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IVF and Miscarriages: is PGT-A a solution? IVF CaseStudy #IVFWEBINARS

Miscarriage is a difficult experience to overcome. It’s not only psychological trauma but very often it has a hidden cause,  including hormonal and genetic problems, infections, cervical weakness or uterine problems. Unfortunately, this is an extraordinarily complex matter and often incomparable from case to case.
Facing this issue a hundred of questions appear, such as why pregnancy loss happens? What test should be run and what additional techniques can be used to know the diagnosis? What are perspectives and solutions if miscarriages keep on happening to us? Should we try again or there’s no chance for success?

This brings us further to the next topic of additional techniques and tests using the most advanced technology. PGT-A. Preimplantation genetic testing for aneuploidy (also known as Preimplantation Genetic Screening) which is a genetic test of embryos prior to transfer into the uterus. It helps to identify numerical chromosomal abnormalities (aneuploidy). Analysing all embryos of an IVF cycle let’s transfer embryos free of the chromosomal aneuploidy.

But what are the benefits of using this method? For whom it’s best? And who should be advised to use it? Is it for couples who already experienced previous pregnancies with anomalies or it’s not linked at all? Is it true that pregnancy rates per transfer increases by using PGT-A? Does it help to reduce the chance of miscarriages? Or maybe increase the likelihood of having a healthy baby?

All those questions or rather answers are crucial while deciding about your IVF treatment.

Watching this webinar with Dr Maria Arqué – International Medical Director at Fertty International  (Barcelona) will provide you with the medical perspective on the issues and will give you all information needed to make a clear decision of using PGT-A or not.

IVF and Miscarriages: is PGT-A a solution? IVF CaseStudy – Questions & Answers

Question:
We have had two miscarriages; we’re affected by male factor infertility. Our DNA fragmentation is very high – it was 41%, now it’s at 20%. Does a “normal” embryo as indicated by the PGS test mean the embryo was made with good sperm? Does it mean no DNA damage is present? I’m about to
undergo my fourth embryo transfer – what are its chances?

Answer:
Without the information about your age or the quality of the blastocyst it’s hard to give an accurate answer – if the blastocyst was of good quality, the chances for a pregnancy are between 50 and 60 percent.

Question:
Do you recommend PGD for egg donation?

Answer:
As I explained in the presentation, that really depends on each patient. I would recommend PGD for any patients who want to minimize the risk of a miscarriage, as it minimizes the number of embryo transfers that need to be performed – we know which embryos are chromosomally normal and they are the only ones we transfer.

Question:
I am interested in an egg donation cycle at your clinic, but I don’t see any mention of blastocyst guarantees? How many blastocysts does recipient get? What do you do if there are no blastocysts?

Answer:
We actually have a blastocyst guarantee – the patient is guaranteed at least one good quality blastocyst from the donor’s eggs, as long as there are no issues with the male factor. On average, we have two or three blastocysts per cycle.

Question:
Is it the recipient who decides whether or not she wants to have the PGD test, or is it decided by theclinic?

Answer:
It depends on the case – there are cases in which there is a medical reason for a PGD test, for instance if the patient is afflicted with hereditary diseases or if there is a high risk of chromosomal abnormalities. In other cases, such as when the patient wants to minimize the time to pregnancy or if they have suffered repeated miscarriages, the PGD test can be requested by the patient.

Question:
What kind of PGD alternatives did you mean?

Answer:
There are a couple of options depending on the situation: the first one, obviously, would be simply not to perform PGD and accept all the risks. In case of a high indication of chromosomal abnormalities in embryos, the alternative to PGD testing would be to use donor eggs; if the abnormalities are caused by the male factor, the alternative would be to use donor sperm.

Question:
You mentioned indications for PGT-A – is abnormal sperm DNA fragmentation an indication for the test, as it wasn’t on the list?

Answer:
Yes, abnormal sperm fragmentation is an indication for PGT-A testing. We also use time-lapse technology to select embryos with the least amount of fragmented DNA. There are of course other factors that have to be taken into consideration based on the individual case history.

Question:
Is it possible to transfer the embryo during the natural cycle in an egg donation treatment?

Answer:
Yes, although it depends on whether or not the cycles of the patient and the donor need to be synchronized and whether fresh or frozen eggs will be used. The synchronization is very important, as the egg retrieval date must be carefully matched with peak endometrial receptivity.

Question:
How long does PGD testing of embryos usually take?

Answer:
It takes about two to three weeks to receive the results. There is also a test called PGD Express, although it is not recommended; while it provides results in 24 to 48 hours, it does not provide nearly enough information when compared to the standard PGD test.

Question:
Can immune issues affect implantation?

Answer:
Most likely, yes. When it comes to immunology, reproductive science agrees that it plays a major role, but we’re still trying to understand its full extent. We know for sure that patients with immunological issues have lower implantation rates; certain issues play a bigger role than others and they can affect the chances of conception.

Question:
My husband has low sperm count and high DNA fragmentation. I’m 36 and he’s 34 years old. My AMH is very good. We had two failed IVF cycles; I have a frozen embryo left over, but I’m afraid to transfer as I’m afraid of another miscarriage. Do you think PGT-A would be a good option, or should we go with egg donation?

Answer:
Considering your age and your AMH, we can safely assume that your egg quality is not the problem; focus on your husband instead. He should avoid smoking, drinking alcohol, switch to a healthy diet, exercise and avoid saunas and other hot environments to increase his sperm quality. Then you should undergo another IVF cycle, using the (tile?) technology to use the least fragmented sperm and then employ PGT-A in order to minimize the risk of chromosomal abnormalities.

Question:
Can I have a fresh transfer with PGD testing?

Answer:
Yes, as I mentioned earlier, there is the PGT-A Express test which allows for a fresh transfer; however, that route raises certain issues for biologists. Every embryo is different and some may be a little slower in their development; as such, they may not be in the best time to perform a biopsy. The results of such biopsies are less reliable than a full PGT-A test.

Question:
Is it true that some embryos which appear morphologically normal can turn out to have chromosomal abnormalities and that embryos which are weak morphologically can turn out to be healthy?

Answer:
Yes, it’s true, on both counts. Usually, when embryos that look bad morphologically they likely also carry chromosomal abnormalities; however, sometimes embryos which look average get transferred and result in successful pregnancies.

Question:
My NK cells test was done via blood test. Is this okay, or is a biopsy better?

Answer:
When it comes to NK cells, it’s important to remember that the blood is not going to be the environment in which the embryo’s going to live – that would be the uterus. As such, in order to get a full assessment I would recommend also performing an endometrial biopsy in order to confirm that the alterations found in the blood can also be found in the uterus.

Question:
As the miscarriage rates grow with age, is there a “cut-off point” at which there’s a strong recommendation to use donor eggs instead of own eggs? Is it dependent on age and/or individual medical factors?

Answer:
There is no clear cut-off point, as it’s dependent on the individual patient. For example, for patients who are 40 and have a very low ovarian reserve, egg donation would be my first recommendation, as that’s the route that gives them the best chance for a positive outcome. There are, however, older patients who still have a good ovarian reserve. Even if the egg quality has diminished to the point that we get one good egg out of every 20 we retrieve, as long as we get that one good quality egg, that patient still has a decent chance of getting pregnant using her own eggs. Although it all is patient-dependent, age and the ovarian reserve are the most important factors that determine the prognosis and the recommended course of action.
Additionally, I’d also say that I would not recommend a patient over 45 to go ahead using her own eggs, as past that age the chance of getting pregnant using your own eggs is extremely low.

Question:
Do you recommend the ERA test before egg donation?

Answer:
The ERA test, or the endometrial receptivity test is very helpful, but I would not recommend it to every patient – those who had repeated implantation failure and those who have had good quality embryos transferred without any success would be well advised to go through with an ERA test. If you want to do the test anyway just to be on the safe side, it’s perfectly fine, but medically speaking, unless you have any of the indications I mentioned, it’s not strictly necessary – out of every 100 patients that undergo  ERA testing, around 70 have completely normal results. That means it’s only necessary in about 30% of cases.

Question:
If 60-80% of miscarriages are caused by aneuploid embryos, what about the rest of the cases? Is there a different route they should follow?  Is it really possible to distinguish these two groups before making the decision about PGT-A?

Answer:
The other causes of miscarriages are uterine malformations and other uterine factors like polyps and fibroids which can interfere with the process, or abnormalities such as thrombophilia. Tests for these issues are always done before we indicate the need for PGT-A. If we determine that the miscarriages aren’t a result of chromosomal abnormalities in the embryo, then the underlying issue is diagnosed and treated before the next attempt.

Question:
Do you find donors who look like the patient?

Answer:
Yes. Under Spanish legislation egg donation is anonymous; that means you can’t know the identity of the donor. However, that same law also states that the clinic must look for a donor who looks as much as the patient as possible. We are assisted in this process by an artificial intelligence device called the PhenoMatch which analyzes over 100 different points of the face to try and find a donor that matches the patient’s appearance as much as possible.

Question:
Could you describe what kind of information patients get from the PGT-A test result? Who makes the final decision about which embryos to transfer?

Answer:
The PGT-A test determines which embryos are euploid, or which embryos are chromosomally normal. That means the results show you which embryos are completely normal, which are abnormal and which are mosaic. For the latter, some information is available as to what kind of mosaicism is present. Once we know which embryos are normal and which aren’t, the decision about which embryos to transfer is very clear; we transfer the normal embryos. In case of mosaic embryos, the decision whether or not to transfer them is based on the percentage of mosaicism and its type. There are guidelines and indications as to what to do in those cases.

Question:
Do you check the level of estrogen and progesterone the day before the transfer? Mine was checked before the transfer and my progesterone level was 8,3. The transfer failed. I was told at another clinic that my level of progesterone was too low – apparently, it should be over 10. Is that true?

Answer:
Yes, we check the levels before the transfer; it’s one of the new protocols we put in place, as there is more and more data showing that progesterone levels are very important in patients who are undergoing frozen embryo transfers or who do egg donation IVF cycles. Before we start the patient on progesterone we check its levels – they should be negative, which avoids the displacement of the implantation window. We check the levels again before the transfer. If the results come back with a progesterone level below 10, the patient continues to use vaginal progesterone and starts using injections as well.
As for your case, we can’t say for sure that the transfer failed because of the progesterone level – if the embryo was chromosomally abnormal, that could be one of the reasons for failure.

Question:
Can a PGT-A biopsy be done on day 3? Is it better than a biopsy on day 5?

Answer:
The biopsy can be performed on both days. The difference is in cell numbers – day three embryos have between six to eight cells. The biopsy on day 3 takes a single cell. Because that’s between 12.5 to 16.6% of the entire embryo, the risk of damage is a little bit higher than with biopsies conducted on day 5; we also get less information. On day 5, embryos have between 100 and 150 cells, which allows us to take more cells for analysis with smaller risk of damage. We also get more reliable information.

Question:
Does the PGT-A test reveal the embryo’s sex?

Answer:
Even though we could know the sex of the embryo during the PGT test, in Spain gender selection is illegal. As such, that information is not available in the test result and we cannot choose which embryos to transfer depending on their sex.

Question:
Can you describe the outline of the IVF process with PGT-A from start to finish? I’m going to be travelling to your clinic from Ireland and I’m trying to calculate how many trips it would take.

Answer:
If you’re starting the IVF process with us, it would begin with an initial online consultation which is free of charge – we can do it through WhatsApp, Skype etc. Once we know more about your specific case, we will recommend you the tests we need to perform. When you decide to start the process, the stimulation can be done in Ireland and you can perform the scans we need at your local gynecologist. You need to come over the day before the egg collection, preferably with your partner so that he can produce a fresh sperm sample.
Afterwards we generate the embryos and let them grow in the lab until they reach the blastocyst stage.
You can return to Ireland following the sample collection. We will call you on day one to inform you of the results of the fertilization, then again on day three to explain the quality of the embryos and finally on day five or six to inform you how many embryos are candidates for biopsy. After about two or three weeks, we will present you with the results of the PGT-A test. If there are good quality embryos ready to be transferred, that’s when we schedule the date of your next visit to prepare you for the transfer. What that means is that you will start endometrial preparation with your next cycle, which will take around 10 to 12 days, followed by a scan. Once we think your endometrium is ready, we will start you on progesterone and plan the transfer, after which we will sort the embryo for you accordingly.

Question:
Do you offer embryo adoption treatments?

Answer:
Unfortunately not, as we don’t have embryos available for adoption in the bank at the moment, however, for patients considering that kind of treatment we can offer what is called a “mini egg donation” which is cheaper and which guarantees four mature eggs from the donor available for your use.

Question:
I had a consultation with you a few months ago. I have some questions I would like to ask you. Is it possible to have a short Skype meeting?

Answer:
Please contact the team at Fertty International at fertty@ferrtyinternational.com and ask my colleagues about scheduling another consultation with me.

Question:
I am very interested in a mini egg donation. Can I schedule a Skype consultation with you?

Answer:
Absolutely. Please contact us at fertty@ferrtyinternational.com and ask to schedule a consultation with me.

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About the Author

Maria Arque

Maria Arque

Dr Maria Arquè is a specialist in obstetrics and gynecology and reproductive medicine. She has worked in a few renowned IVF clinics in Europe. Dr Maria Arquè’s professional interests include preserving fertility for men and women, IVF and reproductive health research, fertility education for patients and the impact of lifestyle/diet on IVF with ICSI success rates. She has studied and worked in Ireland, did some of her training in reproductive medicine in the USA and is now an International Medical Director at Fertty International in Barcelona, Spain. Dr Maria is proficient in a few European languages: English, Italian, Spanish and Catalan."All patients inspire me. Each of the patients I meet every day has a different background and a different approach towards their infertility diagnosis. I learn from all of them every day and I’m grateful for it. The biggest lesson I have learned from my patients is that resilience and perseverance are key if you want to succeed."

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