Podcast & Blog

FERTILIPOD BY IVIRMA

IVIRMA at the 2020 ASRMCongress – Part 1

with EMRE SELLI, EMILY OSMAN, ELENA LABARTA, JUAN GARCIA VELASCO

IVIRMA at ASRM 2020

Listen in for highlights of IVIRMA's research presented at the 76th ASRM Scientific Congress and Expo. Join us as Dr. Emre Seli, Dr. Emily Osman, Dr. Elena Labarta, and Dr. Juan García Velasco discuss their presentations and other interesting topics including preimplantational genetic testing (PGT), slush nitrogen, the effect of ovarian stimulation on embryo quality, and the relationship between obesity and miscarriage.
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Dr. Andres Reig:

The information shared in this podcast does not necessarily represent IVIRMA’s stance. These podcasts are not a substitute for consultation with a physician. Hello, I’m Dr. Andres Reig. Welcome back to FertiliPod, the podcast where we discuss current topics and the latest research in the field of reproduction with some of the world’s leading experts. Let’s get started.

Dr. Andres Reig:

Today, we’re having a special episode for ASRM. In fact, it’s going to be a two-part episode. During these two episodes, we’re going to be talking to some of the researchers from IVIRMA, who presented their work at the recent ASRM Congress, both to highlight their papers that IVIRMA has shared during this recent congress, but also to discuss other abstracts they found interesting and get their thoughts on the latest in our field.

Dr. Andres Reig:

First, we’re going to introduce this episode with Dr. Emre Seli, the chief scientific officer at IVIRMA Global. Welcome, and thank you so much for joining us.

Dr. Emre Seli:

Well, thank you for having me.

Dr. Andres Reig:

Can you tell us a little bit in your role as the chief scientific officer for this very, very large group, how you face ASRM, how you get ready to coordinate everything that’s published and presented at the conference, and how you face what is probably the biggest scientific event of the year for the group?

Dr. Emre Seli:

Well, as you know, IVIRMA has a very robust research program. And it is a very well-defined program with clearly defined aims. IVIRMA allocates an enormous amount of resources into research and scientific development and innovation and aims to find strategies to improve the outcomes of our patients. I guess the research would be defined as clinical or translational. Other than our specific laboratories in Valencia, we do not necessarily invest too much into animal research or model development, but we try to understand and employ quality novel basic science information into the daily practice of reproduction and assisted reproduction.

Dr. Emre Seli:

We are interested in using medications more efficiently. We are interested in identifying and developing new tests that will give us better information about patient outcomes and embryo development, among others, basically. Our investigators are funded internally as well as sometimes from federal agencies in different countries, both in Europe and elsewhere. And of course, we do follow to make sure that there is a production at the end of the funding. When our investigators identify quality data or generate quality data, we would like to share this with our colleagues in the field. And we believe one of the best venues to share this data is ASRM.

Dr. Emre Seli:

Actually, ASRM is a very important event for us. We enjoy it. We enjoy it much more when it’s in person. But we still chose to attend ASRM. We knew it was going to be online. Although, we still chose to register as a whole group, as if it was an in-person meeting because we wanted to support the society with our research as well as of course, financially. And we also thought that asking our members and our trainees, our fellows to write their abstracts and prepare their presentations would motivate them to submit their papers. So the way we prepare is that immediately after ASRM ends, which is right now, we plan for the next one, and the next one. Meaning there are different types of research if you will.

Dr. Emre Seli:

If there will be a retrospective clinical data analysis, or if it’s a translational work on a test development that can use samples in our biorepository, this can be a study that can be ready for just the next one. So 2021 in this case, will be a submission in May and presentation in October 2021. However, as you know, we ask our fellows to have more complex studies, and that we ask each fellow to have a randomized clinical trial by the time they complete their fellowship. So those generally, take two to three years, from IRB approval to the execution.

Dr. Emre Seli:

So probably, the more complex trials that we will submit for 2021 started either last year or the year before. But again, we have the same attitude toward ESHRE. They’re equally important for us because as you know, many of our very important researches are in Europe, and some are in the United States. So we try to attend both of them as well as SRI and sometimes SSR.

Dr. Andres Reig:

It’s clear that there’s been a lot presented, I think. How many abstracts did IVIRMA end up presenting at ASRM this year?

Dr. Emre Seli:

I think a lot. This year, it was around 74. And last year, I think it was even more than that. Overall, our work accounts for 5% to 10% every year of either total abstracts or oral abstracts. Again, we have 17 investigators within our group, and a number of very strong collaborations with leading schools like Oxford University, Cambridge University, Caltech, Yale, Harvard. So a lot of data comes through those efforts.

Dr. Andres Reig:

Absolutely, absolutely. Well, congratulation.

Dr. Emre Seli:

Thank you. Thank you. It’s definitely teamwork, a very efficient team. And also, as you know, we have a central organization located in our foundation in Valencia that really oversees regulatory aspects of research protocols. They are following to make sure everybody complies. And as you know, many of our researchers are clinicians who work every day in the clinic.

Dr. Emre Seli:

They don’t get free time for it. They do it in their spare time because that’s what they love to do. However, sometimes when you’re a clinician and you’re very tired, you may not necessarily want to fill a form or think about the legal aspects of something. So we do have a team that supports that, and I think that’s a big part of our success.

Dr. Andres Reig:

That’s a huge help. Tell us a little bit about one of the abstracts from the group, from IVIRMA that you would like to highlight that was presented at ASRM this year.

Dr. Emre Seli:

If I have to choose one of the IVIRMA abstracts, my favorite is a study that was designed by Richard Scott and executed primarily by our graduating fellow, Ashley Tiegs. It’s a multicenter prospective study. And as its name implies, it’s a multicenter prospective blinded non-selection study that evaluated the predictive value of an aneuploid diagnosis with PGT-A, and also the impact of biopsy.

Dr. Emre Seli:

The reason why I like this study is because it’s huge. It’s a major undertaking. As people who are in this field would agree, it is addressing two questions that are extremely important in the field. The first one is, whether or not we are wrongfully discarding embryos by labeling them as aneuploid. In other words, whether the aneuploid diagnosis is correct. And the second question is, whether seeing the trophectoderm causes any adverse effect on the embryo’s reproductive potential.

Dr. Emre Seli:

Both of them are extremely important, and both of them can only be really answered or studied using a specific design. And that is not a randomized clinical trial, because you will not be able to answer the first question in a randomized clinical trial. Because in a randomized clinical trial, if you know the diagnosis of an embryo to be aneuploid, you would never transfer that. So what the group did in this specific case, for the first part, what they did is they put women through IVF, and embryos were collected as usual. And in our practice, we do a single embryo transfer and we do frozen, thawed single embryo transfer only. And that’s what we did with these patients.

Dr. Emre Seli:

And they also underwent an embryo biopsy. However, the results were not made available prior to transfer. So these women underwent a transfer without really knowing the euploidy status of their embryos. And this was the same for their … their physicians didn’t know and their embryologists also did not know. They were blinded to diagnosis. And a total of 402 participants were included. This is again, a very large study in that aspect.

Dr. Emre Seli:

And as far as the outcomes, basically what we found, of all the transfers that were done, when we went back and looked at how many of them had a diagnosis of aneuploidy, so we found that out of 484 transfers to these women, 102 were diagnosed as aneuploid. 102 embryos were diagnosed to be aneuploid. And of those diagnosed with aneuploid, none implanted. Not a single one. Of course, we will not say that the positive predictive value is 100%, but you would agree that it is quite high. It is pretty close.

Dr. Emre Seli:

And if we go to the second question of whether or not doing a biopsy harms the embryo, well, again, all of these 484 transfers involved embryos that are biopsied and transferred. Some euploid, some aneuploid, some mosaic, whatever they might be. So we compared those embryos to those women who in our practice who underwent a transfer without a biopsy. These women were people who declined to do PGT-A in the same timeframe, and they had similar clinical characteristics. And actually, when we compared both groups there, the sustained implantation rate of the two groups were practically identical. There was like 1% difference between the two, and it was definitely not statistically significant.

Dr. Emre Seli:

So as such, our findings suggest that the way it is done in our practice, trophectoderm biopsy does not have a detrimental effect. And it’s quite comforting for our patients as well as physicians. So I think overall, this was a major undertaking. It involved a number of our centers from Philadelphia to Florida to San Francisco, and very hard work from all of our fellows, and especially Ashley Tiegs, who has done an outstanding job.

Dr. Andres Reig:

Absolutely. I agree, 100%. It’s a huge paper and very, very important to know that we have validated the platform. Can you tell us a little bit about another abstract that you found interesting, perhaps one not from IVIRMA that you can tell us a little bit about?

Dr. Emre Seli:

Well, I think I would highlight the AMH abstract that came from Yale. Reshef Tal was the key author, and the abstract later received the ASRM prize. The abstract’s title was AMH highly correlates with assisted reproduction cumulative live birthrate in women with DOR, independent of age. And this was an analysis of 30,000 plus cycles from the SART database between 2014 and 16.

Dr. Emre Seli:

So basically, what they did is they went ahead and they identified all the cycles that originated from an initial retrieval, and then calculated the cumulative live birth rate for each retrieval, and then associated that with the AMH and assess whether AMH is an independent predictor of cumulative live birth. And they found it to be so.

Dr. Emre Seli:

Now, of course, one might say that it’s should be, that there’s nothing surprising about it because I guess, when you have a higher AMH, you have more eggs. When you have more eggs, you have more embryos. And when you have more embryos, you have more euploid embryos. And therefore, you are likely to have a higher number of cumulative live births. And yes, it is not very surprising data. And yes, it is a retrospective analysis.

Dr. Emre Seli:

But I personally have, I guess a bias in a sense that I really love studies that are trying to associate ovarian reserve versus aging versus outcome. And they are interrelated, but not exactly the same thing. And I think this is a very good addendum to our data, our knowledge, in a sense, and it will help us counsel our patients. As such, I think it’s a solid contribution, and it was a nice abstract. And very nicely presented. And also, the questions were answered beautifully also.

Dr. Andres Reig:

Absolutely. I actually really enjoyed Dr. Tal’s presentation as well. Thank you. Thank you so much for joining us, Dr. Seli.

Dr. Emre Seli:

Well, thank you for having me. It was a pleasure.

Dr. Andres Reig:

Next, we’re talking to Dr. Emily Osman. Dr. Osman is a recent graduate of the Thomas Jefferson University, RMA of New Jersey, REI fellowship program, who has now joined as a specialist. Thank you so much for making time for us, Dr. Osman.

Dr. Emily Osman:

Well, thank you for having me.

Dr. Andres Reig:

You presented a very interesting paper on the use of slush nitrogen for embryo preservation. Can you tell us a little bit about this abstract?

Dr. Emily Osman:

Right. Slush nitrogen has been studied in the past as an alternative to liquid nitrogen for the vitrification, mostly of oocytes, human oocyte, and animal embryos. And what slash nitrogen is, it is liquid nitrogen, and we generate slush nitrogen by applying negative pressure to the liquid nitrogen and dropping the temperature from minus 196 degrees Celsius to around minus 210 degrees Celsius. By lowering that temperature and generating the slush, we’re allowing for more rapid vitrification.

Dr. Emily Osman:

And the question that we sought to answer was, is this a less toxic alternative to liquid nitrogen? Prior to the implementation of any technology or any new method of doing anything really in the IVF lab, it’s critical to perform a safety trial and to ensure that this new substance, technology, et cetera, that we’re introducing isn’t going to be harmful to an embryo. And so that was really the purpose of this study was a preclinical trial, assessing what is the overall toxicity of slush nitrogen? And how does that impact survival of an embryo, and specifically, a mature expanded blastocyst after vitrification?

Dr. Emily Osman:

With the study itself, we utilized mature expanded blastocyst that had undergone PGT-A testing and they were actually aneuploid and donated for research purposes. We used a very specific grade of embryo, a four or five expansion grade, and inner cell mass and trophectoderm grade of B or better because we wanted to use high-quality embryos despite the fact that they were aneuploid. And it should be noted that aneuploid embryos are just as likely to survive a warming process as a euploid embryo, or a genetically normal embryo.

Dr. Emily Osman:

So what we did was we took each embryo and cryopreserved it or vitrified it, and then thawed it over and over again. And this was a randomized control trial. So 50% of the embryos were repeatedly vitrified and thawed in slush nitrogen and 50% of the embryos were vitrified and thawed in liquid nitrogen. And those embryos were matched based on the age of the oocyte that created the embryos, and they were also matched based on the embryo grade themselves. And that was important because you want to make sure that the embryos in each group are equal essentially.

Dr. Emily Osman:

So by repeatedly freezing and thawing those embryos, the embryos that were vitrified in slush nitrogen far surpassed the embryos vitrified in liquid nitrogen in terms of overall survival. They survived more cycles and in better condition than the embryos vitrified in liquid nitrogen, suggesting that the lower temperature of slush nitrogen or this supercooled freeze, has the ability to protect the embryo from vitrification associated toxicity in comparison to liquid nitrogen.

Dr. Emily Osman:

In general, since the advent of vitrification and its utilization in the IVF lab, the survival of embryos and oocytes is dramatically better as compared to slow freezing. But we know that losses of embers and oocytes do occur, and we’re constantly striving to improve those statistics. And so slush nitrogen represents a promising approach to improving post-warming survival of embryos and has really opened the door to multiple clinical trials that are now underway at IVIRMA.

Dr. Andres Reig:

That’s so interesting. Do you have any plans for testing this with euploid embryos, transferring those embryos? What steps are there between now and then?

Dr. Emily Osman:

Right. So now, we have a clinical trial underway, utilizing slash nitrogen with oocytes. We are now utilizing it to see if it enhances the survival of oocytes after vitrification. And we’re also utilizing it for exactly what you said, euploid embryos, to see if they are increased sustained implantation rates after its utilization and implementation. And so, both of these next steps or clinical avenues are very promising.

Dr. Andres Reig:

It is very promising. How generalizable is this do you think, in terms of what is required to produce and maintain the slush nitrogen in general by other labs?

Dr. Emily Osman:

Right. The nitrogen is actually relatively easy to generate. There is one particular manufacturer that makes the slush nitrogen generator that we used in our study, it’s called the Vit Master. The Vit Master, in terms of cryopreservation, it’s easy to pour the liquid nitrogen in, apply negative pressure, and submerge the embryos and oocytes in the slush nitrogen. You don’t have to store gametes or embryos in slush nitrogen.

Dr. Emily Osman:

It’s the initial vitrification that’s most important, and so they can still be stored according to traditional protocols and do this with liquid nitrogen. So slush nitrogen is very easy to implement in laboratories. And especially in laboratories where post-warming survival rates may vary quite a bit, slush nitrogen represents a very promising intervention to help improve those survival rates.

Dr. Andres Reig:

That’s so interesting, that the freezing itself is what matters. And then they can actually be stored at minus 196 like normal.

Dr. Emily Osman:

Right. We used traditional concentrations of cryoprotected agents for both the embryos in the liquid and slush nitrogen group, by potentially lowering those cryoprotected agent concentrations. Especially in embryos utilizing slush nitrogen, also can help reduce vitrification associated toxicity.

Dr. Andres Reig:

Very, very interesting and very, very promising. Thank you so much, Dr. Osman, for your time.

Dr. Emily Osman:

Thank you.

Dr. Andres Reig:

Next up, we have Dr. Elena Labarta from IVI Valencia. She presented a poster titled comparison of the embryo quality obtained after an unstimulated and stimulated cycle in the same infertile population, undergoing in vitro fertilization. Dr. Labarta, thank you so much for joining us today.

Dr. Elena Labarta:

Thank you. Thank you for inviting me to present this study today. It is my pleasure.

Dr. Andres Reig:

My pleasure too. Can you tell us a little bit about your abstract that you presented, about your poster?

Dr. Elena Labarta:

Well, of course. Our study has tried to investigate if the ovarian stimulation that we usually use for in vitro fertilization treatments could be detrimental, or would be bad for the embryo quality. And in order to investigate this, we have compared the embryo quality in the same patient obtained after a natural cycle and after a stimulated cycle. This is the best way to do an intrapatient comparison and to study the net effect of ovarian stimulation on the quality of the embryos.

Dr. Elena Labarta:

For this, we have studied 40 patients who did first, a natural cycle without any drugs. And later on, we did the conventional assimilated cycle. And we have compared the embryo quality from different points of view. First, we compared the morphological aspects of the embryo, how it looks like in the lab. Secondly, we compared the morphokinetics. That means that we are analyzing the way the embryo is dividing itself in the laboratory. And finally, we have compared the percentage of chromosomal abnormalities in these embryos.

Dr. Elena Labarta:

Our main outcome was to calculate the mean number of mature oocytes that we needed to obtain one healthy, one euploid embryo, one euploid blastocyst. This is the best way to see if the stimulation can alter the quality of the embryos. Fortunately, once we saw the results, we have seen that there is no difference in the aspect of the embryos in the morphological evaluation. The embryos coming from the stimulated cycle divide a little bit faster, and this is a good sign. That means that they can’t reach the blastocyst stage more easily.

Dr. Elena Labarta:

And finally, the percentage of chromosomal abnormalities is absolutely comparable. But the most important thing is that the mean number of oocytes needed to obtain one euploid embryo was absolutely comparable, which is the conclusion. The conclusion is that ovarian stimulation does not significantly affect the quality of the embryos that we are generating. Now, this is a really good sign.

Dr. Andres Reig:

That’s good news. I understand that this is actually the second part of your thesis. Can you tell us a little bit about the first part? You were telling me before we started recording that this was published in 2012. Can you tell us a little bit about the first part, and what is similar and different between that first part and this part?

Dr. Elena Labarta:

Yes, of course. The research, it started many years ago when we asked ourselves if ovarian stimulation was detrimental to the quality in a moment in which there was a trend towards mild stimulation because it was suggested that ovarian stimulation was very deleterious to the embryo. And we did a similar design. But in this case, as it was our proof of concept of the study, we did so in oocyte donors because we wanted to study the net effect of ovarian stimulation in fertile patients, just to avoid any bias related to the infertility situation of the patient.

Dr. Elena Labarta:

So we did the same study. We compared the natural unstimulated cycle. This was the first intrapatient comparison between both cycles, and this was published in the journal, JCM in 2012. And we found the same. We found that there were no differences in the aneuploidy rate between natural and stimulated cycles. The advantage of the newer study is that we have incorporated the newest technologies, because obviously, at that time, we were doing the genetic screening or the chromosomal analysis of the embryos by FISH technique, analyzing only nine chromosomes. Nowadays, we can analyze the whole constitution of the embryo with the years.

Dr. Elena Labarta:

Moreover, we have included also the morphokinetic evaluation, because we have nowadays the time-lapse technology in our lab. So it is like another way to further investigate the impact of the ovarian stimulation of the embryos. And finally, and most importantly, the study now has been conducted in infertile patients. We wanted to see if the results that we obtained many years ago were also applicable to the infertile population. And we have confirmed the same, that the results also can be validated in this type of population.

Dr. Andres Reig:

Of course, this study didn’t really evaluate pregnancy outcomes, but instead, it clarifies that stimulation doesn’t affect the embryo quality, at least in terms of aneuploidy, which makes sense, right?

Dr. Elena Labarta:

Mm-hmm (affirmative).

Dr. Andres Reig:

We have the same percentage of aneuploid embryos with more embryos, to begin with, so more euploid embryos overall.

Dr. Elena Labarta:

Yeah, that’s the point. That’s the point, yeah. The problem is that the design of this study does not allow us to compare the pregnancy rate because obviously, the study and control group is the same patient. So you cannot compare pregnancy outcomes between groups.

Dr. Andres Reig:

Right.

Dr. Elena Labarta:

But the most important message is that once I do a stimulated cycle, I will obtain more embryos without decreasing the quality of that embryos. And this is important because finally if I have more embryos to be transferred, and more euploid embryos, my cumulative pregnancy rates are going to be higher. And I will obtain the pregnancy easier. So finally, it’s not only to obtain one euploid embryo, it’s to obtain more than one in order to build a complete family in a single stimulation cycle, knowing that we are not hampering the quality of the embryos.

Dr. Elena Labarta:

And this is the main message. Basically, we have demonstrated that there is no negative effect. And then the interpretation is that having more euploid blastocyst after a stimulated cycle, we will have more chances of having a pregnancy. In fact, I guess to finish, we have seen a linear relationship between the number of oocytes and the number of euploid embryos obtained. So I think that in the context of a conventional stimulation, or being moderate, we are going to obtain a higher number of euploid blastocyst and increasing the pregnancy rates.

Dr. Andres Reig:

You mentioned earlier, one of the more unexpected perhaps, or surprising findings of your study was that the embryos coming from the stimulated cycles were actually faster to divide and reach the blastocyst stage than those from natural cycles. Do you have any thoughts as to why that may be, or what theory is behind that?

Dr. Elena Labarta:

Well, we have thought about it. And if we want to interpret these results, I would say that this is a good sign. We have seen that embryos who develop faster are the good embryos. For example, in aged women, we see that there is a lower division rate. And for example, when we compare embryos coming from their own oocytes versus donated oocytes, we see that donated embryos are also faster. So this is like a super rate of good embryo quality. So at least we are not decreasing the quality of these embryos in the stimulated cycle. We can see that we are obtaining now really good quality in the stimulated cycle. So this is really a good sign.

Dr. Andres Reig:

Do you think we need more studies? I know, as you said, this has been an area of some controversy over the past few years. Do you think we need more studies evaluating the possible harm to embryos from stimulation? Or do you think this puts the whole issue to rest once and for all?

Dr. Elena Labarta:

Well, as always when we do research, we have new pathways to be explored, and the story never finishes okay. But it is true that these types of studies, like the one that we present here today, are very difficult to fulfill because obviously, it is very time consuming, very demanding to do a natural cycle than to obtain such a poor result.

Dr. Elena Labarta:

Because I haven’t said this, but the cancellation rates in the natural cycle are very high. So this is why. Well, obviously, the idea to continue doing research is really good, and there is still room for that. But from the logistic point of view, it is true that to do this type of comparison, it’s not so easy. But for sure, we can continue that.

Dr. Andres Reig:

Thank you so much.

Dr. Elena Labarta:

Thank you for inviting me to present this study today.

Dr. Andres Reig:

Thanks. Thank you for joining us.

Dr. Elena Labarta:

See you. Bye, bye.

Dr. Andres Reig:

Our fourth and last guest for the day is Dr. García-Velasco from IVI Madrid. Dr. García-Velasco, thank you so much for joining us.

Dr. Andres Reig:

You presented an abstract relating to obesity and miscarriages at ASRM. Can you tell us a little bit about it?

Dr. Juan García Velasco:

Well, yes, we presented this oral presentation, which tries to dissect the problem that we still are trying to understand. But it seems that women who have a clear overweight may have a poorer outcome after IVF. So we retrospectively analyzed almost 3,500 single euploid embryo transfers. So we’re talking about discarding all the abnormalities within the chromosomes of the embryo. It has to be as pure in the cell as possible, and we retrospectively analyzed how they went.

Dr. Juan García Velasco:

So we did the classical logistic regression analysis for the different BMI characteristics. And it was as expected, we found that when you have a clear overweight, and especially obesity, your BMI is beyond 30. Your offspring is going to be poor. So it’s not only that these patients require higher doses of gonadotropins, it’s that the miscarriage rate is significantly higher. It’s 22.7 versus 15.1, to be precise.

Dr. Juan García Velasco:

And if you continue the follow-up and you go up to live birth rates, there’s also a reduced live birth rate in obese women. It’s 34.3 versus 44.5. So it seems that there is a metabolic disease within these patients that is not only the chromosomal abnormalities. Something is wrong within these oocytes or maybe the embryos, or maybe the implantation process that induces implanted embryos to go on and proceed to live birth. And this is what we found and discussed recently at the ASRM.

Dr. Andres Reig:

What you’re concluding, is it not so much or maybe not only that the BMI itself is the problem, the weight so to speak, but rather that there’s some underlying pathology that can actually affect the oocytes, the embryos, and the implantation to some degree?

Dr. Juan García Velasco:

Yeah, exactly. In fact, that’s something that is being discussed nowadays. We know that a high BMI is not good. We are still not sure that if you are able to reduce this BMI, your outcome is going to be better. And this is a question that we’re trying to understand in the future. Because we do see differences in the fertilization rate, cleavage rate, euploid rate, all these things.

Dr. Juan García Velasco:

So something may be wrong here within the metabolic system of this patient. We know that overweight is a challenge for this body. What we are not so convinced yet is that if you’re able to reduce your BMI, your outcome is going to be improved. This is probably the key question today because it seems clear that the outcome is going to be poorer when you have a high BMI.

Dr. Andres Reig:

Right. That would be, I guess the key way to study would be to reduce the BMI in the same patient, of course. But it’s not easy to do.

Dr. Juan García Velasco:

Very difficult.

Dr. Andres Reig:

Regarding other things that you saw at ASRM, other abstracts, other presentations that you found interesting, tell us a little bit about what you liked about this year’s edition.

Dr. Juan García Velasco:

Another area that was quite interesting in this meeting was new ideas to treat our patients with pain due to endometriosis. And in the oral session of Tuesday, dedicated to endometriosis, there were a couple of abstracts that, I think they were pretty interesting. One of them was a very nice study. It was a larger study trying to understand the efficacy of a new oral GnRH antagonist, the relugolix. This is a multinational phase three randomized, double-blind placebo-controlled study. So it’s very strong evidence of what they can do, what you can achieve with this combination of medication.

Dr. Juan García Velasco:

The combination actually works in three arms. One arm received 24 weeks of relugolix 40 milligrams, with a combination of estradiol one milligram, and norethindrone half a milligram. The second arm received only relugolix for 12 weeks. And the second set of 12 weeks, they received a combination as in the previous arm. So relugolix plus estradiol plus norethindrone. And the third arm was a placebo, just nothing. And probably this is probably an ideal design for this so-called Acidic Two trial. And as I said, these patients had severe dysmenorrhea, and they had non-menstrual pelvic pain as well.

Dr. Juan García Velasco:

They were randomized in the same number of patients to each arm, and it was a large number of patients. The study was a total of 623 patients. And they clearly showed significant benefits of this combined medication. If we look at the dysmenorrhea and then non-menstrual pelvic pain respondents, 72.8 with relugolix responded, versus 52% in the placebo group. And if we look at daily functioning and opioid-free patients, they worked well significantly higher with the combination of medication, 82% versus 66%.

Dr. Juan García Velasco:

So the efficacy of the combination, I think is clearly demonstrated. And also, the only fear could be the minimal bone mineral density loss, because the placebo group and the relugolix only could be impacting negatively this bone mineral density. And it was almost exactly the same across the three groups. So I think as they concluded in the study, the patients benefited from this once-daily oral combination of medication, and they were associated with a very minimum BMD lost. That was generally very well-tolerated.

Dr. Juan García Velasco:

So I think we have to keep our eyes open to these new products coming into the market. And it’s one more tool to treat these difficult patients. It’s not the final answer to all the problems, but I think we’re getting new ideas and new products that could make these tough patients benefit from new drugs. And in the same session, it was also discussed, a very interesting new product that is being considered for the treatment of endometriotic pain. And this is a vagina ring opposed to tablets and opposed to injections. It’s a vagina ring that contains quinagolide.

Dr. Juan García Velasco:

And quinagolide, as we all know is a dopamine receptor to agonist that may interfere with endometriosis lesion growth and maintains avascularization. And this is a very early trial. It was a phase one trial including 134 female healthy volunteers, and what they were trying to understand was the pharmacokinetics of this vagina ring with quinagolide. And what they found briefly was higher bioavailability of quinagolide that’s compared to oral ministration.

Dr. Juan García Velasco:

This ring is able to provide adequate plasma concentrations throughout the entire menstrual cycle. So it lasts up to 35 days, which is extremely convenient. And it was very well-tolerated and did not alter reproductive hormone levels or menstrual cyclicity, or even the menstrual histology, which is one of the drawbacks of most of the medications that we use for treating endometriotic pain. So, again, new ideas and new concepts that we have to be aware that probably will be available for clinicians in the coming next years.

Dr. Andres Reig:

Absolutely. It was definitely very interesting. In fact, I think another oral on relugolix, but in the setting to treat fibroids was actually one of the winners of the ASRM prize paper.

Dr. Juan García Velasco:

It’s a very interesting molecule. It’s a very interesting molecule. I think we’ve been waiting for this oral antagonist for years, but now that it’s out in the market, I think it’s going to deliver a lot of good news.

Dr. Andres Reig:

Good to hear. Very promising. Thank you so much, Dr. García-Velasco, for joining us today.

Dr. Juan García Velasco:

Thanks so much. It’s been a pleasure.

Dr. Andres Reig:

That is all we have time for today, unfortunately. Thank you so much for joining in for part one of our ASRM special episodes. We will be releasing part two very shortly. We hope you’ll join in and enjoy that one too. See you soon.

Dr. Andres Reig:

This has been another episode of FertiliPod by IVIRMA. Thank you so much for listening. Tune in next week for more research and topic discussions on all things reproductive medicine. See you next week.