How to get 80% success rate in IVF?

Explained by: Roksolana Semchyshyn, MD, PhD, Intersono IVF Clinic
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How to get 80% success rate in IVF?
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From this video you will find out:
  • What can affect success rates in IVF?
  • Embryo quality: the key role of oocyte and sperm
  • Does egg donation increase our chances of success?
  • PGS screening: for whom and when?
  • Implantation: what is important?
  • The first line testing before IVF. What to check if the first attempt was negative – the second line testing before IVF.
 

Is 80% success rate in IVF possible?

Roksolana Semchyshyn, MD, PhD, Head of IVF department at Intersono IVF Clinic is answering the most common questions about improving success in IVF treatment.

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Questions and Answers from the event

What can affect success rates in IVF?

We have two main factors, even three, but the main factors are the embryos. Those are the quality of the embryos, quantity of the embryos, genetic health of the embryos. The second factor is the successful implementation. We need to understand that if we have even a genetically healthy good morphological embryo, we need to have all factors of implantation and to have the success rate in our pregnancy. The third factor is the clinic. I understand that here we have only a very experienced clinic, but still in Ukraine, a lot of our clinics are experienced, and a lot of our clinics have good equipment and a good doctor. So first of all, please pay attention to the experience of the clinic, to the experience of the doctors, and different details especially, if the clinic is open to the patient and can show you all the documentation, show you the clinic itself, and can communicate with you.

Embryo quality: the key role of oocyte and sperm?

Let’s start with the first factor, which is an embryo. Embryo quality, we understand that we have also here two main factors, which will predict the quality of the embryo, this is the oocytes and this is the sperm, so we will look at the oocytes separately, and we will look at the sperm separately. So the oocytes are the main creator of the embryo, and when we are talking about the oocytes, we also have two main factors, this is the quality of the oocytes and the quantity, which I need to get the best success rate, so if you are talking about the quality what factors can influence the quality of our oocytes?

First of all, it is the age, we understand the age for women is the crucial factor because our biological clock is ticking every day, so every day, we are losing oocytes and we are losing the quality of our oocytes. During the fertilization, oocytes are dividing, and for this division, we need a lot of energy. If the oocytes are young, we have a lot of energy, and the division is correct. If the oocytes are older, we’ll have less energy, and you can have the problems with the division, we can have incorrect division. Sometimes, we receive the embryo, which can have chromosomal abnormalities. How age can correlate with our success rate.

If you are at the age of up to 35 years, statistically, out of our 10, oocytes 7, will be of good quality and will divide correctly, and only 3 of them can have some chromosomal abnormalities. If we are talking about 35-39 years, we call it like a gray zone. This means that we can have 50/50 chances, this means that half of the oocytes can have the right division, and the second half will have abnormal division. In the age range 41-42 years, we have 80% of abnormal division and only 20% of normal division. But over the age of 42, we can have catastrophic results, which means that only 2% of all our oocytes will divide correctly, but we understand that in women over 42 years, we have not, so high ovarian reserve and we need approximately 80 oocytes to have 2 embryos of good quality. This is just an unreal situation, this is very hard to receive, therefore, we always ask you to think about the maternity at the age up to 35, this is the best option, but in case you are at the age of 35 – 39, please think about your maternity, and if you are not planning to be a mother now, you can have the option to vitrify your oocytes and to have like a backup for the future maternity.

At the age of 42 plus, you can use your vitrified oocytes and have your own genetic children. The second factor which can influence the oocytes is stimulation protocol. Nowadays, we have stimulation protocols, the so-called short protocol with antagonists, and the long protocol with agonists. Just yesterday, I went through the new investigations that show the information that indeed there is no specific data, which confirms that one protocol is better than another one.

So if you are a good responder, you will be a good responder on each protocol. If you’re a bad responder, then we understand that the quantity of oocytes is not enough, and any protocol for you will not give you better results. The main factor in stimulation protocol is the administration of all medications, just like the doctor prescribed because sometimes it is a big stress for the patients because you need to take a huge number of new medications simultaneously. Some of them, you need to insert intramuscularly, some of them you need to insert subcutaneously, some medications are like tablets, so this is a huge stress for you.

Please, be very specific in the administration of the medication because all these can influence the quality of the oocyte, especially if you will miss the day of administration of the medication, this can influence our results. Also, some medications can increase the quality of the oocytes f. e. LH, which is the stimulating medication, they are beneficial for the patients who are over 35. If we are adding LH supplementation to the stimulation protocol, those patients can benefit from having a better egg quality. Also, if we are talking about the triggering, HCG triggering gives us a better result, we can have more mature oocytes, and the results will be of a better quality of our oocytes. It is very important to insert the trigger exactly at that time which is prescribed in your protocol because if you will miss the trigger, or you will postpone it, it can affect the quality of oocytes, sometimes very rare, but still, our patients are missing the day, or the time of the triggering, in that case, we can have much fewer mature oocytes or even preterm rupture of the follicles, and we can not receive the oocytes during the egg collection.

If we are talking about the quality, the first question is for sure what number of oocytes is adequate for our best success rates, so 12 oocytes are the optimal number of oocytes which will provide us at least 2 embryos of good quality, but if we are talking about the age, we can have morphologically good quality this means that when the embryologist is looking on the embryo, it looks good, but still, it can have chromosomal abnormalities inside, we can’t see them without special investigations, without special testing, which is called PGS, and sometimes we understand that our negative attempts in a patient who is over 42, even with the good quality means that the embryo was with chromosomal abnormalities and so how can we influence the oocytes, or what can affect the quality of the oocytes. First of all, this is AMH level, this is our predictor of the quantity of the oocytes that we will receive and antral follicle count before you start the stimulation, the doctor will monitor your antral follicle count and will monitor your AMH level and the higher AMH level you have, the higher number of oocytes we will receive at the egg collection. We understand that the AMH level is the marker of ovarian reserve, and it is decreasing with age. Age is a factor, not only for the quality but also for the quantity of the oocytes. Over the age of 40, we have extremely decreased levels of our AMH and our ovarian reserve.

The number of oocytes can be influenced by stimulation. If we start with a maximum dosage of stimulation protocol, we will receive a higher quantity of the oocytes. If we start with a minimum dosage of the stimulation protocol, we can not receive the maximum that we can out of our ovaries. Also, the technique used during the aspiration can influence the results. During the aspiration, we need to aspirate all fluids out of the follicle. Sometimes the follicles are hard to reach, and the doctor can miss the follicle and just can’t reach the follicle and this is also the parameter that, which can influence the quantity of the oocytes. In our clinic, we are using the flashing of the follicles. Especially, when we have fewer than 6 follicles, this means that sometimes the oocytes can be fixed to the wall of the follicle, and if you are just aspirating the fluid out of the follicle, the oocytes can stay in the follicle.

Therefore, we’re using the flushing, we insert the fluid inside the follicle called the liquid, we just flush the follicle, and then we will once again aspirate the liquid, and during this flushing, we maximize our chances to receive all oocytes that are in your ovaries. What to do if you have a few follicles or a few oocytes and decreased levels of AMH, how to increase our chances? In our clinic, we use so-called embryo banking, if you have 2 or 3 oocytes during the aspiration, your chances are approximately 40%. Out of 3 oocytes, we cannot receive the blastocyst, but if we fertilize those 3 oocytes and freeze them on the zygote stage, this means that we will freeze the embryo on the 1st day of their living. Then we repeat the stimulation, again receive several oocytes and fertilize them and cumulate several embryos f. e. at least 6, you will increase your chances of being a normal responder, and you can use your own oocytes, and you can increase your chances for a better success rate. Sometimes, if you have a poor quality of the oocytes, we can use the solutions for the cultivation, which are reached with additional ingredients for the better cultivation outcomes. If we have patients who have poor blastocyst rate f. e. out of 8 zygotes, we have no blastocyst, then for the next stimulation protocol, we analyze with the patient our future steps, we can change the protocol, we can change the stimulation medicine, and also we propose to the patient additional cultivation solutions just to give rich ingredients for better cultivation for the patients.

The second creator of the embryo is the sperm. If we are talking about the sperm, the first most important thing for the spermatozoa is the morphology. If you have good morphology of the spermatozoa, we will have the good quality of the embryo and what to do if the morphology is bad. All of our patients are undergoing consultation with a urologist. The urologist is working with a patient and is preparing for the IVF procedure. We understand that for the IVF procedure, we need only 10 or 11 spermatozoa or a maximum of 20 to 25, depending on the quantity of the oocytes, but still, we need them with good morphology, and the urologist is working hard to receive the good morphology of the sperm.

Sometimes we have the patients who, even after this treatment, they do not improve the results of the morphology. What to do in such cases? We started to do the TESE procedure, we are extracting the sperms out of testes, and in case, that in ejaculate we don’t have morphological normal spermatozoa or we don’t have any movement or active movement of spermatozoa, we are proposing to our patients extracting spermatozoa from the testes. This can increase our chances to receive a better quality of the sperm. We can also use the PICSI or IMSI method of fertilization, where we are selecting the best parameters based on morphological criteria and doing the ICSI procedure for the oocytes, this can increase our chances for the pregnancy.

Does egg donation increase our chances of success?

Yes, egg donation increases our chances for success in case you have a low AMH level, and you have no oocytes at all, in that case, we can increase our chances for the pregnancy with egg donation programs, or you can have a combined IVF program. For example, when we receive only 2 or 3 of your oocytes and we understand that your chances for the pregnancy are from 4 up to 10%, but if we want to have a higher percentage rate, we can propose to you combined program this means that you can add to your own oocytes a few more vitrified donor oocytes. These oocytes are a good option because the vitrified oocytes are always available, we have no waiting list for them. They are genetically tested, our donors are fully screened for all the most common genetic diseases and all donors are with proven fertility. This means that they already had their own babies so that their eggs are good enough and we have more than 450 different profiles with different phenotypes, we have anonymous and non- anonymous egg donors, so you can choose your donor in addition to your own oocytes. We will cultivate them separately, you will know whether the baby is out of your oocytes or out of donor material and then we will get the result.

If we have no blastocyst from your own oocytes, you will have the blastocyst for sure from a donor’s oocytes. This will give you a backup and you will not miss the cycle and you will not miss the embryo transfer, and you will have a higher chance of achieving a pregnancy. If you are in advanced age, if you are over 42, you have very high chances of chromosomal abnormalities in the baby, so either you should do the PGS screening, but we need to understand that we can test 3 embryos and all of them can be with some abnormalities. If we have a patient at the age of 45-46 where we understand that almost all oocytes are with genetic diseases in that case, of course, egg donation is the best option for you to have the maximum chances for the pregnancy.

We can look at egg donation when we have poor outcomes in the previous simulations for example, if you had 2 or 3 stimulations, and you didn’t reach embryo transfer ever, this means that you have some problems with oocytes and that it is not a genetic problem, but this is the quality of the oocytes, and this is when we can benefit from the egg donation program, especially from the vitrified oocytes.

PGS screening: for whom and when?

PGS screening is the screening of the embryos before the embryo transfer for the genetic diseases. This is a diagnostic for chromosomal abnormalities, we know that we all have 46 pairs of chromosomes and they have some morphology, they have some characteristics how they need to look like, and we are testing the embryo for the number of the chromosomes and different aberrations in those chromosomes. We can also have the option of PGD, this means that we can diagnose some specific genetic disease, this is the deeper investigation of the embryo, so for whom we can recommend the screening of the embryo? First of all, this is advanced maternal age, we understand that if you are over 42, as I’ve said previously we have very high chances of genetic diseases and abnormal division, so this is the best option to test the embryo for the chromosomal abnormalities and transfer the chromosomally normal embryo. The second option is the chromosomal abnormalities in your karyotype.

If in your karyotype, in your genetic material, you already have some disorders, this means that you will give these disorders to your baby. In most cases, the embryos will have the same disorders, and we will have only 10, up to 15% chances of normal embryos, so we need to understand which embryo is healthy and then transfer only healthy one, therefore if you have some chromosomal disorders in your karyotype or your husband karyotype, this is the indication for PGS screening. If you have severe male factor, especially if you have cryptozoospermia, this means that we have less than 1 million sperms in the ejaculate or especially if you have disorders in the male chromosomes like deletions, this means that we need to test the embryos because in case we have the deletions, and if you will have a boy, it will be transmitted to him. Therefore, we need to choose just a female embryo and we will have a higher success rate for our pregnancy. In case that you have numerous miscarriages, this also can be caused by the genetic disorders of the embryo and this is also the indication for you to do the PGS screening and to understand that we are transferring the healthy embryo.

We can also use the option of the PGS screening for all patients who just want to be sure that we are transferring the healthy embryo to the uterus, and we will have the best options for the implantation. We understand that if we will have a genetically healthy embryo, our chances for the pregnancy are around 80%, therefore PGS screening is a good option, it may not increase the chances, but it can exclude the negative attempts because we understand that the genetic abnormality of the embryo is the main factor and the key role of our success rates. It should be discussed in advance with the doctor who should explain what are the advantages of this testing, explain the benefits, and afterwards, you can decide if you want to do it or not.

Sometimes, it is the indication as to the advanced maternal age, sometimes this is a willingness of the patient. F. e., in Ukraine, it is allowed to perform the sex selection. I know that in most countries, it is forbidden because this is not right from an ethical point of view, but in Ukraine, this is legal. You can choose the sex of the baby, and we have the patients who have f. e. 2 or 3 sons, and they want to have a daughter. They do the PGS screening for sex selection, just to have a daughter, and so this is the option to discuss with the doctor, to ask the doctor the questions like do I benefit from this, if yes, then for sure you have to do it. If not, then this is if you want to do it or not.

Implantation: what is important?

When we are talking about implantation, we need to remember several key factors. First of all, this is the endometrium, and then this is the uterus, and then it is a special window of implantation. I will further describe what these are. We need to take into account our level of the hormones, our immune system, and our coagulation system. Let’s start with the endometrium. If we are talking about the endometrium, we need to detect the thickness, the structure of the endometrium.

We also need to check the presence or absence of inclusions f. e. polyps, or something like that. If we are talking about the thickness of the endometrium, the best option is from 7 up to 13. If you have a very thin endometrium, it is not good, and if you have a very thick endometrium, it is not good as well. If our endometrium is very thin, it means that it can be an estrogen resistant. This means that the endometrium doesn’t have a good structure and doesn’t have enough power to implant the baby. Also, if you have thin endometrium, we have decreased blood flow, which means that the baby that will implant will not have enough blood to grow, and also we can have a miscarriage or the failure of implantation.

If you have a thin endometrium, it can be after the injury of the basal layer of the endometrium f.e. after the abortion, or after a hysteroscopy, when we remove the endometrium out of the cavity. This is a regaining problem, and this is the most difficult problem to solve. What can we do if you have a thin endometrium? First of all, we can increase the dosage of estrogen, for example, if you are undergoing your stimulation, you have enough quantity of the estrogens because the follicles grow, and they produce the estrogens, and we have good enough levels of estrogens to support the individual.

If you are in the cryo cycle f. e., if you are undergoing the egg donation program and you don’t have the stimulation, your estrogens aren’t increasing, then the doctor will prescribe external estrogen, and if you have the thin endometrium, we can increase the dosage of estrogens.

It is the simplest way to increase the thickness, but as I mentioned, we can have estrogen resistant endometrium, and what to do in that case? In our clinic, we practice two methods. First, it is the synthetic growth factor, we are putting growth factors inside the cavity, and we are flushing the endometrium inside the cavity. This means that we are stimulating the growth factor. The endometrium cells grow, and we have good results with it. We are doing this procedure in the cycle of embryo transfer and approximately on day 10, up to 12-13 before the embryo transfer, so this is enough time to react after the growth factor, and we see that in most cases, we receive at least 7 millimeters of endometrium on the embryo transfer.

Sometimes, we don’t have the result of synthetic growth factor, and we are using our natural growth factor. This procedure is called PRP, we are inputting the plasma, which is reached by platelets, so this is your own blood, which would centrifugate, and we receive the extract of platelets, and they contain the growth factor, and we are inputting that plasma, your plasma inside the cavity. This is a natural way to input the growth factor inside the uterus, and we also receive good results on it, and we see that even in the case when the synthetic factor doesn’t work, our natural factor works.

In case we have thickened endometrium, it is easier. It means that we have hyperplasia and this means that this is also not a good structure for providing the implantation for the embryo. We need to remove that endometrium and to give the best chances for the embryo to implant into the normal structure of endometrium. The structure is also very important, we are using ultrasound scanning to detect the structure, and the good structure, this is triple lining endometrium on the ultrasound scanning on day 8, up to 12, also on ultrasound scanning, we are looking for the polyps. Polyps inside the uterus, these are inside the endometrium, which lowers our chances for the pregnancy. So, if we see on your ultrasound some inside the cavities, we need to remove it.

We propose to do the hysteroscopy for that patient, and we are removing the polyps from the cavity. When we are checking the uterus, first of all, we are taking into account the myomas and we are looking for some abnormalities of the uterus. If they have myomas depending on the size of myomas and depending on the layout of myoma, we are choosing the tactic f. e., if I have the submucosal myoma, we need to remove it.

If myoma is less than 3.5 centimeters, we don’t touch it, so you can be pregnant, and this size of the myoma doesn’t influence the pregnancy and outcomes. What about the septum? If you have the septum inside the uterus, it is an indication for the removal of that septum. We propose to do the hysteroscopy and to remove the septum because it will influence not only your chances to be pregnant but also the chances of carrying out the pregnancy.

The investigations show that the patients who have the septums have higher percentages of miscarriages compared to the patient who didn’t have the septum inside the uterus. We recommend for sure to remove the septum of the uterus. If there are abnormalities f. e., the bicornuate uterus,  it is a situation where we can’t do anything. The option is to do IVF, and that’s all. How to differentiate if this is the septal uterus or the bicornuate uterus? The best way is a 3D ultrasound scan where we can see the uterus in the 3D measurements and understand if you have only the septum, and we can remove it, or this is the abnormal uterus, and we just can’t do anything.

The first line testing before IVF. What to check if the first attempt was negative? The second line testing before IVF.

The third option is the window of implantation, which is the time frame when the endometrium is the most receptive to blastocyst implantation. As usual, this is some 5-6 days after the ovulation, and this time frame continuous approximately 24 up to 48 hours. It means that 6 days after the ovulation during 24 up to 48 hours, our endometrium is most receptive to implant the baby.

Therefore traditionally, we do our embryo transfers on day-6 or after the egg collection because approximately 80-95% of our patients they have that window of implantation exactly on that day, but we also have 15 up to 20% of the patients with a postpone window of implantation, this means that that window is closed when we are doing the embryo transfer and in that case, we will have the failure of implantation and we will not achieve the pregnancy.

And how to detect the window of implantation and what to do if the window is postponed, so next option which is very important for implantation is our hormone system, especially the prolactin level and the TSH level, so these two hormones are very important for a successful pregnancy. If you have higher prolactin, we need to decrease it for sure, and if you have the TSH level higher than normal, we also need to decrease it. In case we have higher prolactin levels or TSH levels, we will have higher chances of miscarriages or even the failure of implantation.

The last but not least is the immune system, which plays the key role in our implantation because the embryo is like a stranger who drops into our organism, so the immune system needs to defend our organism from that stranger, and our organism needs to hide the embryo from our immune system, so this is not an easy dialogue between the immune system in our organism, therefore, we are detecting the condition of our immune system before the IVF program.

Just understand if our immune system is aggressive or not because if our immune system is aggressive, it will not take our baby and it will just kill it or make the conditions for the miscarriage, so when we are talking about the immune system, we are monitoring first of all NK cells, so-called natural killer cells and these cells are possible for the immune response of our immune system and for the aggressiveness of our immune system.

If you have higher NK cells, then your immune system is very aggressive. We are also taking into account our thyroid glands, not only the TSH level but also antibodies like thyroperoxidase (TPO) and thyroglobulin (Tg). These are 2 markers of autoimmune thyroiditis, and this is also for us, not a good option, and we need to correct the immune system in that case.

The first line testing before IVF. What to check if the first attempt was negative – the second line testing before IVF?

When we are talking about the first line testing we have two kinds of testing. The first one, these are testing of our general health as the pregnancy lasts long 9 months, so we need to understand that our body is ready for the pregnancy, so we need to check our body and to understand that all mechanisms and all system are working fine.

We start from a GP consultation to make sure that we have no contraindications for our pregnancy. We have a normal vaginal swab, and we have a normal pap test to make sure we have no infections and that we are ready for the pregnancy and also very important is hormonal investigations. We are testing prolactin, thyroid gland, this is TSH level, and also we are testing AMH level because this is the crucial marker of starting dose and choosing all the protocol for stimulation and also we need to check FSH level and LH level and as I said we are checking the immune system in the first line testing because we understand that immune system can be aggressive in a more than 30% of our patients and if we will correct our immune system, we will increase our chances for the pregnancy.

It is easier and cheaper to prevent or to correct our immune system rather than having a second attempt at IVF. This is from the women’s side, and if we are talking about men’s side, then we are testing the spermogram especially, the morphology and the activity of the sperm and also we are testing DNA fragmentation, and this is the testing which checks the percentage of broken DNA inside the spermatozoa. If we have a higher percentage than 20-30%, it is not good, and we need to lower it because if you have a higher percent of DNA fragmentation, it can lead to miscarriages or even implantation failure.

This is important for us before the first attempt at IVF. If we did all this, made the first attempt, and we receive a negative, we have the second line testing. If you have a negative attempt, we need to understand if the reason is in embryo f. e., if we had a bad quality embryo but good quality uterus, we recognize that we need to work with the quality of the new embryo. Sometimes, the reason is in the uterus and in embryo, so if we are talking about the embryo, we have two options to check it. It is karyotyping, we need to understand that your genetic material is healthy.

After the first negative attempt, we are recommending to do karyotyping, and if the karyotypes are normal, then according to your age, we have f. e., if you are up to 35, so 70% of your embryos have to be health. If you are 35-39, this is 50/50. If you are over 40, we have 20% and less, so in case of advanced maternal age, we recommend PGS just to exclude that the embryo is not healthy.

If we are talking about the uterus, then we start from hysteroscopy. Investigations show us that hysteroscopy before the first IVF, when we have no indications gives us no benefits. This means that we have now statistically higher results of IVF outcomes and in patients who did hysteroscopy without indications. But in cases where we have negative attempts, or we have indications, hysteroscopy for sure increases our chances for a pregnancy.

During the hysteroscopy, we look at the endometrium, if there is any suspicious zona in the endometrium, we can do the biopsy of that zona, we can also test endometrium for the chronic diseases. For example, chronic endometritis, which is a chronic inflammatory process inside the uterus and we also can check the level of NK cells inside the uterus because we know that sometimes we are testing the NK cells in our peripheral blood, but we understand that sometimes NK cells, the quantity and the activity of NK cells in our blood is not corresponding to the activity inside the uterus. Therefore, the best option is to check NK cells inside the uterus.

Also, in the second line, we are talking about HLA typing? This is a test to detect your compatibility and your husband. We are comparing your genes and your husband’s genes, you need to be different in those main genes because if you are very similar, we can have similar mistakes in bed genes.

What to do if you have very high HLA compatibility? We can use the medication just to correct our immune system, and then the last testing in the second line is the checking of the window of implantation. As I’ve said, the window of implantation is the period when the endometrium is most receptive when you’re taking the baby, and sometimes approximately from 15 up to 20% of patients this window is postponed, so how can we detect it? We have nowadays, a test called the ERA test, and this testing allows us to understand if the endometrium is receptive or not.

The patient is prepared as for the embryo transfer, but we don’t do the embryo transfer. On the day of the embryo transfer, we are doing a biopsy of the material out of the uterus for the testing, and we test the endometrium for the receptivity, and we can have 3 options: the endometrium is receptive, so we can use that day for the embryo transfer, the endometrium is pre-receptive, which means that the endometrium is not ready now for the embryo transfer and we need to postpone the embryo transfer several days, and the endometrium is post –respective, which means that the window is already closed and we missed it, so we need to do the embryo transfer earlier. This is a good option because, with the investigations, we’ve done on our patients, we included the patients in that group who had 2, or more negative attempts and they have zero pregnancies in that group, so those were the patients with zero pregnancies after 2 or more negative attempts.

We performed ERA testing for them, and in 80% of cases, we had changes in that window of implantation, and afterward, when we did the window of implantation, we proposed them individualization of the embryo transfer. This means that we did the embryo transfer exactly on that day in which the endometrium is the most receptive to the embryo transfer and we received 68% of pregnancies in the group where the pregnancies were zero.

This is a great result, and I widely recommend this testing for the patients who had 2 or more negative results as it is the main testing to exclude the problems with the window of implantation. What to do if you have some disorders in that testing f. e. if you have the disorders in karyotyping, we can do the PGS for a screening of the embryo and to detect a healthy embryo. If you have very severe disorders in karyotyping, we need to change the gametes. We need to use the donation, sperm donation, or egg donation depending on the changes in the karyotyping. If f. e. during the hysteroscopy, we can see the polyp, we can just remove the polyp during the hysteroscopy. If we did a biopsy and we have f. e. chronic inflammatory disease inside the uterus, we can use antibacterial treatment and correct that inflammatory process.

If we have immune system disorders, this means if you have a very aggressive immune system, in our clinic, we use intravenous immunoglobulin to correct our immune system, and we also have good results. We have definitely a higher percentage rate and success rates in the patients with autoimmune thyroiditis and in the patients with aggressive immune systems when we use intravenous immunoglobulin during the embryo transfer.

So let us resume, first of all, I want to ask you not to lose your time. If you decide to be a mother just do it and don’t lose your time. The second one is to choose your clinic, you need to look at the experience of the clinic, doctor and just believe it, you need to follow all the recommendations from your doctor because you must do all the testing the doctor prescribed and take all medications as the doctor prescribed. Last but not least, I think this is the main point, you need to believe in your success, only in case you believe in your success, you will be pregnant.

What is the success rate for the combined program? Is it possible with fresh donor eggs?

The success rates of the combined program depend on your age f. e. if we are talking only about the egg donation program itself without your own oocytes, the success rate for our egg donation program is approximately 65-67 %, this is for vitrified or fresh egg donation. If we’re combining the eggs, it depends on the embryo. If we will receive the embryo from your oocytes and you are young, up to 35, you have a 65-70% of success rate. But in case you are in advanced maternal age, over 42, and we will receive the blastocyst out of your oocytes for sure, we will have a decreased success rate if you will choose the option to transfer your own oocytes, in case you choose the vitrified oocytes, you have the best option, this is 65-67%, even more, if you don’t have any problems.

Is there an average number of frozen embryo transfers women need to go through before they succeed?

If we are talking about the cryo cycles in our clinic, the average rate is 63-65% with your own eggs, this means that you will be pregnant from the first attempt in 60-65%, so out of 100 women who underwent our frozen cycle in our clinic with own eggs from 60 to 67 of them will be pregnant. This is 1.5 embryos that will get you pregnant in the first attempt.

Is it possible to get an 80% success rate in the first IVF attempt? Or is it more often to have to do more than once? I’m 32, and he is 43 years.

Well, if you are young, so 32 years, this is a young age. If you have a tubal factor, this means that you have a good reserve, you have the good quality of the oocytes, you have the good uterus, but your tubes are blocked. This is the ideal situation for the fertility specialist, and this is the ideal situation for the patient. This is 80% for sure. About the husband, the age is not so crucial for the husband and doesn’t influence the genetic material of the sperm in such severe variants, maybe for men over 50, sometimes we can observe that the quality is decreasing, but not at the age of 43. In your case, if you are Young, if you have a good ovarian reserve, you have no polyps, you have a good uterus, you have no abnormalities, you have 80% of success.

Is there any evidence for COq10 supplements? If there is, does this improve the quality or number of the oocytes?

At every fertility conference, some sessions are controversial in reproductive medicines. This means that we have one topic that says yes, and one topic, says no. About coenzyme q-10, we have no evidence-based investigation nowadays, which can show that we have some influence on the success rates. Some investigations show us that may be due to that point that Coq10 is the energy, which we give to the oocyte when the oocytes are of advanced maternal age, and we lack that energy, but we don’t know if it works.

We have no evidence-based investigations on that, and we are not sure. We understand that this is not harmful, and it will not make it worse in that case, so if you will take it, at least it will not harm you. For sure, it doesn’t influence the number of oocytes. If it can somehow influence egg quality, it doesn’t influence the number for sure.

Please, remember that the life of the oocytes starts at least 120 days before the stimulation, so when we are undergoing the IVF treatment, we stimulate the oocytes, which started to grow approximately 120 days before. So if you want to use any supplementation to increase the quality, quantity, or whatever, you need to start it at least 120 days before your IVF treatments.

Is an AMH level of 1.59 a good level to work with if a woman is 36 years of age? How many oocytes on average can get collected?

1.5, even 1.6, this is the average level with which we can work. It is not good, and this is not bad. At the age of 36, we expect up to 10 oocytes,
so 8-10 oocytes to receive. If you will have the good quality of the oocytes, this is enough material to work with, so we expect at least 2 blastocysts for embryo transfer, and hopefully, you will be pregnant for the first time.

I had my 3 IVF cycle at 41. I produced 21, 21,31 oocytes. Most immature. My consultant uses Buserelin as my trigger. Would HCG be a better trigger?

Your doctor used Buserelin as a trigger because he tried to avoid hyperstimulation syndrome in your case. In our clinic, we also use agonists like a triggering in case we have more than 20 follicles to avoid OHSS syndrome. I understand that HCG could be better in your case, at least we can use combined triggering, this means that we can use a little bit of HCG plus agonist for triggering.

In that case, when we have immature oocytes, we sometimes use combined triggering, but you need to be aware that you can get the hyperstimulation syndrome and you need to be treated for it and you need to do some prevention of things for example to avoid embryo transfer and to be under the supervision of the doctor just to avoid severe hyperstimulation syndrome. I don’t know on which size of the follicles the doctor did some aspiration, the best option is to do triggering when the size is 20-21 millimeters.

The literature says from 18 up to 20, but I saw one investigation which shows that the best option is when we have the volume of the follicle at 2 millimeters. This means that it is exactly, 20 millimeters in size. Sometimes we can see that we receive immature oocytes when the trigger was prescribed a little bit earlier f. e. at the size, of 18 millimeters, and maybe you just need 1 or 2 days more of stimulation to have mature oocytes.

I’m 40, AMH 4.2pmol/L & low ovarian reserve. We also have male factor issues, so we use ICSI. We’re going to try our 4th cycle in August. We’re using this time to get our bodies healthy & a healthy sperm. We’re thinking of 3 cycles & then doing a frozen transfer. Only in the last cycle, we got day-5 transfer but no implantation. This was the furthest we got. I know my age is against us but do you think we should do high dose Menopur (450)or mild?

We don’t use the pure Menopur for stimulation. We always combine the recombinant follicular stimulation hormones with menopausal. Because recombinant stimulation hormones are stronger, and we have better results. We have even recombinant medicines LH plus FSH, so investigations show that there is no benefit from the dosage of more than 300 units.

If you will increase to 450, if you will increase to 500, if you will increase it to 600, you will receive the same result because results are depending on the quantity of the follicles. If you have only 2 or 3 or 4 follicles, it’s enough for them to grow on that those that you had, it makes no sense to make a higher dosage because you won’t recruit more follicles that you have. In your case, the banking is the best option for you.

When you undergo several cycles just accumulate the embryos, but we propose to cumulate them on the zygote stage and then to cultivate them all together up to day-5 and do the embryo transfer. You had one negative implantation, so for me, it will be important to investigate also the uterus. If you have all factors that will lead us to successful implementation, that you have a hysteroscopy, that you check your immune system, all your hormones, etc., only after that, we can understand the uterus is ready for the second attempt.

What the best way of taking progesterone for a mock cycle, oral or vaginal?

We are using the vaginal way as the best way because the vaginal way is a straight way to the uterus, so this is the best option. I understand that for the patient, this is not so comfortable because we have discharges on that vaginal way of inputting, but still, we prefer the vaginal way of inputting progesterone.

What are your thoughts on the administration of MENOPUR for men to increase sperm count? Do you think it can negatively affect the quality of sperm, therefore leading to fewer embryos or poor quality embryos?

This is my main rule, not to treat the men because we have an andrologist this is the specialist who is working with a man. If a gynecologist will treat the man, this is not good, so I don’t use Menopur at all for men, I’m only working with the women, but I know it’s a very tricky thing to do the stimulation for men. We can harm, and the doctor has to be experienced in using gonadotropins for the stimulation in men. Sometimes, when we have some correlation of the hormones, we can do even the castration by the administration of Menopur for men, we can stop spermatozoa with using that medicine.

So if karyotype is normal, is PGS testing not really needed?

If the karyotype is normal and if you are up to 35-years-old, PGS testing is not really needed. In case you are of advanced maternal age, this means if you are over 40, even in the case that the karyotype is normal, you need to have a PGS screening to be sure that a healthy embryo will be transferred to your uterus.

What is the risk of damaging the embryo from PGS testing?

We are talking about the highly experienced clinics with a highly experienced embryologist. In that case, this procedure can’t damage the embryo because we are taking a few cells out of the trophectoderm. The embryo has two parts, it has trophic trophectoderm, which is the external part of the embryo, and the placenta is growing from that, and we have inner cell mass, cells from which the embryo will be created, so we are talking only a few cells from the trophectoderm, and this is not a harmful procedure for the embryo, at all. After the PGS testing, we are cryopreserving the embryo, and we can have a problem with the thawing of the embryos.

The percentage of thawing after the cryopreservation is approximately 96 to 98%. This means that out of 100 cryopreserved embryos, 98 will undergo the procedure of thawing, but still from 2 to 4 embryos will die, so if we have 10 embryos for PGS screening, this means that out of 10 with 9 embryos, everything will be good, but if we have only 2 embryos, this is 50/50. In most cases, I need to clarify that we are talking about the highly experienced embryologists.

Does having a corpus luteum mean there is a cyst there. What should be done to get rid of it, is it birth control pills? If so, for how long? Do vitamins, prenatal vitamins, vitamin D, folic acid help?

The Corpus luteum is the normal structure of the ovary. When the follicle ruptures in the place of the follicle, the corpus luteum is formed, so this is the normal structure, this is not the cyst. Sometimes, we can see that inside that corpus luteum is a liquid, in that case, we understand that this is the cyst inside the corpus luteum. We just need to wait because, in 98% of cases, our cysts are disappearing by themselves within 1 month. If you see that your cyst is big or doesn’t decrease or is there for 2 or 3 cycles then, of course, you can have birth control pills.

The follicle needs to rupture, and sometimes, when it doesn’t rupture, it starts to grow and out of the follicle, we can get a cyst, so this cyst produces estrogens, and this is like a circle, the cyst is growing out of estrogen because of estrogens, and the cyst is producing estrogens. So the cyst is feeding itself. When we’re using the contraceptive pills, we are just decreasing the level of estrogens, and the cyst is not growing anymore, but in most cases, you don’t need to take anything, and the cyst will just disappear by itself in a month.

You mentioned you do sperm DNA Fragmentation as a 1st line. If there is a high level of fragmentation, what can you do to fix it? Our clinic said not necessary to check DNA Fragmentation for my husband, but I want to push for this before we do our 4th ICSI cycle.

In Ukraine, we don’t have any insurance and the patients pay themselves for the procedures and the IVF a procedure as well. We are performing all the testing that we can to do before the IVF procedure just to exclude negative attempts, therefore, we have such a high percentage of success rate because we are using all testing in advance just to prevent the patient from a negative attempt.

What about DNA fragmentation, as you said that you have 4 negative attempts, so you have already experienced negative attempts, and you need to understand why your attempts were negative before you will do the next one. I think that DNA fragmentation is not so hard to do because this is the sperm sample, and you will receive the information is its high percentage of damaged spermatozoa or not.

Our andrologist uses different supplementations, vitamins, antioxidants to decrease the level of DNA fragmentation, and we see the results for example we saw that approximately 20% of normospermia when we have the normal measurement of the sperm those patients have increased DNA fragmentation. When we have a negative attempt or we have no embryos for the transfer, and we just start to investigate the husband more because we didn’t do this because we had a normal sperm on a spermogram, and we have no indications for the DNA fragmentation. In that case, if we see you have high DNA fragmentation and our andrologist works with a patient and decreases the level, then we have a good result even in the blastoration rate and, of course, in success rates in pregnancy.

I am 37 and have one ovary after a borderline tumor on the other one, AMH is 0.5, and I had 1 failed IVF last November. Before moving to the 2nd attempt, what tests do you recommend?

The AMH level is not enough information for me. The first question is: was it a blastocyst-stage embryo transfer, or it was a day-3 embryo transfer. For example, in our clinic, we don’t do day-3 embryo transfer, only in very rare cases because we don’t know what we are transferring.

Maybe a few years ago, it was better to transfer the embryo earlier to the uterus because it was a more natural condition for the embryo, and more likely, it would be easier for them to the implant, but nowadays we understand that on day-3 embryo is not in the uterus, on the day- 3 in our natural cycle embryo is in the uterus tube, so nowadays doctors say that if we will transfer day-3 embryo not to the tube but the uterus and we will receive the pregnancy this is like survival because they dropped into bad conditions for the embryo inside the uterus, therefore we are cultivating the embryos, up to day-5.

We understand that we have a blastocyst stage, and we have good or not good embryo for the embryo transfer, and then we can predict some chances for the pregnancy. In very rare cases, when we have f. e. patients from abroad who have only one embryo and the embryo is cryopreserved on day-3, we have less chance that it will survive up to day-5 in our conditions. Then, of course, we transfer them on day-3, but in case we have our cultivation, we don’t use the day-3 embryo to transfer. The quality of the embryos, f. e. on day-3, it can be a five-cell embryo, an eight-cell embryo, a seven-cell embryo, the quality of the embryo, also is a predictor of our chances.

If we have a good morphological day-3 embryo, then we have higher chances for success, if not, then we understand that maybe the reason is in the embryos, also we can’t exclude the uterus. I don’t know which investigations were performed, and if you know that your uterus is ready enough for the second attempt, so maybe you have any myoma, maybe you have polyps inside, or you have adenomyosis, or you have a chronic inflammatory process inside, so we need to have the answers to those questions before you will have a second attempt.

Do you have Guarantee Live Birth packages at your clinic?

We have guaranteed pregnancy packages, but we don’t have a live birth guarantee. The pregnancy is not only the question of the clinic and the team of the clinic, this is mostly the responsibility of the patients because you can have some problems with your health or some different conditions that can influence the pregnancy progress because this is nine months.

We have such packages for the surrogacy program when we understand that we are transferring the embryo to the surrogate mother, and she is under our supervision, and we understand that she is healthy and we understand, which we have, and we can guarantee the live birth. In the case, of patients programs and embryo transfer to the patients, we have the guarantee program, but only for the pregnancy, this means that we guarantee that you will be pregnant, this means that you will have ultrasound scanning and heartbeat on the ultrasound scan.

What supporting paperwork would you need if I sent over embryos?

First of all, our coordinator will contact with your clinic, and we need the tests for hepatitis B, C, HIV, and syphilis, these 4 tests, we need from your clinic on the day of embryo creation. I’m sure you did it at the clinic and your permission that you allow us to take the embryos and to take them to the clinic. Our clinic has its own courier service, this means that our medical courier will go to the clinic where you store your embryo, take the embryo, and ship it to our clinic. Those are specially trained people, so they understand that they can’t go under x-ray, they don’t leave it somewhere in a bag, they are taking the container to the cabin crew, they understand how to carry out and how to handle this tiny and so delicate material.

If at the age of 44, the embryos are genetically tested, and they are normal, what is the success rate? Is it equal to the donor egg success rate, or again age influences the success rate?

If we have embryos tested and they are healthy, you have the same success rate as with the donor eggs because our uterus is ready to implant at age 44 or 54 and so on. If we have good morphological and genetic healthy embryos, we have the same success rate as the embryo of a young woman.

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Authors
Roksolana Semchyshyn, MD, PhD

Roksolana Semchyshyn, MD, PhD

Dr. Roksolana Semchyshyn, MD, PhD, is a Head of IVF department, an experienced IVF and ultrasound diagnostics specialist from Intersono IVF Clinic in Ukraine. She has over 11 years of practical experience in the field of IVF. Dr. Roksolana is also a member of ESHRE (European Society of Reproductive Medicine) as well as a member of UARM (Member of the Ukrainian Association of Reproductive.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

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

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4705 patients’ questions answered by 158 IVF experts during 251 events.

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