- Who is genetic screening for?
- What is the risk of your child being affected by an autosomal recessive disorder?
- Why should I get tested if my family is healthy?
- What are the benefits/drawbacks of carrier screening before conception and during pregnancy?
- What is screening based on prevalence and geographic/ethnic criteria?
- What is the best strategy for testing? Should the male partner be tested at the same time as a female?
Genetic carrier screening in sperm and egg donation
In this live webinar, Dr. Clara Colomé, Medical Deputy Director at Eugin Clinic, explained the process and role of carrier screening in IVF and egg/sperm donation.
Questions and Answers from the event
Is it possible to find mutations in eggs or sperm or we must wait until the embryo is formed?
This is a very good question and, in fact, no, it is not really possible to find a mutation in egg or sperm. You can analyze some things in eggs and sperm but a mutation – we have to find it in a genetic sample, blood or saliva, before obtaining the gamete or once the embryo is already created. We cannot analyze the mutations in eggs or sperm. No, it is not possible yet. What we usually do in our centre is we advise you to do an expanded carrier screening test to all of our patients. When we use our oocyte donor program, we always do the genetic matching between donors and recipients. When the couple is using their own gametes, we always advise them to do this expanded carrier test. We feel very comfortable with it and also patients.
What are the genetic tests that you advise to do before undergoing IVF between a female patient and a sperm donor?
Depending on the situation, we might advise doing a basic karyotype for the female patient. Clearly, we always do a karyotype for the sperm donor which is basic genetic testing and then we advise to do the expanded carrier screening test. Again, the important thing is not the results of the test but the matching with the best possible donor genetically.
Can a double biopsy be done on the blastocyst just in case of a false negative result to avoid damaging the embryo having to be defrosted and done again as a backup?
This is a very interesting question. Here we’re talking about a slightly different situation which is when we do a PGT, a genetic pre-implantation test of the embryo, as you are well aware, we do the biopsy of the embryo on blastocyst stage. When we perform the biopsy, we remove part of this blastocyst tissue and then we vitrify, we freeze this blastocyst and wait for the results. Not necessarily a false negative. It’s just at some time, the result is not conclusive enough and we have to repeat the biopsy and, therefore, exactly what you were saying, we have to defrost the embryo and then freeze it again. Technically, we could do a double biopsy but a biopsy of an embryo is quite delicate – it’s an embryo, it’s a future being that is not very big so we have to minimize the amount of tissue that we remove from the embryo. Even though technically, it shouldn’t be impossible to do a double biopsy, we would never do it because most likely we will definitely have results with the first biopsy. We would risk damaging the embryo too much doing it twice at the same time if it’s not necessary.
Are mutations related to age? As donors are under 35, is it more secure to go through egg donation treatment than own eggs for a 40+ patient?
This is a very interesting question. In fact, the answer would be yes and no. Some mutations are related to age, especially in females. As you all know we have a determined number of eggs at our birth and then we use them until they’re over. Men, on the other hand, continue producing sperm until they die, basically. The older we get the fewer eggs we have but also the more mutations these eggs might carry. Over 35, but especially over 40 the percentage of eggs that carry mutation is high but these are mutation linked to the number and shape of the chromosomes.
That’s why as age advances we are at higher risk of a miscarriage and at a higher risk of having a child with Down’s syndrome which means that your child has three copies of 21st chromosome. This is, however, not linked to the expanded carrier screening test because these Mendelian inheritance diseases are not linked to the age of the patient if you have a mutation you have since your birth. It is more secure to go through an egg donation treatment than with your own eggs for 40+ patients regarding malformations, Down’s syndrome and miscarriages but not regarding diseases such as cystic fibrosis or muscular atrophy, for example.
Are genetic tests always included in the treatment?
We do not force the patients to do it. We always like talking to our patients and decide together which is their best option but it’s definitely always advisable to be performed and almost always done. If you are asking if it’s included in the cost of the treatment, it depends but usually not. It is an extra cost because genetic analysis has to be performed.
The potential donor is an autosomal recessive carrier of two genetic conditions: GJB2-related DFNB1 non-syndromic hearing loss and deafness (Gene GJB2) Variant c.313_326del (p.Lys105Glyfs*5). We were told 1 in 20,000 possibility of a child being born with it; and the other, autosomal recessive carrier: phenylalanine hydroxylase deficiency (gene PAH) variant c.1222C>T (p.Arg408T rp), 1 in 19,000 possibility. How serious would these two diseases be if babies are born with them? My husband does not have these carrier conditions?
Here we have a potential donor that carries a GJB2 mutation which is linked to genetic deafness. There’s actually quite a frequent disease that causes hearing loss, sometimes progressive, sometimes from birth which is not related to any other malformation or alteration and it’s genetic. It’s the most common cause of deafness in the world, genetically. This is what this potential donor could carry and then she carries metabolic disease in mutation which is phenylalanine hydroxylase deficiency. These two diseases are not life-threatening but, clearly, in this case, again you have this information of a person who carries two mutations. This is not what interests us. What interests us is if the partner carries these mutations or not. Your partner does not carry these mutations so usually what we do is we pass these results to a genetic specialist that assesses the remaining risk. Even if your partner is negative and the donor is positive, there is still a risk that the child could be born with one of those diseases. But the risk is usually really low. It depends on the type of tests that you performed because there are tests that are more thorough looking at the gene than others so I cannot really answer you to 100% with the information that I have.
But I think you could go ahead with the protocol without much issue. What we usually do in our centre, after genetic expert consultation, is we discuss the remaining risk with the patients so they can make a decision.
One in 20,000 possibility means that if you had 20,000 children one would be born with this disease. I think this is a risk that you should be able to assume. Of course, each person is different when we usually, for example, when we think about Down’s syndrome when we are pregnant and we do the first-trimester screening test which is done from blood and ultrasound assessment, they advise performing an invasive test such an amniocentesis when the risk is superior to one in 250. If you compare those data, you can see that one in 20,000 is really very low. In our centre, with this rate, we wouldn’t go ahead with this procedure. The risk is never zero.
Have you seen statistics and mothers giving birth to [children] with such problems?
No, I haven’t seen it but it’s technically possible. 1 in 19,000 means that one in 19,000 which is extremely rare and I haven’t seen it but it’s genetically possible. I would be very confident with this remaining risk. Honestly, I would go ahead with the procedure but then again there’s not a warranty that this won’t happen. The good thing with this situation that you have is that those diseases are not life-threatening. To sum up, when we start discussing numbers it might be a bit frightening. I think it’s good to have the information. I think it’s good that we all know that we all can carry diseases but the aim of these expanded key areas screening test is precisely to assess it better and to be able to be more relaxed, to be more confident about your chances of conceiving with a low or high percentage of a very healthy child. We have to discuss clearly the information with our patients so that they understand that if they have a risk that’s lower than one in 500 or one in 1,000, they can be very confident about the procedure. It’s better to know and to be able to detect it than not knowing.