By fertility experts from Spain.
Watch the recording of the webinar on IVF and PGD/PGS testing. The webinar attracted many fertility patients interested in preimplantation embryo testing and willing to learn more before they make important decisions about their treatment. Check the video and listen to the presentation – we hope it will help you to decide if PGS/PGD is for you.
If you have a medical indication for IVF, you have probably started researching the topic of assisted reproduction technologies to be able to make better decisions about your future treatment. This knowledge comes in a package with a whole lot of new vocabulary, medical terms and acronyms like PGD or PGS testing. You may have also encountered the name Preimplantation Genetic Testing (PGT) which has been recently used for both terms.
Due to the enormous interest of patients in preimplantation genetic screening and IVF success rates after PGS, we have decided to run a webinar to cover the topic. We invited Dr. Joaquín Rueda, the Director of the Genetics Unit at Hospital UR Vistahermosa in Spain to talk about preimplantation embryo testing. Dr. Rueda is highly experienced in this matter and his team at the genetics unit is made up of experts who specialise in clinical genetics, cytogenetics and molecular genetics. Dr. Rueda is a physician himself, specialist in Clinical Genetics, Professor at the Faculty of Medicine of Alicante and the Scientific Director of the BioBank.
The incredible advances in medical and reproductive science have now made it possible for embryos to be screened for genetic abnormalities prior to a transfer, after IVF. It’s understandable how the use of PGD (Preimplantation Genetic Diagnosis) can be a valuable tool available for couples using their own gametes (egg and sperm), which could be affected by a range of issues, but is it also something which could aid implantation, and a viable pregnancy, when donor oocytes (eggs) are used?
In this webinar, Professor Dr Joaquin Rueda, Director of the Genetics Unit at Hospital UR Vistahermosa, Alicante, discusses the reasons why PGS (Preimplantation Genetic Screening) might be beneficial, even when using eggs from a donor.
When researching this area and understanding why the use of PGD (Preimplantation Genetic Diagnosis) could play an important role, within IVF conception, it’s useful to start by looking at the beginning; at us.
We’ve all probably heard about DNA (Deoxyribonucleic acid) but might wonder how it relates to embryonic health and implantation chances. DNA is the hereditary material in humans, it’s very simplistically, our genetic makeup and is found within the nucleus of each cell, where the molecule is packaged, into thread-like structures, which are called chromosomes.
The majority of our cells will each have two sets of chromosomes, creating a total of 46, and these are called diploid cells. Gametes (eggs and sperm), on the other hand, only have one set of chromosomes, so just 23 in total, and are haploid cells. In most instances, when these haploid cells (the oocytes and sperm) meet, fertilisation will take place and a new cell, of 46 chromosomes, is created; a zygote (the cells created from the initial union of the egg and sperm). These cells then divide, repeatedly, and go on to become an embryo.
Almost all of us will carry normal chromosomes, however, sometimes there are issues. Gametes can be abnormal and contain an unusual number of cells; this can be seen in both male and female factor infertility.
If abnormal gametes are used, in conception, the zygote is at risk of developing an irregular number of chromosomes, which then has the potential to cause embryonic developmental abnormalities, this is medically referred to as aneuploidy. Dr Rueda advises that these aneuploid embryos are thought to be the main reason for implantation failure and early pregnancy loss. He goes on to explain how the risk of aneuploidy increases with a woman’s age, and how the issue is likely to lie within the oocytes themselves, rather than actually with the woman’s ability to carry a child, which is why donor eggs are a viable option for some.
However, if this is indeed the case, why then would PGS be required when using donated oocytes from younger, healthy and fertile individuals?
Dr. Rueda goes on to explain how even eggs collected from donors may have abnormalities, as aneuploid embryos are potentially more common in IVF. This is due, in part, to the collection of eggs following ovarian stimulation, where the high doses of gonadotrophins (ovarian stimulation hormones) used during the stimming process increases the risk as does the medical cultivation of the pregnancy and manipulation of the gametes such as changes to temperature and oxygen in the laboratory environment. Donor eggs, therefore, can still be affected.
The objective of any cycle of IVF is to transfer a healthy embryo for implantation and the use of PGS allows embryologists to be able to select the most viable. Screening helps to detect any embryos which are shown to carry genetic anomalies, enabling the transfer, or freezing, of only those embryos which have high reproductive potential. PGS is, put simply, a biopsy and genetic analysis of the embryo, after fertilisation has taken place, but before the transfer is carried out.
For patients with an advanced maternal age, a history of recurrent pregnancy loss, repeated implantation failure and where severe male factor is known, Dr Rueda’s advice would be that PGS could make a difference and be used to assist in the creation of healthy offspring for couples who carry genetic diseases. He also advises that even with patients who have a good prognosis, or those who are using donor eggs genetic analysis of embryos can be helpful as there may still be the possibility of adverse pregnancy outcomes.
Preimplantation genetic screening should, hopefully pave the way for more single embryo transfers to take place whilst also helping to lower the timescale it might take for couples to transfer an embryo which has higher scientific odds of implanting and progressing to become a full-term pregnancy resulting in a live birth.
Dr Rueda advises that more research into preimplantation genetic screening and diagnosis in donor gametes is currently taking place.
Check the clinic profile of PreGen which is Genetics Unit at the above mentioned Hospital UR Vistahermosa and employs highly specialized team of fertility doctors and embryologists. PreGen clinic has been in operation for over 30 years ago and possesses broad experience in the field of ART.
This type of testing is performed prior to embryo transfer. If you have a few embryos at your disposal you would certainly want to use the healthiest of them. A healthy embryo will make a healthy baby. Thanks to PGD embryologists can select an embryo that has no known or suspected genetic problem. How does it work? PGD is a method to acquire information about the gene makeup of the embryo cells. PGD procedure is done through an embryo biopsy which removes approx. 3-8 cells from the blastocyst. At that time the embryo remains frozen.
If you have a family history of serious genetic diseases or disease linked to certain sex then genetic testing before IVF is definitely for you. Using PGD embryologists are also able to pinpoint the markers for specific single-gene diseases such as cystic fibrosis, muscular dystrophy and sickle cell anaemia or show abnormal number of chromosomes. With PGD it is easy to select the embryos which are unaffected and most viable.
On the other hand, PGS testing is used to establish the risk of aneuploidy (abnormal number of chromosomes). Properly developing embryo should contain 46 chromosomes. The test in carried out the same way as PGD, via a biopsy on embryo day 5. The euploid embryos which contain the right number of chromosomes are selected for uterine transfer.
The risk to have an abnormal embryo is higher especially for older women. The problems with abnormal embryo may include failure to implant, miscarriage, biochemical pregnancy, late pregnancy foetal death, stillbirth or live birth of a baby with abnormalities.
There are certainly a lot more issues connected with PGD and PGS testing and these are discussed in more detail in the webinar.
It’s very difficult to say if it’s hereditary with only this information because only one part of this pathology is hereditary. If you don’t have any other issues in their family, probably you don’t have to worry. You will have more chances of problems at your age if you are planning IVF with your own eggs as most of the eggs will have chromosomal errors, but you can have some eggs. My recommendation is to do a PGS or if you are already pregnant, you should check the prenatal genetic study.
Most neural tube defects are not genetic. There is another problem related to nutritional defects but in this case, your cryopreserved embryos could be used. Neural tube defects can be studied using echo during the 20th week of pregnancy.
We know that NGS is not a problem because NTA is a technique used to study DNA. The problem is with the biopsy. We take one cell, or now that we do the biopsy of the blastocyst, we take three or four cells, not from the embryo but from trophoblast. Theoretically, there could be damage to the embryo as is, but not necessarily for the future of the embryo. At least, this is the situation, as we currently know it.
There is a lot of controversy with PGS. This is because, in the past, we used a technique with a very early biopsy and no study with NGS. Now, with NGS, we can study the entire DNA. We perform this with an oscillator at five days in the embryo. The results we have had in the last two or three years are very good compared with previous results and most of the articles published verify good results. But, is it true that is controversial, and we can assure you that the results work, in all cases.
If I had to answer with a yes or no, then yes, it can, but the possibility is less than 2 to 3%.
The study of natural killer cells is not related to PGS, these are completely different things. PDS will work regardless of the presence of natural killer cells.
Yes, it is possible for them to auto-correct. But as this happens normally between three and five days and we perform the biopsy at day 5, most embryos at this stage will have already auto-corrected or will have stopped.
We study an adoption embryo in the same way as any other embryo. An adoption embryo is supposed to be good because the egg and sperm are supposed to be good. But as we saw before, if you check the embryo genetically, you can have bad results. If you are using a single embryo transfer, it is good to study the embryo but if you are using more than one, say two, is not probably necessary because one of the two will be okay.
In PGS the biopsy is done from the trophoblast and the embryo develops from the embryoblast, another part of the embryo at this stage. Almost all of the cells come from the cells that become the zygote. The trophoblast and embryoblast should be the same genetically. It is true that sometimes there are differences between the cells, but this is not a very important problem. I think it is safe but if there is a problem the embryo may stop later and will never reach the end of the pregnancy.
At 39 years old, most of your eggs probably have altered chromosome and we would have a failure. Endometriosis is another problem but if you could check the embryo the possibility to have a baby will be higher. The problem of your husband is a different problem than chromosome problem, but you can check for Fabry at the same you check the embryo, to select one without the mutation that caused the Fabry. Probably we need to use a frozen embryo to study it. We cannot have enough time and would have to use a frozen embryo.
Most of the PGD techniques for monogenic diseases could be followed by PGS then you can do both techniques to see if there are any genetic problems.
It would be very bad luck to have one loss following another other, so the risk of having a second embryo with trisomy 7 is very low, and not a significant barrier to you having a normal pregnancy without problems. In clinical genetics, if we have a woman with a previous trisomy treatment regimen, we would normally do all prenatal studies. Although the chance of problems is very low, I would still recommend checking this.
To answer the question I would need to have more information about the problem but probably you can transfer any of the ten. I need to have more information.
Yes. The low quality of the semen means that the embryo, no matter whether with own egg or donor egg, will be of worse quality, i.e. aneuploidy. If you are using donor egg will be less aneuploidy, but we will still have a number of unusable embryos and it is in such cases we recommend PDS.
This is a very important question. We do the biopsy on day 3 or day 5. If we do the biopsy on day 3, we can do this with a fresh embryo because we transfer on day 6. But if we perform the biopsy on day 5, we don’t have enough time to transfer it the next day, not unless you have the genetic laboratory side-by-side with a fertility clinic, as we do. Normally, nowadays, the biopsy is done on day five because we have much better results are using NGS, but the problem is that we have to freeze the embryo and transfer in the next cycle.
PGS is a kind of PGV. PGV is a broad definition of monogenic screening and is a screening technique. In the embryo, to check for euploidy or aneuploidy, we use a type of PGD that we call PGS or now pgtA aneuploidy. We perform pre-implantation genetic screening that is a type of pre-implantation genetic diagnosis. If you are using a donor you are not supposed to have any implantation failure.
This means that you should have fewer eggs and, although I don’t know your age, but if you are older than 35 as I suppose you are, you will have fewer eggs. Most of those eggs will have aneuploidy but you will probably still have some eggs that are normal. For this reason, is good to check the embryo by means of genetic studies.
I suppose your karyotype is okay. I suppose you have a karyotype after the trisomy 7 in the foetus. You cannot do anything more, but the recommendation from a genetic point of view is to do a genetic study in the next pregnancy.
We have a lot of people with balanced translocation and unbalanced translocation. This is not a problem for people who have it. The problem will be to make sperm or eggs, in this case, the sperm. You don’t need to worry about the health of your husband. It means that we will have more embryos with or without all the material or a higher chance of miscarriage. You can study the embryo and in fact, this is a medical indication to perform PGD. Nowadays, with any NGS technique, we can see the translocation and the rest of the chromosomes. Then for this problem, we will do a PGS and this is enough to see the balanced translocation and all the chromosomes. The chance to have a healthy live birth is possible. If you are 39 years old, we’re talking about 15 to 20% chance of a normal embryo. If we genetically study the embryos, you will find a normal one.
Now the techniques that most of the clinics use are NGS and PDS. I think there are a few clinics to use Array, an older technique but you can use Array without any problem, and for the results are similar. NGS is probably cheaper and we can study more things but for aneuploidy, the results could be similar. There are some clinics that do the biopsy on day 3 but most of the clinics are moving to day 5. The best could be the biopsy on day 5 using NGS but you can use Array without any problems.
PGS does not make a better embryo. PGS chooses the embryo without any problems so we can have more embryos without aneuploidy. If we do PGS and we don’t have any embryo with euploidy, we will not have any to transfer. But the normal situation is that with PGS, depending on the age of the patient, we will have at least one that will be okay that we can transfer and have a successful pregnancy. This is a very high chance but not 100%; this is not possible in medicine, as you know.
With PGS we screen all chromosomes. We screen for Down’s and Patau and other anomalies that we can see with NGS but we are not able to check for every genetic disease. The possibility of having a disabled child after PGS remains, but is very low. Even if there are no issues with the parents, this doesn’t eliminate the risk completely. Actually, after PGV we generally recommend monitoring the embryo at a later stage with prenatal diagnosis.
If we have a normal embryo, there is still a possibility that there are some problems in the uterus. We can have a very good embryo but if we have a problem with the uterus, in the endometrium, the pregnancy will be lost. During PGS is possible to damage an embryo but this possibility is less than 5%.
This depends on the clinic because it depends on the genetic laboratory. The genetic study takes around 15-20 hours, but normally in the laboratories, if we transfer in the next cycle, we have the result in two or three weeks. This is because, to perform NGS we need several embryos, and this makes the price very high, but we normally we extract the DNA and keep it DNA frozen until we have several embryos. For that reason, most clinics will say two or three days, but the study itself takes only one day.
To answer these questions I have to tell you that it depends on the program of the clinic. The results that we have now in most of the publications say that a frozen cycle is better than fresh. If the program of the clinic with frozen embryos is good, then the success rates could be better with frozen rather than fresh embryos.
PGS is not necessary at all. PGS is only a recommendation because we know that with PGS we will have better results. With a proven donor, if your husband’s sperm is good, the possibility of success is very high, in our hands around 65%. If you do PGS this can rise by about ten percentage points. In either case, the possibility of success is high.
It depends on the country. In Spain, there is a registry of clinics where all clinics have to give their results to the ministry of health but it depends on the country.
This also depends on the country. If they are normal embryos, and I suppose you mean frozen embryos studied with genetic techniques, they will not be killed.
This is a very good question. PGS tests all the chromosomes and with the same technique, you study trisomy and monosomy and also rearrangement. The only rearrangement that we can currently study is very small but this is very rare. PGH test both chromosomal rearrangement and also aneuploidy.
Xytex is an American sperm bank, however, this would not be possible as all donors must be anonymous, whether sperm donors or egg donors.
Yes, we can do NGS, no matter if it is with own embryos or adoption embryos we can do this.
This is a very good point because we who are working in with embryos are looking for good biomarkers to not damage the embryo. We have only today two biomarkers, morphology, which is a non-invasive technique and genetic studies. With morphology, we have several different techniques e.g. morphology time-lapse techniques, so that we can have a better embryo, but nowadays, with this, is not possible to check for embryo aneuploidy. The only technique we have for this is PGT.
An adoption embryo does not have your genes and if you have another adopted embryo, NGS will be better for chromosomes. If you want the child to have your genes, it would be better to check your own embryo with NGS.