hope that you interact with us for anything that we would have overseen. Thank you very much. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. A short oral number eight presented on Wednesday talked about the issue of central sensitization. And although it's not a mechanical mechanism, that is sometimes explaining why people have a tiny little prolapse and they feel a terrible bulge. So those are two issues I'd ask you to consider. The issue, I think, for the physical exam, sort of not matching up with the symptoms, will be covered in the group that's looking at the associated symptoms, which you'll hear from next. I agree lifestyle. That is something that we sort of, I believe, have a little bit overlooked and we'll address that. I agree with you. I think that's very important. And that's again, why we're presenting it to a much larger audience is we've now got hopefully three or 400 heads thinking about this versus six or seven, and then initially, and then another 20 on top of that. So thank you very much for your comments. Exactly. I mean, what we're showing today is what we think will be the best way to go forward. But we would like to present this project to you today. We're looking forward to hear from your comments, suggestions. This is still the early stage, so please do not hesitate to stand up, take the microphone, and telling us what do you think we should do. One other question for clarification. Where will the mechanistic studies on the nature of prolapse be? Will that be in this committee or other committees? I wasn't clear whether the last line there was just biomechanical models of birth injury or whether that also include mechanistic studies of what prolapse is. I'm afraid I did not exactly understand the question over here. Could perhaps anybody? We couldn't hear it. Where would the mechanisms of birth injury be discussed? Would it be in your chapter? Yeah, sorry. In the chapter on birth injury, we would like to cover that, what exact mechanisms are described. That's why we also included the computational models. But we will try to cover that. At least we consider that our task. And I would suggest it be its own heading if we're talking about prolapse. That we shouldn't only think about what leads to it, but we should also have equal emphasis on what it is. Just a suggestion to consider. John, a little bit of that will be covered as well in the definition when they're looking at the anatomy and how the anatomy of prolapse functions and the various radiographic. And I think that's probably where we'll see a little bit of that come in. But I'd love to hear your thoughts. And if you specifically have any references, please let us know. We'd love to hear them because we'd like to incorporate that as well. Thank you. Great, thanks. Dudley. Thank you very much, Steve. And I'd like to thank Ayuga and the board for offering me the chance to chair this committee on patients' perceptions of disease and the burden of pelvic organ prolapse. I'm Dudley Robinson. For those of you who don't know me, I'm a urogynecologist from London in the UK. And we're being steered in the right direction by Chantal Dumoulin from Canada. So we have a truly international committee. From North America, we have Gerry Lauder and Kathy Helfish. From Europe, we have Maurizio Cerati, Svetlana Lozo. From the UK, we have Suzanne Hagen. I think we just about counted Europe still at the moment. Chiara Getty, also from North America. Simpharos Chan from Hong Kong. And Lisa Prolidigad from the Philippines. So what we wanted was a global representation on our committee, which I hope we've got. So what are the aims of our committee and what was our brief? Well, it's to look at women's perception of prolapse, so how women perceive their symptoms and how that affects them. Going on further than that, the relationship of their prolapse to their own body image, their own perception of their body image, and clearly their own health. The effect of prolapse on health and well-being and how that affects them on a daily basis, and the impact of those prolapse symptoms in terms of their general well-being. We're gonna look at outcomes, so looking at treatment goals. The perception of treatment benefit and how that's measured, what we expect or what we hope to happen following treatment. An evaluation of prolapse health-related quality of life measures. And also, we're gonna have a look at some of the costs of urogenital prolapse to society. So we've done something slightly different to some of the other committees. We've broken it down by section, and then each of us have taken some sections in terms. So this is the section on impact on health and well-being. As you can see, Svetlana's going to be looking at urinary symptoms. She's done an initial search using the search terms you see there, SUI, OAB, nocturia, avoiding dysfunction, and urinary retention. She's identified 500 papers, and she's currently reviewing those to see how many should be selected. Shimpharosa is looking at bulge symptoms. So she's done a search using the search terms bulge and prolapse. She's identified 64 papers, and she's selected 10 so far for analysis. And Maurizio, he's gonna be looking at sexual function and bowel function, and I understand his search is currently a work in progress. Perception of prolapse is being looked after by Jerry, Lisa, and Chiara. So Jerry's gonna be looking at body image. So you can see he's searched for pelvic organ prolapse, found 136 articles, and selected 15. Urinary incontinence, 684. Bowel symptoms and fecal incontinence, 498. And sexual function, 869. Lisa's gonna be looking at the overall patient perception of their prolapse condition, and also within that, looking at the effect of how that changes with age. So she's gonna be looking at physical and psychological impact, the barriers that patients may have to seeking care, and also the motivation that they may have to seeking care as well. So those searches are ongoing. And Chiara's going to look at mood, which I think will be absolutely fascinating. So she's gonna be looking at the association of prolapse with depression, anxiety, sleep, and just general patient mood overall. And she's done a search, and she's identified 158 papers, and she's currently selecting those which are pertinent to what we want to know. So in terms of cost and cost-effectiveness, I think, as Linda said, I think this is an incredibly important thing to look at. So this is being chaired up by Suzanne Hagan with a little bit of help from me. And we're gonna look at this in two different ways. We're looking at the cost to women of having prolapse in terms of their comorbidities, having to take time off their usual activities, and also in terms of sickness absence. And then we're gonna expand that and look at it in a much bigger way, and look at the economic impact of prolapse in terms of society. So in terms of cost to health services, of treating prolapse, and also cost to society in terms of loss of productivity. What we're not going to do is look at individual costs of each operation, because I think that's probably something that's best covered in the more surgical chapters later on. So you can see Suzanne's started her search looking at pelvic organ prolapse, sickness absence, economic productivity, and work are the search terms she's using. In terms of thinking about how we measure outcomes, so this is Kathy Hilfish looking at patient treatment goals. So you can see Kathy's already done her search, looking at the search terms, goals and pelvic organ prolapse, goals and pelvic floor, expectations, pelvic organ prolapse, and expectations and pelvic floor. So she identified 364 papers, 74 she selected for further analysis, and she's used 33. And Kathy's streets ahead of the rest of us. She's already written an initial draft. In terms of prolapse quality of life, this is something that myself and Chantel are taking on. So we're now focusing on prolapse disease specific health quality of life questionnaires. Both Chantel and myself also have a role with the International Consultation on Incontinence. So as one of our source documents, we're going to be using the searches we performed for the sixth report, which was performed in 2016. And then I've now updated that search from August 2016 through to August 2019. And you can see the search criteria. I've used questionnaire, pelvic organ prolapse, and quality of life. And all of those, I've found 262 papers of which I've retrieved 25 for further analysis. So when we're putting all of that together, this is the sections that we envisage in terms of our narrative review. So we'll have the impact on health and well-being, patient's perception of prolapse, the cost of that prolapse to society, treatment goals, and also a short review of health-related quality of life. In our section, this is going to be relatively short because in the next chapter, if you like, chapter two, there's going to be a much more in-depth look at prolapse quality of life questionnaires. We'll finish our narrative review, as I think all of our authors will, with looking at gaps in our knowledge. And of course, that's useful in terms of proposals for future research. So that's our plan. And hopefully this time next year, we'll be able to show you the fruits of our labors. I'd like to finish by thanking all the incredibly hardworking members of my committee and thank them for my support in what's an arduous process. And I'd like to take any questions if you have any. Thank you very much. Thank you, Dudley. Thank you. Dudley, Angie and I have been sitting there looking at the lower urinary tract symptoms, and we think you may have missed lots and recurrent urinary tract infections. Thank you very much. Dudley, there seemed to be perhaps a bit of apparent overlap between your committee and my committee. How are you going to view the different urinary symptoms and sexual symptoms and bowel symptoms in the format of your particular chapter? I think we're aware that there may be some overlap, and I think Steve's very aware of that as well. And so we had a long discussion in our committee meeting yesterday just how to go about that. And we're going to really focus on prolapse, and that's the key thing we're looking for, and then the other symptoms as a sideline. But I think we're going to have to be very careful, and maybe we need to sit down together and look at that together. Thank you, Dudley. Thank you very much. Thank you. Well, thank you very much for being here and interested in this project. We're taking heart into completing. The committee that I was charged with was the one related to the prolapse-associated pelvic floor dysfunctions. And these are the members of my committee. I have to acknowledge their tremendous work and commitment and enthusiasm. We have mostly urogynecologists, but we do have a urologist as well. We have representation from North America, India, Netherlands, Poland, so we have a good sampling. I also would like to acknowledge my librarian who has been instrumental in providing me with research research, and I do have a medical student, Tiffany, that's also assisting me on this project. So the goal of our committee is to describe how pelvic organ prolapse may affect other spheres of the pelvic floor function. So for that purpose, we are going to focus on which other dysfunction women who are affected with pelvic organ prolapse may experience. So we're trying to seek to see which lumbar intract symptoms or sexual dysfunction or pain symptoms or gastrointestinal symptoms are described as being associated with pelvic organ prolapse. So our search was performed by the librarian, as I stated, and what we did is that we searched MEDLINE, Embase, and CINAHL databases, filtering for humans and female, and published no more than 20 years ago. Our committee has native language knowledge in English, Dutch, French, so that we have included those languages. So what we did is we basically performed broad searches in those four spheres of pelvic floor dysfunction, and then we also searched for prolapse, and then we intersected each of those sections between prolapse and other dysfunction. I'm bringing up here the, actually, MEDLINE search words that we use for transparency, and obviously, if you feel something has not been included, I would, I welcome suggestion. We did cast our net very wide. So this is in the, for prolapse, what we searched in CINAHL and MEDLINE, and these are the Embase search. And for lowering tract dysfunction in MEDLINE, we looked at those symptoms, and that will include unitrac infection. And in Embase and CINAHL, those are the search words that we've used. For sexual dysfunction, we also included a number of different aspects, orgasm, libido, desire, et cetera, trying to cast our net wide. For pain, you know, people have symptoms of vaginal pain and sexual pain or back pain and abdominal pain, and so we really decided to go super wide, and this search is actually very broad in order to try to catch all of those different kind of pains. This is why there's actually very few keyword, but it really explodes the word pain in the search. For gastrointestinal dysfunction, those are the text word we use. I do know that there's kidney diseases there. That's a little bit broad, but again, we'll be able to sort out our literature. And finally, in Embase. So at the end of the day, once we did these searches, these are the number of, after we removed the duplicates for the prolapse and LUTs, we had 3,500 separate abstracts for the GI, we had 1,500, et cetera, pain, nearly 2,000. So what we did is that we looked at these and divided the committee members into those four sections, and each of them independently reviewed the abstracts and decided the abstract was suitable for inclusion for full-text review. And we used a software called Covidence, which worked quite nicely for that. If there was a conflict between the two members of the committee in whether or not an abstract should be considered to be for full-text review, then there was a third person that was breaking the tie. So we have come to this point right now where in those different four sub-searches, we have a total of nearly 1,000 articles that we are now going to review the full-text. We're uploading this into Covidence so that all the committee members are able to find the article easily. And they will be looking through the methodology of the studies to see if the information that we're seeking align with our question. So we do have a few criteria that will determine what will be acceptable from the full-text to decide whether or not this article is going to be assessed for quality and extracted. So each member of the committee independently will determine looking at the full-text to see if this article has a value. And to qualify a paper must include primarily a population of women with prolapse, evidently. And it has to be assessed using a validated system, so that would be either the PopQ or Baden-Walker. They also have to have a description of pelvic floor dysfunctions in any of the four major topic area we've covered. And those symptoms should be ideally evaluated through a validated questionnaire. Now we're not gonna take a study that has just a summative score on the questionnaire because that provides no information. We will take studies that will have information on the actual report of frequency of symptoms for each of the questions, or at least a subset of the questions from the validated questionnaire. If there's no studies with validated questionnaire, we'll look at other structured interview that may have been done, or any other reporting of symptoms, even if it's not validated, depending on what the quality of the other studies that we have. As we're going through the abstract, we're seeing that there's a number of articles that are surgical trials for prolapse. And we've chosen to include those patients if they have baseline data. We're not gonna look at the result of how the surgery performed on them. That will be phase three of the project. But we're gonna see if they have prolapse as their inclusion criteria, what were their baseline symptoms they complained of? That will be something that we'll be using to the purpose of this chapter. What we're going to exclude is studies that have, as an inclusion criteria, women that have prolapse and, so prolapse and dysfunction of some sort, incontinence, obstructive defecation, because then that really limits the population, and it creates a subpopulation that would limit the generability of the information that we have. We also exclude a study that will assess women only after surgery, so for which there's no baseline information. And we also excluded studies that look at, as a primary population, women that have a pelvic floor dysfunction that is not prolapsed primarily, and that may or may not have prolapse. So that, by example, I would say, studies that would look at the treatment of having a group of women that have stress and incontinence that have surgery. That's the primary criteria, stress and incontinence. Some may have prolapse, some don't, but that's not what the population we're looking for, so those are not being included. Once we have, the next step at this point, because we have our full text for screening, once we have the data that we feel may have an interest, the article has value, we will be assessing its quality. And we are using the critical appraisal tool from Harvard University, the Specialist Unit for Review Evidence. We're gonna pick a few items on that, not all of it is relevant for this particular project, but we're gonna be able to assess if there's any source of bias that would invalidate the results of the study. The chapter will be divided in four main sections. So one, we will be just clarifying again what was the goal of the committee, what we were seeking to do, what was our review methodology, and this is basically what I presented to you today. And then what will be the results will be in women with pelvic organ prolapse, what is the prevalence of the different type of symptoms, gastrointestinal symptoms, like pain and sexual symptoms as well. That will also help us to identify where is there knowledge gaps to be able to establish priority area for future research. I welcome any questions. Thank you. And I believe that's everybody for the five committees. We've identified a couple of areas that we need to spend a little bit more time on and we'll discuss that within the different committees. Are there any other questions, comments, or concerns? I have a question for the last speaker. Yes. Melissa Cawood, Augusta University. I'm a physiotherapist. I had a question about some of the, you said symptoms, also including function. I can't complete, is there any assessment or inclusion of that as something that interferes with their lifestyle, but maybe also some lifestyle inclusion like Dr. Shelley was speaking about earlier? No. This was not in the scope of this particular chapter in terms of looking at impact on lifestyle. I would be more, I would think on burden of disease. We're looking at specific pelvic floor dysfunctions associated with prolapse. Well, I guess in one of those chapters, you said that you would be looking to pain symptoms. I just wonder about the patient's report of functional symptoms. You know, I'm impaired. I have an impairment because I have this prolapse. Oh, sure, sure. I would like just to clarify, yes, we're looking at that. It might be across an overlap between two committees, Dudley and Marie Hendree. The difference between the two committee is that Marie Hendree will only present the catalog of associated symptoms to prolapse. Dudley will look at the impact of the associated symptoms, including the symptoms that you're looking and talking about might have on the patient quality of life. In other words, in order to respond to your question, yes, we will look at the impact of these symptoms of patient quality of life. Thank you. It becomes a little bit of an issue of severity, doesn't it? Because if I have a little bit of pain, but it doesn't really interfere with my life, that's one thing. If I have tremendous impact on my bowel function and I'm uncomfortable leaving the house for any period of time, that makes it very functional. Well, the bowel and the pain are both symptoms associated with prolapse, but how much do each of those impact the individual and their functioning? So again, it gets back to the patient's perception of the severity of the dysfunction. And that's a tough thing to tease in, and I don't think we're gonna find a ton of research, but I agree, that may be one of the areas we really recognize as we're not spending enough time looking at the severity and how it impairs the patient's functioning, which again, that's kind of what this is all about, is identifying the defects in our knowledge and what we think we know versus what our patients are really telling us. So thank you for your comments. Correct. At the end of the day, we're not just looking at doing a narrative review of what has been published on this topic, but the aim of our project is also to look at what are the gaps that we need to fill up and what are the research recommendation that we can come up with? Hi, I'm Rona Carney with Manchester, UK. I have just a question regarding the different methodologies between the chapters for the inclusion of papers. So one chapter has taken a date cutoff, the other chapter has taken a different way of cutoff. I mean, moving forward, is there any way you can synchronize and coordinate how each chapter decides which papers to include and exclude? A little bit of that stems from, we're trying to have most of the papers cut off about the year to 1999, 1998, and that's because really prior to that, we really didn't know what prolapse was because we hadn't even described systems to classify it. So the POPQ wasn't introduced until 1996 and didn't really have much widespread use. The Baden and Walker had been around for a while, but if you look at the literature prior to 1996, 80% of papers never described how they determined the patient had prolapse. They would just use a term. We had 500 patients with prolapse. How did you define it? And so we're somewhat limited by that. So we did charge our groups to go back, but not too much prior to about 1999, for A, there's not a lot of good research prior to that, and B, we didn't have good methods of actually describing what prolapse was. The methodology was a little bit dependent on the chair and the libraries that they were using. They certainly had the resources of IUGA to help them out, but we kind of left that to the chairs how they wanted to do that. We did recommend that they all use, there's a specialist unit for, sure, a specialist unit for review of analysis. It's a group at the University of Cardiff. We looked at a couple of different ways of looking at epidemiologic papers, and those, they have a series of questionnaires or a series of checklists on case control, observational cohort, case series, et cetera. They're short, they're sweet, and when you look at the literature on evaluating epidemiologic research, that's what they recommend you use. So we found that group of questionnaires. They're very well-validated, and that's kind of what we're using then for determining which papers are, quote, in and which papers are, quote, out as far as which are gonna be used, and that's the degree of standardization that we've used. So, it's not perfect, as nothing is, but hopefully it's comprehensive, and at the end of the day, these are gonna be narrative reviews. These are not meant to be set up as systematic reviews because that's very difficult to do with epidemiologic data, and so that's kind of why we had a little bit of a looser criteria for, or a looser search criteria, but hopefully the same criteria for evaluating those studies. It should be included. Thank you. Hi, I'm Cora Hewitt, also a physical therapist from the United States, and I have a question in regards to the one chapter on perception by the patient. For instance, Donald Price years ago in the visual analog scale, he came up with intensity of pain versus the perception of pain. I can have very intense pain, I'm gonna die, it's gonna be worse, cancer. I have intense pain, I'm having a baby, it's not perceived as intense, or as a factor that is bothering my life as much as certainly if I was dying. So, perception of pain is one, and then also looking at perception of pain in regards to the skills and techniques the patient has been given to take care of the prolapse. I know we have people and patients that we've seen who integrate what you say, and they go on with their life, and other people who have less, much less symptomatology, but they are really almost disabled. I think those are extremely valid points, because again, that gets to severity of disease. We kind of define it, but our patients define it very differently, and that's where we need to get, right? Currently, we define it, but we need to let our patients define it better for us. Part of that will be the patient's perception, severity will be part of the measures we're looking at, but I have a feeling those are gonna be very, very few and far between for studies, and again, that's an area that we hopefully will recognize that we need more work in. I think Becky Rogers did a wonderful job of determining that this is not how you determine sexual function or dysfunction. My two fingers go to the apex of the vagina, and that doesn't mean a patient can have sex, okay? But yet, that's how physicians for a long time have been determining if a patient will be sexually functioned after their surgery. So we do need to come up with a new set of measures, but until we know what we're currently doing, and we've cataloged it, it's gonna be harder to do that, and that's part of the concept we're looking at, is let's find out what we know, because we'll be surprised at what we don't know. For future investigation, thank you. Exactly, thank you. I think all these suggestions are very interesting. I'm so pleased to see all you physiotherapists standing up and giving us suggestions. I'm very grateful for Linda to give us a comment saying why you're putting the pessary management in the evaluation management. I'm so pleased to see the Ayuga board sitting in the first line. Your suggestion to me is saying that we might need to extend this project and include an extra phase, include and separate the conservative management of prolapse with the surgical treatment of prolapse. You gave us a lot of suggestion about looking at the weight loss, looking at the mind-body therapy to treat prolapse, looking at electrical stimulation, biofeedback, pelvic floor muscle training. So I think we should, if the board is happy, to separate this topic from the evaluation and from the surgical and give more space to the physiotherapists or other healthcare provided to contribute in this project too. Will there be an aspect of each committee that will be identifying knowledge gaps and trying to say what is it that we don't have literature on that we should as kind of a summation? It sounds like there's a very good plan so far for further describing what's known in the literature. Will there be any effort at saying these are the gaps in knowledge or is that outside the purview of what the committee is planning to address? No, that's part of each chapter should be at the end kind of summarizing a little bit of what we know and what we don't know and making some recommendations for what we should be looking forward because there's a hundred questionnaires out there that deal with a hundred different aspects but none of them touch one patient completely, right? Yeah. So there is a lot we don't know and that's kind of the point. So one of the charges that we will give to the committee, particularly going forward and we were noticing it the other day listening to the committees is that they each come up with their summary of what we know and what we don't know. Yeah, good, thanks. Other comments? I guess I will leave it to my good friend Alex to just bring us home. Thank you very much. I think as a final comment, before we wrap up and we leave the stage to the annual business meeting, I would like to personally thank the Ayuga board for having believed in us and for giving us the opportunity to run this project. I would like to thank Corey, David at the Ayuga office for their amazing work, help and support running this project. I think I need to acknowledge and I need to thank the steering committee for their leadership, for their guidance and for keeping the committee member all together. I would like also to thank each chair of each committee for having accepted our invitation. That is much appreciated. I think we need also to thank all of the chair that could not accept our invitation. We need to thank the committee member for their passion, dedication and hard work. And I'm sure they will keep this up and be able to deliver a nice scientific quality content at the end of the year. Finally, I would like to thank you all for being here today for listening to us, for your comments and for your patience. And we look forward to receive your comments and we also look forward to see you all more actively involved in the phase two, three and probably phase four of the IUC project. Thank you very much. And Alex and Stephen, on behalf of the IUCA board, I'd like to thank you for your inspirational thinking and coming up with this proposal and the passion that you both have for it. I think this is a really important thing that IUCA is doing and everybody is working hard and really doing a fantastic job, keeping to the timeline and we're fully behind this and we really look forward to further participation from our members to complete this important task. So thank you. I mean, I cannot believe when three years ago me and Stephen approached the IUCA board with our proposal. We could not believe what has happened and these dreams has come true. And I'm so proud to see all this crowd here and listening to you and talking to you. So thank you. No trouble. Now, I know there's a temptation because it is 4.40 to run away quick and be unnoticed, but I am here and we have the ABM starting at five. It's really important that we have a quorum so that we can pass any relevant amendments. So maybe if you need a bathroom break, do that, but please, can I plead with you to come back and support the board and to listen to all the exciting things that are happening within IUCA and to support our committee chairs who've worked extremely hard through the whole year to provide education and to support you. Thank you ever so much.

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