Hello everyone and welcome. My name is Pietro Bordoletto and I'm the Fertility and Sterility Interactive Associate and Chief and Media Editor for FNS Reports. It's my pleasure to join all of you virtually this evening in Europe and this afternoon in the United States.
Tonight's Journal Club Global is a really fun one because we have the chance to compare how we do things in the US and have our European colleagues compare and contrast how their practice looks. We also have the benefit of discussing a really great paper tonight. We're discussing a paper recently published in Fertility and Sterility entitled Common Practices Among Consistently High-Performing IVF Programs in the United States, a 10-year update.
And as a note, this paper is available for everyone who is logged into this webinar by clicking the handout section of your control panel. We are so lucky to have a few of the co-authors with us at this paper, but first I wanna introduce to you the hosts for this evening who will introduce the format and the panel. Joining me tonight are Dr. Dom DeZiegler, Editorial Editor for Fertility and Sterility and Dr. Paul Pertea, Interactive Associate for Fertility and Sterility.
Dom, Paul, welcome and take it away. Thank you, Pietro, this is great. This is a great opportunity to discuss a topic that comes around very often.
Are the Americans doing better than us in Europe? Some people believe. We're gonna see in details what the numbers are and we're gonna look at what the best of theoretically the best are doing. And for this, I'm gonna ask Christophe Bloquil, who is the Medical Director at Brussels IVF to actually give us a summary of the article on the 13 best clinics in the US.
Christophe, go ahead. Thank you very much, Dominique, for the kind invitation. Of course, you can imagine that I feel very honored to be able to summarize the paper that was recently published.
I would like to see the first slide if possible now. Thank you. So this is indeed a title, The Common Practices Among Consistently High-Performing IVF Programs in the US.
So there was a 10-year update. Next slide. Thank you.
So this paper or this survey, a questionnaire study was published 10 years after a first paper by Van Voorhis. It's actually an update of this study and also a co-author of this study with the purpose to evaluate similarities and differences in the clinical and lab practices among high-performing fertility clinics. And of course, the purpose is to have a transparent reporting and with the aim to have a greater standardization and improved outcomes, of course.
Because the past 10 years, there is, as they call it, an explosion of new IVF technologies and innovative approaches that have changed IVF practice. So it is relevant to repeat the questionnaire, we could say. With regard to the M&Ms, so we are talking about the electronic survey and the 13, well, more or less, the 13 best clinics were chosen who had the highest cumulative live birth rates between 2016 and 2017.
And they were asked 61 questions with regards to the clinical aspects, practice demographics, personnel, patient selection, and so on. And also, the laboratory survey contained questions pertaining to andrology, embryology, laboratory personnel, and environments. So you can go to the next slide, please.
We're going to look at the results. So we are talking about clinics with an average of 687 fresh cycles or 1,500 cycles in total per clinic, of course, ranging with a lot of range among the centers between 400 and 7,000 cycles in total cycles, with a median cumulative live birth rate per oocyte retrieval of 59%. And this is, of course, probably one of the topics of the discussion.
So in the young population, close to 60% of pregnancy rates or cumulative live birth rates, better in the population of 35 to 37 years old, it was 47%. There was an average rate of prospective reporting of 85% and a cancellation rate of around 6% overall. When we go then to the personnel, so the results with regard to the personnel, you can see that a lot of clinics, nearly all clinics had, well, all the different kinds of personnel available, physicians, lab technicians, medical assistants, and embryologists, andrologists, and so on.
You can also see that around half of the centers had advanced practice providers, as they call it in the USA. So we will need to discuss what that really means, and then specialized sonographers, and also psychological support was only foreseen in half of these high-performing centers. When people of these clinics were describing why there would be outstanding, then the clinics reported teamwork, weekly meetings for communication, consistency in practice, and careful attention to details as the real tools to be critically important.
And last but not least, of course, the excellent lab staff to be present all day. With regard to the medical practice, are there any restrictions on the use of O-sites? Well, average upper limits to allow patients in the clinic was 45 years old. The BMI, they're quite liberal with BMI, with an average of 40, but going to 45 to allow patients to the clinic, so very liberal, I would say.
If there was a limit for ovarian reserve, there was an FSH limit also varying between 12 and 25. Assessments before the cycle started, so not during the cycle, was, of course, the assessment of the uterine cavity with a mock ET performed in the preceding cycle in most of these high-rank, or let's say high-performing centers. With regard to the supplements, do we need to give supplements to patients with diminished ovarian reserve? Well, coenzyme Q10 was recommended.
Acupuncture was allowed, and metformin and aspirin and testosterone was actually not recommended at all in those patients. With regard to DHEA and growth hormone, there was no consensus, really a split between yes and no in, well, let's say, in half of the clinic. When we talk about PCOS, then weight loss was recommended.
Metformin was now and then prescribed, and the same for acupuncture was allowed, and DHEA was not at all recommended. Do we schedule the ovarian stimulation? Well, yes, the birth control pills were prescribed in around 65% of the cycles. That was quite striking to me.
And of course, we do know that, let's say in 70% in the world, but in probably 100% of the high-performing centers, there is a combination of FSH and LH administered to all the patients, whether it is a step-up protocol or in a step-down protocol, this was completely variable among the centers. Should we measure progesterone? Well, yes, a huge variation. Sometimes patients were getting a blood sample during every, well, a progesterone measurement during every blood sample throughout the cycle.
Actually, only 30% of the doctors required a progesterone measurement on the day of trigger. So not real consistent there with regard to the progesterone measurement. Embryo transfer should occur by ultrasound according to the high-performing centers.
And of course, we should also perform a single embryo transfer in the vast majority of the cases. IM progesterone will be administered to all patients undergoing frozen embryo transfer cycles as luteal phase support. So important to mention this is also a huge difference with European standards.
PGTA to all the patients? Well, the answer is no, because it was only recommended in patients of advanced maternal age from the age of 38 years old onwards. With regard to the mosaicism, if there was a mosaicism of less than 50% present, then there was an embryo transfer performance. Should we do male testing? Well, yes, of course, they said, but no additional tests such as DNA fragmentation, sperm culture, or anti-sperm antibodies testing was not performed routinely.
With regard to the lab techniques, not at all all the centers prescribed ICSI for all the cycles, only ICSI for male infertility. Assisted hatching, well, only if there was a purpose for PGT, but also some centers required assisted hatching, or let's say advised assisted hatching in frozen embryo transfer day three. And popularity for the collapsing, collapse of the blastocell prior to embryo freezing with vitrification.
With regard to the lab equipment and the setting there in most of the center, there was a combination of the benchtop incubators together with the so-called big box incubator. Time-lapse, should we use it? Well, it was only used in two of these high-performing clinics. So time-lapse imaging was not very popular in these clinics.
With regard to the culture medium, there was no consensus so ever. So of course there was commercially available media. Maybe we can discuss this later.
When we go to the lab equipment and the tools used by the lab to control the air quality, there was quite an agreement with regard to the positive air pressure, the HEPA filtration, the volatile organic compound filtration, and so on. Less consensus when talking about humidifiers and the microorganisms controlled by UV lights, but quite some consensus with regard to these two for tools for air quality. The KPIs or the performance indicators, well, of course, everybody checked their fertilization rates, IVF or ICSI.
Day three was not a performance indicator, but of course, day five, embryo quality. The lack of results following a PGTA was also a performance indicator. And of course, survival rates after thawing per embryologist was also a parameter.
Last but not least, clinical pregnancy rates for elective single embryo transfer per physician and per embryologist was calculated in all these centers. So then we can go to the next slide to have the discussion. The discussion, of course, gave in brief what has been set in the survey.
And actually, we can summarize that there was a kind of a similar practice in these high performing programs. There is really a consistency in the vast majority of the cases. And of course, there is some variation.
When we look at the results of the Van Voorhis paper, which was published 10 years ago, then we see really similar results, looking at the ultrasound scan performed during ET. We see FSH and LH combinations, and so on and so on. This was really similar as compared with the previous survey.
Factors for success were standardization. Standardization, we should strive for a standardized practice, although there was some skepticism among the physicians to standardize all the patients. We are more going to this individualization of the practice of good clinical practice.
Good communication is a key factor for success. And let us look at the details. Also, a very crucial aspect to go to their success.
What has changed as compared with the previous survey? Well, PGTA. PGTA, especially in patients of advanced age, more than 30 years old, that's one. And then a very good element is, of course, the single embryo transfer policy, in terms of avoiding the twin pregnancies, of course.
Live birth rates is quite spectacular. And maybe we should ask the authors how they can explain this huge improvement in the last 10 years in the young population, going from 35% to 60% of live birth rates for oocyte retrieval. The authors mentioned the limitations of this study.
Of course, we are talking about 13 clinics who filled in 61 questions. So the sample size is small. Of course, there's always a possible bias with those surveys and also the lack of control group.
So it is very possible, for example, that a center who is performing all this, who is putting all these elements into practice have less pregnancy results, of course. This was my short presentation, Dominic. Thank you very much.
Thank you, Christophe. Thank you, Christophe, for presenting so well this paper, similar paper from FNS, and for underlining the key points of this paper, which probably, in my opinion, is critical and fundamental. And I assume the 10 years update, that was the data of 10 years, was incredibly hard to get.
And the work that the authors put into it was incredible. And this is why I have the pleasure to introduce to you to Dr. Amy Sparks, who is one of the authors, a well-known doctor in IVF all around the world. And let's hear it from the authors, what they think about their work and how they defend the certain weaknesses.
Thank you for the kind introduction. Appreciate it. And I appreciate the invitation to participate in today's discussion.
It was my privilege to participate in developing both surveys, both the 2010, as well as the most recent survey, and writing the manuscripts. But I think it's clearly important that before we delve into the insights from the recent survey, we need to understand the way live birth rates were calculated. So remember here in the US, we have a federal mandate that requires all ART centers report every single treatment cycle.
In 2005 and 2006, where we pulled centers for the 2010, the original publication, the live birth rate was calculated based on live birth rate per cycle start for OSI retrieval. That was the measure to select the top performing centers. So back then, if you had to freeze all embryos and forego a fresh embryo transfer, you were penalized as that was recognized as a negative outcome.
So we all were practicing differently than we were doing many more fresh embryo transfers. And again, if you did a freeze all, that was actually viewed as a negative. So as we try to work on encouraging single embryo transfer here in the United States, it was clear that implementing that penalty for failing to get a delivery from that fresh embryo transfer was a problem.
So today SART, the Society for Assisted Reproductive Technology uses the cumulative chance of a live birth resulting from transfers that occur within one year of the initiation of stimulation for that OSI retrieval as the measure of success. So it's important to understand that patients may have to undergo multiple transfers of embryos from the cohort that resulted from that egg retrieval. This means that programs are no longer penalized for freezing embryos and foregoing a fresh embryo transfer.
This change was initially discussed in 2013 and intended to promote single embryo transfer, which could lead to a lower delivery rate than if we were transferring multiple embryos, but would significantly reduce, as we know, the risk associated with multi-fetal gestation. Over time, this change in reporting has also proven beneficial for programs that choose to forego the fresh embryo transfer, either due to concerns about endometrial receptivity or a desire to incorporate pre-implantation genetic testing into the treatment plan. So that is one of the key components that leads to this leap in the live birth rates from 2010 to the current manuscript.
We're giving centers perhaps multiple transfer attempts in order to get that live birth from that single egg retrieval, as opposed to the original publication where it was one and done. You either got a delivery from that retrieval, one transfer, or you didn't. Okay, so the other part that's important to understand is that regarding the additional selection criteria that were available for the recent center selection, authors were able to indirectly assess reporting accuracy by looking at the prospective cycle reporting rate and the cycle cancellation rate.
So the prospective cycle reporting rate wasn't available in 2010. Today, this figure represents the frequency that stimulations for an egg retrieval are reported within four days of initiation of gonadotropins, or if you're doing a flare cycle loop runner. So the average prospective reporting rate for centers that were selected was 85%, whereas the average nationwide prospective reporting rate was about in the mid 50s for the two years that we looked at.
In addition to having a decent prospective reporting rate, the centers needed to have a realistic cancellation rate. So there were centers that had great outcomes, but they had a zero cancellation rate. We're not suggesting that they were cheating, but on the other hand, a zero cancellation rate isn't all that realistic, suggesting that if you have a low prospective reporting rate and a zero cancellation rate, maybe not all cycles are getting reported, and that artificially elevates the live birth rate.
So those are two elements that are, I think, important to keep in mind when we're looking at this perceived leap in improved outcomes here in the US. We appreciate the comments in the reflection piece that accompanied the manuscript, and we agreed more information regarding cycle-specific data, such as whether programs performing a fresh embryo transfer shift from a planned A5 transfer to a D3 transfer when embryo development's not looking favorable. And it would have been nice to have inquired about program policies regarding maximum gonadotropin dosing.
That said, we do have cycle-specific data, and I think sometimes a better source to answer questions about those specific cycle characteristics would be the cycle-specific data rather than assessing a program's practice. So we can dig into that a little bit more later on. I do want to clarify the point about the use of assisted hatching, because in the presentation of the paper, we're talking about using hatching for day three FET.
That's not the case. So assisted hatching was used before PGT, and typically that was on day three. Centers also reported using assisted hatching for FET, but those were thawed blastocysts for the most part, and they were just doing a little assisted hatching before proceeding with transfer.
So there wasn't a lot of day three FET. Frankly, there weren't that many day three transfers done across these programs. Most of them were day five.
On behalf of all the authors, I want to say we're incredibly grateful that all 13 invited clinics participated. I will say it took a little encouragement from the author team to get some of these centers to respond because this was a lengthy survey. It contained 61 questions with branching of some of the responses.
And some of the questions required individuals to go back to their own database to provide a response. And I don't know, I'll admit, sometimes I stop participating in the survey when I hit those roadblocks. So we are incredibly grateful for the time and effort the medical director and lab director put forth to complete the survey.
As for the limitation in the reflection, that only two individuals, the medical director and lab director, were asked to respond to the survey, it was clear that most of the centers cited standardized teamwork and adherence to shared protocols as common factors that led to their success. And so these comments were reassuring and led us to believe that the responses they provided were reflective of their team and not necessarily individual practitioners. So again, I want to thank the organizers and hosts for selecting our publication for this discussion.
And I'm looking forward to a really interesting discussion at the end of the presentations. Thanks, Amy. This was a great comments.
I'm not gonna pass on the discussion to Jim Stoner, who is one of the discussions. Jim is a long time friend, and he's gonna give, so to speak, the U.S. perspective, how this COP clinics compare to average clinics, but I would also purposively ask him to comment on one of the two items that were found in all the clinics of the paper, the combined use of HMG and pure FSH, and maybe Amy wants to jump in as well on that, as well as injectable progesterone, because there's been recently in Europe lots of publications about progesterone levels and pregnancy rate when Vaginal was used. And again, all those 13 clinics used injectable.
So maybe Jim is going to give his comments and maybe answer these questions. I would like also that Jim tells us, us being the Europeans, what is the advanced practice providers which actually are used in several of those clinics and for us, we don't know who they are. Jim.
Well, thank you very much, Dominic, for the invitation and the chance to speak to this audience. I think we all acknowledge, given the nature of this study, that we can't infer cause effect, right? These clinics did certain things. These clinics had high pregnancy rates, but we can't draw a causal link necessarily.
You know, there's always gonna be a 10% top, even if there's nothing underlying the practices. But I do think, and you can put up the first slide, Thea, there are some features of this common practice that have been subjected to randomized trials and show value, such as, and Dominic asked about this, adding LH or some HCG activity to FSH stimulation, this so-called mixed protocols, seems to produce, even in modeling studies, maybe not quite as many eggs, but at least as many mature eggs and better developed blast conversion rates in more pregnancies. So there's evidence that that's effective, as is there evidence that intramuscular progesterone in medicated FETs leads to fewer miscarriages and more live birth outcomes.
Obviously, uterine cavity evaluation, ultrasound guided transfers, et cetera, et cetera. We have independent corroboration that these things are useful. What I thought I might do, kind of to comment around some of the things Amy was mentioning, Dr. Sparks was mentioning, was sort of some external influences outside the clinic itself that in the US, I think, favor success and also encourage almost homogeneity of outcomes.
And let me spend a few minutes describing that. SART is our professional organization that's been around for nearly 40 years, and from the start has provided annual reporting of clinic-specific outcomes. That is a stick.
I mean, if you're across town from a clinic that every year shows better pregnancy rates than you have, that's concerning. And you start worrying about what can I do to kind of match my colleagues, because at least in this country where most patients are allowed to select any clinic they want because they're self-pay, that's an intense motivator for a practice to get it right. So this whole element of transparency, annual reporting, I think undergirds a lot of the success that we have because it motivates people to get better at what they do.
And also, as Amy suggested, we've recognized a flaw in the first version of the reporting where people were, because the initial output that got featured was live-born per fresh transfer, right? So everyone's throwing in all these embryos to get a higher pregnancy rate, higher delivery rate, and sort of saying, yeah, well, there's twins and triplets, but we beat you all in terms of the top-line number, which is a live birth per transfer. So we've recognized that's a problem, multiples are a problem, and now the top-line number is singleton delivery rate per stimulation start. So it takes out all the incentive to put back more than one embryo or to spend some time over successive cycles in getting that good pregnancy.
So the nature of the reporting itself has really had an enormous impact on pattern of practice here. SART also publishes guidelines regularly and updates them regularly about how to run a lab effectively and limits on the number of embryos that ought to be transferred. And those things get evaluated.
SART has committees, validation, quality assurance that looks for outliers. And every year, the 5% underperformers by virtue of low birth rates or high multiple pregnancy rates are contacted and said, this isn't okay, you're out of range. And we have kicked out clinics who have persistently had bad performance.
Because this is a voluntary organization and we don't want people flouting the rules. So I think the guidelines, the practice, the committees that verify the data are correct and that people are practicing within the guidelines and not having egregious outcomes are also one factor that causes homogenization, right? Because you're showing everyone what the mean is, you know whether you're above or below the mean and the underperforming 5% every year get a letter and maybe a visit saying, can we help you improve your practice? There's also even advertising guidelines and all of our clinic websites get looked at every third year to make sure we're not exaggerating, that we're not making claims that aren't supported. We don't allow clinics to compare themselves to one another.
So again, all of this I think is maybe different than the European experience. And as part of what undergirds the success we've had and the lack of wild variation in outcomes. As Amy alluded to, there's certainly been enormous changes in practices in the past 10, 15 years.
In the US, the blastocyst transfer rate, just to give you an example, went from 5% 15 years ago and is now 70%. Freezols went from 5% to 62%. PGT went from 5% to 40%.
Elective single-member transfers went from nothing 20 years ago, even in the youngest group to 80% now. And with all of those changes, the net, again, delivery rate has been maintained. So I think we're doing pretty well.
You asked me personally, in addition to these external factors, which I think are motivating to clinics, I do think that the highest performing clinics are those who really pay attention to detail, practice as a team, kind of stay up on the literature so they incorporate things when they're demonstrated to have efficacy. So I do think it's sensible for all of our clinics to look at what these 15 are doing, 13 are doing, and adopt them even potentially absent hard data yet. Because it's a very complicated equation that leads to success.
And some things are proven, some things are not, but still, for me, I'd rather go with patterns that the most successful clinics use, even if there's no hard evidence. So thanks. Thank you.
Thank you a lot for this intervention. And we fully agree with you. And I fully agree with you on all that you have said.
And now in order to give the talk and the right to talk to someone from Europe, I invite Dr. De Getter to present his opinion on the results of Europe and how this paper can influence Europe. Thank you. Thank you for having me in this group of people.
And I'm happy to describe to you the European situation. I prepared originally seven slides, but I had to limit myself to only one, which we are not seeing. I'm a bit of a mathematical person.
I would like to draw your attention to a fundamental problem or difference in the data acquisition in the United States as compared to Europe. In the United States, you have a legal act many years ago that enforces the centers to report their data. And basically it would also entail external visits to validate the data.
In Europe, we have 54 countries, among which five tiny countries do not have assisted reproductive technology, so they don't report. And all the others have very different legal backgrounds, very different mentality in data reporting. For that reason, some of the data are quite incomplete.
Also, although we have now managed to have 91% of all the existing IVF services offering institutions reporting now. And we have also very different social backgrounds. Some of those institutions that are reporting do IVF, but they do normal deliveries, they do normal gynecology as well.
So IVF is only part of their business. So that I think that the level of dedication is certainly different. These are the latest reports, latest data of the European IVF monitoring, which is a consortium of the issue, in which each figure corresponds to one country.
And I did not denominate the countries because I did not want to start another war with this. We've got one already, huh? The best, yeah, that would be the second one. The best data we have is the number of aspirations, not the number of initiated cycles, but the number of all site collections.
And we have quite good data also on the delivery outcomes of the pregnancies. And I give you here the data on conventional IVF, on ICSI and on thawing cycles. And as you can see, each of the columns have different lengths, because in some European countries, IVF is not performed anymore and all treatment cycles consist of ICSI.
So we have fewer countries that report an IVF, but as you can see in the first column, the span of the delivery rates varies between 10.4% and 40.9%. So a huge span, which certainly is in part due to the under-reporting, but I think that if you then look at all the results together, we cannot have similar results as in the more uniform data collection as given by SAAB or by CDC. If you look at ICSI, the span between the country with the lowest delivery rate after ICSI is 12.2% to 36.8%. And then in the thawing, looking at the thawing, the span between the lowest and the highest performing countries is 3.2% to 37.8%. From another committee, I know that there are countries in Europe still today that do not perform any freezing of all sides of embryos. So this is the situation in Europe.
In some countries, there are very good data and there is one country, Belgium, that has published recently cumulative outcome data because those reports are cross-sectional data spanning only one year. So cumulative outcome data's looking at various, several years, one after the other. And there we have a similar cumulative delivery rates as compared to these high-performing institutions in the United States.
So it's in part the worst outcome results coming from Europe are due to legal and social problems, but also due to reporting problems. This is my contribution to the discussion. Thank you, Christian.
I think we have now to address a few things. One, and to see whether there are differences between the US and Europe. One of the issues that strike me is that in those best performing clinics, there was little reports about add-ons.
We are plagued by patients requesting a year add-ons. The whatever test for endometrial receptivity and so on and so forth. I would like to hear everyone's opinion on that.
We are absolutely plagued. People go on internet, they read about this or that endometrial assay. And of course, in France, the problem is complexified by the fact that we don't have PGTA, it's forbidden by law.
And therefore we have lots of failed implantation just because we transferred unemployed embryos in all the women. We're absolutely plagued by requests for add-ons. I would like the panelists to actually comment on that and whether there's a difference between what we have here and US.
Well, I would say we're plagued as well. I think we may have a little more luck with pushback because most of these add-ons are self-pay and absent efficacy that you could show them clearly, a lot of the patients would back off. And maybe we can talk them into not doing the ERA ever or after one or two more failures than might be the case in Europe.
But yeah, I think we're all plagued with these. I think perhaps at an academic institution, it's also a little easier to deny these services because we can sort of act professorial and say, well, there's no strong data, we're trying to act on evidence and... Yeah, I think that's fair. I found this one of the nicest conclusions or the nice findings from the paper that add-ons were not used in most of the, virtually none of the add-ons was being used except PTTA.
Amy, do you want to? Yeah, I have to agree with Jim that what happens is centers that are performing well can provide their data to their patients and say, look, these are the outcomes we get without the add-ons. And certainly, as we call it, Dr. Google steps in the room often, but it is self-pay, so that does make a difference. And it truly is the team.
And every member of that team has to be committed to not caving. That's the other problem, I think, is just making sure you have consistent delivery of the information and a policy across the board. So even if the physicians each have their own private practice within the center, everyone has an agreement, so a patient won't jump from physician A to physician B because B will let you do the ERA or what other additional add-on might be introduced.
So I think that that's what these teams have built over time. This is a very important point. I would like to ask Christophe to comment on this because Christophe is the head of the group.
I was also happy, actually. I was also happy that, let's say, the non-evidence-based add-ons were less popular in the high-performing centers. But on the other hand, and maybe being the devil's advocate, and also, as we read in the limitations of the paper, it is still a survey.
And of course, no one of the physicians is afraid to mention that they use IM progesterone or are afraid to tell the community that they use FSH and LH combinations. But of course, the add-ons are already more delicate. And maybe when filling in the questionnaire, we should not mention everything.
Maybe, I don't know, I don't know. But of course, if a patient comes to your clinic, and of course, in the US, everything is self-paid, and you know that we in Belgium are extremely spoiled. All the IVF cycles are fully reimbursed.
Well, six IVF cycles are reimbursed. So we can just tell our patients, no, dear madam, we are not going to use any add-ons here because there is no evidence. I think it remains a more delicate situation in the US.
Isn't it, Amy? I think it is delicate. We do have a decent amount of insurance coverage that is improving access to care for our patients. And certainly, there are many centers that are adding on.
It just happens to be that these 13 at the time have not been adding on. How they practice stay could be very different than how they responded to their survey a year ago too. But it's, and patients will jump clinic to clinic until they find what they're looking for if they don't have success.
That's the difference too. Yes, I think Amy touched on an important point, which is the best tool we have to fight against this onslaught of add-ons and specifically data from your own center. So I think a lot of what you see at large centers in the United States is people doing retrospective studies, small prospective studies on these add-on technologies and being able to say in our hands, in our patient population, in the way that we practice IVF, we have showed no benefit.
Therefore, we do not recommend it or do not allow it. I'm gonna give a shout out though to SarkCores. That's the registry we use.
And we've built many tools for the centers that use this. And the centers can now query their own data and essentially use it as their own cycle-based database to run all kinds of analyses. We've also started to build in some quality assurance features where they can start tracking fertilization rates and blastocyst conversion rates.
So we are trying to give back while this is a tremendous amount of work to collect all this data. And it is federally mandated. We're trying to give the programs tools to create their evidence-based practices and be reassured that they don't need to necessarily put in these add-ons into the patient plan.
Well, I just think we might actually dwell on for a second is progesterone. There's been a long time that people have said that the best clinic in the US use IM progesterone. And therefore, it might actually play a role in having better results.
Some Europeans, and I was part of those, believe that Americans always go for the concept that if it doesn't hurt, it doesn't help. And therefore, they give IM progesterone in a very nasty way. Now, in the past five years, we have been amazed by the amount of publications regarding vaginal progesterone that actually singled out the case of about a third to 50% of the women who have lower progesterone levels, doing less well and having higher miscarriage rates.
Now, Jim and I have worked with progesterone for a long time and we believe that vaginal gave high tissue concentration. So there seems now that not just tissue concentration is important, but also circulating levels, possibly for being responsible for the immunotolerance that is necessary for things. I would like to know whether you have impressions and comments on progesterone and the mode of administration.
Dominic, I'm still waiting. I think for a fresh cycle, any kind of progesterone is sufficient because you've got a corpus luteum, but I think you're right that when you're trying to program a cycle with exogenous medications, it seems like vaginal is insufficient for the reason, probably for the reasons that you described. The local concentrations are fine.
They're probably higher than you get with IM, but there's something missing because we do see more bleeding and more miscarriages. So I think five years after Crinone was launched, many of the clinics in the U.S. that had been early adopters and then experienced that side effect went back to intramuscular. Christophe, any comment about your practice and development? Well, of course, we also started measuring progesterone on the day of frozen transfer, but I'm still waiting for an RCT showing the, well, let's say evidence-based benefits of adding another route, for example, of progesterone because we do measure progesterone and Labarta, who is an excellent scientist and others have published in prospective series, but never in an RCT that it will enhance pregnancy rates.
But I think that we should do, and it is still ethical to perform an RCT to see whether patients with low progesterone measured, of course, always on the same moment of the day will have better outcomes when adding another route because like in Asia, we can also give three different routes of progesterone. Why not? But I think there is also an upper safe limit of progesterone which we should not go beyond. I don't know whether the U.S. colleagues would like to comment on that.
Amy? I'm a labby, but I can say that the data, at least it wasn't at the Shady Grove paper, Jim, the Faring study that showed that at a minimum, altering at least every third day getting injected in IM progesterone was required as opposed to strictly just vaginal support for the FETs. Our program has always used IM. Yeah, we go for the pain here.
We've always used IM progesterone for the most part. Yeah, Shady Grove was an RCT and they had to shut down the vaginal-only arm early. Yeah.
Yeah, to the VEEN paper, you mean? Uh-huh. That one, yes. Christiane, do you want to make comments? I would like to point your attention to a European medication in which progesterone can be given subcutaneously.
Hm. And that injection is not as painful as the intramuscular injection. So if you want to do an RCT, you should do it with that one.
And why not with an oral compound of dihydrogesterone? Mm-hmm. But there, on the leaflet, it's contraindicated for oral use during pregnancy, as I was told. Well, no, well, it used to be off-label use, but now it is on-label since a couple of years now.
We keep talking about what the best way to give progesterone is. What if we just started emphasizing the natural cycle in ovulatory women, or doing ovulation induction in inovulatory women to help them create a corpus luteum, and really stop figuring out how much progesterone can we give and what's the best way to give it? There will be less preeclampsia and there will be less obstetric complications with your natural cycle, you're right. We think so.
In Europe, is there a trend towards the natural cycle? We're starting to see it here locally in the United States where patients are coming to us asking for a transfer in the natural cycle because they have started to do their own research and there's some data that it may be safer, particularly for women who have preexisting risk factors for poor obstetric outcomes. Yeah, Peter, you're right. I want to take a follow-up on that.
So we do not know about cycle control. But you're right, Pietro, that we start having women who come to the office and have read about it and ask. Of course, one of the problem with natural cycle is it happens anytime.
You know, for example, in France, we don't work on Sunday, okay? And if you ask people to work on Sunday, they go on strike. The natural cycle may actually be safer but there are problems for organizing those cycles and those transfers. Paul, do you want to make any comment? Just don't forget the pain.
You just said that if there is no pain, it doesn't work. We're seeing more and more natural cycle FET and as an embryologist, I hear a lot of feedback from colleagues is that there is a challenge with workflow and we do work on Sundays here. We work every day.
But you can only handle so many FETs in a day. And so if we do get to that point, then perhaps we're going to have to prepare patients that, okay, after 10 patients or however many you're going to do in a day have made criteria for transfer on Saturday, oh, you're going to have to wait a month for the next cycle. So there's a challenge.
Is that in order to have the results that you have in those good practices, you have to work every day? Is that one of the confusing? I guarantee you that everyone works every day in those practices. Given the fact that the time is limited, before giving the opportunity to each of the speaker to have some final thoughts and some key points, I would like to announce the next journal club, which will take place in March 24 in Palm Springs on the topic of non-invasive embryo selection technique. So this is the Pacific Coast Reproductive Meeting.
So now please, we'll start with Dr. Sparks, women first, some final thoughts, and then we'll go to Christoph, then James, and then Christian, please. When I started in ART in the early 90s, everyone was very secretive and wouldn't share their best practices. And it's really refreshing to have this conversation and to have conversations with colleagues all over the globe about best practices.
And this is the only way we can get better. We need to continue to collect data, we need to measure, analyze, and share our information. So I thank you for this invitation and let's keep the discussion going.
Well, I would like to thank Amy for her nice paper and 10 years ago and today, it's very nice to see some evolution, a little evolution, but some evolution. So I'm really much looking forward to 2031 for the next paper. Let's see what life brings us.
Of course, it burns here under my seat because I really want to do a copy-paste of your study in Europe. It's not very sure whether this will work in the same way, but you know, we are not so bad in Europe. We are also very good in Ikea.
Jim? Thanks for the opportunity to be involved with this. I guess I would kind of mimic what Amy said. I think there's a real advantage to a transparent reporting system for all involved, the patients, the providers, the insurance companies in our case.
In fact, most insurance companies who do provide coverage in the States require that the clinic is a SART member because they know then they're getting solid data. So I think that's one of the elements of being successful is being in an environment where people are willing to or forced to say what they did and how it turned out. Is there any questions? Christian? Yes, there were three measures that I found quite convincing.
The one is the standard operating procedures. So the procedures were written down based upon evidence, I guess. Then the key performance indices.
And the third one is the meetings in the team. And if I would add all three together, the only words that describes this is dedication. Now, I would make a final comment to actually thank this Pietro and Mika who is not here to actually dedicate some of those journal clubs at the European time so that we don't have to get up at one o'clock in the morning.
And I think this is great that Fatigue and Serenity opens to that. I think we had a great opportunity to discuss these issues, good practices in the US and comments from Europeans. So I would like to thank you all very much for participating.
And we'll see you at the next journal club in Palm Springs. Thank you, everyone. Thank you.
Thank you. Okay, bye-bye. Bye-bye.
