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What is the role of the endometrium in Repeated Implantation Failure (RIF)?

Vladimiro Silva, PharmD
Scientific and Executive Director, Ferticentro

Category:
Embryo Implantation, Failed IVF Cycles, Success Stories

WHAT IS THE ROLE OF THE ENDOMETRIUM IN REPEATED IMPLANTATION FAILURE (RIF)-Ferticentro
From this video you will find out:
  • How does the quality of the endometrium impact the success of embryo implantation in cases of Repeated Implantation Failure (RIF)?
  • What is the significance of endometrial receptivity in the context of repeated implantation failure (RIF)?
  • How does the timing of embryo transfer align with the optimal window of implantation?
  • How does the endometrial microbiome influence implantation success?
  • How do immune responses within the endometrium influence repeated implantation failure, and are there strategies to modulate these responses?

What is the role of the endometrium in Repeated Implantation Failure (RIF)?

During this event, Vladimiro Silva, Scientific and Executive Director at Ferticentro shared the secrets behind recurrent implantation failure (RIF) and explored the crucial role the endometrium plays in fertility challenges.

 

Clarifying definitions and causes of Repeated Implantation Failure (RIF)

Regarding the definition of Repeated Implantation Failure, there’s not much consensus in the scientific community about what should be considered as recurrent implantation failure. Normally, it is referred to as the failure to achieve a pregnancy after at least 3 embryo transfers with good quality embryos or maybe after the transfer of 3 or 4 good quality blastocysts. What does this mean? For example, if you are trying with your own eggs, and you’re getting great blastocysts, you transfer 3 or 4 of them, and you still don’t get a pregnancy, you can consider this as recurrent implantation failure. If you are 43 or 44 years old and your eggs are not that good, then not having a pregnancy after 3 or 4 blastocysts is unfortunately more likely to happen than the opposite. You can even be 48 or 49, and you’re trying with egg donation with 3 brilliant embryos, and you don’t get a pregnancy, then you can talk about recurring implantation failure.

Statistical considerations and misconceptions

Some people argue that this is really just bad luck. We know that humans are not a very fertile species. A man and a woman at the age of 25, if they try to get pregnant naturally, if they are in perfect health without any reproductive issues or any other concerns, just have a 25 to 30% pregnancy rate in the natural way every month. In IVF, for example, when egg donation is performed, we are just very above that. It’s possible to get to a 60% pregnancy rate or 70% pregnancy rate with egg donation. However, statistics are what they are, and they can deceive us. If there is a 60% pregnancy rate, which is kind of the standard for egg donation, this means that if an embryo is transferred to 100 patients, 60 of them will become pregnant. We go to the remaining 40 and transfer another embryo, so 24 will get pregnant, and 16 will not be pregnant. If we go to the 16 and transfer a third embryo, 9 will be pregnant, and 7 will not be pregnant. After these 3 embryos, there is a 93% accumulated pregnancy rate, but in reality, it was always 60%.

Statistics depend a lot on the way that we look at them. We can’t make overall assumptions. We need to make sure that there are no confounding factors, meaning if the embryos are really good, if the endometrium, which is the tissue inside the uterus, is also good, then we might need to take a deeper look into it. If those conditions are not assured, maybe we’re just on the wrong side of statistics.

Examining the role of endometrium

Keep in mind that it’s always 60%. The reality is that IVF treatments fail, and many times we don’t know why. There was a study published a few years ago in Human Reproduction Update, which is one of the main scientific journals in the IVF world. This is the official journal of the European Society for Human Reproduction and Embryology (ESHRE). These researchers have concluded that when patients are not getting pregnant, they often come to the clinic and say, “Why did it happen? Why is it not working for me?” And so, was it the egg, the sperm? According to this study, in 70 to 80% of the cases, it was the egg, in 10 to 15% of the cases, it was the sperm, and in 10 to 15% of the cases, the causes rely on the endometrium. This 10 to 15% are the endometrial causes for implantation failure, knowing that 85 to 90% of the problem is not the endometrium, it’s the embryo.

The sperm can also play a role even before the formation of the embryo, but also afterward because in some situations of sperm issues, the risk of miscarriage is increased. The endometrium is this tissue that coats the inside of the uterus, but this is only responsible for 10 to 15% of implantation failure situations, according to these statistics. There’s no consensus about this. When the issue is with the embryos, we’re talking essentially about chromosomal abnormalities. When the concern relies on the uterus, we can have an issue in the endometrium. There can be an issue with the window of implantation, the endometrial receptivity issues, but also anatomical abnormalities, immune factors, and things that are not directly related to the endometrium but rather to the uterus like some malformations and so on. It’s important to mention that typically the concern is on the endometrium side after we exclude the problems with the embryos because 85 to 90% of the time, this is where the problems are. The main way to exclude issues with the embryos is by genetically analyzing the embryos with Pre-implantation genetic testing for aneuploidies (PGT-A). What are aneuploidies? These are numerical chromosomal abnormalities. This means that your embryo has the wrong number of chromosomes. Either it has 1 chromosome extra, a chromosome missing, or other factors.

These situations are typically age-related.  It means that with the progression of female age, on a very significant minor degree with male age, but essentially with female age, this type of chromosomal abnormalities increases. That causes the embryos to carry anomalies that are not compatible either with implantation or with having a healthy baby. Statistics shown on the slide were taken from Igenomix, which is one of the main labs in the reproductive genetic labs, we can see that in all age ranges, and all age classes, the probability of pregnancy with PGT-A, is pretty much the same. There is a slight difference, however, if we look at the non-selected population, pregnancy rates go down with the progression of age. Why does this happen? Because it is the transfer of embryos that have a normal number of chromosomes.

It’s important to mention that PGT-A doesn’t improve the quality of the embryo. If an embryo is not good, it will not change the embryo. It just helps to understand what’s the status of this embryo and that helps to make decisions. This is kind of the first step to study the endometrium and to understand whether the embryo is viable. Even for the best possible cases where the patient is below 35 years of age where we are transferring an embryo with the correct number of chromosomes, pregnancy rates are never above 60%. This means that in the remaining 40%, we have the other causes of implantation failure. This is where the endometrium lies.

On the other hand, if we look at another graph presented, we can see that the probability of miscarriage increases a lot when we are transferring to an unselected population. While in a selected population where we’re just transferring normal embryos, pregnancy rates, and miscarriage rates are pretty much the same. There’s a slight increase associated with age, and those are again probably endometrial factors, but it’s relatively steady on the gray bars with age when we transfer good-looking embryos.

When discussing the quality of the endometrium and its relationship with repeated implantation failure, we need to first rule out whether the issue lies with the embryo. This is because the chances of the problem being in the endometrium are relatively low, at around 10 to 15%. In cases where we have transferred good quality embryos, such as nice blastocysts or PGT-A tested embryos, and we still haven’t achieved pregnancy after three attempts or after transferring four good quality embryos, the Endometrial Receptivity Test, also known as the ERA test, is one of the first tests that has been widely used around the world in recent years.

Understanding endometrial receptivity

Addressing the endometrial receptivity consists of three parts. One of them is the window of implantation, another one is the microbiome, and the third is assessing whether there are any signs of chronic infections in the uterus, called chronic endometritis. Regarding the window of implantation, we use a test called the Endometrial Receptivity Array (ERA) test, other brands are doing the same. What is this? Another graphic from Igenomix shows that in a normal cycle, there is ovulation around day 14, and then, between day 19 and day 21 is when the endometrium is ready to receive an embryo and implant. This is what is called the window of implantation, where the endometrium is ready to receive a blastocyst, which is a day-five embryo.  Before this, the endometrium is pre-receptive, and after this, the endometrium is post-receptive. Why is that? The endometrium being receptive means that the endometrium starts to be under the action of a hormone called progesterone. It starts to be more vascularized and ready to receive an implant and nourish an embryo. The window of implantation sometimes is not the same for all women, and 30% of the patients have a displaced window of implantation according to studies.

So what happens? Another graphic from Igenomix shows that when you transfer an embryo, a day-five blastocyst, it needs to be within the window of implantation. This window of implantation can be corrected if, for example, the endometrium is only receptive later or earlier, and so we need to adapt to the moment when we will transfer the embryo. Why? Because we know that the endometrium needs to be ready to receive the embryo. If it is a blastocyst, it should be at five days of progesterone because that’s when the endometrium is ready to receive a day-five blastocyst. However, we know that in some cases, the endometrium, after seven days, is only ready to receive an embryo after 6, 7, or 8 days of progesterone. On the opposite, after 3 or 4 days, it is already ready with day 3 embryos. When we are outside the window of implantation, the chances of having a pregnancy are lower, the risks of miscarriage are higher, and there is a risk of wasting precious viable embryos for transferring them at the bad moment. How can we correct this? It’s relatively easy. We do a cycle preparation, like if we were doing a frozen embryo transfer,  except that on the day of the embryo transfer, instead of doing the embryo transfer, we take a little piece of the endometrium, and that goes to be analyzed on a genetic slot. They run a panel for 248 genes, and the result will show whether the endometrium is receptive or pre-receptive. Since the biopsy was done at 120 hours of progesterone, we know that at that very moment, the endometrium is ready to receive an embryo or not. It’s crucial to find what is the moment to do the embryo transfer, and it doesn’t require special medication. Performing this test on those patients who had failed transfers produced better results, transferring on the day that is supposed to be done 54% of pregnancy using this information. They moved to 70, they gained 18% of pregnancy, and the cumulative rate went from 70 to 95%. The time for pregnancy was also reduced because 71% of all women gave birth within one year. These are the results of a study made in certain very specific conditions, but it’s important to keep in mind that studies done on a larger scale where they were doing this test to all patients regardless of their conditions, the test proved to be useless. Therefore, doing the test for everybody is not recommended. However, for patients that have a documented repeated implantation failure case, there is some benefit in doing this test.

Understanding the microbiome

Another test that can help is the test to check the microbiome and chronic endometritis. What is this all about? Until a few years ago, medical doctors believed that the uterus was sterile, it was proved that in fact, there are bacteria inside the womb. The microbiome refers to the kind of environment of bacteria that exists inside the womb. We now know that this needs to be at least 80% Lactobacillus.  It means that we need to have the right bacteria inside the uterus to prevent the wrong bacteria, the pathogenic bacteria, from implanting and creating an infection because we know that a balanced microbiome with at least 80% Lactobacillus will improve your reproductive prognosis resulting in an increased chance of pregnancy and life births.

Many studies that have been done in recent years show that 30% of all infertile women have pathogenic bacteria in their uterus. Numerous studies show that having pathogenic bacteria and others is very linked to embryo implantation failure. So what we do is this. How is it done? Another preparation cycle is performed, but on the day when we should be doing the embryo transfer, instead of doing the embryo transfer, we will just do an endometrium biopsy. A little piece of the endometrium is taken and sent to be analyzed on a genetic slot. We can use that piece to check for the 248 genes related to the window of implantation mentioned, and we can also check to see what bacteria are in there. We use the test to have a view of the endometrial microbiome composition to see if there is the right percentage of Lactobacillus. Another test is called ALICE is used to see if there are bacteria associated with chronic endometritis.

From those results, we get a recommendation on what is the antibiotic that we should be using. The next real case presented a real patient case where the result was a mild dysbiosis profile. Lactobacillus were just 59 instead of 80%, but there were no pathogenic bacteria involved, so they didn’t find out any of this. Probiotics were prescribed to the patient. Sometimes, after the probiotics, another biopsy is done to confirm if it is back to normal, sometimes not. In this particular case,  it was a mild change, so there was no need for that.  However, as Vladimiro confirmed there were cases where the percentage of Lactobacillus was 0%. In those cases, antibiotics are prescribed just to kill potentially harmful bacteria, and then the probiotics are added to populate the uterus with the right bacteria, then it has to be checked again to make sure that everything is fine, and then we move on with the embryo transfer. There is not a universal solution for every patient.

Evaluating uterine health

Another thing that needs to be checked while evaluating the uterus is anatomic abnormalities. There is an exam called hysteroscopy where we go with a video camera to see the inside of the womb. This is used to check for polyps, to check for endometritis, myomas also known as fibroids, adenomyosis, malformations, etc. Some of these can be surgically corrected, some don’t, and that is treated with antibiotics. One of the studies showed that congenital uterine abnormalities can lower the reproductive outcome. However, there is no consensus about it. In the review from the Cochrane Library, it is explained that in women who have septum, there is no evidence to support the surgical procedure in these women. They say that it’s preferable not to remove the septum because it’s surgery, it’s aggressive, it can do worse than not to remove it. If a patient has repeated miscarriage or repeated implantation failure, we can look at it in another way. As a first approach, surgeries are not always recommended.

Understanding other fertility challenges

As mentioned before, problems with the uterus represent 10 to 15% of all cases. That 10 to 15%, specifically is focused on the smaller pieces within that percentage. This is probably the smallest of all these pieces: the immune and dermatological tests. There are numerous tests available in the market. For example, in France, there is a test where they assess the immune environment at the uterine level. Many other tests focus on various aspects such as NK cells, autoimmune diseases, and thrombophilia screening. However, most of these tests lack substantial proof of their efficacy. To establish their benefits, large-scale studies would be necessary. Yet, conducting such studies is extremely challenging due to financial constraints and the difficulty in finding a homogeneous sample of patients. In the realm of IVF, each patient is unique, with various contributing factors, making it hard to find a sample where the only differing factor is the presence or absence of a particular condition such as autoimmune diseases or specific genetic markers like KIR or HLA.

Therefore, the efficacy of these tests remains largely unproven. Nevertheless, we still conduct these tests as part of the protocol. From our experience at Ferticentro, one test we rely on more is the KIR-HLA test, which was found to be beneficial in numerous cases. Correcting for these factors has led to successful pregnancies and the birth of healthy children. However, it’s important to note that this process can be lengthy, especially when working with donors. In such cases, specialized protocols are crucial. There’s no one-size-fits-all approach in such cases; hence, individual assessment is crucial. Ultimately, the main goal is to achieve successful implantation in the uterus and a healthy baby.

Real-life cases

Case 1 –  a 42-year-old woman, with 5 years of infertility and 2 previous miscarriages, multiple fibroids surgical removed  before seeking treatment at Ferticentro

Due to her low ovarian reserve, 2 stimulation cycles were conducted, the first to freeze her eggs and the second to retrieve more eggs for IVF. Despite these efforts, the embryo resulting from the IVF cycle was found to be aneuploid, rendering it nonviable. Subsequently,  egg donation treatment was recommended, resulting in 6 blastocysts, 5 of which were euploid. After additional tests and adjustments to her protocol, she successfully gave birth to a healthy baby boy.

Case 2 – a 30-year-old woman, had experienced 2 miscarriages and was diagnosed with polycystic ovarian syndrome (PCOS)

Despite her previous miscarriages, she opted against preimplantation genetic testing of embryos. After successful ovarian stimulation, 6 blastocysts were obtained, all of which were frozen. However, the first embryo transfer resulted in another miscarriage, leading to exploring lifestyle modifications, including weight management. Additionally, probiotics were implemented, antibiotics, and a personalized progesterone protocol was introduced. These interventions ultimately resulted in the birth of a healthy baby.

Case 3 –  a 44-year-old woman with a diminished ovarian reserve, who underwent an egg donation cycle.

Despite transferring 4 blastocysts across 2 cycles, both attempts were unsuccessful. Further investigations revealed issues with endometrial receptivity and microbial imbalance. Additionally, it was found that she was found to be a carrier of an autoimmune disease and had thrombophilia. Collaborating with specialists, her treatment was tailored accordingly, which ultimately led to a successful pregnancy and birth.

These cases highlight the complexity of fertility treatments and the importance of personalized care. The correct approach underscores the significance of thorough evaluation and tailored interventions. Every case is unique, and the most important thing is to provide individualized care to each patient.

- Questions and Answers

I have endometriosis, but my uterus and endometrium are fine. How thick must the endometrium be before IVF?

The first thing: endometriosis is when you have endometrium growing outside the uterus. The endometrium is the tissue that coats the inside of the uterus, so it should be inside the uterus, not outside.  Endometriosis has nothing to do with the quality of the endometrium. You don’t need to worry about that if that’s the case. Regarding the thickness of the endometrium, the ideal is that the endometrium is above 8 millimeters in thickness. The above 7 is already okay. Above 6 is, we have pregnancies; below 6, we also have pregnancies, but these are more difficult. Normally, what we say is we always try to get 8, and if we don’t get 8, we prefer to start over and try a different protocol, a different approach. If, after some attempts, we don’t get to at least 8 millimeters, we will see, and we will work with what we have. Sometimes we use growth factors, etc. These are also strategies that are not completely proven, but we actually have some good results with them. But this is normally what we say, is that those are for sort of more desperate cases when the traditional proven therapies are not working. Then we can start trying things that are still more experimental to see if we can get results. We had children born from 5.8 and 5.6 endometrium. That doesn’t happen every day, but we always aim for 8 mm.

EndoTrio tests came back normal, endometrium always looks perfect, I had 3 failures with PGT-A tested embryos, 5 failures altogether. I tried immunology treatments too with no success. Previously I had a naturally conceived pregnancy. What are my options?

This is a difficult case. EndoTrio tests that I was talking about are the tests for the window of implantation, the microbiome, and the chronic endometritis, and the endometrium was okay. You also say that endometrium also looks perfect, always looked perfect. So you’re probably talking about the thickness of the endometrium. Then, 3 failures with PGT-A tested embryos. I would go for those very rare cases, for example, one of the things that we would definitely try in this case was to test for the HLA compatibility. Normally, this is kind of complex, but in the uterus, there are some genes called the KIR genes, and in the embryo, there are other genes that are called the HLA-C genes. When the genetic profile of the uterus is KIR-A, there could be a problem of compatibility if the embryo is HLA-C2. We receive an HLA-C from our father and an HLA-C from our mother, and so while forming the embryo, the embryo can be C1C1, C1C2, and C2C2. If the embryo is C2C2 and the uterus is KIR-A, there is a risk of implantation failure, miscarriage, preeclampsia, and lots of problems during the pregnancy. It’s a complicated situation. There are protocols that we can use with steroids, with growth factors, with aspirin that can help us to control that risk, but it’s not ideal. In some situations, we need to involve donors in order to solve the problem. I actually had a case, we had at Ferticentro, a case very similar to this one. The patient had 6 miscarriages, we’ve tried everything with her, and actually, it only worked when we did double donation. We transferred her PGT-A-tested embryos, we did everything you can imagine, and something else. She was already being moved from clinic to clinic, it lasted for maybe 10 years or so, and so we ended up doing a double donation, and that’s when it worked. Actually, the child was recently born. The only explanation that we can think of is probably some factor that was never found, that was solved by replacing one of the gametes involved, meaning the egg and the sperm, and we worked with 2 donors that had a good pregnancy record in the past. The good message from this case is that even for the apparently worst prognosis cases, there could be hope. Because you also had a natural pregnancy, which is even more strange, sometimes these immune problems are triggered by a first pregnancy, and they develop an immune rejection for a second pregnancy. That can happen, obviously, but I really don’t know. We would need to take a look and study it.

Are NK cell tests for blood better than uterine NK cells cell biopsy?

It’s very difficult to answer this question. My first answer is we don’t know. If I had to choose, I would prefer to rely on the results from uterine NK cells. Apparently, those are more related to the cases of immune rejection at the uterine level, but the reality is that it is not proven. This is one of those tests that still need to have larger studies, large-scale studies to prove. A lot of doctors and clinics are trying, are working, and making decisions based on that, but it’s what I was saying during my presentation, it’s like the desperation stage, when everything is apparently okay, we don’t know where else to look, and so we try to solve these, to work with these things that are not completely proven. None of them is proven. If I had to decide, I would go with the ones inside the uterus. Those seem more important. But the reality is that there is no consensus and no good quality studies showing that this is something that we should be looking at.

Would you expect the bacteria in the uterus to mirror what is found in the rest of the vagina?

A very good question, I’ve seen people saying this and also the opposite. In principle, it shouldn’t be the same because the uterus is normally a closed cavity. There is an entrance, but it shouldn’t be the same. The bacteria in the uterus are the most important ones for the implantation process. Checking what happens in the vagina is not enough for us to know what happens inside the uterus. If you have chronic endometritis, will this be present in the vagina? Yes, there is that risk. But the fact that there’s nothing in the vagina doesn’t mean that it can happen inside the uterus. Therefore, we need to always check the inside of the uterus if we want to exclude this vector, we can’t skip that. Otherwise, it would be easier.

Are there lifestyle changes that may enhance the success of implantation in cases of repeated failure?

There are things that you can do. For example, normally, we always say, that the healthier you are, the less likely you are to suffer from infertility. If you’re a smoker, if you’re a drinker, if you do drugs, these are very easy-to-fix lifestyle changes. And this will certainly increase your chances of implantation. Then there is, for example, if you take the correct amount of folic acid and if you do a well-balanced diet, you will have it in your vegetables and so on. If you eat fast food every day, you will have problems at various levels. This is obviously also causing problems at the little veins that do the microcirculation in the uterus and so on. We work with a company in Switzerland and what they do, is they have nutritionists working for them, they correct the lifestyle of a patient, they balance the nutrition, they have nutrition programs, and the reality is that we’re getting very good results. We have patients who got pregnant after doing these programs that were having very negative results before that.  I would say, yes, until a certain degree. If the problem is genetic, if the problem is with the embryo, that will not be enough. You can be the healthiest person on Earth, but if you’re not putting a healthy embryo inside your womb, it will not implant. What we can do is kind of optimize all the factors that we can control, and lifestyle is definitely one of them.  I would say, definitely, let’s control everything that we can control and leave the rest to medicine.

Which autoimmune diseases can affect the receptivity of the endometrium?

Most of them is the answer. There are a lot of autoimmune diseases. They affect different systems in your body, but what we know is that people who have autoimmune conditions typically have a higher risk of rejecting an embryo. When we do those panels, we’re talking about the things that are not completely proven, to check for immune hyperreactivity in cases of repeated implantation failure, we get a lot of anti-nuclear antibodies positive, anti-thyroid hormones positive. Those are maybe the most common. We know that there is an association. It’s very hard to quantify. What we do is we try to regulate it with steroids, with medication, to suppress that immune hyper-reaction. These are the things that we do that we try to control when there is nothing else that we can do.  I can tell you a story of a patient because these patients were actually personal friends of mine. We have known each other since we were 3 years old, both of us. So, we’ve known each other for all of our lives, and they came to the clinic as patients, and I remember that we did an egg donation treatment. We transferred 2 very good embryos, 2 embryo transfers, and no pregnancy after both of those transfers. And they had another 4 embryos, I think, and they said, “Well, that they’ve registered in the public service. They were also being followed over there, the public service in Portugal, too, in the endocrinology service. So, they were followed by that, and then a year and a half later, they came back to the clinic and said, “Well, we were lucky enough because one of the endocrinologists in the public hospital got interested in our case, and she ran all the tests that you can imagine and then ended up diagnosing a disease that I’d never heard before an extremely rare autoimmune disease.” She treated that patient for that. This was in a public hospital, so it was free for the patient, but the total cost of this test was like €6,000 or so, but obviously, the patient paid nothing because it was in a public hospital.” And so they found out that she was affected by this autoimmune disease. They treated her. Everything went back to normal. Then she came and asked us to transfer 2 embryos, and because we were not doing her first treatment, she had tried elsewhere before, and we agreed with that, and she immediately got pregnant with twins. This is a very clear example of an autoimmune disease that was probably the cause. And we see a lot of that. But these are rare cases that we see from time to time. These are not first-line situations where we can start checking. We do some panels to screen for the most common things, but we use protocols to try to control when there is a sort of prophylactic way.

Could the very high endometrium thickness cause implantation failure?

I would say, yes. Normally, so at our clinics, we consider the optimal range to be between 8 and 16, with 16 being kind of too much. Normally, we like it to be between 18 and 14. That’s the ideal range because a very high endometrium increases the risk of polyps and other complications in patients. If we were to choose, we prefer to have a problem of excess endometrium than the opposite. It’s just a question of fine-tuning the process, but we will end up having a good-looking, regular, not-too-thick endometrium. It’s just a question of finding out the right protocol. If the endometrium is always at 4.5 and so on, it’s a lot more difficult to treat. Having to choose between the two of them, we would prefer the endometrium, which is too thick. However, if it is, let’s say, 20 or 18 or something, it can also cause problems.
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Authors
Vladimiro Silva, PharmD

Vladimiro Silva, PharmD

Vladimiro Silva, PharmD, embryologist, Scientific and Executive Director at Ferticentro and Procriar, two of the leading IVF centres in Portugal. Doctor of Pharmacy, Faculty of Pharmacy, University of Coimbra. MSc in Health Economics, Faculty of Economy, University of Coimbra. Post-graduated in Health Services Management, Faculty of Economy, University of Porto. Post-graduated in Clinical Analysis, Faculty of Pharmacy, University of Porto. Author of hundreds of lectures, oral communications, posters and scientific articles in Portugal and abroad. Vladimiro Silva speaks: English, French, Spanish, Italian and Portuguese.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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