By fertility experts from Spain.
How can I go about preserving my fertility during the Coronavirus times? Is any non-stop treatment possible during the quarantine? Danny Daphnis, PhD, Scientific Director at Mediterranean Fertility Center, Greece, explains fertility preservation and social egg freezing and answers patients’ questions.
Fertility preservation is when we are trying to preserve our fertility for specific reasons. What is preserving our fertility mean, we all know that male patients have sperm which is a gamete and female patients have oocytes which again is called the gamete. The best way to preserve your fertility is to freeze those gametes, either the sperm or the oocytes. You might hear the word freezing or cryopreservation- it’s the same thing, we’re freezing these gametes either the sperm or the oocytes in the laboratory to be used later on at this stage suitable either for the male patient or the for the female patient. This is done in laboratories throughout the world, specifically IVF laboratories, and it is a way to keep your fertility because there is a specific reason that you need to delay childbearing or to start the family.
Fertility preservation is mostly done for either men or women. The most common reason for fertility preservation, unfortunately, is a bad reason. If a patient either male or female has to undergo cancer treatment, that means chemotherapy, radiotherapy or any kind of therapy that will affect the patient’s gametes sperm or oocytes., That person is a candidate before any cancer treatment to freeze their sperm or their oocytes. The reason I’m saying this is because those are the patients who need preserving their fertility the most.
The second group of patients who like to preserve their fertility is because of social reasons. They either have to pursue a career, they don’t have a partner, and they wish to keep their sperm or the oocytes in cryostorage for later use. This might sound a little bit egoistic, but as all fertility specialist say – it’s best to start a family as early as possible. The reason is simple – we all know that female infertility declines quite rapidly, at the age of 40 around 15-20% pregnancy rates are reported throughout the world. That means that the sooner we freeze and preserve oocytes, the better quality oocytes are going to be. We’re going to have better results later on. If a lady opts to follow her career or she hasn’t found the right partner to start a family, then it is the best option to perform egg freezing process to store her gametes and keep them for later use. Therefore the second reason, the social reason is equally important as the first one. Also, another reason why patients do fertility preservation is when they want to be able to have a backup. We all know that during fertility either when you’re doing fertility treatment or when you are waiting for fertility treatment like right now f.e., you want to keep your eggs, you want to keep your sperm safe, it’s the best way to do this.
I’m gonna start with the sperm freezing is a simple process. We require 1, 2 or 3 sperm samples in an IVF laboratory which are stored according to each IVF laboratory protocol. That’s why it’s how simple it is for a man, and I think it’s best to mention it so I can go into the actual question. There are actually two stages in the egg freezing process. The first stage is the stage where we prepare the lady to have the egg collection, and the second stage is the actual freezing procedure as you all know. Before you start an egg freezing process, you need to visit your IVF specialist or even your gynaecologist who knows about these things. The IVF specialist will assess your fertility by doing specific exams, like blood hormone measurements and the vaginal ultrasound, and whatever tests he or she might think are important to assess your fertility. Once that is done, the patient is prepared, we utilize a patient cycle, there are two ways that you can preserve your eggs. You can either preserve each egg that comes out of a lady during ovulation every month and freeze that egg every month. You can also undergo hormone therapy, so within one cycle, you can eject specific hormones to your body to grow more than one egg, hopefully, 5-10 eggs. If you choose a natural cycle egg freezing process that means that we follow the ovulation of a lady and just before ovulation we perform the procedure called egg collection. The lady is put under very mild sedation it’s no general anaesthesia, it’s mild sedation, and we aspirate the follicle, find the egg and then go to the second stage of freezing.
Most women opt for the second option they would like to store more eggs on one go. We place the patient under hormone treatment approx. 10- 12 days, we monitor the patient during this time to see how follicles are growing and once the follicle is ready, just before ovulation, we go through mild sedation but instead of operating one follicle, which is done on a natural cycle, we aspirate all the follicles. We find all the eggs, and then these eggs are taken into the IVF laboratory.
There comes the second stage of the egg freezing process, which is the freezing and storing phase. We collect the eggs, clean them and check which eggs are of good quality morphologically, and which eggs are mature. Only good quality mature eggs are usually cryopreserved. Nowadays, we use a technique called vitrification procedure. We have the highest percentage of around 85 to 95% success rate in freezing the eggs. As an embryologist, I always say to patients that an egg is the most difficult cell to freeze. The reason behind it is that the egg is the biggest cell of the body. That means that the egg has a larger quantity of water inside it. Unfortunately, as all of you know, when you freeze water, you create ice crystals if you do that in a cell that will rupture the cell. That is why we use vitrification, and that is why we have higher percentages of success rates during the freezing process.
Lastly, according to ESHRE guidelines, some patients have found their partner, but they are not ready to have a family yet. So you can also have embryo freezing process which is exactly like the egg freezing process, however, before freezing the egg, you fertilize it with a single sperm, or each egg is fertilized with a single sperm. You create an embryo which divides from 1 cell to 2 cells to 4 cells or to a blastocyst which is 150 cells, and you freeze it at that point. That is for patients that for whatever reason have found a partner and they want to delay having a family.
Everything that is done and is medical has a small risk, but this risk is quite minimal. There are two aspects that usually patients will pick up on and ask us quite often is it harmful, or would I have a problem later on in life. The first thing that most patients ask is if you don’t do an actual cycle and do a hormone therapy to create more eggs or more embryos, then you take hormone injections, and the patients are always wary when they hear the word hormone injections. Most big studies that have been carried out, they have not found out that there is a link between having a hormone treatment, one or 1 or 2 hormone treatments and having cancer later in life. Except for patients that there is an underlying problem, that is why all patients are always checked thoroughly, before going through a hormone therapy treatment to double-check that they do not have breast cancer, ovarian, endometrial cancer. We always check our patients. We need to know that a patient is clear, and they don’t have a medical history, even from their mother or the grandmother of any cancer-related problems before going with this procedure. Ovarian stimulation is a safe procedure. It does not create any issues, as long as everything is thoroughly checked. The risks of social freezing are very minimal. It should be done in a licensed IVF centre whereby doctors and scientists are properly trained and have the right qualifications to perform the actual treatment.
According to all American and European guidelines, everything should be performed under constant supervision and in a licensed IVF centre. It can be done in all IVF centres which have the correct personnel, from doctors to embryologists to nurses and midwives. It is important in order to keep patients happy and safe.
It is safe for the patients, and it is safe for the people who are treating the patients since there is a quite minimal risk to contracting the virus as long as everybody is taking the necessary precautions. In our IVF clinic, we are currently doing quite a bit of fertility preservation, even during the lockdown. But we should be at least 2 meters away from each other, we schedule everything properly, we don’t have many patients to patient contact, so the IVF centre is properly screened, we don’t have just patients walking in etc. From the patients to the IVF personnel – all are following what our governments are advising so washing hands, wearing a mask, and trying not to interact with each other etc.
The fertility preservation is one part of the whole procedure. The procedure is done. So later on in life, either the man, the woman or the couple can have a family. This is a very good question because we should not only think of the first part, but we should also think about the second part. When we are trying to either use the sperm, use the eggs or use the embryos., If it’s about sperm or eggs it is important to be able to utilize these gametes so we have good quality at the beginning so we can have good quality in the end. Once you’ve found a partner or once you’ve gone through cancer therapy, you come into the centre to freeze either the eggs or the sperm. Once you are ready to start your family, you come to the IVF centre, if you have frozen eggs, you come in with your partner, he gives a semen sample, we warm the eggs, we fertilize them with your husband or partner sperm and perform the whole IVF procedure. If you have frozen the embryos that means that you have already found a partner, but now you are ready to start the family, then we just thaw the embryo, it’s already prepared, and we just do the embryo transfer procedure. Another important aspect is of great importance, to start early because what comes after the fertility preservation depends very much on what has happened during the fertility preservation round. We have to have as good quality gametes sperm and eggs, and embryos at the beginning, to have good result in the end.
It depends on – the laboratory, at good laboratories you can expect around 85-90% thawing rates. What does that mean in simple terms? It means that once the egg is vitrified and then warmed, so thawed – it has 85-90% chances of surviving like it was never frozen before. So those are the survival rates at the moment that are being quoted in the literature in good laboratories.
So sperm, eggs and embryos can be stored, and there is no limit. The HFEA (Human Fertilisation & Embryology Authority) changed their consent to have all these either sperm, oocytes or embryos stored for 55 years or more. If they are stored in proper conditions, according to ESHRE and ASRM guidelines, in the IVF license centres these gametes and the embryos can be stored indefinitely. Each country has its own laws, some countries say that you can keep it for 10 or 5, 15 years so I cannot comment on the policies in each country. It has been stated in the literature that it does not affect the gametes nor the embryos if they’re frozen for 1 week or 10 years. At the moment, it all depends on each country’s government policy.
There is insufficient evidence on this, at the moment. I urge people to go to www.eshre.com. They have made a statement on what people should know during this coronavirus period. As I’ve mentioned there is no evidence that actual virus can go through the oocytes or sperm influencing at firstly the quality of either oocytes or the sperm.
It depends on sperm quality. Any embryologist will tell you that a rough estimate is around 50% survival rate of the sperm, so if you have 10 million sperm f.e. five million will survive. Once the sperm survives, there have been quite many publications testing DNA fragmentation and testing DNA integrity, testing the viability and quality of the sperm. Overall, all the data suggests that if the sperm survives after a freezing procedure, again in a licensed IVF Center which has qualified scientists, it does not affect the result of an IVF treatment. That means that if f.e. a patient had 30% chances of getting pregnant with the fresh sperm, they would have 30% chances of getting pregnant with the frozen sperm.
According to the protocol each laboratory performs, we can freeze 2 embryos and 2 oocytes in one straw. Usually, patients like to freeze one per straw, and then the answer is very simple, it does not affect the quality of the embryos. I want to state this, if you freeze two embryos or one embryo, it does not affect the quality of the embryos. If you freeze two embryos in one straw or one embryo in one straw, it will not affect the quality of the embryos before or after the vitrification procedure, however, advantages of freezing singularly, are just for patients. That means that by freezing singularly, you thaw fewer embryos or fewer oocytes. You can do it one at a time and see how many survived, especially if we’re talking about blastocyst vitrification when we do opt to freeze singularly because we think these are quite precious embryos, they have high chances of implantation. We want to limit the percentages of having twins. So we opt for singular freezing, thaw one, transfer one and hopefully get one healthy baby.
We are located in Crete, which is an island in Greece, and it is COVID-19-free, at the moment. There have not been any COVID patients here, there’s only been one or two in the farthest end of the island, and they’ve both been hospitalized. They’ve been traced that they don’t have any other relatives or friends who have been infected. Therefore, we have not asked our patients to perform the 300 euro test, that they would have to pay to do this. If a patient has symptoms then, we would ask them to perform the test before getting into the clinic as a measure to avoid contamination or avoid spreading the virus. Before coming to the clinic, we ask our patients to do a blood test to check that they don’t have any raised leukocytes or they don’t have the C-reactive protein high (CRP) and of course very simple measures of taking their temperature.
I know especially for IVF patients who go through so much in order to get pregnant, to start their family and then to have somebody tell them to stop. Because at the end of the day, IVF is not done for fun, it is to start the family. They are not saying to stop having sexual intercourse and, I totally agree with you, I understand the reason behind it but, I think governments who have restricted IVF treatments because they don’t want for the virus to spread and, they want to limit people visiting IVF clinics. As I’ve mentioned, according to ESHRE, it is not banning IVF treatments, it’s just saying it should be reduced because of limited data.
First of all, family balancing or gender selection is exactly the same thing, and it is not performed, in almost any countries. There are very specific countries that do it. There are countries which forbid it, there are states that forbid it, so you have to be informed where you can do it. If it is allowed by the government, you can use your frozen eggs, fertilize them, do the procedure of gender selection and transfer this gender that you prefer. If it is embryos, it is a little bit more difficult depending on what stage they are frozen, so if f. e. you already have embryos frozen in an IVF lab, you will need to ask your lab if they’re able to do the procedure of gender selection. Gender selection is not possible in Greece. It is only allowed if there is an underlying problem, another chromosomal problem from the patients. So it’s to test sex-linked diseases, then you can do the gender selection but not for family balancing. It is not allowed to do it for social reasons.
This is a very broad question, and I would love to answer this question, but it’s probably going to take us an hour to discuss it. Without knowing anything about your medical history, I must mention this. Remember, that I am an embryologist, not a fertility gynaecologist so I will answer it from an embryological point of view. It does depend on the embryo quality that you’ve had those five times you did IVF, it depends on the age as well, I know you’ve stated that egg quality and all the results are fine, however, if they are fine there is another underlying reason why you’re not getting pregnant. Embryo adoption is definitely a way to proceed since you’re using embryos which are from as I’m guessing a couple who’s done IVF before and, they don’t want their embryos and, you’re going to use those embryos, this is what usually embryo adoption is, in most clinics around the world. So I would say yes, however, you always have to take into consideration that the embryos from these fertility couples which they have not used anymore, they are from patients who have also experienced a fertility problem. We have to be aware of that because, if the fertility problem was the closed tubes, that’s not a problem. However, if the left-over embryos, even if they got a pregnancy, were because of a sperm factor then that might not give you the highest chances. Perhaps, the embryo donation would be a better option.
First thing I want to say is the influence in provoking cancer, if there is no underlying problem and also your family medical history is checked, it is quite low. I am not able to give you the percentage for the risk of cancer at the age of 49 because I am not a specialist. This should be answered by an oncologist, not even from a fertility specialist because other underlying issues need to be considered.
IVF centres and IVF specialists try to limit the twinning because of IVF. We want to keep it below 10%. In an ideal world, we would like to be able to choose the best embryo, which will give the best chance of giving a pregnancy and get a healthy baby. The reason why we want to limit the chances of twins is that twin pregnancy carries more risks than a singular pregnancy. A gynaecologist will tell you that twins are a blessing, however, the women who will be carrying the twins might have higher risks of preeclampsia, blood pressure and maybe will have intrauterine growth restriction (IUGR) and a little bit more difficult pregnancy.
Unfortunately, no. Our country has a very strict policy of anonymity either of sperm or egg donors. In Greece, the law states very clearly that the donors have to be anonymous.
The first thing that I will quote is not medical so much, I would like I to say to almost all of our patients it will depend on your spiritual, psychological strength, and the strength that you get from your partners. The first thing that you need to see is not putting a number on it – 3,4, 5 or 10 times. If you can gather your strength and be able to overcome a negative result, you should go ahead. And how many tries is considered healthy, that is a different subject? I would suggest, scientifically speaking, when you’ve done 3,4 or 5 attempts – double-check that everything is okay. I would go through your medical history again, I would check if there are no underlying problems, I would do a proper breast ultrasound or a mammogram, a pap smar test and even an MRI for the low region to see if it is not affected in any way and if you are a healthy person even after 5,6 or 7 IVF attempts if you have the strength with your partner to go through it, by all means, go ahead.
I guess like with the eggs, there is minimal contamination because we take repeated washing steps for culture and a freezing protocol which will create a high dilution of all possible contaminants. That means that all the procedures done in the IVF laboratory try to minimize the chance of either in semen or an egg to have the virus present. I cannot give you specific data because there is no specific data, however, it is assumed that sperm, eggs and embryos do not have specific receptors for this the virus, therefore, they do not carry the virus.
It depends on each IVF clinic. At the moment, at our the clinic, we freeze the semen as it is because it is assumed by many papers in the literature that it’s better to freeze it raw, to freeze it as an ejaculate which kind of protects the sperm during the freezing procedure.
The egg is the largest cell of the body, that means that it has more water inside it. During the freezing procedure, we have higher chances of having ice crystals if the egg survives intact, it will give a good percentage of implementation. We are aware that the egg does not freeze as
nicely as an embryo. That’s why if possible we push patients to freeze embryos if there’s no other way, we freeze the eggs. So the exact reason is the nature of the actual eggs.
There is no scientific limit for how long embryos, sperm or eggs can be stored. It only depends on the country policy, as each country has a specific policy in place to state that they should be stored for either 5,10, 20 or 50 years, they do not deteriorate, once you freeze it, it stays in what we call a stasis. All gametes, sperm, eggs and embryos are frozen and stored in IVF licensed centres at minus 196 Celsius degrees. That is very low temperature, it’s the liquid nitrogen temperature, and they stay there at a constant temperature at minus 196 throughout the period that they are stored. They remain locked in time, so if you freeze it for one day or 10 years, it is not affecting the quality.
There is no recipe, I am afraid. If you stay in Bed 24/7 for 14 days until you do your beta HCG, your pregnancy test or you move freely, as it has never happened, there is no scientific evidence stating one is better than the other. I would say that it is somewhere in the middle. You shouldn’t stay 24/7 in bed because it’s going to ruin your emotions, your psychology, you’re going to be looking at the ceiling, and thinking am I going to be pregnant, I’m not going to be pregnant etc. There is nothing that you do or don’t do after embryo transfer, keep it simple, don’t stay in bed 24/7, take the medication the doctors have prescribed, you can start getting back to normal life after implantation window has taken place.