Progress and debates in the IVF field

On 10 November 1977 history was made. The very first IVF procedure was performed in the United Kingdom and on 25 July 1978 the world’s first IVF baby, Louise Brown, was born. More than 40 years after this moment, it was estimated that 8 million children had been born worldwide using IVF and other assisted reproduction techniques. One of the best experts in this field, Prof. Dr. Tayfun Bağış – the Head of the Assisted Reproduction Department from ACIBADEM Altunizade Hospital – talks in the following material about some long debated IVF related topics. Was vitrification actually revolutionary? Do the fertility incubators and the fluids that accommodate the embryos influence the pregnancy’s chances? Is 5 days embryo transfer really better than the 3 days transfer? Are all modern IVF related tests actually useful? All the answers, below, from the ACIBADEM expert that has performed until now around 15.000 IVF procedures.

Long protocol vs. short protocol

“When I started this job in 2003, there was only one protocol for IVF. It was a long protocol, we are still calling it the long protocol. In this protocol, if you are going to perform the IVF procedure this month, the treatment starts the month before, in the 21st day. And the patient starts to make injections until menstruation, then comes to the clinic, and we are starting again injections to stimulate ovaries. So basically, each month the woman ovulates, develops one follicle. In ultrasonography we cannot see the eggs, we can see the follicles, the eggs are in the follicle. So if we follow only and we do not give any medication, the woman is going to develop one follicle, but we don’t want just this one because we know that as much follicles you can obtain, as much eggs you will collect and your chances are going to be bigger. So we stimulate ovaries by injections. The first step is ovarian hyperstimulation periods. This takes nearly seven to ten days in the first phase until menstruation and after we are starting the second injection round, we are constantly following the patient, it’s a long process, it takes 4-5 weeks. Nowadays, nearly 96% or maybe more of the cycles are being done using short protocols. When the woman has her menstuation, in the beginning of the cycle, she comes here, we are doing an ultrasonography and if she doesn’t have any pathology that may prevents us to start in vitro fertilization, we are starting the injections and we are stimulating the ovaries only a few days before the egg collection, not a few weeks. We are following the patient’s treatment days by injections, and when the follicles are ready, we are giving some drugs that trigger ovulation, we make sure that the oocyte in the follicle becomes mature. In the past, we were using intra-muscular injections. It was a very painful experience. Now, the technology has developed they have special syringes with small needles and the patient can make the injection by herself – a very big advantage. Also, women who take these modern injections have a lower risk to can develop ovarian hyperstimulation, a serious condition that make you lose fluid in your vessels and that may kill you if it’s not managed correctly. The risk is now nearly 1% or lower”.

Minimal stimulation vs. conventional stimulation

“There was some concern about an increased risk of ovarian cancer in women who had procedures for stimulating the ovaries. But the data did not support this conclusion. If you had your ovaries stimulated many times, it does not increase your cancer risk. Infertility increases cancer risk more. If you don’t have a baby, cancer risk is high for breast cancer, also ovarian cancer. So if you can have a baby, your risk to have cancer is going to drop. I don’t have any concerns about risk related to ovarian stimulation. But now there is two concepts: one concept is minimal stimulation, the other one is conventional stimulation. By minimal stimulation, the aim is to take a low number of eggs, but of much better quality. If you take more quality eggs, you don’t need to stimulate ovaries a lot. The statistics from European countries and United Kingdom had the followimg conclusion: if you increase the collected egg number, the pregancy chance is going to increase. Take as many as you can, until 20-25. So for that reason, the concept of minimal stimulation is seen as the second place from up here”.

Vitrification, a major step forward

“In the beginning of my career we were freezing the embryos or the eggs using slow freezing method. During the last 10 years, a new system has developed: vitrification. By vitrification, it takes no more than 10 minutes to freeze embryos or sperm cells. It’s very easy and very successful. When we defreeze it, and we use it, the success rate is higher. We use to say it’s like fresh material or even better due to vitrification. This technique has also helped solving the ovarian hyperstimulation cases. If the woman is at risk to have an ovarian hyperstimulation syndrome, we do not continue with the procedure, we freeze the material using vitrification and we come back to IVF later. Actually, I don’t remember any patient during the last 5-10 years that I have hospitalized for ovarian hyperstimulation syndrome. Before that, nearly one third of the clinic was full with women suffering from hyperstimulation syndrome”.

The importance of the medium that accomodates the embryo

“In 2003, after the eggs retrieval procedure, we were putting the embryos, the fertilized egg, in a special fluid. We call these fluids “mediums”. They are very special fluids, and very costly. 16 years ago there was only one kind, maybe two kinds of medium, but now there are many. And a very interesting aspect – we don’t know exactly the content of these mediums, because companies do not reveal the ingredients. Of course each company is trying to convince the doctors to chose their medium so they are saying often if you use our medium your pregnancy rate is going to increase. And it really happened! I did see that, really, pregnancy rates increase dramatically. We now have alternatives, good ones, that was not the case before”.

The new generation of fertility incubators

“The eggs and sperm are mixed together in the IVF lab so that fertilization may occur. At this point, they need to be placed in a protected environment – in an incubator – so that they can begin to develop safely. Now we are using – not for all the patients – the EmbryoScope a special type of incubator which supplies the ideal nutritional and environmental conditions for embryos to grow outside the uterus and that uses a time-lapse imaging system. The EmbryoScope allows infertility specialists to monitor the progress of fertilized eggs around the clock without ever removing them from the protected incubator. This high-tech device is used in the IVF laboratory during the incubation period between fertilization and implantation. The machine takes photographs every ten minutes and it makes film out of them so you push the button like a computer and you see the progress of the embryo, what happened, when it becomes two cells, how long later it becomes four cells and so on. There is a debate about is it, whether it really brought a progress or not, but I think we learned a lot of things about the evolution of the embryos. Now we can classify embryos according to EmbryoScope scores. When we are selecting some embryos, even if they look like the same quality, we know how they have developed and we can chose better I think”.

The endometrial receptivity test for implantation failure

“The ERA test – endometrial receptivity array – it’s being done in Spain. It was considered a new development, but they made a multicenter study and found out that whether you do the procedure with ERA or without ERA it makes no difference. In ACIBADEM Altunizade Hospital we don’t advice patients to do this test, we are not sure about it. It Turkiye there’s nearly 151 IVF centers, and only one of them is using ERA. So we don’t believe that ERA is working. Many things come and go like that. I remember many things in this medical field that became popular and then they went to trash”.

3 days vs. 5 days embryo transfer

“You should know we are giving embryos a lot of stress when we are leaving them outside until day 5. In my clinic, the going blastocyst rate is nearly 60%, so for many patients we are going for blastocyst transplant. But if the woman has enough eggs, we obtain enough embryos and we should not fear that of we would wait until day 5 we will lose many if not all of them, we are going for day 5 transfer. But if we have obtained a very limited number of embryos, it’s just not right to wait 5 days. So many patients feel that if the transfer is made on day 5 the changes of pregancy are higher, but we are putting the embryo into a very stressful area, it’s not very easy for embryo to survive outside the natural space of the uters, in vitro conditions. I can also show you some data that say that when you put embryo in stress, it can increase the chromosomal abnormality rate. So why are we waiting until day 5? We can transfer the day 3 embryos and wait for the other ones, for example. It’s not a simple, but you should trust your doctor, you should trust he is going to get the best decision”.

The multiple pregancies debate

“Many doctors, and now many medical papers, say that best result of IVF is to have a single baby. This way you avoid complications. Before 2010, our Turkiye legislation did not restricted the embryo number. But now it does, because we had a lot of cases of women with triple pregancies and the premature new born services could not cover all the patients. They had to deal with three very soliciting, delicate, patients in the same time! And then they said that until 35 years old, in your first two IVF trys, you should put one embryo, and after 35 you can put 2 embryos. Now we are putting nearly 2 embryos, we try not transfer more than 2 embryos. By this method, our triples rate is very, very rare. Sometimes we can put 2 embryos, and it can become triple pregnancy, but the risk is very very low. We do obtain often twin pregnancies. I always discuss this topics with colleagues, also in congress meetings – which one is better a single pregnancy or twins? When you compare the preterm laboring rates or another complications, it is definetly higher in twins. But you have to compare 1+1 and 2 together. The chance that you are going to have a preterm labor is 18% in twin preganancy and in single pregnancy is let’s say 10%. Yes, the risk is higher in twins, but to have one baby, you will wait 9 months and have a 10% risk, and for another baby, 10 months more and again 10% risk, 20% in total for the two babies, so maybe, the risks are the same?”.