Women over 40: what are your fertility options?

Chrysa Karakosta, MSc
Lab Co-Director & International Patient Manager

Advanced Maternal Age

Women over 40: what are your options?
From this video you will find out:
  • Is 40 too old for IVF?
  • What are the most important tests a patient needs to have to evaluate the ovarian reserve?
  • Can PGS (NGS) improve success rates in own egg treatment cycles in older women?
  • What are the possible reasons for repeated failed IVF cycles in older women?
  • When should I start thinking of egg donation?
  • How is egg donation run in Greece?
  • How soon can I start treatment in Greece due to COVID-19 as I’m worried that my fertility is dropping?


Fertility options for women over 40

Watch the Online Patient Meeting with Chrysa Karakosta, the Lab co-Director at Newlife IVF Greece and the International Patient Manager. Chrysa answered questions about motherhood options after 40.

Chrysa started her talk by explaining that nowadays, the majority of patients that come to the IVF clinic are over 40. The reason for this is that women postpone maternity due to focus on their career or lack of a suitable partner, and it’s an increasing trend in Western countries to start families later on.
The main problem with that is that as a woman’s age progresses, the oocyte quality decreases and the chance of chromosomal abnormalities also increases. In women between 20-30, the percentage of abnormalities is at 23%, while in women between 40-42, the percentage is already 62%. Therefore, the major issue for such women is their eggs and their quality. Another aspect is the number of eggs they produce, and with a lower number of eggs, there is a lower chance of getting good healthy quality blastocyst.

Therefore, the first approach is IVF with own eggs. It’s important to provide individualized treatment for each patient and find the best protocol to achieve the outcome, and perform only day-5 embryo transfers because then the final assessment of the embryo can be fully obtained. Sometimes, it’s best to perform PGT-A testing to make sure that only euploid embryos are transferred.

If IVF with own eggs fails, another option is egg donation treatment. Each country has its own legislation regarding egg donation, so the patients must make an informed decision and choose the best option for them. In 40-year-old women and older, the pregnancy risk exists, so it’s significant to be careful and not transfer 2 or 3 embryos which can result in developing gestational diabetes, hypertension, etc. Therefore, the clinical staff must always inform about the risks involved. All cases are different and should be looked at individually.

- Questions and Answers

Is 40 too old for IVF?

Absolutely not. 40 is not too late. The only thing that I’m going to point out is that if a woman starts the trial to have a child when she’s 40, she should not wait too long at the time before she should do at least some initial testing. If there is an issue and you need to perform IVF, it’s better to do it in your early 40s. This is because, as I mentioned earlier, there’s a huge decline after the age of 43 due to the dramatic increase of chromosome abnormalities in the eggs that we have.

What are the most important tests that one needs to perform to evaluate the ovarian reserve?

Nowadays when a patient contacts us I usually request them to have a blood test for an AMH and Anti- Müllerian hormone. This is a blood test that can be performed on any day of the menstrual cycle and it shows us the dynamics of the woman, basically what her ovarian reserve is. It’s more accurate than the older hormonal profile that women used to perform like FSH, LH, estradiol because it doesn’t get affected by certain things. The second test that is just as important, is a transvaginal ultrasound scan performed between day 1 to day 4 of a woman’s menstrual bleed and it’s called an antral follicle count scan. This is important because it gives us more information. It shows us the number of follicles that exist in the ovaries, but also it’s very important to look at the sizes. Depending on some sizes if a woman has two large follicles and many small follicles, she needs to be pretreated before she starts stimulation. Otherwise, if we start stimulation without pretreatment, the big follicles will grow very fast and the small ones we’ll never catch up. It’s very, very important for us to also have this image to be able to select the best protocol for each patient.

Can PGS (NGS) improve success rates in egg treatment cycles in older women?

I’ll start off by just explaining what PGS is. It stands for pre-implantation genetic screening. NGS is the latest technology that we use, it’s called next-generation sequencing. It is a technique where we’re able to check if the embryos that we have are genetically normal or not. This test used to be performed, or it can be performed on day three or day five of embryos development. It’s more accurate to perform it on day-5 embryos. It can help certain women, and I do point, that it is in certain women. We need to carefully select which people we perform PGS testing as it’s not suitable for everyone. We need to be very careful because PGS as a technique has its downsides. It is an invasive procedure in which we perform a biopsy on the embryo on day 5. We zap it with a laser, we take certain cells and send the cells for genetic testing. Studies have shown that 5 to 10%of embryos can be damaged during the biopsy, so we need to be very careful not to test it all, because it may damage the one healthy embryo that a woman has. Sometimes, we may not get a result from the PGS testing, because the genetics lab has not been able to amplify the material that they’ve received from us. And sometimes we receive what’s equivocal sort of results. It is a case of the mosaic embryos. So an embryo has both healthy and unhealthy parts in it. In those cases, these embryos can be used in certain cases, as a second option. It can improve success rates in certain women, but these women have to be carefully selected. Each case is different, we need to individualize each and every case.

What are the possible reasons for repeated failed IVF cycles in older women?

I’m going to start by saying that for every single IVF treatment cycle two main parameters lead to a successful cycle. 80% of it has to do with embryo quality, and 20% of it has to do with endometrial receptivity. When it comes to the embryo quality, the best way that we can possibly assess embryos is once we fertilize them in the lab to culture them to the day-5 stage. I know that there’s a lot of clinics and doctors that say let’s transfer the embryos on day-2 or day-3, but if we transfer them so early on, we don’t know their final assessment. We don’t know if the embryos can implant. For an embryo to be able to implant it needs to get to the blastocyst stage. There’s a fear there what happens if they don’t last in the lab and they don’t develop into blastocysts. We have the technology to be able to create a blastocyst. If any number a woman produces is going to survive in the lab and we have the good culture media, technology and the knowledge, so I don’t think that’s an excuse not to take embryos to day- 5. We as a clinic, take every single cycle to the last stage at the moment. Even in natural cycles, where we only get one egg. It is the best way to have a final assessment and find out reasons why certain treatment cycles don’t even reach the transfer. I think it’s good for the patient if they don’t have a proper embryo to transfer, not to perform a transfer. I think when we’re performing a treatment cycle, we also need to give answers to patients. We need to explain to them why it failed. Is it the egg’s fault, is it the sperms fault, do we see something in the lab? Things like this can be shown in the lab. For example, the paternal gene in the sperm, the effect of this gene on the embryo kicks in on day-3. If you transfer the embryo on day-3 they may be perfect, but they may stop developing after day three. So we definitely need to take the embryos to the day five-stage. A possible reason why we have repeated failures in IVF cycles may be chromosome abnormalities in some women. Many of the embryos that they have despite they look nice on day-5 may be abnormal. This is something that, unfortunately, we cannot change. It’s something we have to face as older women. But at least taking them to the day five-stage we allow nature filters to stop certain chromosome abnormalities, so we’re transferring healthy embryos on day five. The other reason for implantation failures may be poor quality not just genetically but how the embryo looks like morphologically in the lab. We see this sometimes. 20% of the success has to do with endometrial activity. Certain women also have a problem with receiving and accepting an embryo. Nowadays in certain cases, we also suggest that specific tests are performed. One of these is called the endometrial receptivity assay, and by performing this assay we can see if an endometrial lining is receptive but also the time the embryo is most likely to take to the lining. It gives us information that’s very important for a future cycle or when we’re performing a frozen embryo transfer. It’s not for everybody, as I said. We have to individualize every single case.

When should I start thinking about egg donation?

Egg donation is often thought to be a solution only for older women. We always have to remember that egg donation is something that younger women also have to use in certain cases. We have women that have premature ovarian failure, I have had cases where they’re in their 20s, and we still have to use egg donation. The second reason would be a very diminished ovarian reserve, if we see that the AMH levels are very low, antral follicle count is very low, if we try stimulating them, and we don’t get eggs or if we do get eggs and they don’t reach the blastocyst stage, or we have repeated failures. Another reason to move on to egg donation is a genetically transmitted disease that we need to bypass. One thing I definitely want to point out though, is I know it’s the easy way out because it gives us high success rates, but emotionally it’s the hardest type of treatment for a woman to follow. One thing that we need to point out, is that in women that have not decided that they are ready for egg donation, it can be delayed. Egg donation success rates don’t have to do with the age of the woman, it has to do with the way a donor is selected and the age of the donor. It’s important to know this information because sometimes it puts your mind at ease if you’re still considering own egg treatment cycles. It gives you the opportunity to be able to follow those own egg treatment cycles through and then move on to egg donation when you’re ready. It’s very important to carefully select the donor. You have to select the clinic that will do that careful selection for you and also that you do it in a proper way knowing all the facts.

How is egg donation run in Greece?

Egg donation in Greece is anonymous. You’re able to find out some information about your donor, her characteristics like height and weight, hair colour, eye colour, ethnicity if they’ve had past pregnancy. You find out a lot of information, but you cannot identify the donor, neither can the child even when they turn 18. The donor obviously cannot find anything about the recipients either. In Greece, according to the legislation we’re allowed to use donors that are under the age of 35. In reality, we have been able to drop the age to age to under 30, which means that we get better results. The legislation allows us to use eggs in three different ways. It allows us to use fresh egg donation, frozen egg donation or to do what’s called eggs sharing. We only use fresh egg donation cycles. This means that on the day of the donor’s egg collection will either have to have a husband here to produce a fresh sample so we fertilize the eggs or we’ll have a frozen sample and use that to fertilize the eggs. This means that we have the highest possible success rate because studies show that we have frozen eggs, we have a 10 % lower success rate. Certain clinics use frozen eggs because it’s easier to do it. It’s easier also to split the eggs between recipients. This is something that we do not do. We only use fresh egg donation cycles, the eggs of a donor go elusively to one recipient. This means that one patient gets a large number of eggs, which means they have a high probability of getting a good day five embryos. Not only just to transfer but hopefully to freeze the surplus. In the majority of cases, they’re able to complete their whole family through one donation cycle. One other thing that I’d like to say is that in Greece the costs compared to many other countries are much lower, so that’s another thing that is important to point out. The final thing that I want to mention is a new development that we have in Greece, actually a very recent one, there is a central database of donors. It has been a problem up until now in anonymous donation cycles due to the data protection acts for the donor. This is very good because it will enable tracking how many donations each donor does at different IVF clinics it will help generate a sort of traceability in the egg donation field.

My daughter was due to have her egg donor treatment in Barbados on 12. 04 of this month, the day before she was due to have her pre-treatment. It was all cancelled due to COVID 19. She will be 50 on the 3rd of June and has missed her window. Is there anything she can do?

Obviously, your daughter needs to speak to Barbados clinic and see if there are any new changes that the national authority there has stated. About age here in Greece at the moment what they’ve stated for patients who have been having treatment with us and were on that limit 50, is that we may possibly extend that period of treatment for a couple of months as soon as the restrictions are lifted. I’m not sure what happens with new patients that are over 50. It’s something that I would have to ask individually our national authority because I know that the regulation that they’ve stated exists for our current patients. I think the best thing to do is to contact the IVF clinic directly and ask them if they have news from their side.

I have been advised the DHEA is good for fertility for women over 40. Could you explain more about it?

There are a lot of other supplements on the internet, and I get a lot of questions. Some studies showed that the use of DHEA in older women may help increase ovarian reserve by a very small margin. For DHEA to have an effect we need to take it for at least three months according to certain studies, and sometimes by delaying treatment for these three months, we may have a decline in the fertility. My recommendation is that you could start taking it. I will not harm you, but whether it’s going to make a huge difference is debatable. I need to point out something that Dr Thomas, our medical director states, that a lot of the time the IVF world is also an IVF business. If there was a miracle treatment that we can offer to people to improve their chances, we would all do it. I wish there were magic potions, lotions, treatments that we could offer to magically improve ovarian reserve but unfortunately, there are not. We need to remember that the ovarian reserve may differ from month to month, so it’s not just saying I want to start treatment, we need to select the proper month to start treatment. A woman on one month may have an antral follicle count of 3 while we’ve seen initially that a month before she had an antral follicle count of 5. It’s best to wait at least four months or two to see perhaps that she has a better answer for follicle count and better sizes before commencing treatment. In the lab, if we manage to get one or two extra eggs, it makes a huge difference in being able to get to the blastocyst stage and have healthy embryos.

Can you tell us something about ubiquinol? Many ladies read ‘It starts with the egg’. How much should we know who should we follow what is written in that book?

There’s a lot on the internet advice. I know the specific book I’ve been asked about it many times. There are studies that state that they do help, there are studies that say that they don’t help. If it was something that was medically approved and a 100% sure we would offer it to every single patient and say definitely take it. It will not harm you. But I wouldn’t put my bet on it. I wouldn’t start ubiquinol and DHEA. If we delay the treatment for six months in the hope the results will improve, they may not have that effect. We need to be very careful because if we delayed treatment sometimes in women that are over 40, like 40 to 43, sometimes we may have the exact opposite of what we’re wishing.

At 46 years it is best for me to have an egg donor as I had a baby at 42, a miscarriage at 45. What is the best option my own eggs or donor eggs? 

I have to be honest that at the age of 46, unless you have an extremely good ovarian reserve and were able to genetically test your eggs, embryos once they were created. I would say your best option is to move to egg donation. Live birth rates at that age are low, and we need to also look at what the chances of you having a healthy pregnancy and not having miscarriages are. I would only suggest moving on to own egg treatment at that age if you have an extremely good of ovarian reserve. Some women do, and we are able to create a good number of blastocysts, which we’re able to test genetically and transfer a healthy embryo.

For women between 40-42, how many cycles of IVF, in general, do you need at your clinic.

The whole IVF world has changed. In the past, we used to say that we want to focus on cumulative pregnancy rates and do cycles, but nowadays with the technology and knowledge we have, we’re focusing on the time to pregnancies. We’re hoping that by carefully selecting treatment protocols, every woman will get the maximum out of her own ovarian reserve. She is able to create good quality day five embryos and transfer very good embryos that hopefully will give her a good chance at pregnancy. Nowadays, we do not see women doing 8 or 10 IVF cycles. There isn’t a specific number of cycles I can say for a specific woman until we see her medical history. Sometimes we see women who have had cycles in the past and don’t know whether to do their own cycles or move to egg donation. We need to see, their cycles to see, a lot of the things that we would like to have answers for have been answered because they’ve had many transfers on day two or on day 3, where we don’t know if she can create good quality embryos. We need to see your medical history, and I need to see your ovarian reserve and have more information about you to say if it’s worth you doing one, two or three more treatment cycle or if it’s worth moving to egg donation. It all depends on things developing in the lab and in the IVF unit, so if we see a woman that has very poor quality eggs, we will say this woman and explain to the couple that their chances are much lower than we were anticipating to see, and it’s not worth carrying on with the treatment. These are things that we need to see on an individual basis.

How do you ensure safety with the pandemic?

Europeans Association of Human Reproduction and Embryology has given us guidelines on how to move, but also our National Authority has given us instructions about safety measures. Obviously, all staff completed specific questions regarding how we move, how we act, how we live if we have someone infected in our families. First of all, we make sure that the staff is safe. We make sure that they don’t have any symptoms that we should know about. If we see that someone does have symptoms like coughing, a fever or something that relates to the viral situation, we stop them from working. We have split the IVF unit staff into groups. If certain members of staff do get infected, the unit will not stop working and offering treatment cycles. Visits to the IVF unit are only upon appointment for everyone, so only very small numbers of patients will be at the clinic at the same time. There are separate designated areas in the IVF unit where people will wait for their appointment. They will go straight in, and they will be seeing specific people. Everyone wears masks, patients and staff. Obviously, there is a hand sanitization. There are things in the lab that we do. There’s a whole list of things that we need to follow and radiations that we have. We have standard operating procedures that we’ve put in place and we will be following throughout the treatment. When it comes to international patients, we need to see first of all the guidance that we’re going to have from our Ministry of Health to see what’s going to happen, quarantine periods and then we will be able to discuss it. We will probably need to test patients for COVID before starting treatment. If someone is tested positive, they will not be able to proceed with treatment because this is done in order to make sure that everyone’s safe. There are specific algorithms that have been set by the European Society of Human Reproduction Embryology that is following. There’s a triage questionnaire that patients will be filling out two weeks before starting treatment when they start treatment and during treatment. So there are a lot of stages and steps that will be followed throughout this process. It’s going to make our lives much more difficult to cope with it.

Is there a cut-off regarding AMH level to do own egg IVF?

I wouldn’t say there’s a cut-off level. We need to see each individual patient because sometimes we do have women that despite having very low AMH levels still want to proceed with their own eggs. We will in certain cases, follow stimulation protocols and sometimes will do modified treatment regimes in order to try and get one or two eggs. I cannot see there’s a cut-off of AMH levels. I need to see, each patient’s individual history to be able to say if it’s worth pursuing. Also one of the things that we are very adamant on is we always give a patient their risks. We inform them of the risks of cancellation or that you will not reach an embryo transfer. The patient is fully informed about what’s happening at each stage. An important thing to note is that AMH levels show us numbers they don’t tell us anything about the quality. If you may have a younger woman that’s 35 years old and she has a low AMH level and is able to create two eggs after stimulation, those two eggs, because of a younger age, are much better than say getting five eggs from a woman that’s 45 years old, because quality-wise those eggs are going to be better. They’re going o have a higher chance of reaching the five-day stage and being chromosome-wise normal and healthy, hence our success rates will be higher.

Can you please give us some thoughts and advice on tandem cycles. I am 44 and my last AMH test in November was 5.6.

There are two different topics. Tandem cycles are something that we do not perform. We will not run IVF with own eggs and a donation cycle simultaneously. One of the main reasons is because of the way we perform our cycles. All our donations, as I said, are done with fresh eggs, not with the use of frozen eggs. The reason is that fresh eggs, that are fertilized on the day of the egg collection give you much higher success rates. Frozen eggs, give you a 10% lower success rate. Our legislation does not allow us to transfer an embryo created from donor eggs and our own embryo at the same time, so we usually say to patients it is best to finish a whole treatment cycle. Now regarding the AMH, we don’t have the units, so I cannot refer to it.

You mentioned you use the only day five embryos. What if the embryo doesn’t make it to day five. Also what grades of these embryos are you looking for?

Nowadays we have the technology, but if an embryo will make it in the uterus, we’ll make it in the lab as well. When we decided to move on to performing only day five transfers, one of the things we’ve had to consider as an IVF unit, was whether cancelling many cycles is going to impact us financially. What we saw was that there wasn’t a significant drop in the number of cycles we had or the number of transfers we performed. The reason why we state that we only do day-5 transfers is that on day-5 we actually know the final assessment and of an embryo. Just to give you an example, even in an egg donation when the eggs are from a 23-year-old woman we may have 10 fertilized embryos. It doesn’t mean that we’re going to get ten beautiful blastocysts. On day -3, we may have 8 beautiful day-3 embryos. Some of these will stop developing, some of these will not create good quality blastocysts. This is something really important to know because only a blastocyst will implant. It’s very important to get the embryos third stage also when we were able to perform chromosomal testing on day three embryos and day five and ruse. You would see that on day five we have a lower number of chromosomal abnormalities because simply nature filters certain embryos that have these abnormalities. Nature’s on our side. So why not use nature and filter those embryos and only transfer the quality embryos. I know it may mean that certain women may not have a transfer, but to be honest, with the woman that will not have a transfer because they do not have suitable blastocyst they will never get pregnant. So why perform that transfer and have a low chance. We were very adamant that you will only pay for the treatment that you have. So if the treatment cycle stops before your embryo transfer, you will not pay for the embryo transfer, because you wouldn’t have it. The second part of the question is what grades of these embryos we are looking for. I am an embryologist, and quite often I get reports or emails from patients and they’re saying: ‘I have top quality embryos’ and when I ask them for photographs I see different readings compared to what the paper states. Rating is a very personal thing. We need to be very strict on the grading. At New Life, we are very strict on the gradings that we have, because simply we need to know what quality embryos a person creates in order to be able to guide them. Not just for the cycle they’re having now but for future treatments. If a woman does not create a good quality blastocyst once or twice, we need to let her stop. This isn’t the right way. We’re not here just to perform cycles without end. We’re here to be able to guide people, to say this is the point where you need to stop. These are your chances, these are your risks of cancellation.

I have 5.6 AMH, but the consultant said the normal range was 6 to 25.

It’s probably in picomoles from what I understand. You have 5.6, so we’re talking about low fertility. I’m just looking at the different numbers here. I need to really know your medical history, apart from just your AMH. If you’ve had past cycles. It’d be great to see an antral follicle count scan. The scan is that will show us not just the number of follicles that you have, but also the sizes. I need to point this out because sizes are also extremely important. Many women sometimes send me an antral follicle count scan and we see seven follicles, and they’re great they have a great reserve, but we see that four of these are very small sizes. No matter what medications we will give, even the best of combinations from our protocols, even the best of medications, some of these follicles will not respond to treatments. So we need to be very careful in how we account it for our patients, in order, so they understand what their real chances are, how many eggs are expecting to get from a treatment cycle. That way, they can wave options and see what’s best for them. I would suggest performing an antral follicle count scan at the beginning of the menstrual cycle, between day 1 to day 4 of her cycle. I would suggest letting the doctor know that you need to know the accurate sizes of the follicles as well. If people can have images that are great as well because we can confirm the numbers that the report states. I’m more than happy to look at it if you send these things through. I’ll be able to write a personal email and even offer a one-hour free consultation, where we can discuss your case in detail.

Does the grading of embryo matter for better success?

I need to point out that when we see embryos on day five at the blastocyst stage, there are two things that we need to keep in mind. One is the grading, so how an embryo looks and we may have possibly a great embryo, a grade AA, grade B, grade C embryos, I’m trying to simplify things for people to understand, but also there’s the genetic component. I’m assuming the question is asking about the morphological criteria. It plays a role because a top-quality embryo has higher chances of implanting and sometimes higher chances of being normal. On that one, I am not going to be so adamant, because I have seen sometimes through genetic testing that even lower quality embryos can be genetically normal. But generally, grading does play a significant role.

I’m 43 with early ovarian failure, FSH of 76. What is my best chance of moving forward?

FSH is not an accurate estimation for us to see what your ovarian reserve is. At the age of 43, a level of 76 is quite high I would say. I would say the best bet is to move to egg donation. That would be my recommendation, but obviously, if you have more information and you can share that with us it would be good. Egg donation would be my first suggestion.

Do you think that melatonin can improve the oocyte quality when taken in the month before stimulation? What dose does your clinic use and does the slow release version work?

I’m going to get back to what I was saying earlier regarding DHEA and other supplements that I was asked about. Other studies showed that it could help but also other studies show that it doesn’t help. Melatonin has been shown to sometimes have a borderline improvement according to studies. But again it’s not going to work miracles. I don’t want people to delay their treatments because they believe the supplements are going to change the world. It can have borderline improvement, but it can’t be 100%.

What do you use for pre-treatment to ensure follicles grow from a similar standing start and avoid asymmetrical or uneven growth? Do you do oestrogen priming?

In older women, we need to select the protocol properly. As I said, if we have an antral follicle count scan showing certain follicles that are large and certain ones that are small, sometimes we may go with the long protocol. We start a down-regulation regime about a week before the menstrual bleed just to correct size. Sometimes we use oestrogen priming. It differs from case to case. It’s also important to select the proper stimulation in older women. If we have a lower ovarian reserve, apart from FSH, it’s very important to use a medication that has LH. LH is a primer to accept FSH, so sometimes we use Menopur that has FSH and LH, and we try to avoid sometimes using just FSH because this is a better modification for women that are younger and with a better ovarian reserve. Sometimes we also use antagonists during the luteal phase at the previous month. There various things that we use as I said. Sometimes we may suggest you shouldn’t start this month it’s not a good month for you, you should start the following month because we see something in your ovarian reserve.

At the age of 38 and AMH 1.07, what protocol do you suggest for stimulation? Mild one or a protocol with bigger doses?

Again my question will be what international units is the AMH measured in. I don’t believe in mild or bigger doses of stimulation as such. I believe in our stimulations we sometimes use a really high dose. From those patients we hear they had doses of 450 sometimes, I’ve even heard of 600. Nowadays, we don’t use such high doses, because studies have shown that such extreme high doses of medications don’t really make a difference. There’s a threshold up we should reach for FSH. In these cases, we believe in a balanced stimulation, so we take advantage of the maximum that a woman can produce and be able to get those eggs in the lab. I need to point out that if we see that on a woman’s antral follicle count scan she has two follicles, even if I were able to give her two tons of medications, she wouldn’t create more than one or two eggs. This is something to always have in mind. A lot of people believe that through IVF and through stimulation, we create more eggs. We don’t, we take advantage of what each one has so the best thing for us to do is individualize everyone’s treatment, care and take advantage of the specific ovarian reserve. When it comes to AMH of 1.07 in nanograms, it’s low, but it’s not very low. We need need to see the antral follicle count to be able to tell you what’s the best protocol for you. I am going to say this again and again, just based on an AMH level we cannot select the protocol because it may mean you have very small follicles and we need to advise you if these will not respond to treatment. When we see the sizes, then we choose your pretreatment. There’s a lot of things we need to see. So the best thing is to perform antral follicle count scan, it may be an extra cost to you, but it’s going to give you so much more information about your ovarian reserve and what’s the best way forward.

Could you provide your opinion on PGS? It has been downgraded but HFEA in the UK as there is not enough evidence to suggest its success?

If you were listening to how I started the discussion of PGS, I did say that it can improve certain success rates but for certain women. It is an add-on, and we agree certainly. We were extremely happy when the HFEA created on their web page this traffic light system and said no to certain add-ons because it was getting out of hand. A lot of IVF clinics were offering a lot of add-ons that patients were paying for. But they were not getting much information out of it. PGS should be used in specific cases. It should be used in women of an older age that have a low ovarian reserve, create a good number of blastocysts, and we want to limit the number of transfers they have. We only do a few transfers with healthy embryos. The great thing and I were going to keep this as a closing remark is I actually received an email today from a very good collaborator. In the summer, there is going to be an announcement that it may be becoming routine to be offering what’s called non-invasive PGS testing. Now, as it is PGS testing that we’re using is invasive. As I explained earlier, we zap the embryo with the laser, we take cells, so we may be damaging the embryo. We have a 5to 10 %chance of damaging embryos, so if a woman only has two embryos, it’s risky to perform a PGS testing. In the summer they will be launching what’s called non-invasive PGS testing. How will this work? As we culture the embryos in the lab, we will be able to take the culture media and send that for testing without touching the embryo itself. That fluid will be tested and will give us information if an embryo is normal or not normal. If that’s launched and if it has the accuracy that we want and we’re able to implement it in routine IVF treatment cycles, I think it’s going to be the future. I think that’s going to save a lot of women from unnecessary transfers and it’s going to give us better results.

I have very low AMH 0.2 and two failed IVF cycles. Should I seriously consider egg donation? I am 43.

I believe that egg donation would be your best option. It would give you much higher success rates I need to of giving you an idea about success rates just, so you understand what we’re talking about. In women aged 42 and above success rates are much lower. New Life success rates are slightly above 20% in women aged over 42, but this isn’t a highly selective population in women that can create eggs which get to blastocyst stage, that we do perform tests and transfers. In egg donation, when we transfer to de-facto quality blastocysts, we have a positive pregnancy rate of 68 %. So you can understand these are the worlds apart. I believe that egg donation would give you the best success rates. Obviously, if you’re not ready for it, we need to look at your past failed IVF cycles, see why these failed and see if there’s any room to improve this result. If you ask me what my suggestion would be it would be to consider egg donation.

How long in advance should I prepare for a cycle? Does no alcohol or diet make that much difference at nearly forty-three? Can we do anything to improve the chances, or is it now luck?

Preparing for an IVF cycle is like preparing for a pregnancy. You need to imagine yourself as if you’re pregnant. Would you like to enter a pregnancy being overweight? It’s best to go onto a diet, if you’re overweight lose weight, have a healthy BMI because we’re really preparing our bodies for pregnancy. Everything that affects our healthy lifestyles like alcohol, smoking should be stopped. The earlier you stop, the better it is for you. There isn’t a timeframe of one or two months. I believe that trying to have a baby we should lead a healthy lifestyle, eat proper food, do proper exercise, try and limit alcohol, cut smoking. We should do everything we can to prepare our bodies for pregnancy.

I am 45 yrs old – over the last 7 years, we had 9 own egg IVF cycles (around 14 embryo transfers from these cycles) with implantation only once five years ago, unfortunately, this ended in a miscarriage. Since then, I have had aqua scans and hysteroscopy and basic immune blood tests (Chicago tests) with no real issues showing. Slightly raised NK cells, but not major and my clinic treats empirically with steroids anyway. Last year, due to my age, we moved to a donor egg cycle, which gave us 6 excellent/good quality embryos (all frozen). From this, I have had two transfers (1 x AA blastocyst each time), but both negative. Should I have any other tests before transferring the next embryo? I feel there is something else wrong since two top-quality young donor egg embryos have not worked. In follow up to my previous question, I should have mentioned that I also had an ERA test, which came back as receptive at the standard 5 days of progesterone.

My comment on this one is to hang in there because you’ve only transferred two embryos. They are donor embryos, which means that if the clinic that you had treatment with selected the donor appropriately, these embryos are good quality. I would just pursue further treatments. You’ve only transferred 2 embryos. With another clinic,just to give you an example, with the first transfer of two top quality blastocysts we have a 68% chance of having a successful outcome, but cumulative pregnancy rates if we have three transfers it goes over 90%. So you can understand the way forward in your case is to move forward with further transfers. You’ve got the transfer done properly, and I believe it will get you that positive outcome. Make sure that the quality of the embryos is very good. If possible obtain information about the embryos. Try and get photographs of the embryos just, so you confirm that indeed the blastocysts that your transfer are top quality. Sometimes clinics do freeze embryos that are low quality, and patients sometimes believe that they are top quality while they are not. This is something significant in order for you to know with your history.

At the age of 40 how many ICSI with own eggs are recommended? I have done three so far and have read statistics that the cumulative success rate increase until the sixth, but then there is only a limited likelihood from thereon.

What happens with treatment cycles is we do get an increase in the success rates due to cumulative pregnancy rates and the number of embryos we transfer. At some point, they do reach a plateau. I believe we start reaching a plateau after three to four treatment cycles. But I need to point out that you need to check how these extra cycles have been performed. You’ve performed three cycles so far. Did you do day five transfers? Do you know what stage embryos you were transferring? Because if you tell me that you’ve performed three extra cycles and they were day two or day three transfers, we don’t know if you actually failed because something else is wrong or if it’s the embryos. There’s a big question mark here as we don’t know the final assessment of the embryos.

What do you mean precisely by carefully selecting the donor?

I will explain to you a bit about the criteria on how we select donors. A donor, first of all, needs to be young. Greek legislation states that donors should be under the age of 35, we’ve been able to drop it down to under 30. This means that we’re getting better quality healthy embryos free from chromosome abnormalities. It’s good to do testing on them to make sure that they don’t have any diseases. We also do genetic testing on them. We did character testing to make sure that there isn’t something that will come up later, we like to use what’s called proving fertility. So the donor either have had a pregnancy of their own. We need to make sure that they don’t have any gynaecological problems themselves. Like a woman that has endometriosis should not become a donor. There are huge profile things that we do apart from testing. Like, seeing them grow, we also need to check character things, make sure they’re leading a healthy lifestyle. All of these things go into place before selecting a donor.

I am nearly 40 doing this as a single lady AMH is 8.28 AFC is 8. I’ve had three rounds of IVF/ICSI. I am a poor responder, only had 3,2,5 eggs respectively. They got fertilized but did not reach blastocyst. Is there anything I can do to improve quality? I’ve used two different donors and done short, long and mild protocols.

Do we have any information regarding what happens in the lab? The first couple of days, so where is the problem. Has your IVF lab given you information regarding embryo quality? Do the embryo stop on day one, on day two, or day three? All of this information is really important to understand where the problem lies. Also, you have an antral follicle scan of eight, what are the sizes of these follicles? Have they given the correct count? I know you use the short, long and mild protocols, but it’s not just about selecting protocols. It is important how it’s used and how the doctor selects the month that you start treatment to take advantage of your antral follicle count. I would say because you’ve had three rounds of IVF, the best thing to do is for us to review your medical history. If you’d like I’m more than happy to do it. If you send your past records to the clinic for us to fill out a medical questionnaire and we will have a consultation with you to let you know if it’s worth trying again. is there anything

I had an AFC scan last year on cycle day three, but they didn’t see any eggs. What does this mean? I’m 40.

My first question would be who performed your antral follicle count scan. Was it someone that knows how to perform antral follicle count scans? Sometimes we do receive scans that we see follicles, and the doctor says no follicles. To confirm this result and make sure that this is an accurate result, I would suggest a blood AMH test. The result will show us your reserve or how they’re working and will give us more information, and we will be able then to guide you on what to do.

My wife is 38 I’m looking forward to having a baby by PGD. I am interested in gender selection.

Gender selection in Greece is prohibited. I would say if you’re interested in such type of treatment to get in touch with Egg Donation Friends. I know they collaborate with certain countries that do offer such treatments and will be able to better guide you.

If you have reached the blastocyst stage but implantation was unsuccessful is this a good sign to do IVF again?

If you have done a treatment cycle and we see that you do create a blastocyst and just you’re unsuccessful the first time around, I would say that very possibly it’s a good sign to have IVF again. It means that your body can create blastocyst and it just happens the one blastocyst or the two blastocysts that you transferred were, unfortunately, chromosome abnormal. This does happen in older-aged women. We just need to persist, because hopefully by transferring a further blastocyst we will get to the result that we want.

Is there a waiting list? Is there an issue with being single? How much does it roughly cost? 

There isn’t a waiting list for donor eggs. I don’t know if you mean donor eggs or donor embryos. I will clarify this in a second. There isn’t a waiting list as such, but we do need usually two to three months to find a perfect match for you and be able to perform the treatment cycle. We need to recruit someone that looks like you, that matches your blood group, that has the requirements that you will request in a specific form that you will fill. Now there is no issue in being single in Greece. We are allowed to perform treatments in single women. The only thing that they need to do extra is to sign a specific notarial deed. We organize this here at the IVF unit. This is basically something that the legislation has put in place in order to protect the unborn child. In your case because you are single and you’ll be using donor eggs and donor sperm. A lot of clinics use donor eggs or embryos that are leftover from past treatment cycles. At New Life, we do not use donor embryos leftover from the past treatment cycles, because these will possibly give you lower success rates. We go on to create embryos for you, so a specific donor that we will select together for you and we will select together again a specific sperm donor, and we will create embryos for you. This means that you end up having a good number of day five blastocysts, so you have a very high chance of succeeding. Many times having many surplus embryos will help you have baby number 2or number 3 without having to do further cycles. The costs of an egg donation cycle in Greece is 6000 EUR, and this is a total package cost. The only thing it doesn’t include is your medications and your preliminary tests and then the donor sperm commences from 250 euros and above, depending on the type of sperm you select. These are the rough costs.

I froze my eggs at 38 and now 48 and looking to use my eggs but have to transfer them abroad to use them. Should I carry the embryo or would it better to use a surrogate? I’m finding it difficult to find a clinic which can transfer an embryo on women over 50, just in case I can’t do transfer for some time due to the virus and if my first or subsequent attempts aren’t successful. Where would you recommend? 

I personally don’t know which countries. Even at the age of 48 if there are no issues with your uterine cavity, even if you’ve stopped menstruating, we can still create an artificial cycle, get the uterus back in shape, and you will not need to use a surrogate. You can go on and carry on with the pregnancy by yourself. You need to take into account that older women have higher risks during pregnancy, as we explained, high risk of gestational diabetes, hypertension, but I don’t believe that you would need a surrogate. If your uterine cavity is fine, and there are no abnormalities that would prevent pregnancy. I would suggest that you carefully select the clinic where you transfer eggs. It’s sometimes difficult because a lot of clinics have the problem of shipping eggs and receiving eggs and the quality of the eggs. It’s something you’ll need to see and carefully select. But you have about 2 years ahead so you shouldn’t be thinking that the coronavirus is going to have such a long term effect. I believe things will be sorted much sooner than that.

I am 43 next month and have had 6 consecutive miscarriages over the last 3 years from natural pregnancies. Are you able to help investigate cases of recurrent miscarriage before IVF? Would we be able to use IVF with PGS?

First of all, the main risk for miscarriages is chromosomal abnormalities in the embryos. At the age of 43 chromosomal abnormalities are high in the embryos so we’re talking about over 75% of embryos that will carry chromosomal abnormalities. The second thing that we would investigate possibly if this hasn’t already been done, is blood clotting issues. If the blood that leads into the uterus does not clot more easily than it should do. There’s a what we call thrombophilia panel of tests that we suggest. This will indicate if there is such an issue. If there is an issue what we use is low molecular weight heparin in order to prevent this from happening. Normally, using low molecular weight heparin does not help with implantation. Studies have shown this, and these are the guidelines that we have from the European Society of Human Reproduction and embryology. Not all women should be using low molecular weight heparin in all cycles. We see this in many cycles, and they shouldn’t be used because the use of low molecular weight heparin does not help with implantation. It only plays a role in miscarriages and only in women that do have an abnormality in there from the thrombophilia panel. The third reason for miscarriages is structural abnormalities of the uterus. I assume after so many consecutive miscarriages, the uterus has been screened. Nowadays, we do not need to do invasive procedures like hysteroscopy. There is 3-dimensional scanning that we can perform to visualize if there are any abnormalities. If we do detect something, then hysteroscopy may be needed in order to solve the problem. These are the three main risks we need to assess. The fourth category is the immunological issues. It’s a very controversial area. Some studies have been performed that show, that they do play a role. However, there is no accurate testing or the treatments that are offered for such issues., It does not seem to play a role. The guidance that we have from our societies is that immunological treatment should only be offered under a research institution because there’s no medical evidence to back it up as yet. If you have good enough ovarian reserve, and we can have blastocyst at the day-5, it’s worth doing it without risking things. PGS would be an option. You and your husband should perform karyotype testing on yourselves to see if there are no other underlying issues for chromosomal abnormalities in the embryos.

Do you offer surrogacy as well? What is the cut-off age for intended parents in Greece, and what is the legal situation? I am Greek-born, but my husband is British/Australian? 

Surrogacy is indeed allowed in Greece. There are specific issues with surrogacy. The surrogate that we use needs to be a resident of Greece. The difficulty that we have as a clinic is finding surrogates. The reason I state this is because finding donors is easy, and we can monitor them and vouch for them, what they do and how they act and how they are during the donation. Here, with surrogates, it’s a huge obligation because there is no way we can monitor a woman and what she does throughout pregnancy for 9 months. What we say at the clinic is that if a woman has their own surrogate, obviously a resident of Greece, we are happy to help her, get all the paperwork ready, create the file, because in order for us to proceed for a serving case we need to get a court order to allow us to do it as a clinic. It’s something that we’re working on, and we’re hoping that in the near future we’ll be able to have more surrogates on board to be able to offer it to all our patients, but at the moment it is a difficult situation. I’m not negative towards it, so I would say to send me her details, and if a surrogate does come up, I will be able to help her.

What are the chances for a woman who is 40 years old as I am to have a successful IUI with a sperm donor?

You can go forward and have a successful IUI at the age of 40, but I would be very, very careful not to use a lot of the time with IUI treatment cycles. The reason I say this is because usually, success rates with IUI treatments are low. In order for us to be able to get the success at IUI, we need to have a block of 4 to 6 IUI cycles. The chances of IUI at the age of 40 is 12 to 15. You should understand in order to get the success rate similar to what we have in a single IVF treatment cycle, it takes time. International IUI treatment cycles are not recommended, so if you live in the UK, for example, I would not recommend that you go abroad to have IUI treatment cycles, because the cost gets higher and higher as you have to travel over more. It’s not just done in one cycle. I would assess your ovarian reserve, make sure that you have a good ovarian reserve if you’re trying IUI, because by losing time to do that block of 4 or 6 IUIs to get to a possible pregnancy, you may lose some of the eggs. Eventually, you may be forced to try IVF treatment, and time is valuable for IVF. If you have a lower number of eggs, we have lower success rates and higher miscarriage rates if you get older.
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Chrysa Karakosta, MSc

Chrysa Karakosta, MSc

Chrysa Karakosta is the Lab co-Director at Newlife IVF clinic and the International Patient Manager. She studied Applied Biology (BSc) at Kingston University, UK. She has two postgraduate titles: MSc Human Reproductive Biology from the Imperial College of London and a Diploma and Certificate in Clinical Embryology from the Association of Clinical Embryologists (ACE) Training Committee and the Institute of Biology (IOB), UK. She specialized in IVF and ICSI at King’s College Hospital, London. She periodically visited the Bridge IVF Clinic, Lagos Nigeria to organize and supervise the laboratory set up. She worked as Senior Clinical Embryologist in large IVF Centers in Thessaloniki. She is a certified Senior Clinical Embryologist by ESHRE. She is a member of the Pan-Hellenic Society of Clinical Embryologists (PEKE), ESHRE, and ALPHA Scientists in Reproductive Medicine. She was also board member of PEKE.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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