Journal Club Global: Defining the "Normal Uterus" – Normative 3D Ultrasound Reference Values from the NURSE Study

During this one-hour interactive webinar, we will discuss the Normal UteRus asSEssment (NURSE) study, a multicenter, prospective cohort study conducted at 15 European gynecology centers between January 2021 and May 2024. Although every major society has proposed a classification of congenital uterine anomalies (AFS/ASRM, ESHRE/ESGE, CUME), a precise, measurement-based definition of the normal uterus has never been established, leaving the boundary between normal, arcuate, septate, and T-shaped uteri open to interpretation.

The NURSE investigators enrolled 442 nulliparous women aged 18 to 35 years with regular cycles and no known uterine anomaly, and performed standardized 2D and 3D transvaginal ultrasound in the proliferative phase. Using the interstitial portions of the fallopian tubes as landmarks on a standardized coronal plane, they measured multiple uterine lengths, thicknesses, and angles and expressed them as percentiles. Key findings included a median fundal indentation of 1.7 mm (90th percentile 4.8 mm), a median interostial-to-outer-contour distance of 9.1 mm, and a median indentation angle of 161.8°, with high interrater and intrarater reproducibility and consistent values across centers.

Join lead author Dr. Marco Gergolet and an international panel of experts as we examine how these first normative reference values may reshape the diagnosis of uterine anomalies, what they mean for the septate and dysmorphic uterus debate, whether cut-offs derived from a young nulliparous population can be generalized to the infertile patient, and how they might influence the decision to operate.

Presenting Author:
Marco Gergolet, M.D. – School of Miaedicine, University of Ljubljana, Ljubljana, Sloven

Discussants:
Antonio La Marca, M.D., Ph.D.
Baris Ata, M.D., M.Sc.
Kate Devine, M.D.
Marina Bellavia

Moderators:
Paul Pirtea, M.D., Specialty Editor, Fertility and Sterility
Yannick Hurni, M.D., Interactive Associate, Fertility and Sterility

Hello everyone, my name is Paul Pirtea and I'm happy to invite you to participate to our journal club global for fertility and sterility. This will be our third journal club this year. I think we have one hour of very nice debates over one interesting study coming from Italy and including many other European countries trying to define the normal uterus.

That's the real question. So I'm happy to introduce Yannick Hurni which is my co-host today and he will guide you through the next steps. Hello everybody, good evening.

So as said Paul, today we are going to discuss a very interesting and probably simple question which is what is a normal uterus? To do so we are going to discuss the results of the NURSE study. The study was published in Fertility and Sterility in August 2025 and this is extremely interesting because as we already know there is a long-term ongoing debate around the definition of uterine normality, uterine malformation, when to propose for example a surgical correction of uterus and so on. So ASRM guidelines definition, ASHRAE guidelines definition, there are long-term debates and so it is of a great interest to try to define uterine normality and Marco Gergolet and the NURSE group tried to do this, try to define population reference values with this big and very interesting study, the NURSE study.

So at this point I will ask to Marco who is an assistant professor at Ljubljana in Slovenia and was the coordinator of the NURSE study group to explain us a little bit the results of the study and so we will start from this to discuss about it. Please Marco. Thank you very much, I will share my I will share my presentation.

Okay, so thank you. Do you see the presentation? It's okay? Yes. Okay, so we are talking about normal uterus but we and we are talking also some other times about the difference between normal and abnormal uterine cavity but we never defined what is we know according to several classification and ton of papers what is acetate uterus, T-shaped uterus, so on but never been defined what is normal.

Until now normally so is only what is not abnormal. So we have to see which is the normal uterine cavity and of course we have to have the standard of normality if you have if you want we want to consider what is outside normality so it is abnormal. If we go to look to the old books and the atlases we see that the normal uterus is represented always like a inverted delta shape, a triangular shape of the uterine cavity either in the Sobota, Nater Atlas or in the Bible of the uterine of the anatomy like the Testu.

Keep in mind always this shape of the uterus which is always represented like this and this also a delta inverted delta shape of the uterine cavity. Also in the classification of 1988 there is no classification no class of the normal uterus but we see how in the class one when we have abnormality of the cervix and the vagina we see how the uterus is drawn is represented like a triangular delta shape uterus and not like a septate uterus or an arcuate uterus. So in this case our predecessors they defined the normal when it has this shape and not this or this shape.

So the first time was defined and classified the normal uterus in the ASHRAE classification in 2013 and we needed to have this class of the U0 normal uterus. Why? Because having the normal uterus class we can combine the uterus with abnormalities of cervix and the vagina. So we can have a normal uterus but we can have an anomaly of the cervix or of the vagina.

So this is the definition of the normal uterus according to the ASHRAE. So normal uterus is any uterus having either straight or cubed interstitial line but inter-indentation not exceeding 50% of the uterine wall thicknesses. This was not an opinion of 10 experts but it was a consensus after two rounds of the LC procedure and was published like this.

Then we had the classification of the SRM when they didn't define the normal uterus but the normal uterus was defined per exclusion. Why? When they said okay we have the septate uterus when we have an indentation at least one centimeter or more when we have a septal angle of 90 degrees or less and what is less than one centimeter of indentation and more than 90 degrees of angle is normal or archway which is considered normal. Also the Kuhn group defined the normality by exclusion.

They said okay what is not septate is normal and the septate uterus for the Kuhn criteria is when we have more than 110% of the ratio between indentation and interosteal to outline contour when you have an internal angle of the indentation of less than 140 degrees and we have an indentation that should be 10 millimeters or more. But also in this case it's an opinion of 20 experts it's not a random course of trial I don't know or a great cohort study. They defined also the criteria of the T-shaped uterus and they said what is not T-shaped is also normal so they said the T-shaped you have to have the lateral angle of less than 130 degrees, the lateral indentation which should be seven millimeters or more and the tubal angle which should be 40 degrees or less.

So this is the representation of a typical T-shaped uterus according to Ludwig. We see here beautiful T-shaped uterus. This is a T-shaped uterus.

This also is a T-shaped uterus. This should be also very very similar to this but it's not true because according to this paper these uterus are normal and these are T-shaped but I cannot really I cannot understand where is the difference between this uterus and this uterus or this uterus and this uterus but according to this classification and according to the paper because this is a picture from the paper this is a normal uterus this is a T-shaped uterus. So there is a big confusion between what is normal what is abnormal because normality has not been never been defined and so this is why we decided to try I had this idea and I enrolled a lot of friends in this project to define what is normality.

What is normality? This is the trielo famoso when we have the classification and let decide which is the right classification and which not. So this is the normal uterus assessment study which was a project supported by the University of Ljubljana and involved 15 centers in five European countries. The goal was to establish the reference distribution for uterine length, thicknesses and angle using standardized 2D and 3D ultrasonography.

So we said 15 European centers, 442 patient women enrolled between 18 and 35 years of age, recruited work between 2021 and 2023. All women were belonging to the general population so without any attempt to conceive, without any previous pregnancy and of course already no uterine anomaly. So they were belonging to the normal or the general population.

Maybe during the discussion we'll see why we choose to perform the ultrasound in the follicular phase and not in the luteal phase. So these are the measures that we are looking for. These are the uterine lengths A, B, C, D, A, F. Then the indentation Z. Interosteal to outer contour is Y. The thicknesses of fundus, lateral walls and the angles, lateral wall angle and tubal angle.

We will see later on the data. These are the data. The indentation in this patient is 2.2 millimeters in the mean value and with a median of 1.7 millimeter.

And we'll see also that the lateral wall angle is 149, 150. The tubal angle was around 48 to 50 degrees. But we'll see later on expressed in a graphic way.

When we are looking for the percentile, we see how the indentation, the full indentation, so-called the septum, the 15 percentile is 1.7 millimeters, 90 percentile is 4.8 millimeters and 95 percentile is 6.7 millimeters. So these are the other measures that I'm recapping all the measures that we have seen already. The fundotixis median is 11 millimeters.

And the lateral wall was 150, 151 according to the left or right side. And this is also the angles, lateral wall angles and tubal angles. So this is the representation of the median values of our measures.

So we have to see here the indentation, which is very small, 1.7 millimeters, 9 millimeters in the outer outline, 14 millimeters the thickness of the left and right lateral wall and 150 degrees of the lateral wall in this representation. So if we go to compare the ASRM, the ASHRAE, ASJ classification, we can see that according to the ASHRAE, we say that septate uterus, when we have an indentation Z, which is 50 percent of the world thickness, so it means that between the interosteal line and the outer occultum. So having a median of 9.1 millimeters of Y, the septate uterus should be when we have a indentation of 4.55 millimeters.

Instead, when we are looking for ASRM, when they say, okay, we have septum, when we have an indentation when it's more than 10 millimeters and an angle of less than 90 degrees. So we see that 10 millimeters of indentation lies between 97 and 99 percentile in our study and the indentation angle of 90 degrees lies below 1, the first percentile. So we can say that this data suggests that we can have a potential overdiagnosis of septate uterus according to the ASHRAE classification, but we have also another diagnosis with the ASRM classification.

So this is the paper. Sometimes T.C. Lee, now he's based in Hong Kong, but he was in Sheffield before, he told me, you know, Marco, there are two kinds of people, two kinds of surgeons, the keepers and the cutters. So we know that we are more keepers, we are looking, maybe we are underestimating some indentation when we are cutters, when we can overestimate some indentation.

You know, we are human, we are biased by also our conviction, our formation. So I say, why don't we ask the machine to the computer to measure this in uterine wall and uterine cavity in order to lose this bias according to keepers and cutters. And we asked to the University of Ljubljana, Faculty of Computer Technology, and we gave to them all our volumes of the patients that we measured.

So we gave them the volumes. They have done the neural network training after manual painting of the slides. Then the delineation of the 3D shape of the uterine cavity automatically without any human involvement.

Then the shapes were aligned with a sequence of different mathematical geometrical methods to decrease the curvature of the sagittal plane. And then we had the calculation of the average shape of the alignment without any human involvement. So this is the result.

This is the result of the shape of the uterus after manual alignment. This is after automatic alignment. And this is the visualization of the average shape in the general population.

And how we can see, this is the shape which is very, very close to the shape that we have measured with our measure on the same patients or the same volumes of the patients. This was published in an open access paper. So just to conclude, this NARSTAT is a population based reference for uterine length, thicknesses and angles.

It's a common quantitative language for future classification studies. And there are no surgical thresholds. So the aim of this paper is not to give the surgical indication to the uterine anomalies or uterine which are not considered normal.

But next the question is which deviation are from the normality in the patients with unexplained infertility. So new data are coming soon. And soon we will present also the measurement in patients with unexplained infertility.

So thank you very much. Well, thank you, Marco. I think it's amazing what you managed to achieve.

And I think that reaching to some kind of evidence based normal uterus kind of picture, it's very helpful also for creating research. Because we all know that whether ASRM or ASHRAE, it's an arbitrary decision about what should be one item or the other. And given that evidence is always something to debate on, we have among us one of the discussants, Antonio Lamarca, that does an introduction that actually wrote a letter arguing that your conclusions are not necessarily as strong as we might think.

So please, Antonio, help us understand better your point of view in this debate. Yeah, thank you. Thank you very much, Paul.

And let me thank the scientific committee of the Journal Club for the very kind invitation. Well, also let me thank Marco for his great work. This is, well, it's a very needed article like this one.

Because in reality, as he said, well, to my knowledge, this is the first prospective, well-planned study investigating with the 3D ultrasound the quantitative aspects of uterine dimensions. And, you know, well, when you want to understand what is normal, well, it's not so easy to understand what is in reality the population you have to focus on. And then I know this because, well, we have published at least three, four articles on normative data or normal values for some hormones, for example, such as AMH, but also for the answer follicle count.

And, well, I've spent so much time with the statistician discussing on what is normal. What is the normal population? What is the normal uterus? So Marco and his team, they chose to define normal, what is in between the fifth and the 95th centile for each measurement. And of course, this is very soundness, you know, and the goal was in the end to define uterine malformations, for example, on a mathematical basis.

Anything falling outside the fifth and the 95th centile may be defined as abnormal. Now, if we go back, however, in the materials and methods of this article, we will find that they stated that, well, authors, clinicians, they excluded from the analysis patients with congenital uterine anomalies. So from a methodological standpoint, I think this is not, well, this is not completely right.

If you are excluding from the beginning patients for whom you are considering that the uterus is normal, is abnormal, sorry, in the end, your analysis has been performed on a selected population. Can I ask Marco to reply to my first comment? I have three comments today for Marco. Oh, thank you, Antonio.

No, you know, the study was not started, didn't start with the aim to give any clinical indication. So we defined what is normal, like in the other categories, where we are looking which are the normal values for sodium. We are looking for apparently healthy people.

We are measuring the sodium and then we are, we establish the normal values of the sodium. Of course, there are people who are still alive with a sodium which is 147 milliequivalent liter and so on, or 150. But this is, our goal was this.

Then we, you cannot link the function with the normality because all of us met some patient who delivered it normally and then after the delivery or during the C-section was diagnosed with a unicorn weight or hemiuterus. But this heuterus is not normal. It doesn't mean that, it doesn't mean nothing because, you know, you can have a very important anomaly like a unicorn weight heuterus, but the patient can be pregnant and can deliver normally also with a very important anomaly such as the unicorn weight heuterus.

But you cannot consider the unicorn weight heuterus as normal. And also, another thing, when, you know, we have a general population. So, if you go to read the paper of Saravellos, 2008, I think, he found, I prepared because I knew a little bit what was the debate.

I prepared also this slide I will show you by Saravellos when we see that in the general population, in the general population, we have, I just don't know how to do it, in the general population, we have a prevalence of uterine anomalies, which is 6.7%. I will show you. According to Saravellos, 6.7% of prevalence of anomalies. This was a paper of Saravellos and it is a review where he studied several different kinds of diagnostic tools such as 3D ultrasound, hysteroscopy, laparoscopy, and so on.

So, if you consider that we have in the general population 6.7%, according to Yurkovich, I think he reported 10% of anomalies, W. Yurkovich in his paper in the general population. And according to Pedro Asien, where he reported in patients who delivered at least once a prevalence of 3.4% of anomalies, but in newly gravidate, 15% of prevalence of anomalies. That is normal that we can find in our population also extreme values when we are, it's very far from the so-called normality.

And we don't know if this patient who participated in our study will experience in next years a problem of recurrent miscarriage or of unexplained fertility and so on. So, this is only a picture of the normality and we have to look not to the extreme values or to the tail of the Gaussian curve, but we have to look to the median and median in order to have the picture of the normality. So, when we are talking, when we are writing a paper about septate uterus, we say, okay, this is a septate uterus.

According to ISRM, it's a septate only when you have one centimeter, it's a septate according to ASHRAE, when we have 0.5 centimeters, but we know that normal is this. It doesn't mean that we have an indication of six millimeter septate or not. This is not the goal of this paper.

We want to say, okay, this is normality. Thank you, Marco. Thank you so much.

I think that now we should probably give the discussants to express their point of view. I would start with Kate. Ladies always first.

Kate, what do you think about the paper? What do you think about the arguments and what is your opinion, your own opinion? Thank you, Paul and Marco and Antonio. This paper represents a remarkable piece of work and derives from a remarkable dataset. I think that it succeeded in grand fashion on its own terms, in terms of describing extremely rigorously a very narrow population.

Specifically, they're looking at young women who not only were nulliparous but had never tried to conceive from Italy. This is a population that is well-described by this paper. That said, based on the narrow inclusion criteria, the data are not particularly generalizable.

That doesn't mean that it's not valuable. It just means that it's not generalizable. I agree with Antonio's point that the functional capacity of a uterus is truly its defining characteristic.

I agree that the authors have this spectacular population that is now so well-phenotyped. It would be almost a shame not to do the longitudinal study that Antonio describes in his editorial, in terms of looking to see how do these patients perform from a reproductive standpoint going forward. In particular, the population that were below the fifth and above the 95th centile for some of the parameters that were assessed in this paper, it would be very interesting to see, is there a difference in terms of the fecundability of these women and the duration in terms of time to conceive? Furthermore, I'd be really interested to understand the breakdown of 84 percent of the population they assessed for inclusion in the study, in terms of why were they excluded? It's a brilliant opportunity to be able to assess the incidence of many gynecologic conditions that we don't have a true understanding of what the incidence of these conditions is.

I hope that they have those data, and I hope that they will report on it. Of course, I want to hear the opinions of the rest of my colleagues here, of this brilliant panel that you assembled, Paul. Thank you, Kate.

I think that the task of defining normal uterus is a very complicated one. I personally don't necessarily believe that normal is something that we can actually define, but that's to be discussed later on. Baris, have a go.

What do you think? Hi, good afternoon, everyone. Thank you for the invitation. I agree, it's a lot of work.

It should be applauded in every way, but today, here, we are to discuss, right? Fine. So, I won't repeat the same things. I mean, we've already mentioned that it's not necessarily in the context related to function, so we can't call it healthy normal.

It's a statistical normal. Good. And I don't have an issue with excluding obvious anomalies, like unicorn rate or bicorn rate.

So, they're clearly different. You wouldn't even have the same measurement. But what I would wonder is if women with any length of indentation was kept in the cohort, like would be diagnosed with septum somehow.

We see a small minority, like what? Two percentile? The Z distance is deeper to be diagnosed as a septum, so I guess they kept them in, but I'd like to know. I'd like to highlight one thing. When I saw the paper, I was curious to see what percentage of women in the study would fit into the dysmorphic criteria, defined by the Kuhn criteria.

So, now, I think there's a missed opportunity, but which can be recovered because you have the volumes, you can reanalyze them. So, the definition of the tubal angle is different than the definition of the T angle in the Kuhn criteria. In Kuhn criteria, it's the angle between interosteal line and the lateral wall of the sidewall from the tube.

Here, it is the angle between the line from the tip of fundal indentation to the cornea, to the tube, and then the lateral wall, right? So, this is a narrower angle. So, we can't extrapolate these findings to Kuhn criteria, but with the volumes, it would be interesting to see what percentage of women would fall into this dysmorphic criteria. So, we can have maybe more meaningful data.

One limitation I'd like to highlight is maybe intra-rater agreement can be overestimated, okay? Because the raters, the assessors, I understand from the paper, they reanalyze the same stored volumes, okay? So, they didn't capture another volume and analyze it. So, it may be a little bit overestimated. And ICCs, in general, just give us an idea about the correlation, and so the reproducibility, but doesn't give us an idea about the absolute difference, the range of absolute difference between repeated measurements.

So, it would make the paper much longer, but for follow-up work, you know, a bland ultimate analysis can be informative in that regard, you know, how much it can vary. And two last things about measurements. So, these were done in the proliferative phase, but we also know the urine shape could look, you know, different in the luteal phase and the proliferative phase to some extent under progesterone exposure.

And maybe, maybe, for obstetric outcomes or maybe for reproductive outcomes, maybe the luteal shape is more relevant. That would be an interesting point to study. And finally, as shown in the reproducibility analysis also, you know, the wall thickness, some measurements should, you know, not for the purpose of that, but in general, your uterus contracts and relaxes.

So, basically, you know, a variation would be expected in these wall thicknesses, particularly. I don't know if the patients or the participants, let's say, were observed for a while, and the measurement was done at a certain time, you know, when the uterus was, I mean, thicker or thinner, or was it just a snapshot? And now it was just taken at that point without regarding the dynamic changes. I'm sorry, it's been too much.

I can. No, no. No, I think it's, I think it's great, because this is the whole point in trying to understand better this kind of information that we received.

Yannick, I know you've been extremely excited about this paper, more than I have. I was, you know, I really like everything is associated to the uterus, fertility surgery, and so the discussion between Marco, Antonio, and I know we received them for the other letters that had no space for publication, but I had the possibility to speak with other authors and other colleagues trying to ask things or trying to demonstrate how this data could be useful or not. And I think the discussion here is extremely, extremely important, because we're trying to give basis to build new studies, not for the moment to build new classifications, but probably to build studies, to build indications and guidelines on how to, for example, treat or not treat a patient due to the shape of the uterus.

So I think the discussion is extremely interesting, even if it's not that easy to define how to study this. I don't know, what do you think, guys? And we also have Marina with us. I don't know if she wants to express her idea about this.

Marina, can you hear us? Thank you. It's me, it's correct, yes. Thank you, Marco, for the excellent presentation.

I completely agree with Yannick. I think that this study is a very important starting point to try to understand in our job with the infertile patient, what is really a normal uterus and abnormal uterus. And for me now, I have two questions.

Should we do the 3D ultrasound for every patient, fertile and infertile patient, to understand the basis? So if we have a normal uterus or not. And essentially, I have also to say that it's not so easy to take all the measures, all the angles. So could we have a software with the AI to help us to define a normal uterus or not? These are two questions that I have for you, Marco.

So, Marco, it's your time to defend yourself. I will start from the lady, of course, for the last question. So, what I suggest is the way we have a patient who is coming by in your office with problems with infertility, with at least one miscarriage.

I don't need that she has two miscarriages to perform a 3D ultrasound. Because nowadays the cost of the ultrasound is not so high. All the specialists in infertility, they have the 3D vaginal ultrasonography.

And so why not to control this? It's a problem where we are performing just for a joke, maybe, a 3D ultrasound to a young girl who is not attempting to have pregnancy. Because also when I see a young girl with a septate uterus or a T-shaped uterus, I never say to her, no, you know, you have this uterus, you will have to undergo surgery. But you say, OK, maybe in your future, if you will have some problem with conception, you know that maybe this is a problem.

But otherwise, it's better even not to look for this. But nowadays, with the 3D ultrasound, you can bypass most of the time the hysteroscopy and absolutely other more invasive procedure. Yes, it's true, there are more, the patients are especially from the Mediterranean play space, so more Italians and so on.

And this is a pro and contra because, you know, I was talking with a colleague from Asia. He says, OK, the fact that these, from the point of view of the ethnic group is especially done by European patients, you cannot expand this model of the uterus to Asians or Africans or so on. But the advantage is that the group is more homogeneous.

So in the European population, you have this kind of uterus. We don't know yet if there is another, that the uterus is different in a population of other parts of the world. So I agree with you that is a limitation.

But the other side is a pro because the population is more homogeneous. And about Baris, why the follicular phase is not a luteal phase? Because if you have a cavitated organ or anything which is cavitated, if you bulge inside, you deform the uterus. So we know that a luteal phase endometrium can bulge the uterus.

It's a bulging effect and so can distort. Also in the paper of Saravelos and Lees, they describe this when they have seen that the interosteal distance in patients in the luteal phase is completely different between luteal phase and the follicular phase. And also not another thing.

Most of the time during the luteal phase, you see the uterus, the foetus of the uterus, which is not concave, concavic, convex, but concavic. OK, but in hysteroscopy, you never see this concavic uterus. We see also a convex uterus, not a concavic uterus, which you can see in the luteal phase in the 3D ultrasound.

So the idea is this, never perform ultrasound if you have inside something which is bulging the cavity, such as the luteal phase endometrium. So this was the logic. And the second thing is that in the preovulatory phase, you have more clear the border between endometrium and myometrium.

So we decided to do it in the follicular phase. I don't know, I forgot something, maybe some question. What about the description of the patients that were excluded, particularly those that met all of the history-based inclusion criteria, but then were subsequently excluded based on the findings at ultrasound? Are those data that you have and can report on? Yeah, yeah.

Sorry, the exclusion, I mean, the number of excluded women is very, very high. 84 percent. Yeah, exactly.

Yeah, of course, because all the women recruited were women who were excluded immediately, you know, because, okay, you had already one pregnancy excluded, you have a myoma, you're excluded, you have adenomyosis, you're excluded. So this is why we had a lot of women which undergo 3D ultrasound that was excluded because they didn't meet our inclusion criteria. But there were also incidentally, like, incidental findings that led to exclusion, correct? If at the time of the ultrasound, there was a pathologic finding that met the exclusion criteria that wasn't known previously to starting the study, those women were also excluded, correct? For example, a fibroid was noted that wasn't previously known.

I would be interested to see the data as to what proportion of the exclusions those types of findings, you know, made up. Okay. Yeah, no, they were excluded also because of all these cases.

I think Antonio would like to say something. Yeah, yes, thank you. Am I allowed to show my desktop? Yes, yes.

Meanwhile, I would just like to tell the attendees that at any moment, they can write in the chat if they have questions. I'll try to answer them with the help of Marco. Do you see my desktop? Yes, we see it very well.

Okay, so this is the table number one or table number two of the Marco's study, where you see here the distribution of some measurement. It could be the angle of indentation, left and right angles, and you see the fifth centile, the tenth centile, fifty, and so on. Okay, so the tenth centile may be regarded as a normal measurement.

So let's pick these measurements and let's design a uterus according to this angle of indentation and these left and right tubal angles. And in the end, we came to this. So this is a uterus with the measurements according to the tenth centile of Gergoletz measurement.

So this must be a normal uterus. But look how similar it is to the T-shaped uterus or Y-shaped uterus according to Kume or to the American classification. So in reality, I think that the vast majority of us will think that in reality, this is not normal.

Marco said that the objective of writing this article was not to give us a guide when to operate or not, but in reality, my perception is that some clinicians may follow these rules, you know. So my question is, do you think this uterus is normal according to your clinical experience? And in particular to Marco, I know you are a very well experienced surgeon and I'm pretty sure that in your practice you are operating women with a T-shaped or Y-shaped uterus. So since you have published this very brilliant article and now we know that this uterus is normal, have you changed your own practice? You're waiting an answer from me? Yeah.

Yes, of course. But you know, you put together all the extreme values in one uterus. It's like to say, okay, you have a micro car, which is very, very narrow and also very short.

And you have a limousine of six meters long, which is very long and also very wide. But if you put a normal micro car, so a one meter wide car, which is longer, five meters, on the first cure, you are out of it. So you created a monster using all the extreme values taken by all.

But it's not, what is stated that if you have this tubal angle, you have also the other values, which are extreme. You know, we can have one or two extreme values and not all of them. Of course, if you take all the extreme values of patients, you can create a uterus, which is a Frankenstein, like you created.

But it's not in the real life, it's not the same, you know. This is what I want to say. We can definitely feel the passion, the Italian passion in this subject.

This is why I'm trying to cut it and put some pragmatism from Baris. Okay. So, I mean, some support, say, for the paper.

Antonio, they don't define, as you wrote in your letter, I mean, healthy or functional uterus. So they excluded obvious anomalies, and then they define the person. So the point I was trying to make, referring to the Kuhn paper and dysmorphic, you know, so it's exactly the same point.

You see, so this falls somewhere less than the tensile time. So maybe, and we don't know if dysmorphic is a functional abnormality yet. I mean, the evidence is not there.

Okay. But this paper gives us an idea that it's probably, because of the differences in some measurements, you know, how they defined it, is somewhere around 5%, okay, in otherwise normal looking uterus. I think the best opportunity for this, I mean, valuable work is to follow up these women, even over time with phone calls or whatever, to see what happened to them.

I mean, did they conceive easily? Did they have a preterm delivery? Did they, you know, whatever, whatever. So then we will know. So this is like a great first step.

The only problem is, which is inevitable, the number of women in the extreme ends are small, but because they are in the extreme ends. But I don't think, you know, the paper claims that, you know, anyone in the fifth centile, second centile, or one centile is functionally normal. It just shows the distribution.

Yeah. And dysmorphic is still not proven functionally abnormal. Yeah, there's some personal touch to it.

I think that there are many women who delivered and they have myomas, and they have many dysmorphic uterus, and they have no issue whatsoever, even the unicornus can actually deliver. And we find that in during the C-section that there is a problem. So I'm not certain that the normal uterus can define a direct relation to fertility, because it's not only about that.

Yeah. Please, go ahead. Apologies.

No, sorry. I didn't. Go ahead.

You know, we shouldn't take any of these measures in isolation. So the paper doesn't report scales. Okay.

It's shorter interosteal distance could be associated with a shorter uterus in the axis too. So maybe it's shape-wise normal. So that reminds me of the semen analysis parameters now.

So one parameter could be off, but the others can compensate, et cetera. So we should look at the totality. So that's what we're missing.

You know, the scale is missing in this data. Yes. I really think this is a very good paper.

I already said that we missed a paper like this, you know, but I like to think about this paper as the starting point, because as you all said, I mean, now the most important data is what will Marco for sure give us in the future, the outcome of fertility and pregnancy in those women. Is there any correlation? This is the most important question to all of us in particular to the IVF doctors, but I will say to all doctors involved in reproductive medicine, including including Sargions, of course. I have a question from the audience.

So they asked whether the myometrium contraction that you mentioned before was measured, for example, five minutes after and whether you consider this to be important or not. No, we didn't look for it. We performed the ultrasound without waiting for the myometrium contraction and so on.

No, this is not. Of course, I read all the paper of Barisata and we have the myometrium contraction and sometimes you can you can see some uterus, which seems in brackets abnormal during the contraction and normal outside the contraction. But it's part of the random of the random volume taking, you know, so maybe we we took some some patients during during the contraction.

Maybe not. We asked our ultrasonography to perform a standardized ultrasonography procedure, which didn't last only 10 seconds. So always we take two or three scans of the uterus in order to have the best the best image that we can measure as well.

So I can exclude that some of the of the volumes was acquired during the contraction. I cannot exclude it. I mean, yeah, sorry.

Sorry, Daniel. Please. Yeah.

May I ask the scientific board to comment on endometrial thickness, because they also gave us the measurement, the normative data on endometrial thickness. So I see the fifth centile is 2.3 and the 95th centile is 11.6 millimeters. The median value was 6.4. Any comments by you? Any thoughts? Well, I can I can answer.

I don't think endometrial thickness matter that much. I think there is a minimum that is required and a maximum that can be supposed to be something other than normal. But I think the the the the range from six to 12 or even 14, it's quite proven by strong evidence that it doesn't matter for infertility reasons.

Yeah, I think that it's important to understand the difference between fertility and difference between women that have been taken into a European country and screened for an ultrasound. As mentioned before, this does not apply to other continents and other ethnicities and so forth. So but but with concern to endometrial thickness, Mariusz is the right person to tell you.

I'd like to ask Marco. So these are these these measurements are taken in the probably early proliferative phase and not necessarily on the same day, not necessarily on the same day in every patient. So in the context of ART, we measure we are referring to endometrial thickness on the day of trigger, on the day of progesterone start, etc.

So if the day of measurement is not standardized in the cycle, which cannot be in the context, you know, I think it's it's it's it would be expected to have a wide range. I mean, you know, even two, three days make a huge difference in the early proliferative phase. Yes, I noticed also something else.

But I'm going outside the study because it's only anecdotal data. I have seen the patient that I consider T-shaped, for example, because of my my parameters. You can you never see a thickness of the endometrium, which is very high.

You know, you see very, very small thicknesses. And after endoplasty for T-shaped uterus, you have you see that at the time she has a good thickness of the endometrium, because sometimes in the eighth, in day eight, day 10, you find endometria who are three, four, four and a half millimeter of thicknesses. But this is this is outside the purpose of this, you know, just local data.

You raise your hand. Yeah, I don't think that this paper should have reported on endometrial thickness at all, because they defined the proliferative phase as day 11 to 14 for these patients having regular cycles. But they did not define what regular cycles were.

And the timing for that particular patient was not normalized to their follicular growth or hormonal assessments or anything. So we have no idea where these women were in their proliferative phase from a hormonal perspective. And so the endometrial measurements are meaningless.

I think we all agree with that. Yeah. Thank you.

Yannick, do you have something to say? Yeah, I have a question and probably a suggestion for future studies. I don't know all the studies until now, they focus on shape, angles, measures, and never on volumes. Hormonoscopies too.

And I think there's a quite a big difference between a T-shaped uterus where we cannot see the tubal ostium from the isthmus, but with a big volume and probably a good distension with fluids and a very narrow, very tight uterus. And I don't know, even for future, probably also we know T-shaped uterus can bear a pregnancy. And sometimes it's not only the shape, but also the volume and flexibility, for example, of the uterine wall that can have an impact on the function of the uterus.

I don't know how to do this. I thought about it. I don't know if there is a way to measure it perfectly or correctly with ultrasound or other techniques.

I don't know, Marco, if you thought about it. I will spoiler the results of 220 patients with unexplained infertility. And there is a significant difference in the thicknesses of the lateral walls, anterior-posterior wall, and fundus.

I just want to cut in because unpublished data should not be disclosed in a webinar. So any data published here should be peer-reviewed and should have some kind of... So please do not share data that has not been published yet because it has to... Okay. Okay.

Yeah. It's also better for me. No spoilers.

No spoilers. No spoilers. Anyway, I think the discussion was very nice and very rich.

And passionate, I would say, at times. I think that it shows that we are still very far from being able to define what a normal uterus is in a way that everyone would agree upon. But I think that we should applaud Marco's work and time that he invested into this subject, which I do believe it's important.

It's a very important first brick in the wall. So I really appreciate you participating. It was very much fun.

I wish you all a great day and I thank you all. See you soon in ASRM. Don't forget to... Thank you.

Bye-bye. Thank you. Bye-bye.

Bye-bye. Take care.