Preimplantation genetic testing (PGT) – for whom and how does it help?

Explained by: Luca Gianaroli, Dr., S.I.S.Me.R.
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Preimplantation Genetic Testing (PGT) - for whom and how does it help?
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From this video you will find out:
  • How to define aneuploidy?
  • When PGT-A screening is indicated?
  • How the genetic analysis is performed?
  • If an embryo biopsy always has to be invasive?
  • What genetic pathologies PGT-M and PGT-SR help to detect?
  • Why embryo banking strategies are recommended before PGT-A?
 

Should all embryos be tested before implantation?

Preimplantation Genetic Testing (PGT) is a technique that has been around for almost 30 years – and for almost all this time it has been a topic for a hot debate. In this webinar, Dr Luca Gianaroli, Scientific Director of S.I.S.Me.R. (Italian Society for the Study of Reproductive Medicine), is explaining PGT in details, together with its possible results and the indications for such a test.

In medicine, there are two important concepts to differentiate between: a diagnosis, which means looking for a specific disease or a specific disorder, and a screening, meaning testing individuals in order to find out if there is something that is not working properly. Dr Luca Gianaroli thinks that such a differentiation is crucial in order to understand the idea of PGT properly.

The background

Until a few years ago, there were two terms in common use in the assisted reproduction field: pre-implantation genetic diagnosis (PGD) – this was referred to when fertility specialist were looking for some specific genetic disorders; and PGS – when they were looking for chromosomal abnormalities that could impair the patient’s chance not only to get pregnant but also to carry the pregnancy to full term. Dr Gianaroli says that nowadays both of these definitions have been abandoned and there is only one term that is being used – namely, preimplantation genetic testing (PGT). PGT can be done for different reasons – and that’s why there are different types of it.

Preimplantation Genetic Testing for Aneuploidy Screening (PGT-A)

Aneuploidy (the opposite of euploidy) is the presence of an abnormal number of chromosomes in a cell. It can be due to oocyte and/or sperm abnormalities or by segregation errors during the early stages of the embryo development – even if both spermatozoa and oocyte were perfectly normal. Dr Gianaroli differentiates between three types of aneuploidies: monosomy (when only one copy of a chromosome is present), trisomy (when there are three copies of the same chromosome) and nullisomy ( when both chromosomes of the same number are not present at all). PGT-A is a procedure aimed at detecting aneuploidy (any potential extra or missing chromosomes in embryos) before the transfer. It is a screening procedure and – what has to be highlighted – it is not aimed at detecting a specific pathology.

PGT-A is generally indicated in all those cases when it is more difficult to get a patient pregnant via IVF or ICSI. However, from the clinical point of view, there are five categories in which performing PGT-A is especially beneficial.

They include:

  • advanced maternal age,
  • a severe male factor of infertility,
  • high incidence of sperm chromosomal abnormalities (detected by the FISH test),
  • repeated implantation failures and recurrent miscarriages.

Patients in all those categories are usually able to produce embryos but the majority of these embryos are chromosomally abnormal.

What dr Gianaroli stresses here is the fact that PGT-A is not going to increase the quality of the genetic material – it is only going to shorten the time to pregnancy thanks to selecting the best embryos to transfer. At the same time, it helps to exclude the embryos that are chromosomally abnormal and may either not implant or cause a miscarriage.

The way PGT-A is performed

The analysis aimed at detecting potential aneuploidy is done via biopsy. It can be done at the level of oocytes by removing the polar bodies or when the embryo is in day 3 of culture – by removing one or two blastomeres. It can also be performed at the stage of a blastocyst – then a few cells are being removed from the trophectoderm (the outer cell layer that surrounds the cell which will give rise to the embryo). Dr Luca Gianaroli says that recently a biopsy has also been done in a less invasive way – by removing the blastocoelic fluid instead of cells. The blastocoelic fluid contains several substances including DNA and thanks to the fact that it is located in the inner compartment of the blastocyst, in direct contact with trophectoderm and inner cell mass, it should be informative of the embryonic condition. The procedure of removing the blastocoelic fluid is much simpler and it does not involve any specific training for embryologists.

Out of the sample of the genetic material, DNA is extracted and amplified. It is repeatedly replicated and once there is sufficient amount of DNA, the aneuploidy screening is done. It is performed using array and next-generation sequencing (NGS) solutions which help to classify the embryo as either transferrable (with a normal number of chromosomes) or non-transferrable (with a chromosome loss or a chromosome gain). According to dr Gianaroli, no matter which sophisticated technique is used to perform PGT-A, the main aim remains the same: it is about excluding all the samples that have a very limited chance of implanting or – if they implant – they can cause a miscarriage or give rise to an affected individual.

Taking all the above into account, it is clear that Preimplantation Genetic Testing for Aneuploidy Screening (PGT-A) has one undoubted advantage: it increases the chances of pregnancy thanks to selecting the embryos which do not have chromosomal abnormalities. Furthermore, by avoiding the transfer of abnormal embryos, it is possible to reduce implantation failures and miscarriages, treatment cost and the time to pregnancy. Dr Gianaroli stresses that, independently of the performance of the IVF centre, the technique used and the risk of multiple pregnancies, if you have a control group in which PGT-A is not done, there are many more cycles needed to get the same results in terms of live births and deliveries.

Preimplantation Genetic Testing for Monogenic Diseases (PGT-M) or Structural Rearrangements (PGT-SR)

Dr Luca Gianaroli says that in case of PGT-M or PGT-SR we’re not talking about infertility anymore. It is a procedure aimed at detecting a specific disorder or a pathology – in this case single gene disorders or structural rearrangements. The former refers to hereditary diseases caused by the mutation of a single gene (e.g. cystic fibrosis, haemophilia, spastic paraparesis, Fragile-X, thalassemia, etc.) while the latter are chromosomal abnormalities involving a change in the structure of the native chromosome, that may generate gametes missing genetic material (e.g translocations). These abnormalities can cause infertility, miscarriages or hereditary diseases.

PGT-M works differently than PGT-A. Before performing the treatment, it is necessary to carry out a pre-clinical study of maternal and paternal DNA (either in the form of a blood sample or a buccal swab) aimed at increasing the accuracy of the subsequent analysis. Dr Gianaroli stresses that is possible to generate a specific probe with markers able to detect the genetic disease even in a very small amount of DNA collected during the embryo biopsy. Once DNA is amplified, the search for a specific mutation begins. When it is detected, the embryo that is affected by it is not being transferred.

Monogenic disorders can be divided into dominant and recessive. If they’re dominant, a mutation in a gene in a single chromosome is sufficient to cause the full-blown disease. If they’re recessive, the disease is full-blown only in case of a mutation of a gene in both copies of a chromosome. If the mutation is present only in one chromosome, the individual will be a carrier. During the DNA analysis, the embryo – just like in case of PGT-A – is classified either as transferable (when its karyotype is normal or it inherited a balanced form of the translocation) or non-transferrable (when there is a loss or gain of one or more chromosomes).

From this point of view, selecting embryos that do not have the mutation associated with a specific disease makes it possible to prevent its transmission to the offspring. Dr Gianaroli says that if we go back to the concept of aneuploidy and combine it with the search for a specific monogenic disorder, we will avoid transferring abnormal embryos and manage to prevent almost totally the birth of affected children and miscarriages as well as avert termination of pregnancies in case of transmission of the pathology.

The conclusion

According to dr Luca Gianaroli, if one considers PGT-A as a selection technique, they have to have a high number of embryos available for the analysis. Only in this way they can increase the likelihood of obtaining transferrable embryos. That’s why, sometimes more than one cell collection is required and – in order to achieve the goal – embryo banking strategies could be recommended.
In order to be able to undergo PGT treatment, a referral from a specialist is necessary. In case of the PGT-M/PGT-SR program, it is important to have a frank discussion with a geneticist who will provide a patient with all pros and cons of such a decision. Because, as dr Gianaroli stresses, none of the testing and diagnostic techniques gives us 100% of true results. However, thanks to sophisticated technologies available nowadays, PGT-A offers even up to 98-99% of accuracy. With such help and information, it can simply be easier for a couple to make the right reproductive choice and decide how they want to navigate further in their fertility journey.

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Questions and Answers from the event

Could you confirm what the risks of the actual process are? As we understand, there is: a risk of damaging an embryo during the biopsy process; a risk of the freezing process; a risk of false positives and a risk of false negatives.

First of all, the risk of damaging an embryo is like in any technique that involves surgery. It depends on the skill of the surgeon. You need a heavy training and you need to be supervised during your learning curve. Of course you do prefer to have a surgery in your tummy done by an experienced surgeon but you would also accept to have a surgery performed by a young fellow, as long as he has been put in good training and is supervised well. Let’s say that in a routine biopsy, the risk of a damage made to the trophectoderm varies between 0% to 2-3% in a well-established centre in which this biopsy is performed. When it comes to the freezing process and vitrification, 97% of the blastocysts that have been biopsied survive the thawing process – exactly as those blastocysts that have not been biopsied. And that is not the gold standard – this is the average standard in, again, experienced centres. The risk of false positives and the risk of false negatives is the accuracy that I have just shown to you – it varies between 1% and 2%. What you can do is a double biopsy – so we are testing not only the cells but also the blastocyst fluid. In doing so, the risk that both of them are false positive or false negative is reduced – so this 2% will be reduced again. If you have contradictory data between the two biopsies, then you can even perform an extra biopsy on the same embryo. So you take a risk but you know in advance what the possibility of false negative is – you can check it during pregnancy, using invasive or non-invasive technique, such as chorionic villus sampling (CVS) and amniocentesis. The risk of false positive is the only risk that we have to take into consideration. It constitutes around 0.5 -1% of all the embryos that we do not transfer because they look chromosomally abnormal – and which actually could be transferred. This is a risk that you can mitigate if the centre agrees to perform another biopsy on the same embryo.

Is there a minimum number of embryos you should have before PGT could be used? What if you have only one or two embryos? Should you use PGT or not? I am 45 and my AMH is 1.8.

This is a very good question. It is a difficult type of a patient because at this age, 95-96% of the oocytes are chromosomally abnormal – so the diagnosis is almost done from this point of view. If you want to enter the PGT program, we should take it another way. We know that at the age of 40, 70% of the embryos are chromosomally abnormal – so if you want to give yourself a chance to have one or two transfers, we’d probably need 8 or 9 blastocysts. Now the point is how many eggs do we need to get 8 or 9 blastocysts? And this is the calculation that you make according to the quality of your partner’s sperm, your age and so on. Once you decide that you need, let’s say, 20-25 eggs, then you calculate how many oocyte retrievals you need to accomplish this goal. Let’s say that – because of your age – you need 3 oocyte retrievals. You do an oocyte retrieval, you let the embryos grow to the blastocyst stage, you do the biopsy – but you do not develop the biopsy so you save the psychological cost and the economical cost. Then, a few months later, you do another oocyte retrieval and again, you store two or three embryos that have already been biopsied but the test has not been performed. When you reach the number that you have planned and you have 8 or 9 blastocysts, you ask the genetic lab to develop the results. Then you can say: ‘Ok, the embryo number one from the oocyte retrieval number one and the embryo number six from the oocyte retrieval number three are the embryos to be transferred.’ Then you transfer one embryo each time, exposing the patient to the percentage of pregnancies that increases with the number of embryo transfers that you do. So this is the right way to do PGT. It’s possible that, for some patients, it is not convenient to do PGT – because they are too much of poor responders or they are too old, etc. So it has to be a combination and it has to be a personalised treatment for each couple. It has to be planned in advance – it has to be a designed strategy for each single couple.

The previous question was in relation to having a single egg collection – is there anything you can add to it?

No, there isn’t because a single egg collection can end in either one or ten oocytes – so the collection by itself is just one piece of the whole system. It’s not enough to predict the potential result that you can have. I think that this is a parameter that we shouldn’t use when we are looking for a successful IVF program.

My husband and our potential donor do not have the same autosomal carrier conditions but we were told by a genetic counsellor that there is 1 in 20,000 risk for one potential GJB2 gene and 1 in 19,000 risk for phenylalanine hydroxylase deficiency in potential babies. Can we test this in PGT 24 which we will be doing anyway or can we have a specific probe developed for this? How long would that specific probe take?

Let’s start from the end: a specific probe could take between 2 and 3 months, mainly if you are not successful for the first time. When you prepare the specific probe, you must be sure that they have an accuracy of 98-99%. So if it is good enough and sometimes also if you are lucky, it can happen in two months – and sometimes it could take more than two months. The concept of these two disorders is interesting because the chance to have an affected individual in these two cases is very low. And here you have to ask yourself an ethical question: is it possible that there are any other disorders for which your husband and your potential donor have not been screened and that can give you a much higher percentage of an affected baby? The point I want to make is that: please, don’t believe – even if you are entering a donor program – that because of PGT, you will have a perfect baby. The risk of chromosomal or genetic disorders is still there. What you do by PGT is to mitigate this risk as compared to nature – because you are removing the embryos that are the carriers of a specific disorder from the reproductive arena. When you have 1 out of 20,000 or 1 out of 19,000 risk, you have to actually ask yourself if it is worthwhile to take this difficult route – compared to the risk that is really minimal. I would advise you to think about it in case of disorders in which we have 25%, 30% or 50% risk of having an affected individual – but not really in case of 1 out of 20,000.

We have screened 301 genetic carrier conditions (288 from the general panel and 13 from an add-on panel) as my husband has recessive carrier conditions from both – but not the same as our potential donor. Can you comment on that?

No, I’m just confirming what I said before: I think that you can go ahead .

What is your opinion on testing a potential surrogate for any genetic carrier diseases so that the pregnancy with our embryo doesn’t bring to life any of the carrier conditions of my husband and the donor – even though neither are the same?

Again, let me repeat it: despite my work in this path and the fact that I’ve spent years of my life trying to get the best and the healthiest embryos to transfer, I must say that I wouldn’t be for the need of testing everybody for everything – for the simple reason that, by doing so, you would always be a worried and unsatisfied individual. I’m saying this because there is accumulating evidence that roughly between 15 and 80 diseases every year derive from a genetical disorder. Think about all the cancers and all the disorders related to the late onset. We cannot assure ourselves a 100% healthy baby. Be also aware that sometimes the panels that are supposed to test everything, have some economical advantage or interest first of all. So I would like to focus on the fact that either you have a serious risk to bring to life a sick or a non-healthy individual or you stay with the game of the genetic roulette. And the latter is very rare in normal patients. In case of a surrogate, I don’t think that there is any need for testing genetic carrier diseases – unless you are using the oocytes of a surrogate that has already proven to be a carrier of some disorder. But in such a case, she should not be admitted to be a surrogate mother at all.

In PGS-NGS for blastocysts biopsied on day 5, what percentage of embryos would you expect to get no results for? I mean the situation when, for example, we are not to be able to say if there is euploidy or aneuploidy.

It varies between 2% and 3%. Again, if you repeatedly have this problem and once you are sure that the lab has all the standards that it is expected to have, then you can argue that this is generated by the gametes that we are using in this test. Sometimes these gametes are not giving any answer – it means that DNA contained in those cells is fragmented, is not correct or is in very small amount. If this happens repeatedly in a couple using the same gametes, then we can expect the problem is not from the lab but it is due to the genetic material that has been used.

I understand that HFEA the UK has recently graded PGT-A as red, meaning ‘not recommended’. What are the reason for it?

First of all, you have to take into consideration the fact that each National Health Service has different approach regarding the costs of the treatment and the background that has led to it. In other words, you have exactly the contrary of this message in other countries with competent authorities, such as Spain, the Czech Republic, Italy and so on. Why is this? The reasons are very simple. On one hand, the data in the literature is sometimes very fragmented and not clear enough. On the other hand, there is no specific indication given for the couples to do PGT-A. In other words, you are not going to make your genetic material better. You are only going to make a screening or a diagnosis and that would accelerate your final decision whether you want to continue or you want to reduce the time that separates you from your pregnancy. For example, in the UK, if you have up to three or four miscarriages, they don’t do the karyotype of the aborted material. They just tell you to try again and sooner or later, since miscarriages can occur randomly because of aneuploidy, you will deliver it. In other countries, after two miscarriages, the first thing that they do is the chromosomal analysis of the aborted materials – and if it is chromosomally abnormal, they focus on the individuals. This is because they think that the wasted time and the burden of a miscarriage is too much – as well as the cost for the National Health Service. So it varies very much from country to country. The opposite approach to the UK concept is presented in the United States where they have the highest instance of PGT-A cycles when compared to all the other countries in the world.

What is the accuracy for PGT-A?

This is what I’ve just told you and this is what you should find in the formal consent . The risk of a misdiagnosis varies between 1% and 3% – with an average of a little bit less than 2%.

What would be the result if the actual embryo was damaged by puncture in the PGD test itself and then transferred?

It is the same like while performing ICSI – you can damage an egg and it will not be fertilised. When using the technique of the trophectoderm or the blastocele fluid aspiration, the risk of damaging the whole embryo actually does not exist. So once the embryo is frozen or vitrified and survives thawing – assuming it’s been recognised as a healthy embryo – it can be transferred. That’s not a problem.

My husband and I have both the genetic mutation MTHFR ( a mutation to the heterozygote state). We had many failures after the implantation. Do you think this can be the reason of failures and does PGT could be a solution for us?

MTHFR, a mutation in a heterozygote, is not an indication for PGT and by itself, it is not a reason for failure. What’s extremely important for you, if you have this mutation, is to combine the panel of tests regarding coagulation and thrombophilia. This mutation can be dangerous in terms of reducing the chances of pregnancy, especially if it is associated with mutations such as Factor V or Factor II. So it’s very important that you and your husband undergo a full screening of your status. Afterwards you can decide if there is a need to do some specific prophylactic therapy just before the oocyte recovery – using Heparin or other drugs – or if you need to reduce the risk of miscarriages by using other different strategies. But MTHFR alone is not enough. So go for the full panel screening test before entering the PGT treatment.

I am 42 years old and I will do the treatment with an egg donor. Do you encourage women to do PGT to the embryos regardless of the fact if the donor is healthy and young? Good quality of egg does not mean the same for the embryo itself, right?

That’s correct. But my question to you is the following: if you have conceived naturally at the age of 28 or 30, would you have done chorionic villus sampling or amniocentesis to try to find out the possible 0.2/0.4% risk of having a chromosomally abnormal fetus? If the answer is ‘yes’, it means that you are very anxious or you really want to know everything – then you can ask for pre-implantation genetic testing with donors as well. However, if you would not have asked for an invasive procedure in a pregnancy that would come out naturally when you were 12 or 13 years younger, then this is the same in case of the treatment with donor eggs. It means you would not need it. I want to make the same point here as I tried to make a few questions ago: don’t think that you have to look for a perfect individual because this doesn’t really mean that you will have a perfect baby – even if you do the most sophisticated thing or treatment. If it’s a matter of your economical situation and you look at the final result, I would prefer to have one extra cycle of oocyte donation rather than having PGT done in the program in which an egg donor has already been screened and is considered a young and healthy individual – even if, as you said, not all of the donor eggs will be good or will bring a healthy baby.

Would you recommend an amniocentesis test to be done with twins and a surrogate, even if PGD with a young donor was done? What would be the chances of any problem occurring, even after having all these tests, a young donor, a surrogate, etc.?

First of all, the major problem is twins. We will never look for a double pregnancy so we should never transfer two embryos. For you as an individual and a potential future mother, it is doubling the risk of chromosomal abnormalities: if you have a risk of chromosomal abnormalities of 2%, in case of twins it will be 2% plus 2%. Please also take into consideration the fact that if one of those two is chromosomally affected and you decide to go for a termination of pregnancy of that specific sac, the risk of terminating the other fetus as well is quite high. It is between 30% and 45% – even with the best clinician. So first of all, skip the concept of twin pregnancy as much as you can and push your clinician to transfer only one embryo. Noninvasive prenatal testing (NIPT), that is a blood sample taken from you, will not help very much if you have twins. So again, if you have a healthy young donor, your risk is limited and you should probably skip amniocentesis or villuscentesis. However, if you really want to reduce those 0.3 -0.4 % of risk to 0.01- 0.02%, then the only way that you can have it is by an invasive technique .

I’m just thinking of the cost of PGT as this will be our twelfth IVF and with a fifth donor. It is so expensive to do do another surrogacy journey.

For sure, there must be some reason why you failed so many cycles. There is a limited number of patients that failed in such a bad way as you did. I think that before looking for another cycle, you need somebody independent that would review all your history and all your data. I can see only two possible conclusions here. Either they tell you: ‘Hey, we have missed some important piece of information and you need to do this or that exam that could give us necessary explanation’ or they tell you to stop as you have done everything that you could be done and there is nothing else that you can do. These are the only two potential answers to your situation for a very simple reason: if we assume that all you have done, has been done in serious and qualified centres, you should have already been pregnant more than once. So there must be something that is blocking your situation – and if there is not, having the knowledge that we have now in 2020, you should probably be recommended not to go ahead any further. You need a deeper analysis of all your data. My suggestion to you is to go to an independent doctor that has experience not only in IVF and related techniques but also in endometriosis and all the other disorders. You need an independent view of your situation before you take a final decision. And you don’t need to see a doctor directly – you can have an electronic or virtual meeting. It will surely take a lot of time because I suppose that the amount of material you have is enormous. This is the only thing that you can do.

Would you do this review? I supposedly went to four of the best clinics in the world.

It means that the review will be even more difficult. Yes, I am prepared to do so as far as you comply with my request in terms of all the necessary materials and documents. If you need any suggestion, there is also my college who would probably be closer to you. But again, as I said, I don’t think that you need to see him in person – you just need to to fill up him with all the documents.

What are the chances of finding aneuploidy in PGT-A according to the age of a woman?

It increases with the woman’s age and the starting point is 40 years old. At the age of over 45, on average you have 95-98% of embryos that are aneuploid. But please do not consider the age as a milestone parameter because it is different for a woman that is at the age of 40 and has started to have periods at the age of 9 or 10 and for a woman at the age of 40 who has started to have periods at the age of 14 or 15. There is also a difference between a woman at the age of 40 who has BMI of over 30 and a 40-year old woman whose BMI is below 25. There is a difference in terms of aneuploidy if a woman at the age of 40 has experienced endometriosis or if she has not experienced it. It also refers to the history of miscarriages and the history of infertility or subfertility in her mother and so on. So the age is important as a general parameter. What we need to do in case of every patient is to use a sort of precise medicine – it means we have to adapt all our protocols, all the things that we know and all our tools individually to every couple. That’s the only way in which you can get the best out of these techniques – and it’s exactly the same in any other field of medicine. No good clinician will give the same amount of the same antibiotics to an individual of 8 years old and to an individual of 10 years old only because there is a fever – even if the pathology is the same. We need to adapt our treatment to each individual before there is a final decision.

You mentioned that if PGT-A biopsies return repeatedly as ‘No result’, it could be a problem with the gamete. Is it possible to assess if it was because of the gamete and which partner it could be due to?

Yes, there is a test that is quite difficult for the lab so many labs do not offer it because it costly and time-consuming. It is called the FISH test. If you do a chromosomal analysis from your blood, your blood corresponds to all your organs: liver, spleen, skin and so on – but not to the sperm of the male partner or to the oocyte of the female partner. It is because the gamete has a different route in embryogenesis. So from the chromosomal analysis of a blood sample we will not understand if your husband has good sperm – in terms of chromosomal percentage of normal sperm. There is a test which is a chromosomal analysis performed in each single spermatozoa – and it is called the FISH test. If it comes out that your husband has a high incidence of chromosomally abnormal sperm, it doesn’t matter if you do PGT-A. You will never get out with a proper result anyway. The same story with oocytes that you can check only by analysing the polar bodies. When you have problems like these, we first look at the sperm because it is easy to collect and it doesn’t require a surgical procedure like in egg collection. The biggest limit of the FISH test is that – if we have very poor sperm quality – we have to use all the sample and we cannot freeze a part of it for you to decide if you want to use it later or not. The other limit is that it’s a very time-consuming test because you need to analyse the maximum number of chromosomes. Three or four is not enough – it is a too wide filter and it doesn’t filter enough. So you’d need to have at least eight or nine chromosomes to be analysed in the FISH test.

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Authors
Luca Gianaroli, Dr.

Luca Gianaroli, Dr.

Dr. Luca Gianaroli has been a specialist in Reproductive Medicine since the end of the 1970s. He is the Scientific Director of S.I.S.Me.R. (Italian Society for the Study of Reproductive Medicine) and he holds the position of Scientific Director of I.I.A.R.G., the International Institutes of Advanced Reproduction and Genetics and of IIRM SA. He is also an Honorary Professor at the School of Biosciences of the University of Kent. Dr. Gianaroli is an active member of several international scientific societies in which he has covered and currently covers roles of primary importance, he has served as Chairman of the Italian Society of Reproduction and of the European Society of Human Reproduction and Embryology (ESHRE). He is a member of the ESHRE Certification Committee and he is the coordinator of the Steering Committee of the ESHRE ART Centre Certification Program. Dr. Gianaroli is author of more than 250 papers in international scientific journals and publisher or co-publisher of 9 books. Throughout his professional career, he collaborated with several Italian universities (Università degli Studi di Teramo, Università degli Studi di Modena e Reggio Emilia, Università degli Studi di Trieste, Università degli Studi di Roma Tor Vergata, Università di Bologna).
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is an International Patient Coordinator who has been supporting IVF patients for over 2 years. Always eager to help and provide comprehensive information based on her thorough knowledge and experience whether you are just starting or are in the middle of your IVF journey. She’s a customer care specialist with +10 years of experience, worked also in the tourism industry and dealt with international customers on a daily basis, including working abroad. When she’s not taking care of her customers and patients, you’ll find her travelling, biking, learning new things or spending time outdoors.

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