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Murat Önal, MD
Medical Director at Gynolife , Gynolife IVF Center
Category:
Donor Eggs, Genetics PGS / PGT-A, IVF Abroad, Success Rates
Family balancing or sex selection is an interesting topic for both fertility patients undergoing IVF treatment with PGD and for fertility specialists who deal with IVF on a daily basis. Watch the recording of the webinar and find out the answers to the most common questions patients ask.
IVF gender selection is an incredibly controversial topic, and one which raises many ethical questions, depending on the reason selection is being sought. In this webinar, Dr Murat Onal, Medical Director of Gynolife IVF centre in Nicosia, Cyprus, discusses why parents may want to carry out sex selection testing, and if so, what exactly it entails.
There are two main reasons why potential parents-to-be may decide to go ahead with gender selection; genetical reasons, or family balancing. It is currently illegal, in some countries, to undergo gender determining procedures solely for parental preference, where there are no genetic or chromosomal concerns.
To fully understand why gender selection may play an important role, when researching genetic health, it is important to look at the chromosomes within humans, specifically in relation to the differences between the sexes.
Men and women basically have the same set of around 20,000 genes, with the only physical difference, in the genetic make-up, being the sex chromosome; the Y chromosome is only present in males and although both sexes have the X chromosome, females have two (XX), whereas males only have one, to accompany their Y (XY). During fertilisation, an XX oocyte (egg) is produced and fertilised by either an X or Y sperm. These chromosomes then fuse together to create either an XX (girl) or XY (boy) baby.
Chromosomal linked disorders can be carried by either parent and depending on the anomaly, have the capacity to cause defects in birth, as well as embryo implantation issues. In these cases, testing may be advised in order to eliminate any potential risks, to the unborn child, and to increase the chances of achieving a viable, healthy, pregnancy. As genetic problems are known to lie within the chromosomes whether a disorder will be passed on to any offspring, is dependent on both who the carrier is (mother or father) and the gender of the child, as chromosomal irregularities can be gender specific in their continuation down a family line.
Whilst it might be advantageous to offer genetic selection in some situations in order to safeguard the pregnancy or health of the child is it actually possible to tell the sex at embryo stage, or even determine this beforehand, and is testing safe? Dr Onal outlines the different methods and procedures, his clinic uses, and answers some of the main questions, surrounding the issue.
At Gynolife IVF centre, two main categories, of gender determination, are used; sperm selection and/or PGS (preimplantation genetic screening).
PGS is only available as an IVF treatment as the screening takes place using cells removed from an embryo. These cells are then tested for any anomalies and/or gender. Dr Onal advises that embryo biopsies can delay cycles of IVF, although, three-day, or blastomere, biopsies are possible, allowing for a fresh transfer to still take place. After 72 hours, it is expected that an embryo will contain between seven to eight cells, and in order to complete the screening, one to two, of these cells, are removed and examined. Tested embryos should then recover and continue with their development again. However, due to the invasive technique of the biopsy, Dr Onal warns that conducting PGS this early, may in fact have a negative effect on the embryo. He also cautions that a day three analysis may not always give embryologists the full picture of embryonic health; embryos can, and do, correct themselves, meaning an embryo on day three which appears aneuploid (abnormal), could potentially right itself, given additional time. Day three information may not always be accurate in the longer term.
Another PGS option, for gender and euploid (normal embryo) selection testing, is a trophectoderm biopsy which would usually, happen at blastocyst (day five) stage. With this technique only cells from the crust, or inner line, of the embryo are retrieved, allowing for a less harmful effect on any tested. This crust contains the main cells and enables the genetic lab to identify, and review, all the chromosome pairings with increased accuracy, as each sample tested includes more than just one or two cells, as per blastomere biopsies. Trophectoderm biopsies are, currently, the most common method of PGS used.
At the Gynolife clinic, Dr Onal says that gender recognition is 99% accurate, from both the blastomere and trophectoderm biopsies.
All of the techniques, mentioned in this webinar, can be used with regard to family balancing too, however, Dr Onal stresses that there are ethical considerations in gender checking, for this reason alone, and as a result, this is only, legally, available in a few countries, within Europe.
We are an IVF centre. If we are going to do a genetic testing we have to have a perfect genetic lab so we send this to a big genetic lab to have the most accurate results. You have to have a very good genetic specialist to give you the results you need and the best genetic conditions in the lab. So we prefer to send tests to a genetic lab, not to do this in-house.
With the NGS technology, we are able to see the X and Y results.
We also see the results, which are, of course, an information sheet, so patients may not understand everything. We do not expect patients to understand everything, so we have a consultation and decide together how many embryos we should transfer and their gender.
They may be a slight risk because of the biopsy procedure. There may be a negative impact on embryo development and also issues during the pregnancy; the risk of miscarriage or a biochemical pregnancy may be increased. But, with day-5 embryo biopsy, trophectoderm biopsy, these risks are very low.
Yes. In Cyprus, you can do this, but according to our Ministry of Health, you need to show approval from a cardiologist and internal medicine specialist to proceed.
Yes. If the IVF centre is able to tell you, and this is not possible in every country, and is able to give that opportunity, then you can select.
Yes. We have to have embryos to do the biopsy procedures. Other techniques are just for sperm selection and with those techniques with lower probability have gender selection. You can then do intrauterine insemination, but to do PGD or PGS you have to do IVF.
First of all, PGD testing will give us information about chromosomal abnormalities. Of course, there are other genetic abnormalities, for example, some single gene disorders like Thalassemia or Sickle Cell Anemia, but with these kinds of genetic abnormalities, we cannot give guarantees using this technology. If you are a carrier of a mutation and if your husband also carries the same mutation, you can tell us and we will do the setup procedures to have a look at that specific gene problem. There are approximately 5,000 genetic abnormalities, and it is accepted that every person has one to ten genetic disorders. Even if the patient is healthy, there may still be a risk that she carries some genetic mutation. This will only be important if her husband is also a carrier. If we are talking about somatic mutations or X-linked mutations, this is another matter and she can do gender selection for this reason.
If you wanted to screen all of the chromosomes, for example, to avoid trisomy-21, a Down syndrome baby or such kinds of chromosomal abnormalities, of course, you can do PGS and during this process, you may learn the gender of your baby. However, being a carrier is one thing and having a chromosomal abnormality is quite another.
If we had good quality, chromosomally normal embryos, you have the right to freeze those embryos.
Yes. The process, from beginning to end, is approximately 17 to 20 days and not all patients are able to stay in Cyprus for so long. Generally, patients start their treatment in their own country or city and come here for the final days, for ovulation induction or for egg collection, and wait until the egg transfer.
There is no maximum age for men for these treatments because we select the sperm and do genetic testing. We can use the sperm of a 45-year-old man because it is not like with women; usually, men have a comparatively longer fertility period.
In my centre, we generally recommend NGS for egg donations to patients who have had lots of failed attempts with egg donation. For example, if I see four attempts failed attempts, I advise them to go to NGS to check for chromosomal abnormalities whether it is with egg donation or not. Importantly, being young and healthy doesn’t mean that all of the eggs are healthy. They may seem to be of good quality but the internal structure, the genetic part, may not be. Of course, the percentage of unhealthy eggs is very low in egg donors, which is why I don’t recommend it as a first step. However, if we have a lot of unsuccessful attempts, we may think about NGS for chromosomal screening. The woman may be healthy, but the chromosomes not. For women in their twenties, 90% of eggs are healthy, but according to some research, for women aged 43, this is only 8%. There is no such thing as 100% normal at any age, so to be sure, doing NGS is the right decision. However, if you are young, if your egg donor is young, as a first step, I would not recommend NGS.
For the transfer of embryos with PGS, for example with NGS, the implantation rate is very high, so we may want to transfer one embryo. If patients want to have twins, and if they have healthy embryos, we can transfer two embryos, but with PGD we would not recommend three embryos or more.
This not very common topic in the science field, since, after moving from CGH technology to NGS, a more sensitive technology, we can easily detect mosaic embryos. We consult with our genetic experts and if the percentage is less than 20%, in our centres, we strongly recommend transfer. If it is more than 20%, we discuss this with the patient and act accordingly. We do not transfer all mosaic embryos because this is not our first aim. It depends on the percentage and the chromosomes: these are important.
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