Top tips for turning IVF failure into success

In our clinic, 100% of our staff speak English fluently, and between us, we speak about 10 foreign languages, so on balance, we can treat patients from all over the world. After the quarantine, we had people flying from Singapore as far as Dubai, Saudi Arabia, we have patients from the U.S., Australia, Spain, and of course, most parts of Europe, so foreign language is not a problem.

Yes, interestingly, after the quarantine, we had an absolute flood of donors, egg donors coming in to donate, and we were quite shocked by it because we never expected it. For most of them, the explanation was that they felt that was a way to help their fellow human beings, so that was a reflective reaction from people wishing to donate and offer, so yes, we still get quite a few donors.

This is a very technical question, and for me, it’s very simple and very clear. Ovarian stimulation is a subject that we could explore for days without even getting anywhere near sorting it out and agreeing on what’s best. It has a few very important principles. First of all, is how do you define success? What’s the optimum number of follicles and oocytes one would expect from each individual and there’s a lot of markers that would define that. For example, age, the AMH, the AFC is one of the essential markers. If we have a 35-year-old within normal AMH and a follicle count of say 10, we know by definition that if we get less than 10 eggs, then perhaps there’s something wrong with it, so this is very important to communicate with our patients. I mean the AMH, as most of you know is a very important target market for that, and my team and I have been one of the few in the world who studied and published that more than 10 years ago, so it is important for the woman who is about to be stimulated to have ovarian stimulation to be aware of what’s the successful outcome and what’s the definition. Following the protocols, there are quite a few, so the definition of a successful protocol is the one that helps the patient to reach the number of follicles and oocytes that were defined initially. There’s a lot of things that can go wrong with the protocol, over the years I found that ovarian stimulation varies, and of course, there’s a fixed way you can do I, which means that you can more or less standardize the protocol, which means that you stimulate roughly with one way, with one mode, with one principle if you like. Minimizing the number of visits and scans at the clinic, which is very tempting and very convenient for our patients. Especially, for the patients that are far away or when scanning and blood testing is expensive, so it’s convenient for the patient. If you tell them, you don’t need a baseline scan, and we don’t need to see you before we add on the antagonist, and we’ll see you once or twice at the minimum cost and then go for stimulation. Although in some cases, this may work, if we want to tailor-make our program and if we want to be bespoke, this may fail perhaps from 10 to 10 of our patients, and of course, this is an absolute disaster. In my opinion, if the unit has the facilities to provide tailor-made treatments, tailor-made protocols, I think it’s very important to have a baseline scan. Plus, another two to three scans to define the optimum dose, and of course, the optimum timing and the method for the final trigger. Another big issue, of course, is how to trigger, when to trigger, do you trigger at 17 millimeters, or do you trigger at 19 millimeters? Can you pick up, for example, on Saturdays and Sundays, or can you only pick up on Monday, Wednesday, Friday like some units do and of course, this is something that the patient should reflect on perhaps after a failure or even before the failure by evaluating those important factors? Is the clinic working seven days a week? Is the clinic able to scan and get the reports of blood testing within a couple of hours or 4 hours, any time of the week? This may influence success a little bit, and this may not be that important for the 35- year-old with 10 eggs. But it may be very important for the 41-year-old with 3 eggs because it would make a huge difference to collect from a 40-year-old 1 egg or 2 eggs, so ovarian stimulation is not an easy thing and is not, in my opinion, something that should be totally standardized and totally rigid. It has to be individualized, and we have to have the opportunity to modify the protocols depending on the response, and of course, how do we measure hormones, and what kind of hormones do we measure? Do we measure progesterone? Do we measure LH? Is it important, if we measure estradiol? Then we’re going on to the pickup, most of us, when we’re learning, we were told that perhaps the egg collection is suitable for a more junior doctor, whereas the embryo transfer should be in the hands of the more experienced doctor. I would probably disagree, again, the technique of the pickup is very important, and the technique has to do also with the patient, with the anesthesia. Some people still do ovarian pickups without anesthesia or with very mild local anesthesia, which may be fine for most of the patients. For the individual patient with difficult access or with some sort of pelvic adhesions that doesn’t allow the operator to collect all the eggs, it may make a little bit of a difference, and who is doing the egg collection? Is it a research fellow with all due respect, that’s how we all learned, but of course, the yield of eggs and the quality of the eggs that were collected maybe a little bit different if you have an experienced consultant versus a young research fellow? The conditions in the lab at the time of their collection are important, I could go on forever, so in my opinion, a failed pickup, for example, or a bad stimulation or a bad egg collection doesn’t necessarily mean that this is the potential of the ovarian capacity of any woman, and I’m sure there is always, perhaps a little room for improvement.

I think most people know what they should do. The question is whether they can do it or not. I know, for example, that I should be seeing my children a little bit more, but I can’t do it and equally, if somebody doesn’t have a perfect lifestyle, they know what they need to do, but they can’t do. What do they need? They need a bit of motivation. I’m not going to give any particular tips, all I’m going to say is that respect your body, your soul, and your mind, and they will pay you back. If you invest in them, the investment will grow, so invest in your body. How to start with a small investment? With 30 minutes a day, take a short walk, take a longer walk 30-45 minutes a day. For most people, that’s more than enough, and the same applies to diet, any techniques for relaxation perhaps, for acupuncture, for fertility massage if it’s available in your area, anything that could empower and cultivate your soul and your mind would be helpful. Smoking, alcohol, most people know that, so we all know what we need to do, it’s just a matter of deciding that tomorrow is the time to start.

There’s a lot of controversy concerning genetic testing like PGS, PGT-A, as it’s called now. I can begin by saying that it’s not for everyone, there are only some indications in which it may improve the success rate, and that in some countries including, Greece, they are heavily regulated by fertilization authority so that it’s not sold to the patients as a size fits all and as the holy grail of IVF. More or less, I respect that opinion, so somebody who started IVF at 35, who’s had maybe 1 failure or no failures, I don’t think that PGS would make a huge difference, however, somebody with repeated failures or with miscarriages or of the female age is 40, in that case, yes PGT-A may be associated with a better outcome, not necessarily a better success rate but may be better experience because it’s more empowerment to the couple to know that at least they are transferring healthy embryos. The reduction of multiple pregnancies by eliminating the abnormal ones and therefore implanting one healthy blastocyst for example and so forth, so the straight answer is that genetic tests are not for everyone, that we should be very scientific about it and less commercial, and I think there’s still a little bit of way to go before the indications grow more compared to what I’ve just mentioned.

The age limit, the female age limit is 50 for the female, and there’s no limit for the male. We’re hoping that the female age limit will be moved up to 53 if not 55, in the next few months. You know, I’m on the board of the Hellenic Fertility Specialist Association, and we have put in proposals to increase the female age to 53. Now, with regard to the egg donors themselves, the indicated age is between 18 and 35, however, in our clinic, we only use donors up to the age of 30 maximum to maximize the results and success. Yes, we do offer surrogacy. It is legal in Greece and is regulated. Greece is the only country within the European Union in which service is legal and regulated. We have a lot of requests from patients from all over Europe. Also, across the Atlantic like the USA and Australia. The benefit of having a European Union country is, of course, the ease of travel especially now in Covid times, as you probably all know traveling with the European Union is possible whereas it’s not possible to travel outside the European Union for example in Greece we have a border with Albania and the Albanians are not allowed to travel, into Greece at all neither are people from Turkey and Serbia at the moment, although people from EU are allowed to drop, to fly on conditions from the UK, there are no particular conditions apart from the passenger locator form, from other countries in Europe like Belgium where it was a few days ago, the passengers need to have a Covid test done, however, it is possible. The implications of that in surrogacy, you can understand how important it is to be able to travel and pick up your child when your child is born if you’re not living here, or to visit the surrogate if you’re not living here when there’s an issue. o. This is one of the main advantages. The second main advantage with surrogacy within the EU is the exit process of the child, so after the child is born from surrogacy getting all the papers to bring the child back home to the UK, or to other European countries is very straightforward, unlike other countries outside the European Union where indeed there could be major issues with the exit process. The last advantage is that the general standards of IVF and obstetrics and delivery in hospitals are quite similar in most EU countries, and this is building trust, and this is improving the experience. One of the last advantages about surrogacy in Greece, and this is one of the reasons why we have a lot of Australians coming out and preferring Greece as opposed to the US, is that the court order is issued before the process of surrogacy begins, which means that the child is of the Barents, the intended parents before it’s conceived, and of course, you understand the importance of that in both legal and practical terms.

I think you need some heavy counseling, and of course, fertility counseling with regards to your options. It’s not impossible for a 43-year-old with a 44-year-old man with poor sperm to be successful with their genetic material, however, that has to be explored separately, and the option of egg donation or embryo donation is there as well. It is very difficult to answer. All I have to say is that if you have miscarriages, please, do not underestimate the importance of your anatomy assessment. Let’s talk now a little bit about the hysteroscopy. In my opinion, this is an amazingly useful procedure, and most of us including our team, we are able to perform the hysteroscopy, which is a little bit more advanced than any scan, it doesn’t require anesthesia, and it ensures that there are no major issues with the uterus. Be aware that endometriosis may have damaged your ovaries, and it may have damaged your tubes. Please, exclude conditions like hydrosalpinx before you move on to another implantation. Whether acupuncture can improve or not sperm, I think, his frozen sperm I’m not sure, but in general, acupuncture does have some benefits for fertility patients as long as it’s used in an integrated fashion as part of the overall, rounded approach for the individual couple.

I have a very clear view on this depends. If the fresh transfer is optimal then, in my opinion, we have no reason to freeze electively and move on to frozen embryo transfer. Now, how do we define an optimum fresh transfer? Firstly, we don’t want hyperstimulation, so we don’t want more than perhaps 12 or 14 follicles, and we don’t want very high levels of estradiol. We don’t want high progesterone levels on the day of trigger or one or two days before that because progesterone would be detrimental for fresh embryo transfer. We want a healthy-looking endometrium on scan with normal thyroid lamina appearance and normal thickness and all that, and if all of this is optimal, then I can’t see why we can’t go on for fresh embryo transfer. If there’s any doubt about any of those factors, then again depends on how many embryos we have. For example, if we have 3 top-quality embryos and one of those 3 factors defining the optimum conditions for the first transfer. If one of those factors is gray, then perhaps we can do a single embryo transfer on the first cycle and then freeze the other embryos so that we have another attempt, so it depends.

We can use any genetic material through surrogacy, and this is why I mentioned earlier that with surrogacy, we can guarantee a 95% plus success rate. You can imagine how successful one can be when one is using a healthy surrogate, and a healthy embryo donation or donor eggs, donor sperm, or donor embryos that can be used with the surrogate.