Journal Club Global: SREI Fellows Symposium 2025

Journal Club debate: do surgically retrieved sperm match ejaculated sperm in donor-egg IVF? Review of evidence, blastulation, fertilization, outcomes, equity.

Fellow Discussants:

• Alexandra (Alexie) Poch
• Aileen Portugal
• Sam Thorogood

• Jen Eaton
• Paul Shin
• Shruthi Mahalingaiah

• Dr. Kurt Barnhart
• William Catherino M.D., Ph.D.

It's global because it's broadcast and can be seen by anybody around the world, and it's generally on a hot topic and it always is on a paper in F&S. So this debate, I'm going to have everyone introduce themselves in a second, is going to be, I'm going to turn it into a mildly clinical debate, but it's based on a paper in F&S which I'm going to review in just a second. So because it's a debate, I think the best way to do a debate is I'm going to ask you guys a question, and we'll do it without numbers, just raise your hand, and I want to see how many people agree with it, and then after the debate, we'll ask the same question to see how many people, whether that number changed.

It'll be higher or lower. Okay? You with me? So we'll show you the paper in a second, but the question is, is there current evidence to support that the use of a surgically retrieved sperm has the same clinical outcomes in the use of ART? How many people think there's evidence right now that supports that statement? No one believes that a surgically retrieved sperm can result in the same outcomes as ejaculated sperm in IVF. They think that they're very different, or are they similar, or does the evidence support that if you can get the sperm, they're roughly similar outcomes? Okay, so who says they're similar outcomes? Okay, I'm going to say that's 50%.

Yeah? Okay. All right, so that's the question I'm going to... That's the question. Now what I'm going to do is the question is going to be based on this article, which was recently published in F&S, comparing blastulation rates of surgically retrieved sperm with ejaculated sperm in donor oocyte cycles.

An illustrious group here. You can see all the people that participated in this. A couple things.

This is a great paper. It's multidisciplinary. It's multiple sites.

It has statisticians. It has urologists. It has a great practice.

It's from Shady Grove or U.S. Fertility, and this is all the good parts of the paper. So very briefly, to evaluate the availability of single... So usable blastulation rates with donor oocytes fertilized with surgically retrieved sperm versus... Again, there's some subtlety here we'll go into, whether they had obstructive azoospermia or non-obstructive azoospermia. And the conclusion, when comparing donor oocytes fertilized with surgically retrieved sperm with ejaculated sperm... I have my glasses.

The chance of at least one usable blastocyst per donor oocyte was similar for each sperm group. However, there was decreased blastulation rate and fertilization rate when comparing fresh and fertilized eugenics. So that's the conclusion of the paper.

Very briefly, since I'm the objective person here, I'm going to show you the data, because these two teams are completely not objective. They're trying to prove their points. So this was a paper that looked at a large group of people that had ejaculated sperm, because that's the majority of people.

Then there's people that had obstructive azoospermia, therefore surgically retrieved sperm, and then non-obstructive azoospermia that had ejaculated sperm, but that had similar azoospermia. The demographic I just showed you here, it's donor egg. So the average age was around 42 for the male participants and also around 42 for the female participants.

And the donor egg age group was around 26. I'm just reading across the tile here. And then here are some of the stats.

The number of mature oocytes was the same in each group. That's the first line. The number of zygotes was mildly different between the three groups.

The number of usable blastocysts you can see there. There is a statistical number there. And then they give you the main result, which are the cycles with at least one usable blastocyst, and there are no statistical significant differences there.

There are differences across the groups, but the confidence intervals and the adjusted relative risks all cross one. And here are the clinical outcomes. And again, the number of patients who had a transfer was the same.

The number of fresh embryos was exactly the same. And then you can see the clinical outcomes there. So what they're saying is that you're going to get a usable blastocyst and you're going to get the same number of pregnancies.

Now, I just gave you a high-level view of the paper. We're going to let these team members here start discussing a little bit. So who's going first? I think it's pro, con, pro, con.

Pro, cons. Why don't we just take 10 seconds to just go ahead and introduce yourselves. We'll go down the list, and then we can see who the participants are.

So please just say hello, give your name, where you are, and then we'll get started. Hey, I'm Alexie Poch. I'm currently a third-year fellow at the NIH.

Hi, I'm Sam Thorogood. I am an andrology, a.k.a. male, infertility fellow at the University of Utah. And I'm Aileen Portugal, third-year fellow at WashU.

She, her, pronouns, and ready to get this debate started. All right. Who are you up against? You don't even have to use a microphone.

Is it on? Yes. Hi. I'm Jen Eaton.

I'm the division chief and fellowship director at Brown. I'm Paul Shin. I am one of the reproductive urologists at Shady Grove Fertility, and probably responsible for 200 of those 218 patients.

So this is a bit of a weird position. I'm so glad to have you on this con side. Shruthi Mahalingaiah, one of the fertility physician scientists at Mass General Fertility Center.

And over in the corner, Bill, do you have a microphone? No. My co-host. So Bill Catherino, F&S Science at Editor in Chief.

Okay. So let's kick it off. You want to get up here or you want to do it from your thing, whatever you want to do? I don't think we have slides, right? No.

Okay. All right. We'll do it here.

Okay. Does that sound cool? Okay. So this paper sought to compare the likelihood of obtaining at least one usable blastocyst from a donor lot between patients utilizing ejaculated sperm and patients with a diagnosis of obstructive azospermia or non-obstructive azospermia with surgically obtained sperm.

Of note, they had to have had surgically obtained sperm after the procedure. Looking at percentage of cycles with at least one usable blast, we see that the ejaculated sperm group had 90.1% of cycles with at least one usable blast. The obstructive azospermia group had 86.8% of cycles, and the non-obstructive azospermia group had 87.8% of cycles.

After adjustment for male age and age of oocyte donor, there was no significant difference found between the groups. And yes, as you just saw, the other metrics of fertilization, blastulation, absolute number of blasts did show reduced efficiency, but that wasn't the primary outcome of the study. And we saw that of the surgical sperm cohort, they were still just as likely to obtain one usable blastocyst.

And admittedly, this is a small cohort. We have Dr. Shin, who might have been almost all of them, sitting right here. However, it's not necessarily powered to address some of those downstream metrics that may be tempting to analyze.

However, outside this paper, outcomes between these groups have been reviewed and they have been addressed by our governing bodies. AUA and ASRM practice guidelines acknowledge that surgically extracted sperm have generally similar outcomes compared to those using fresh ejaculated sperm, provided that adequate numbers of viable sperm survive cryopreservation and thawing. Shouldn't we follow the practice guidelines from the experts in our field? Yes.

Once again, though this is an exciting finding and a usable blastocyst is a milestone towards a live birth, it doesn't necessarily answer the question that patients often ask, which is will they bring home biologic offspring. However, the strength of this paper is not comparing the outcomes of live births, but instead it's giving these patients a chance to participate in donor bank blastocyst guarantee programs, potentially bringing them one step closer to live birth. Very interesting.

So first and foremost, this paper has unfortunately many limitations which severely limit the clinical utility of the findings. As we know, it's a retrospective analysis, but they didn't control for any confounders other than the donor age or the partner age. Also, the external validity of the paper is severely limited as they only included partners with azoospermia in the surgical extraction groups.

You cannot extrapolate their findings to patients who are having surgically extracted sperm for other indications, such as for DNA fragmentation. They also excluded all conventional insemination cycles. So how many of the ejaculation cycles actually had XE due to underlying male factor, we have no idea because we don't have any data presented.

Keeping all of these severe limitations in mind, though, we believe that the findings actually suggest worse outcomes with surgically extracted sperm in these oocyte donation cases because the fertilization and the blastulation rates were significantly worse in the surgical extraction groups, even in a subanalysis of patients who had obstructive azoospermia due to vasectomy. Also, we want to argue that the primary outcome is unfortunately not relevant to anybody who desires more than one child. So presumably, those patients would be less likely to achieve their family-building goals because the mean number of usable blastocysts was only 2.7 in the surgically extracted groups as opposed to 3.7 in the ejaculated groups.

Unfortunately, the study did not examine whether patients achieved their desired family size or not. Also, type 2 error may have resulted in the lack of statistical significance between the groups in the individual comparisons because actually, if you look closely at Table 3, you see that the p-value is less than .001 for the difference in the primary outcome among all the three groups, despite them saying that there was no statistically significant difference. Also, the pregnancy and live birth rates for the first embryo transfer are approximately 10% lower in the NOA group, but not statistically significant, probably because the numbers were so tiny.

There were actually only 65 transfers in that group. Okay, so in the context of donor egg IVF, at least one usable blastocyst is a clinically meaningful benchmark of success, and there are really four reasons why I'm going to highlight that that's the case. First, it does correlate with pregnancy potential.

Secondly, it reflects embryo developmental competence. Third, it aligns with how labs and how banks guarantee outcomes. And fourth, it is an understandable and realistic endpoint for patients.

So from a clinical outcomes perspective, we know that the blastocyst stage is the strongest predictor of implantation. This is in contrast to cleavage stage embryos. And development to a day 5 or 6 blastocyst does demonstrate embryo competence and developmental potential.

A single blastocyst is also known to be sufficient for pregnancy. So in the context of having donor eggs, who are typically young, healthy donors, one high-quality blastocyst does have a high live birth rate potential, often stated as greater than 50 to 60% per transfer, obviously subject to individual clinic data. And the clinical utility of even one single blastocyst is that it provides the couple with a viable chance at pregnancy without necessarily needing multiple embryos.

From a laboratory perspective, this emphasizes quality over quantity with the idea of blastocyst being the guarantee. The oocytes, banks, and donor cycles often discuss these guarantees because a single blastocyst is a meaningful endpoint. Biological attrition is expected.

We know that not all eggs fertilize, not all zygotes cleave, and then not all embryos reach blastocyst. So having at least one does show that the process is working to some extent despite natural attrition. And then, of course, usable in this context means transferable or freezable.

It means that the couple can move on to the next stage of the process, which is transfer or vitrification. In the context of donor oocytes specifically, which is an important thing to note about this paper, is that it is a realistic counseling tool for patients. So instead of promising them multiple embryos, this sets the benchmark as at least one blastocyst, which is both realistic and reassuring for patients.

And importantly, as we will emphasize, it aligns with egg bank guarantees. So many of these banks structure the guarantees around blastocyst development and not egg numbers, which really underscores the importance of this as a clinically meaningful endpoint. Lastly, from the patient's perspective, this idea of guaranteeing one blastocyst or having one blastocyst be sufficient reduces uncertainty.

They don't always understand the idea of egg attrition, but they can grasp the idea that they have at least one good embryo to transfer. It's a clear and actionable goal for them, and it simplifies complex embryology into a concrete milestone for them. If you have one blastocyst, you do have one at least viable attempt at pregnancy.

It also avoids the false reassurance of egg counts. So having six eggs sounds reassuring, but the true success benchmark is whether or not any of those will develop into blastocysts. I wanted to take a few minutes to talk a little bit about the heterogeneity of the population and how it's really difficult to compare.

For starters, the azoospermic men don't really have another alternative in terms of an ejaculated sample. And so a more interesting comparison obviously would have been testicular sperm in patients who have ejaculated sperm, which is a current hot topic of debate. But over the course of this study, we're talking about tens of thousands of donor egg cycles, there's a lot of heterogeneity with donor eggs.

Were they fresh? Were they frozen? Under what program? How many eggs did you start with? We've gone through a couple of different iterations of shared risk where couples can opt for a live donor that is done in cycle with a test, or you can purchase eggs from an egg bank, hence the guarantee. So there is a certain amount of heterogeneity in terms of, even though your goal is one blast, how many eggs did you start with? Which then manifestly has a deference with subsequent pregnancies down the line. Most of the sperm were also treated in a different way.

We typically do obstructive azoospermics on a pre-cycle basis, freeze ahead of time, makes everything a bit more logistically controllable. But for the NOAs, we pretty much do all of those on an either egg-thaw or fresh retrieval basis with a microtessie. So if we had 75 successful NOAs, that probably means we had about 200 patients where we tried to do sperm retrieval and failed, because it's about a third retrieval.

So this is a really difficult study to take a look at and draw some of these conclusions from because of the sheer heterogeneity between the number of donor eggs, what the state of the donor eggs were, as well as how the sperm retrievals were done. And it gets back to the whole fresh versus frozen debate about sperm integrity. Thank you.

All right. Well, you've heard my colleagues on the other side that say and keep on reminding us about the study limitations, and it does have limitations. We did see that, and we do agree with you in that.

But I also want to point out, and we want to point out, that there's broader literature that supports what they said about the one usable transferable blastocyst, the American Urological Association, ASRM. Their recent guidelines, 2024, just last year, explicitly stated that fertilization, pregnancy, and live birth rates are comparable whether sperm are retrieved surgically or ejaculated fresh or frozen as long as modal sperm is available. And that is our national organizations, right? And not just that.

Large-scale data confirmed this. The 2023 SARTCors registry and there's a 10-year U.K. national cohort. They both showed equivalent live birth rates across ejaculated and surgically extracted sperm.

So this is just one paper, but if you look at the broader literature, it does support that surgically extracted sperm will at least give you one blastocyst to transfer. Now this is where I kind of want to take the discussion one step further. So let's think about how our patients actually experience the treatment.

So you first have to go get a donor, egg bank or cryos. Let's just say they went to cryos. They look at the website, and it does say blastocyst guarantee.

And they might be lured into this because of that, right? There's a guarantee, and if you don't get a blast, they'll give you a whole new cohort of oocytes. But there's a catch, right? There's a fine print that says using surgical retrieved sperm does not qualify. So everything, you know, TESA, MESA, TESE, none of those would qualify.

If we're practicing evidence-based medicine like Dr. Ginsburg mentioned earlier today, the exclusion of this patient population is not supported by the data. This doesn't hold up. So in this paper, the primary outcome, if we just look at the primary outcome, it was that we are going to have at least one transferable embryo.

Did it show that? Yes, it did, right? In other words, when you look at the patient, they already are using donor eggs for whatever reason. And now the male patient has to decide whether to have biologically their own child or forego that for the guarantee. And that's a hard choice, right? Especially when the evidence says that they're going to get at least one blastocyst.

Like the guarantee that they're wanting is actually already happening. They will get at least evidence shows the data supports that. And again, this isn't just an isolated finding.

There are meta-analyses that have shown this, not on donor eggs, but just autologous. Like, you know, the same patient shows similar outcomes. So that's also something I want to point out.

And I also want to point out that there was a study that showed that extracted sperm actually performed better than ejaculated sperm because there was DNA fragmentation. So in some cases, actually extracted sperm is actually superior. So when we decide to exclude obstructive atherospermia, NOA patients from this guarantee, we are not following the data.

We're perpetuating inequity for a group of patients who already face some of the greatest barriers to biological parenthood. Evidence-based medicine means aligning the policy with the guarantee program. And to exclude them is just not just unfair, but it's also unscientific.

So we are focusing our discussion on the con side, does surgically retrieved sperm result in worse outcomes in oocyte donation cases? And we propose that the question is not answered by this article. And would like to consider that in order to truly isolate the impact of the surgical retrieval process and on blastulation rates or ongoing pregnancy and live birth, a different kind of approach needs to be undertaken that will allow for inclusion of ejaculated sperm as well as surgically retrieved sperm in an approach such as a case crossover design with donor oocytes within each male individual. As such, including individuals with azoospermia, especially obstructive azoospermia, would not be part of the consideration regarding surgical retrieval as those individuals would not be able to have childbearing opportunities otherwise.

So we found that this study, as reported here, does not really allow us to truly answer this question. And we continue to argue the con side of this argument. Thank you.

So we open it up now to your questions. I'm sure some of you are right on the fence given these outstanding presentations. So what question comes to mind that's going to help you clarify whether you agree or disagree with the question that Dr. Barnhart started with? Just raise your hand.

We have multiple microphones, this one and that one, to come to you to make sure we answer any of your questions for this esteemed panel. So, Kurt, can you repeat the question? Well, I had trouble with the question because the question matters, right? So there's lots of questions that we can come up with here. One, the first question would be, do you believe this paper convinces you that there's similarities or that the results are similar? Because that's what the conclusion is.

That's one question. It's not the question I asked. The other question would be, I think I know your answer, if you only have surgically retrieved sperm, how many people would use it based on this data? Is there anyone who wouldn't? Right.

So that's not the question either. So the question I asked was, does the current state of the evidence suggest that there are similar outcomes with the use of ejaculated and non-ejaculated sperm for reproductive outcomes for IVF? This is now adding to the current amount of data. What do you mean by outcome? Is it blastulation? Is it live birth rate? Ongoing pregnancy rate? What are we looking for? And I'm a bit confused about it.

Can you clarify that? I'm purposely confusing you because that's the problem. So I heard some wonderful things about this paper. I heard that people agree that this was a nice model to donor egg that took away some of the variables.

There was some disagreement about the outcome, if blastulation might be the right outcome or not. Some people talked about decreasing power in the study and confounding. So is the truth of this paper really the truth? These are the things that I'm asking you guys to digest.

And now I'm going to get off the stage and let them go. Let's start with Jen. Yeah.

So I think this is really important, right? Like in any study, the primary outcome, the choice of the primary outcome is super important. And Dr. Barnhart, you yourself have written on this very topic. Thank you for educating us on this.

I'm not sure how this debate turned into a should these patients be excluded from guarantee programs because I don't, you know, we're physicians. Our primary outcome for our patients should be to help them build their family. Do I want to play games with insurance companies or, you know, guarantee programs? No.

I'm here to get my patients a family. And so in my mind, whether or not at least one blastocyst is achieved, that is not why I'm here. I am here to help my patients grow their family to the desired size of the family.

And actually, that has not been shown in any literature. In fact, that SART study from 2023, which was performed in autologous cycles, actually showed the exact same thing. Fewer blastocysts in the surgically aspirated group than in the ejaculated group, which, fine, if your goal is only one baby, maybe that doesn't matter.

But to say, well, who cares if their goal is only one baby? Because really the most important thing is did they get a blastocyst so they can qualify for the guarantee? I don't know. That's not how I choose to practice medicine. Response? While they're getting the microphone, do you guys at the table have a response? So, yeah, I hear you thinking about the patient in front of you and giving them the best chance.

At the same time, with that same patient, so what I'm hearing is that you're suggesting use a donor sperm as well. Or you can say the data that we currently have right now shows that we can at least get one blastocyst and let the patient kind of decide to take that chance to have their own biological child or not. And I think that the reason they kind of went into this guarantee blastocyst format is because the paper, the introduction, the reason that they wanted to do this study is because they wanted to show whether this group should be excluded from that guarantee program.

And that's how we got to that point. All right. Thank you for this nice debate.

The biggest criticism about this paper, and I would like to ask the urologists here, don't you feel like we're comparing here apples to oranges to salaries? We're lumping non-obstructive azoospermia all together. I mean, we have non-obstructive azoospermia due to testosterone. Others have other conditions.

We're lumping everybody together. On top of that, with obstructive azoospermia, which method was it retrieved? How long was the obstructive azoospermia? Was it due to vasectomy or not? This paper has major flaws, and even the groups that are being compared are so different that you can't even compare them together. You can't put them together and compare them.

So let me turn the question around on you guys. If you are in one, two, three more years going to be out in practice, and you get approached by a random donor egg bank, and they say, Dr. Smith, we're going to offer you a guarantee for your embryos, but do you want to include surgically retrieved sperm in that guarantee? Based on what you see in this paper, and then I'll tell you what we did, based on what you see in this paper, would you allow patients who require surgical sperm retrieval into your guarantee? Raise your hands if you would let those patients in. Well, isn't that always the incentive? No.

Well, your incentive is to – the whole point of a guarantee program, right, is it's truly a shared risk, right? So the patient maybe pays a little bit more, but has some guarantee that they will leave with a baby, right? And the fertility center is, in effect, covered for at least two cycles if something goes off the rails with the first one, right? So there's a kind of meet-in-the-middle concept with many of these guarantee programs. And so, you know, but there is a break point, right? There's a break point beyond which you don't want to do four cycles of this, or else you'll take a bath financially and you can't afford to do that, right? But at the same time, you know, you don't want to overcharge patients for something that you could achieve easily in one, right? So that's why, you know, a lot of these shared risk programs have certain criteria for qualification, and the topic of debate is whether or not you, as a medical director for your IVF group, would include your surgically-retrieved patients. So raise your hand if you would put those patients in the guarantee.

Okay. Just for apathy, how many people would not? Not everyone raises their hand, as I can see. Okay.

So just as of right now, I just talked to our medical director to confirm this, but surgically-retrieved sperm is still excluded for our guarantee. You guys had a comment. Yeah, I just wanted to address the comment in the audience as the urology fellow on the panel.

Completely agree with you, right? This is not an ideal study where we would have a nomogram, we'd be able to predict based on the number of sperm retrieved, based on where it was, based on how long they were obstructed, hormone panels, et cetera. That's what we need. That is definitely not anywhere near where this paper is reaching.

I don't think that they claim to try to do that. The way that I try to think about this in our practice is we get someone probably already been seen on the REI side, referred to us, saying there's an abnormal semen analysis. We know if it looks obstructive, we know if it looks not obstructive, and that might be the only information that we have, and they've already done UI.

So we, in a practical sense, are often put in the situation where we have very little information about the patient, and they're asking our opinion about whether or not they should go through with using their own surgically-extracted sperm, or if they should just throw that out the window and move on and do donor and would their outcomes be better in that situation. So that's how I tried to frame this in light of those obvious limitations on the urologic side. Any other comments? Yes, please.

Surgically-extracted sperm and a donor egg, so totally from equity and patient's care perspective. But on the other side, there's other concerns. The mean age was 26 for the egg donor group.

Our patients are usually older, like female patients. We often have patients who are older than 35, and I think that there's probably some corrective mechanism that's happening through the oocyte when the sperm and egg are coming together, which there could be correction of whatever is different between the two groups that we are not seeing. And for the purposes of people who are using donor egg, it makes total sense, but for thinking about general population who are using surgically-retrieved sperm, I think there's something that we are not catching here because of the study design, and there could be differences because of older female age.

How quickly we can get the microphones ready. There's some hands up over here. So I'm going to ask the panels real quickly.

That was a great point. It's a great model to test donor eggs, but it has limitations. So do you guys think that this data can be extracted, can be generalized to non-donor eggs? So that study has been done, and it showed no difference.

There's a couple of citations that the paper does say in the introduction. These papers, specifically Hays 2021, showed that surgically-extracted sperm with autologous oocytes, there was no difference in outcomes, in clinical pregnancy, fertilization, clinical pregnancy, and live birth, those three things. So to answer your question about the discrepancy in age, there's actually more than one study that has shown that there's no difference.

Yeah. So I think when you say no difference, what are you talking about? Because it depends what outcome you're talking about. No difference in one live birth, in the rate of having had one live birth, that is true.

Was there a difference in the number of blastocysts that ultimately were frozen for future children? Yes. And that includes in the SART study that included over 60,000 autologous cycles. Going back to our original question, because, again, before people vote, I just really want to express that the question being asked here is not whether these patients should be excluded from a guarantee program.

The question is does the bulk of the evidence show that the outcomes are similar for surgically extracted versus masturbated sperm in patients undergoing donor egg IVF. That is the question at hand, not should these patients be excluded. Now, everybody I know voted to say that they thought it was similar and that they should be included, so how many patients in this study who had the surgically extracted sperm used frozen eggs? Does anybody know? Sixty.

Sixty. And that's what they're citing when they say there was no difference in outcomes. One of the groups had 20 and the other group had 40.

So keeping that in mind and thinking about now, do we have data to say that they shouldn't be excluded? Just be very cautious when paper says that there's no difference, like what are they actually saying? Can I make a quick comment before we? Can I say something? Sure. That's coming from here, by the way. I can see you looking around.

So I just wanted to say something very similar. The question was our primary endpoint of this study, which is one blast. And in the REI world, I think it's hard to argue with Dr. Eaton's point of family building.

One blast in my mind is far from reassuring. That is concerning in my mind. That's a coin toss shot at a baby.

So I think that's a pretty meaningless primary outcome. Maybe the secondary points are more useful, which is the number of blasts. I would take 3.7 over 2.7 any day.

That will slightly increase my chances at a live birth, I think. In REI land, it's really hard to, unfortunately, side with the fellow side of the argument as much as I would like to. I mean, we want babies.

So one blast really, that's not very meaningful, I think, to us. So it's kind of hard to, I don't know. Sorry, fellows.

Nope, it's fine. I will say that's why we spent so much time harping on, is it a clinically meaningful endpoint to talk about one blast? And, you know, in that context, we are talking about some of the more practical concerns around IVF, such as specifically in the context of getting donor eggs. And one of that point practically is interacting with the bank, and that's why we spent so much time really highlighting that that's a practical concern.

There were some questions raised in the middle here. So that was a great comment. Does that mean I should be ashamed of myself for accepting this paper with the wrong outcome and the wrong data? Should this paper, like, never have seen the light of day? No, I mean, I'm rhetorical, of course.

This is the kind of thing that gets in the journal because we discuss it, and because it is a good paper, and no paper is ever going to be perfect for you, and there's always going to be limitations. But this is the kind of thing that gets us to talk and debate. Somewhere in here I saw a mic being handed.

Go ahead. I had, like, a similar point to Michelle, that, you know, the way the initial question is, like, are they clinically equally competent? Not, like, we kind of, if you read the paper, know the outcome of one blast is the same based on this paper. And so that question seems to be decently answered.

But my other point is to the guarantee, and I think what happens in clinical practice, at least where I practice, is we deliberate, like, well, we can't find a modal sperm. Should we inject with non-modal sperm? Or, you know, we often don't have six modal sperm. I think there is a risk that's taken because what is perhaps done in this paper doesn't reflect practice in different populations with a worse prognosis.

So the granularity of a paper is always a concern, and I'm glad we brought that up. I think I would just kind of bring our attention back to talking about qualifying for the guarantee as a good outcome. I think unless they report a live birth as their primary outcome, you can't guarantee that qualifying for the guarantee is actually a good thing for that patient because they might basically have a blast, get a transfer, no live birth, have to pay for another cohort.

So I think unless they justify it from a live birth standpoint, that argument doesn't necessarily hold up. Raise your hand. We'll get to you on other questions.

I think that this is... Actually, this is a super organic... I feel like I'm at an external club, actually. This feels... Or even our F&S talks. The thing is that we're talking about what we want the paper to give us, right? And we're talking about a whole slew of different endpoints, which we've heard up here, we've heard here, that the endpoint that we really want, and I think Kurt said it well, that you're not going to have the perfect paper that addresses every single endpoint that we want, but it's important to say with this manuscript, did it address the stated endpoint? We can debate whether it's a good endpoint or a bad endpoint.

In fact, we should. We should be sitting there saying, for us, does this matter? But in the end, the paper itself, it stands and falls based upon whether the endpoint, the stated endpoint, was either supported or refuted. So I think it's important if we're going to... We shouldn't be judging this based upon an endpoint that we make up.

We should be judging it based upon its original endpoint. Anybody else want to join us before we start summing up? Any other comments? So I can't help but jump on that point before I go back to the panels to give their final say. You guys can decide who wants to give their final point.

Let's go back to... This is what I look at in the paper, which a lot is... I'm just giving you the abstract. Obviously, the whole paper matters. But this is why I like this paper.

First of all, it was thought-provoking. It was carefully done. It was meticulous.

It had the right statistical analysis. It tried to control for confounding and multivariate analysis as best it could. Yes, it didn't control for everything.

There's limitations. But, again, let's look at... Let's read the conclusion. Maybe not.

Of course, I don't have my glasses again. I don't have much pocket equipment. Do you think this conclusion stands on its own? Because this is one of the main things that determines whether your paper gets in the journal or not, is how valid your conclusion is.

When comparing donor oocytes fertilized with surgically retrieved sperm with ejaculated... I'm sorry. Surgically retrieved sperm with ejaculated sperm, the chance of at least one usable blastocyst per donor egg lot was similar for each sperm group. That's the main point.

Is that a true statement? Yes? No? Okay. However, there was a decrease in chance of blastulation and fertilization when comparing fresh and frozen gametes. Agree? So I like this because it was a measured conclusion.

It stated what the facts were. You can't argue they're not wrong. They're not overstating it.

They're not saying, and therefore, the question I asked you, therefore, QED, we've just established that ejaculated sperm has the same reproductive outcome as surgically retrieved sperm, and it's not saying our goal was for the guarantee. So this was a very measured comment. Now, we all talked about it.

I went from the review of the paper to why it gets in to why you should be reading these papers and talking about it because it brought up ten other questions and hopefully five other research studies that you're going to design and are ultimately going to get in this study. All right. Before we revote again, let's give one final and passionate thing.

Did you guys come up with ideas? I think the pro was going to go first. Give us your final summary of the arguments, and then we'll give you guys a chance. Yes.

Of course, we first want to thank the con side for being so thoughtful in their questions and bringing up a lot of really good points. I think that our team would also agree with a lot of the points they made and a lot of the points that you guys all made. And, you know, like we said, it might be tempting to want to know what the live birth outcomes are for them to be comparable, to know the amount of eggs that you need to make a blast, to transfer, to have a baby, how many blastocysts do you need to bank in order to get more than one live birth, just like you've said.

And the reality is the paper can't tell you that. However, the value really lies in the primary outcome, which is can they have a comparable chance of one blastocyst. And, you know, based upon this paper, we can say yes, and it can at least be either a counseling tool or something to provide patients with when we think about these programs.

And obviously Dr. Barnhart included it in F&S, so it does have some clinical importance. That's the mic drop now. That this paper did define its outcome and answer its question with a major limitation, as they even summarize in their table three showing statistically significant differences in blastulation between ejaculated sperm and azuspermia for OA as well as NOA.

And this demonstrates that actually outcomes are worse with lower number of blasts. And additional limitations include an inability to distinguish the subpopulations within each group for further patient counseling. All right.

First of all, thank you to our panelists. So I'm going to take a prerogative and ask you just a couple series of questions, probably showing my bias. But so let's, we'll get to the final question last.

First of all, who believes that, well, we didn't get into the science of this at all. Who believes a sperm is a sperm? It doesn't matter how you get it, where it comes from. If you find a sperm, it's going to give you the same reproductive outcome.

Who believes that? Who doesn't believe that? Okay. So that's where we're starting. So that's a consensus, right? The next consensus is who believes that if the only sperm you're going to get is surgically retrieved sperm, that it gives reasonable reproductive outcomes and that's a reasonable option and you should go forward with that with all the information that we have.

Great. Okay. So consensus.

The third question would be who believes this paper proved their point that at least their outcome of one blastulation, one blastocyst is the same whether you get any of those three groups, normal ejaculated sperm, ejaculated sperm, and supposedly a non-obstructive azospermia and then retrieved sperm. Who believes this paper proved that they're similar? Who believes that they didn't, the paper missed the mark and that's a conclusion they can't make? Not too many. Okay.

So that's where we start to differ and then we go back to the questions. Not just this paper. The question I asked to see technically who won the debate, not just criticizing this paper.

The question I asked was does the current literature, including this paper, support the statement that says you'll have similar reproductive outcomes with IVF whether you use ejaculated or non-ejaculated? Who believes that that's a true statement? The current literature supports that reproductive outcomes are similar. It was 50% a second ago. So who believes that that statement is incorrect? I only see 30% going.

It was 50% agreed with it a second ago, now 30% disagree with it. So if we had to say, to give a score for this debate, it seems to me that more people were dissuaded from that statement than actually convinced of that statement. And that's why I like these journal papers.

We took one paper well regarding fertility and had a great discussion, a wonderful discussion about a general topic. And look, it might have actually changed some minds. That's wonderful.

So this is what a Journal Club Global is. For those that are watching online and later, again, I'm Kurt Barnhart, the Editor-in-Chief for Fertility and Serility. This is a sponsored Journal Club Global by Fertility and Serility here at Park City at the Fellows Retreat.

I got to give that introduction to begin with. It was my pleasure to have this illustrious panel and I think it was a wonderful discussion and I hope you will tell your friends to watch the next Journal Club Global and all others. So thank you.

Thank you, Dr. Barnhart. And thank you, Dr. Catherino. Panelists, if you don't mind, make your way back to your seats.