Freezing your embryos – what’s it all about?

Explained by: Karen Schnauffer, RHG – IVF Life Group
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Freezing your embryos - all you need to know
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From this video you will find out:
  • What is the development of an embryo?
  • What do healthy blastocysts look like?
  • What is the procedure for freezing your embryos at the clinic?
  • How long can I store my embryos in the UK now?
  • What are the success rates with frozen embryos?

Is it time to freeze your embryos?

In this webinar, Karen Schnauffer, Consultant Embryologist & Laboratory Director at RHG – IVF Life Group, UK has explained how freezing your embryos work and provided an interesting Q&A session.

Is it time to freeze your embryos? - Questions and Answers

How long can eggs be frozen without defect?

Embryos are suspended in time. There has been evidence where embryos have been frozen for 50 years, and there has been no effect. I can’t say that these were used in treatment, but it has been shown that freezing them in liquid nitrogen means they just don’t age. They don’t change, once they’ve been frozen. It’s reassuring for long-term storage because some people are storing their eggs for many many years.

Are you able to tell if due to Covid-19, you see that more and more people are interested in freezing their embryos rather than going for the fresh transfers?

No, I haven’t seen that. It seems to be pretty normal. People are coming through wanting treatment. One of the ways of treatment is finding a good embryo quality and hopefully freezing it. So there hasn’t been a specific increase that I’ve noticed in patients wanting to freeze their embryos to then use at a later date specifically, because of COVID-19. Maybe other colleagues have had that experience, but I haven’t spoken to anyone who was presented with those concerns.

I have frozen eggs that I might use sometime in the future, and PGS will be good due to my age and PCOS, but it’s illegal here, so I might want to ship them abroad. What are your thoughts about that?

Well, we do move embryos from country to country. It does depend on what exactly you want the PGS for. In the UK, if it was to do a sex-selection or something like that, it’s illegal in this country. You would have to look into where you wanted to move them in terms of what you would be allowed to have there. If your concern is moving them and it’s that process of traveling or transferring them from one clinic to another, it’s fairly routine nowadays.

Even in the UK, you get people moving their embryos from clinic to clinic. You use specialist couriers that have to have all the appropriate equipment including the monitoring. I wouldn’t have any concerns about that if you use an appropriate professional courier who specializes in moving embryos and gametes. You do need to check where you’re sending them, or you’re thinking of having treatment. Make sure that the kind of treatment you want to have there is legal.

How do you defrost an embryo?

The thawing process, which for vitrification we call warming, is a little bit like the reverse of the process that I mentioned earlier. Except the embryo goes into solutions for shorter periods, and it’s more solutions. The whole process takes about 12 to 16 minutes. But what is critical about the warming process is the initial step from bringing it out of the liquid nitrogen and placing it into the first media. That’s a critical step, which has to take place within seconds from it being moved out of the liquid nitrogen and placed into that first dish that contains the culture media. And then after that, it just carries on depending on what protocol you’re using a various number of minutes in various solutions. And then, at the end of it, you can see whether or not the embryo has survived, and then you normally leave it for maybe one or two hours to let it fully recover before you would consider transferring that back into a patient.

For a woman who is 41. How many embryos/blastocyst should one freeze ensuring the success of pregnancy because I am not yet ready to have a baby. 

So I’m assuming the person is 41 at the moment. That is an interesting question. It isn’t a straight answer with this one. There isn’t a certain several blastocysts that you require to achieve a successful pregnancy. I did mention that a lot has to do with the quality, and unfortunately, as women get older, egg equality decreases, and our chances of pregnancy decrease. You do get some ladies in their 40s, who are not physiologically 40 and respond quite well to treatment. You would need to have all your tests and find out what your chances are of stimulating.

You should get a rough idea of how many eggs would be expected to get. There’s also the sperm side of things, so you need to see what the sperm quality is like. I’ll have to have a look at the whole picture. Age is a factor. I’m sure, if you spoke to someone, they would possibly be suggesting that if you’re interested in it, you should perhaps act fairly soon if you’re 41 already. It’s quite unfair for women, but that’s, unfortunately, the reality.

Does a high BMI affect IVF success with frozen embryos?

The BMI is more to do with the stimulation. To create the embryos in the first place. However, it is beneficial not to have a raised, or too raised BMI for treatment anyway. Just because of o the risks with regards to the pregnancy. That’s more something that a consultant would discuss with you, but yes, there are links. If you wanted more details, I could pass you on to one of my colleagues who could provide more details about that question for you.

How much time can coronavirus stay active in liquid nitrogen? 

I don’t know the answer to that question. As a result of us not knowing about viruses and how long they can be active in liquid nitrogen. Anyway, most centers that I’ve worked in would use a closed straw, so the system for freezing would be closed. It’s sealed at both ends, so nothing can get in. And this is a good example of why having a sealed system is ideal, so that you’re not exposing anything. So really, even if there is a coronavirus in the liquid nitrogen tank, it wouldn’t be able to get anywhere near the embryos. Then the processes we have in place in terms of how we handle straws containing embryos, either putting them in liquid nitrogen or removing them from liquid nitrogen means that there is no cross-contamination because of the processes we have in place to ensure that that doesn’t happen.

Do the chances of pregnancy with frozen embers for women over 40 and women under 35 stay the same? I would like to know if freezing impacts the embryo quality for older women knowing that they are not the best?

Pregnancy rates for ladies over 40 are less than for ladies under 35. Under 35 is considered the group of patients who have the best chance of pregnancy. In the UK, the regulators split that into all the different age groups. You’ve got the under 35s, and then you’ve got the 35s and 36s, and then you have the 37s to 39s or the 40s, and then you have the over 40s. It’s because the chance of pregnancy does decline quite steeply once you get over 40. I think, in general, the chance of pregnancy using fresh or frozen embryos would be lower.

A good part of this question is the fact that you’ve recognized that there would be a possibility of a poor quality embryo because the eggs are older. The only thing I can say would be that only embryos that are of a certain quality are suitable to be frozen. There’s also a chance that the embryos may not be suitable for freezing in the first place, and those that were suitable for freezing would be of good quality. What’s happening within them from a chromosomal point of view is unknown, but if they’ve met all the criteria to be frozen, then there is a good chance of pregnancy. But it is not the same chance as under 35 or under 40.

I have frozen my eggs at 40, and I am wondering if the quality will stay the same after thawing. I heard that older eggs usually are very fragile.

Yes, that that is possible. Egg freezing is not as stable as embryo freezing, but it’s getting better and better. Working in the laboratory we have seen that the eggs that come from older ladies are not the same quality as the younger groups that we were describing. I don’t know how many eggs you had. Normally, if you were going through treatment, they would thaw quite a few of your eggs depending on the program, and depending on your circumstances, they most likely would take quite a few eggs out if you have them.

If you have 16, they may decide that they should take eight out and they work on eight, or they may decide depending on your circumstances, it should be fewer or more than that. What they would do is fertilize them and grow them. Then, take it from there and see what the embryo quality is like.

I have stage four endometriosis. We did stimulation last month, and currently, we are preparing for frozen embryo transfer. Probably next week. It will be a month since stimulation and six months since my laparoscopy where one tube was removed. Do you think my body has a good chance of pregnancy and was the waiting between stimulation, and transfer alone enough?

This is a question for a medical colleague. I’m afraid I wouldn’t be able to comment on that. I’m a scientist, not a medic, so I’m very happy to take that question away, and we can respond to you directly.

Regarding the eggs that would be moved, it is to not have a sick child or many miscarriages. I just wanted to check that it’s not too much freezing and unfreezing, so it might be better to stay here.
So this is going back to the PGS question and moving them to another clinic because that PGS process was illegal in the country that you are in.

To move embryos they are not thawed, they are transferred frozen, so if you worry that they would be thawed, and then transferred and then frozen once they got to the center that you’re transferring them to, that’s not what happens. They stay frozen the whole time they’re transferred in a little bit of liquid nitrogen, but also the vapor, which is still very cold. It’s minus 190 degrees, so they never warm. I mentioned we call the thawing warming, so the unfreezing doesn’t happen until you’re ready to use them. I’ve just thought that the PGS of frozen embryos does involve unfreezing, but that’s nothing to do with moving them to another center. They would have to be thawed, and then they would have to be left for one or two hours to assess whether or not they are fully recovered and survive the freeze, thawing process.

Then you would proceed and do thePGS by removing some cells, and then you would have to re-freeze them. If you were moving your eggs to do the fertilization, you’d thaw the eggs, you would then fertilize them and then grow them up, and anything’s suitable. The moving process will not change the whole process apart from the fact that where you are now, you’re not able to have PGS, so I’m assuming, what you mean is that you would have your eggs, and then, you would thaw them and have ICSI and then not have any genetic testing, but you would have an embryo transfer from those warmed eggs. That means there is one freezing process less, so that’s the normal process for frozen eggs.

You have your eggs that have been frozen, you thaw them, you have to have the ICSI process. If you’re having frozen eggs, so you do the fertilization with ICSI, you then grow them up to day-5, and then, the best embryo goes back, and any other suitable embryos would be frozen. It means the only extra freezing would occur if you’re having the genetic testing, and you do have to freeze the embryo after you’ve performed the genetic testing.

You freeze it and wait for the genetic result, and then you thaw them again to plant them.

Do MI eggs usually survive thawing at the same rate as MII eggs?

In the UK, the centers I’ve worked in, and the centers I know don’t freeze M I eggs. So just to explain for people who may be not sure what this means. A mature egg that has undergone all the maturation processes and is of a suitable maturity to fertilize at the metaphase II stage, and we calI MI. We use this as a grading system when we’re preparing eggs for ICSI, so we only inject MII eggs because MI eggs can’t fertilize. But obviously, there are places in the world that may freeze MI eggs and then do maturation afterward. This procedure is not routine yet. Some centers are trying to develop it, but it’s not something that has taken off. I do know some centers that have studies or had studies that were looking at maturation processes.

In the beginning, will you explain how you can have fresh embryos and how long they stay fresh? I’m 48, and I’m single. Will you recommend to use embryos better than to select or have a donor and sperm donor? Can you choose the nationality of the donors of the embryo?

So you’re 48, and you’re thinking about embarking on IVF treatment using my fresh embryos, I think you mean using your eggs to create embryos and have those used in treatment. At 48, it’s very unlikely, that you would be able to use your own eggs for treatment, and it’s not just a case of the fact that you know our egg quality declines as we get older. Possibly, we wouldn’t even get any eggs in a 48-year-old patient.

I think that your options would be to have an egg donor, and as you’re single, you can choose a sperm donor. That depends on the clinic and the country you’re in, whether or not that is a simple process. I can’t see why anyone would object to you choosing a donor of a different nationality. I can’t see why that would be an issue, but that’s something you would have to question with the center that you go to.

Do you think that different items and solutions can affect freezing and thawing embryos?

Yes, I do. I’ve used various solutions, but also various freezing systems. By the system, I mean the straw that we place the embryo in. My choice would always be a frozen system, where the embryo is in a completely sealed unit. Some systems are open, and although there haven’t been any issues recorded with regards to safety, that’s not a device that I’ve always felt very comfortable with.

But I know they work perfectly well, and some people believe the fact that there isn’t an outer sheath means that the survival rates are higher. But survival rates now in a good freezing system is at 90 percent. I’m happy with that, but we do specifically select the freeze media.

Media is the solution that we want to use in a lab, based on the evidence and the survival rates, and we move from one to another if something else comes along, and there is evidence that the survival rates and pregnancy rates are improved. It’s something that we’re always looking into and improving in our laboratories.

Is the success rate when thawing embryos the same as when thawing eggs?

I mentioned earlier that eggs are not as stable as embryos, so now, they don’t survive as much. I mentioned before when I answered one of the questions about if you had the 16 eggs, they may thaw, and that’s not only to do with the fact that you want quite a few eggs to be able to fertilize them and create the embryos and then grow them up and have the choice.

It’s also because the eggs are not as stable, but as time’s going on, you know the eggs are improving the survival rates, and pregnancy rates with the eggs are improving, all the time, but are not as high as they are with blastocysts. Even though it’s the same process we use. We vitrify eggs, and we vitrify embryos; it’s just a few adaptations. The actual freezing process is slightly different because the eggs are not as stable.

If I have leftover embryos after IVF. Do clinics usually charge per vial or one cost for all of them regardless of how you want to group them?

This is referring to how the embryos are frozen in the device that I would have mentioned earlier. That depends on the clinic.

Normally, from my experience, you would have the charge based on if one or ten embryos got frozen, but that might not be the case for some clinics. It might be a different charge per embryo, the cost varies depending on how many you have frozen, so it might be cheaper if you only have one frozen as opposed to 10, rather than one cost for the whole lot. Perhaps if you’re looking at clinics that you want to have treatment in, that’s something you can do.

Do you usually know the age of the embryo donors, and are they always real couples?

You do get told the age of the donor. In the UK, there are certain bits of information that you can find out. In the UK, embryo donors need to be 35, or under. You get egg donors who are single women or married women, or divorced women. All sorts of people put themselves forward to offer a donation, and they don’t have to be in a couple. They also don’t need to have had children themselves.

Do embryos from ICSI survive thawing at a lower rate than embryos from IVF? 

From my experience no, there’s no difference. The survival rates are roughly the same, and as I mentioned, a good freezing and thawing program in IVF centers should be in the 90%, and I haven’t come across one being more susceptible to damage from the freeze-thawing process than the other.

Why should frozen eggs be fertilized only using ICSI after thawing? I’ve heard that ICSI could damage the egg.

The process of egg freezing means that the cells that naturally surround the egg has to be removed, and the egg requires those cells to be able to fertilize, so for IVF treatment, the sperm makes its way, and there’s lots of chemicals and chemical reactions as it works its way through all those cells to reach the egg and without those cells being there, it can’t fertilize.

The egg’s survival is based on those cells being removed, so without the presence of those cells, you can’t do IVF, so ICSI is your only option in terms of damage to eggs. In the UK, the damage is acceptable up to 10, but in reality, it’s more likely between five and ten percent of eggs can be damaged by the actual ICSI process.

Just in case people don’t know what ICSI is, that’s where we take one sperm, and we inject it into one egg using a very fine needle. So it’s quite invasive. You are pushing a needle into the egg. Survival rates are normally between five and ten percent. That can alter if the egg quality is poor because we have touched on that. So poorer eggs may have a higher chance of damage and perfect ones lower.

Do you have frozen donor eggs? If not, do you buy them? Do you have a donor database?

No, we don’t. We have ladies who come to the center because they wish to donate their eggs, but we don’t have a donor bank. There are donor banks around the world. In the UK, the law makes it very difficult, so it’s not something that can’t be done, but it’s also something that isn’t routine. There aren’t national or international donor banks in the UK, but there are special companies.

If you have a look on the Internet, there are donor banks that can provide them, and they ship them throughout the world. Again depending on what country they’re shipping to, you’d have to look into some specific information. The clinic you go to would give you advice on whether or not they would be able to accept those eggs.

That’s the same for the UK. It doesn’t mean we can’t accept them, it’s just a process where you have to, depending on where they’re coming from, do lots of checks and make applications to the regulator. Our center does not have a donor database, but we do have egg donors, and we do treat patients wanting to have treatment with donor eggs.

Do you show photos of the donors and some details?

Photos are not allowed in the UK. That’s not possible. I know in America, you can get photos of some sperm donors or egg donors and get photos of them at various stages of life, i.e. when they were babies and toddlers and children. The information we can provide would be hair color, skin color, eye color if their hair is straight or curly, height, built, some details about their interests and their occupation. That’s about all that we can provide to recipients in the UK.

However, in the UK, when a child born from donation reaches 16, they’re able to be provided with further details about the donor, and then once they get to 18, they can make an application to the HFEA and find out who the donor is. They can get full details, so we don’t have anonymous donations in the UK.

Why would you freeze eggs if they didn’t turn into embryos?  

Well, they do. They do turn into embryos. Some people don’t have any choice. There may be a single woman who hasn’t got a partner and wants eggs to use in the future. It could be somebody who has found out that they need to have chemotherapy, so it might be a process where everything is very quick, and they have to undergo the egg freeze before they start chemotherapy.

Many centers in the UK and around the world may give patients the option of freezing eggs or creating embryos. If you create embryos then, they also belong to the man, and if it’s not a stable relationship or the relationship breaks down at a later stage you may then be faced with not being able to use the embryos in treatment. If the partner who’s created the embryos decides in five years that he doesn’t want to have children, then you wouldn’t be able to use those embryos, whereas eggs could be then fertilized with the sperm of a new partner or a donor.

Then you have the possibility of using them, so that’s why you would have frozen eggs instead of embryos. Normally, when you’re counseling a patient, you have that question with them. There’s always the possibility that eggs might be a better option than embryos under specific circumstances.

When would you have ICS over IVF?

ICSI would be suggested, if there were any male factor issues, for example, it could be low sperm count, it could be surgically retrieved sperm, maybe some of the parameters that we measure may not be ideal. IVF needs good quality sperm, and the difference between the two is very extreme.

With IVF, you prepare the sperm, and you’re looking at a concentration of a hundred thousand sperm per ml for each egg, and with ICSI, you need one good quality sperm for an egg, so they know the extremes are very different. In some people, the sperm just is not good enough, and it has to meet certain criteria to be able to have a chance of fertilizing through IVF. It might also be people who have had failed IVF, so they’ve had failed fertilization following IVF treatment. We would then recommend they have ICSI because we know that the IVF hasn’t worked.

Also, if there’s ever any indication that ICSI is the better option, you do tend to stick with the ICSI. Once there’s been an issue with a sperm sample, you do tend not to risk having IVF, and the chance of a failed fertilization. Again this is on a case-by-case basis and everything is looked at to see what is the best treatment for the patients.

I’m a single woman going through IVF, and it was thought a better rate of pregnancy for IVF than ICSI.

Probably as a single woman, you’d be having donor sperm, so you haven’t got any specific problems. I’m assuming you’re having treatment because you’re a single woman without a partner, so you need to go through this treatment to have a baby. So, there are no underlying fertility issues apart from you being single, and you’re not with a partner who would provide sperm. In that case, IVF would be the option that we choose for you.

If you came through and you had IVF, and it was a failed fertilization, there’s a possibility that the donor sperm may not be of a suitable quality on the day. Therefore they would convert it to ICSI again to rule out a higher chance of failed fertilization. But for a single woman coming through for IVF using donor sperm, the first option that we would offer would be IVF rather than ICS. Success rates with IVF under these circumstances are very good.

How soon after a failed implant can you try again with a frozen embryo?

Well, there’s no reason why you can’t go through the following month. You do get some people who have a failed implantation, and they go through with the next cycle. On the other hand, you get some people that try and recover from the whole experience. It’s not just physical but psychological as well.

You may need just a month or two to fully recover before you embark on a frozen embryo. As far as I know, there’s no physiological reason why you couldn’t just continue with your treatment, that’s something that your clinician would advise you on. I know that some centers may have different protocols. Some centers may insist that you do wait one or two months, but again, as far as I know, there isn’t a physiological reason why you would need to do that.

Do thawing embryos from day 3, 4, 5, and 6 have the same success?

I did mention in my presentation that over the years, the survival rates have improved. It is because we introduced the vitrification of the blastocyst stage. The blastocyst stage is 5 and 6. Those embryos do have a better survival rate over the day-3 or day-4, that has been shown. It’s also quite rare for people to freeze on day three and day four nowadays and on the earlier stage, which is day one at the just fertilized stage.

Between day-5 and day-6, the protocols are normal, you want your blastocyst to be fully expanded, like the ones I’ve been showing you on day-5, and you give yourself the extra day, which is day-6 to give the blastocyst the benefit of the doubt, just in case. It’s just a little bit slow, it just needs a bit longer.

So the survival rates of day five are higher than day-6, and I’m sure some programs say that they have no differences, but when I was looking at the survival rates, which are up in the 90s, we’re finding that the survival rates and the best chance of pregnancy would be from a day five, but you do still get pregnancy from a day six embryo, which is why we do leave them until day six. We also have the quality to take into consideration, as well. It may just be that the embryo was just a little bit slow, and it was a really good quality by day six.

If they freeze embryos in solution from one company and when they come to thaw they don’t find the same company and thaw embryos by other company’s solution does this affect the embryos?

In theory, no, it shouldn’t be a problem. We are never 100% sure about the recipe from different companies for their free storing solution, and the safest thing would be to go by the manufacturer’s recommendation, so if an embryo was coming to our center that had been frozen somewhere else, let’s say solution A. We use solution B, we would buy the thawing solution that is specific to the embryos to continue with the treatment. We wouldn’t use our own solutions of choice because we follow the manufacturer’s recommendations to make sure that nothing goes wrong. My advice would be to thaw them in the thawing solution that the manufacturers recommend that you use.

Authors
Karen Schnauffer

Karen Schnauffer

Karen Schnauffer is a Consultant Embryologist with a career spanning nearly 25 years. She has a huge amount of experience within the world of IVF, and not only being a working embryologist has also been instrumental in setting up four IVF laboratories, and introducing new services and new technologies in the world of Assisted Conception. She is also responsible for providing training to many embryologists from the UK and abroad over the last 23 years. Karen has previously been responsible for leading the largest embryology team in the UK and was the first person to be appointed as a HFEA Person Responsible over two separate IVF centres. She is frequently approached by colleagues, both nationally and internationally, for advice and support, and has been invited to sit on various expert groups for the HFEA and within the commercial sector. She has held numerous positions for the Association of Clinical Embryologists and was a member of the steering group to amalgamate the professional bodies; the Association of Biomedical Andrologists (ABA), the Association of Clinical Embryologists (ACE) and the British Andrology Society (BAS) to form the Association of Reproductive and Clinical Scientists (ARCS). For the last four years Karen has also been the Programme Chair for the annual Fertility meetings for the Association of Clinical Embryologists and now continues this role for the Association of Reproductive and Clinical Scientists. Karen has a strong interest in research and although her passion is in the world of human IVF, she has previously successfully developed an ICSI programme in horses and produced the first time-lapse images of equine embryos.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is an International Patient Coordinator who has been supporting IVF patients for over 2 years. Always eager to help and provide comprehensive information based on her thorough knowledge and experience whether you are just starting or are in the middle of your IVF journey. She’s a customer care specialist with +10 years of experience, worked also in the tourism industry, and dealt with international customers on a daily basis, including working abroad. When she’s not taking care of her customers and patients, you’ll find her traveling, biking, learning new things, or spending time outdoors.

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