Ask the expert: egg freezing on the rise - all you need to know...
Seems to us, that egg freezing is on the rise. So, we sat down with Harley Street Gynaecologist and Obstetrician Mr. Mahantesh Karoshi to discuss the trends he is seeing in his clinic (a big rise in the last two years in particular), what he thinks is behind the rise plus a look at the new technology and its advances. On top of this, we go through the process in detail: when to do it, what to expect, the pros/the cons, what ‘success’ looks like and what you can do if you think this is something for you….
But before we dive in: What is egg freezing?
This is where eggs are extracted, frozen and stored unfertilised (vs. fertilised embryos).
*** PODCAST ALERT: If you prefer to listen to the interview with Mahantesh in full click here for our podcast (or search Better Babies on all major podcast providers) or read on below for the key highlights….***
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Let’s start a the beginning with some context: What is the background to egg freezing? How did it start?
It actually all started with the birth of first IVF baby 40 years ago. The success of this process gave confidence to do more than just direct IVF (which started with fresh embryos). From there they started to experiment with freezing sperm samples and found that the process of freezing/unfreezing was successful. Even more interesting was that it was found that frozen embryo transfer (embryo = fertilised egg) worked better than a fresh embryo transfer. Next the goal post was moved to freezing eggs which also has evolved and has proven very successful.
Frozen embryos doing better than fresh? Really? Why?!
The issue with fresh embryo transfer is that the obtaining eggs involves hormonal stimulation which can impact the endometrial lining. This is the lining where an embryo will hopefully implant and therefore needs to be in optimum shape. If you have just had stimulation (which is the case if you’re transferring fresh embryos) it can make it difficult for the embryo to implant. By freezing the embryo you can allow time for hormones to settle and the endometrial lining to return to normal (a gap of 1-2 months) encouraging an embryo to implant.
Egg freezing: is it on the rise?
Yes, it is happening more. The typical patient coming into my office is well educated and informed, typically they have had friends who have done it and they don't want to ‘miss the boat’. The last five years it has been slowly building in terms of popularity, but, in the last two years in particular it has really grown in popularity. Now around 50% of the patients coming through my door are at least exploring the option.
Why is this? Greater awareness, more socially acceptable, more trusting of technology or are we just getting older when we consider having kids?
The biggest thing seems to be social awareness and people being increasingly open and trusting the procedure which is in reality relatively simple. Having that security to ‘live freely’ and not feel so worried about the constraints of age and being able to have a child is also increasingly appealing. Boundaries around how and when we have children are certainly being moved.
What does the ‘perfect candidate’ for egg freezing look like?
The main thing to remember is that the aim of egg freezing is to obtain a genetically normal embryos. Therefore the single most important criteria is age. Age 25 is the perfect age because at this point on average around 80% of the eggs released are genetically normal. That means that say 8 out of 10 eggs collected will be viable and chromosomally normal with a decent chance, once fertilised, of developing. At this age 50-60% of fertilised eggs will likely make it to a viable pregnancy. From then onwards, you are in decline. At age 35 on average 50% of your eggs are genetically normal and then 36-40yrs old it drops to 35% and then between 40-42 it drops to 20% and post that it is less than 10% that will be genetically normal.
How do you find out which eggs are ‘genetically normal’?
The technology exists, it is known as a pre implantation genetic diagnosis or screening. You take one or two cells from a day five embryo just before it gets frozen. Once we have the results, we know which are genetically normal and can choose to implant these over the others. When you transferring genetically normal embryos the rate of implantation success grows up dramatically to as much as 90%. Without the test you get a lower rate of implantation success, particularly if you are older. It essentially allows us to pick the eggs that have the greatest chance of success.
Do you automatically get this screening done with the egg freezing process?
When you decide to get your eggs frozen you do not automatically get your eggs tested. The process is: day five embryo (five days after the frozen egg has been fertilised with the chosen sperm) is tested and you have to pay extra for this. Most IVF clinics will at least offer this. Arguably it is better value for money to do this as it means that the chances that the cycle works first time around is higher.
Is there risk of damaging the embryos by doing this testing as you are taking cells from them?
So far no evidence of this has been shown, and in fact rates of implantation are higher with genetically screened embryos. In fact the consensus is increasingly for this screening to take place rather than not.
Is this even more important with age to do? You said that there is higher chances of genetic abnormalities as you get older:
Yes. For example, when it comes to egg donors they are typically university students or younger people which is part of the criteria you match to become a donor. When you go through egg donation you’re not offered this because they know that on average 80% of the embryos will be genetically normal.
Is there more egg donation going on as our lifestyles and circumstances change?
That is certainly the case. It is something that is highly worth exploring especially if you’re older as typically there is much higher chances of success the younger you do it.
What happens if you are older, can you still freeze your eggs?
Freezing eggs is an invasive intervention so you shouldn’t take it lightly. However, being older is not a reason to reject. Generally speaking at +40 years old many clinics will not want to proceed because of the high percentage of eggs that will not be viable which makes the risk/reward of the process much less attractive. Ideally you need to harvest 10-20 eggs because and less than that is not enough to really make it economically viable as on average you get at least a 40% drop off rate. Up to 40 is ok but ideally you want to be between 25-35 years old when you do this.
Ideally you want to harvest 10-20 eggs - why that number?
You typically get a 40% drop off rate as a combination of genetic abnormalities or other factors so you need enough still to be able to use.
Thinking about some of the common terminology that is used. What does ‘day 3’ or ‘day 5’ mean in the context of egg freezing?
If you’re going for an IVF cycle you’re thinking about embryos ie. fertilised eggs. Day 1 is the first evidence that putting egg and sperm together has achieved fertilisation. Once you see evidence of two cells (ie. a cell division) that is evidence that fertilisation has occurred and that is classed as ‘Day 1’. They then start to multiply. While this starts you see different morphological factors. You also start to see abnormalities develop and you can see the quality of the embryo by day 3-5. If there is an abnormality they call it a ‘stopping of further growth’. If the embryo is biological normal or uploidy it will continue to grow from day 3 to day 5. If you are plus 40 majority will stop growing from day 3 (the ones that stop growing are known as aneuploidy). So if you make it to day 5 we can have confidence that it will continue to do well following that. That is also why you tend to screen for genetic abnormalities from day 5.
Some people get day 3 implanted and some get a day 5, why the difference?
You have lots of day 3 embryos and less day 5 as you get this drop off rate. Some clinics believe that you are more likely to create a more biologically viable environment by implanting earlier and therefore more of the day 3 embryos will survive internally than they would in an artificial environment. However, generally speaking the clinical research does not support this. The ideal scenario should be day 5 embryo transfer, that typically yields greatest chance of success as it is a stronger more viable egg.
Grades are given to embryos: what is the difference and does it relate to age?
Yes. They look at different parameters: how the cells divide, how the cells divide, cell wall thickness for example. They also look for ‘cloudiness’ of cells or ‘cell debris’ when considering how you Grade the embryo. The higher quality the higher the chance of success. When it comes to age, a 25 year old is more likely to only produce ‘Grade A’ embryos but a 40 year old highly likely to produce majority Grade B or C embryos.
The process: what does it actually look like, what is the actual process that you should expect?
The simplified version is this: STEP ONE: you need to do two things before egg freezing cycle can even begin. First a blood test to test your AMH level (click here for all you need to know on AMH) essentially this measures your egg reserves. The second thing is an ultrasound to see how you ovaries are functioning (any cysts etc). Why these two? AMH will predict how you will respond to the ovarian stimulation. If you have a reading over 15 then on average you will use a standard dose, less than 15 you use double the dose. With PCOS a patient will typically have a high AMH, so in that case you use half the dose as you have risk of hyperstimulation. The initial dosage however will be monitored to see response so this is just a starting point. If the response is suboptimal you will alter the dose.
What about the drugs that are used? How do they work?
These are used to mature the follicles. You produce as a woman FSH which is known as Follicle Stimulating Hormone. It does what the name suggests as induces immature eggs (or follicles) to mature for ovulation. When it comes to egg freezing you want to induce far more than normal the amount of follicles to mature as you ideally want to collect between 10 and 20 eggs. So we give more FSH in order to stimulate greater maturation.
What are you looking for when you look at the ovaries initially?
Imagine this. We start to give you FSH injections, but how do we know you are responding? We need to get a baseline look at your ovaries to see your starting point. From there you can get a proper picture how things are changing depending on follicle growth etc and then you’re in a better position to alter the dose and monitor its effects appropriately.
What is STEP TWO from this point?
A video to show you how to inject these hormones. Usually the injection phase lasts around a week. After this point we do another scan to check the level of response to assess the response to the dose we have given and adjust if required. Usually if you’re a good responder you produce follicle sizes from 12-16mm: that is the aim. If you get to that, we count and if you have 10-20 that have reached that size then your goal is achieved.
Are these injections painful?
They’re not that bad. When you say injection you think pain but it is usually more fear than actual pain.
Do you have to start these injections at a particular point in your cycle?
Yes. We start by developing ‘artificial synchronicity’ - we biologically reset with birth control pills for a month to reset the cycle and give you an artificial period. Day one (when you get your period) is when the scan takes place to see if you have any follicles/cysts in the ovaries and to see the starting point. This is the baseline scan. At the same day this is when you measure AMH to decide the dose of the stimulatory injections. Following this you are given your pack of injections to take away and administer for seven days.
STEP THREE: After the injections what happens next?
You have a scan on day seven. Ideally you have grown between ten and twenty 14-18mm follicles, then you stop the process (you don't want the 18mm to become 20mm as otherwise you start to ovulate on your own). To do this you give Anti FSH injections so that further stimulation is blocked and the process is halted to give you time to then collect the eggs. You can then plan the egg collection at a convenient time usually 36 hrs later.
What about the risk of hyperstimulation if you have Polycystic Ovaries?
In the modern era hyper-stimulation (where you produce far more than 10-20 eggs something that a person with PCOS can be prone to) is becoming less of a challenge because you can adjust the dose (now less than 1-2%) so it is not something we worry about so much anymore.
STEP THREE: The collection process: what does this look like?
Ahead of your egg collection day you stop eating the night before as you will be sedated for the procedure (although you wont be put to sleep). In terms of the process itself: it is guided by vaginal ultrasound. However, the probe itself is a modified version with a special device which enables you to pass the needle in order to puncture the follicles and aspirate the eggs for storage in the test tubes. Once the eggs have been collected in this way, an embryologist will check and confirm that the aspirant contains an egg. From that point they will be numbered and taken to be frozen.
How long does the process take?
This process takes around 30-45 minutes depending on your response and how many eggs you have. If you don't have as many as ten, you may have to do what we call ‘egg banking’. This is when you go on to do a second or third round so you get closer to the ten to twenty required eggs.
How will you feel after the process?
Obviously there has been a lot of hormonal stimulation during the process, we have taken control of the cycle artificially, so you will feel bloated and a bit bruised, plus there is usually an emotional reaction depending on what you have managed to collect. One thing to bear in mind there is a 1-2% risk of bleeding (it is an invasive procedure) from the collected surface of the ovaries, if this occurs you may need a keyhole surgery to address this. It is rare though.
How do you know if you have a bleeding issue following the procedure?
We don't allow patients to go home straight away, usually we keep them in for 2-4 hours to make sure you’re feeling well and there have been no complications. However, if you do start to feel unwell, throwing up/a lot of pain, this is when you should go straight back in and contact your doctor as soon as possible.
How long does it take to adjust back to normal?
In terms of your cycle, it is usually around 6 weeks to settle down.
In terms of ‘success’ it used to be the perception that freezing embryos (fertilised eggs) was seen as better than simply freezing (unfertilised) eggs. Is this still the case?
Not anymore as technology has evolved. People have moved away from slow freezing to fast freezing of eggs known as Vitrification. The unfreezing process has a much higher rate of success 90% vs 50% previously and it is this vitrification process which means that freezing eggs vs embryos is no longer a worse option.
What can you do to put yourself in the best state ahead of egg freezing? Do you believe in antioxidants, avoidance of chronic inflammation, exercise etc as having a beneficial effect?
Yes. I think that it is absolutely worth taking care of yourself ahead of the process. Antioxidants, CoQ10 (click here for much more on this), green leafy vegetables, exercise, avoiding chronic inflammation are all good things to do.
Are there any risks to manipulating the cycle and using a lot of hormonal stimulation? What does science say about the consequences?
Usually you only do 1-2 cycles of stimulation so it shouldn’t cause long term issues. However, there are anecdotal reports and links to breast, ovarian, uterine cancer, but, it is not conclusive and short term use (ie. 1-2 cycles) does not appear to have long term health risks. However, repeated stimulations could indeed raise the risks. By repeated we are talking 5-6+ rounds.This used to happen more in the past before the embryo freezing technology evolved (more rounds were needed when fresh embryos were transferred) so the risks of needing this many rounds are reduced.
What is the average cost? Is there a big variance?
It is around £5000 for one cycle. Most clinics don't include drug cost, and they will be £5-800 depending on the dose. A higher dose will mean more expense. Usually the initial egg freezing consultation itself is for free.
What about the maintenance/keeping it frozen/how long do they last?
Usually first couple of years is included and then storage cost is typically £5-800/annum. They usually ‘last’ for ten years but frankly it is probably indefinitely. However, you have to bear in mind that practically there is a limit to when you can put them back in. The uterus gets less receptive as you get older. The uterus on average ages around 10 yrs later than eggs. In Spain the last embryo transfer is 50yrs and 11 months. In the UK there is no age limit. However, north of that that is not very common, there are associated complications as you get a lot older.
What about cost variance? Why are some clinics more expensive than others?
There is usually a price disparity depending on clinic location. The Vitrification process (the fast freezing) is now standard but there are different manufacturers who provide the technology some being more expensive than others, so that cost is usually transferred to the final price. There isn't typically much difference in storage cost/fees.
How do you choose the best clinic for you?
The first thing you should take a look at in the UK is the Human Fertilisation and Embryology Authority website. By law all the clinics have to publish their data including their mistakes, results etc. So it is a great resource to use to do your homework. The other thing to consider of course is that you have a good rapport and feel comfortable with your doctor.
What happens if you don't pay the yearly maintenance fee?
This is something I want my patients to carefully consider. There are always going to be economic factors that you may not foresee into the future, so, this is going to be an ongoing cost that you will have to pay the longer you keep your eggs stored so you should bake this into consideration when you go through the process. By law however, eggs cannot be thrown away just because the yearly premium isnt paid. However, if you don’t pay, and want access to your eggs you will have to pay the full amount owed before you are given access. Some clinics will allow you to pay the maintenance fee upfront for ten years to minimise the stress which is something to consider. You can also move your eggs between clinics - although that is expensive to do to transport them. It is doable.
Companies in Silicon Valley are offering to pay for employees to freeze eggs now. What is your view on this?
I think its a good thing. From their perspective it makes sense as if you become a mother in your early 30s for example you are taking away a chunk of time which is theoretically a time you would be highly productive as an employee. By freezing eggs you take the pressure off and allow focus on work while not having to worry about the biological clock. Bigger picture I think it is a positive thing for society because a person who has eggs frozen at age 30 will have a much higher percentage of good/genetically viable eggs than someone doing it at mid to late 30s so in my view it is a positive thing to offer as it is an expensive process for an individual but less for a large corporate.
From an age perspective, what do you personally think is a reasonable limit to allow a frozen embryo to be implanted even though UK for example doesn't have one?
I think for me personally, up to 50 is ok.
People may be freezing their eggs because we are increasingly living less ‘conventional or traditional lifestyles’. What is the next step from taking a frozen egg to a frozen embryo to implantation?
So, after the eggs have been stored you are given a choice to take to the next stage. Either you use your partner's sperm or you can choose a donor. In the EU you can choose an anonymous donor. In the UK it is a named donor. or a named donor. Now, that doesn't mean you know the name of the person donating. It means that when you child reaches 16 they will have the right to find out. This is why some people from the UK choose to go to Europe as they prefer the anonymity.
How does an egg become and embryo, what is the process?
Once again, ahead of this Preimplantation genetic screening can be offered. If you use a donor you can match skin, eye and blood group - blood group is most important to match as that can help reduce chances of rejection. The frozen eggs are then put into a Petri dish with the donor sperm and you wait overnight to see if fertilisation has occurred. The rest of the process is then similar to IVF.
If you’re using a donor egg or surrogate does it increase chance of rejection?
Yes. There are some clinics that will use an Immunomodulator which blunts the immune response as you are using foreign egg and sperm cells which you body has to accept. So first 12-14 weeks you are offered the drugs. The dosage will depend once again on your response.
If you’d like to find out more or to speak to Mr Karoshi direct please send us an email: Sarah@betterbabies or to book in to see Mahantesh direct: contact 108 Harley Street: please phone: 02075631234 or email email@example.com. Alternatively check out Mr Karoshi’s instagram: @gynaecologist_london.
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