How many IVF cycles are needed for a successful pregnancy?

Elias Tsakos, FRCOG
Medical Director , Embryoclinic

Category:
Donor Eggs, Embryo Transfer, Failed IVF Cycles

From this video you will find out:

Why the individualised approach is so important before starting an IVF cycle?
What are the various IVF tests performed before undergoing IVF for males and females?
How many rounds of IVF is typical?
After how many attempts with your own eggs and in which circumstances should egg donation be recommended?

How many IVF cycles are needed for a successful pregnancy?

How likely are you to have a baby after one, two or three IVF cycles?

During this webinar, Dr Elias Tsakos, FRCOG, Medical Director at Embryoclinic – Assisted Reproduction Clinic in Thessaloniki, Greece, talked about factors that affect successful IVF cycles and how many cycles are usually needed to achieve pregnancy. Dr Tsakos started his lecture by answering the main question of the topic: How many IVF cycles are needed for a successful pregnancy? According to Dr Tsakos, a very clear answer is: it depends on the individual case, how you set up before you start your possible successful outcome, etc. The first thing we should do is try to define what is a successful outcome by investigating all the individual circumstances and setting out a possible number of treatment cycles necessary. We always need to take the couple’s history, and their particular circumstances into account. It’s very important to define the chances that this particular couple has. If we have a young couple in their early 30s who haven’t done IVF before. The female has a possible tubal factor, her partner has a small male factor or even with unexplained infertility, we’re talking about a 40-50% of success rate per embryo transfer. Statistically, within a couple of transfers, this couple could be successful. With 1 stimulation cycle, we can more or less ensure 2 or 3 embryos for transfer if a couple is in their early thirties and if the female has a normal ovarian reserve. A maximum of 2 or 3 embryo transfers would suffice for achieving a successful pregnancy in such a couple. However, things may be more complicated if this couple has been unsuccessful before. The more failures a couple has, regardless of their age, the less chance of success they have regardless of whether they change units or not. Therefore, Dr Tsakos emphasised the importance of adequately investigating the couples.

Essential investigations before IVF

Dr Tsakos agreed that checking the karyotype or checking very standard endocrine profiles, including thyroid function and prolactin levels, is part of the essential investigations. Some people would go a bit further and would include some sort of elaborate tubal or uterine assessment with hysteroscopy as part of their investigation. Unfortunately, there’s no agreement between doctors all over the world sometimes, there’s not even an agreement between doctors within the same unit as to what consists of baseline investigation. In the last 10-20 years, the way of investigating patients have been changed in what is essential and what is not. Thirty years ago, scan machines were not as technologically advanced as they are today. We used to perform more laparoscopies than we do now. On the other hand, Dr Tsakos added that his impression is that doctors tend to investigate less and less. If we have a couple in the mid-30s, at 35-37-year-old females with more or less the same age or slightly older or younger male partner, then the success rate decreases, and in general, it is between 35-40% per embryo transfer. In such a case, we would probably need 2 or 3 embryo transfers to achieve a successful outcome. This changes dramatically when the female age is near the age of 40. It is normal for the AMH to be low at that age. The success rate decreases dramatically to 20% per embryo transfer, and in those cases, we may need 3, 4 or even 5 embryo transfers to achieve success. Beyond the age of 40, the success rate drops even more, and in those patients, we may need 5 or 6 embryo transfers if we want to achieve pregnancy. This is all in general besides the age factor, we also have additional factors like previous failures or previously diagnosed pathology related to infertility like endometriosis, PCOS, pelvic inflammatory disease, multiple IVF failures, miscarriages, male factors infertility, and so forth. In those cases, the couple may need more IVF attempts to achieve a pregnancy. It’s crucial to work with the patients as a team and work together to improve the odds by improving factors that can be improved. If we have a 40-year-old female, we cannot make her younger, however, we can give her the best possible chance by addressing all those factors that influence success, all the physical, emotional and psychological factors. It’s up to the whole team to ensure adequate support and counselling to empower a couple to move on after the failure.

I always like to lay on the table all the other possibilities and all the other options. For example, if we have a couple and a female is 40 or a single woman who has tried 3-5 implantations in the past with adequately normal embryos then I would like to offer them something extra. There’s no point expecting a different result by repeating the same technique. I’m a big fan of a thorough investigation, I’m a big fan of exploring all the important areas of investigation before I move on, especially in couples who had a failure in the past.

Other important aspects of investigation include genetics, endocrinology factors, also stimulation protocols that need to be correct, we need to ensure that the collection and embryo transfer are done perfectly. We also need to make sure that the lab is working well based on the Key Performance Indicator.

PGT-A indication

The possibility of success associated with couples or single females using their own material sometimes can come to the end. If a female with or without a partner with their own genetic material is in her early 40s and she has tried 3-5 times with her own eggs, and if she has explored all the genetics, immunology or anatomy assessments and everything seems to be optimized, and there has been a failure, then maybe we’ll have the last resort of PGT-A because as we all know when we see a healthy embryo under the microscope, it doesn’t necessarily mean that this is a genetically intact embryo. PGT-A testing of the embryo is giving us this extra confidence that we’re transferring a euploid embryo. That would be a step further to ensure that we give the couples the maximum possible chance.

Male factor

When the genetic factor has been explored, we need to investigate the male partner. For a male with normal or fairly normal sperm count or with reasonably normal parameters that will allow us to use the ICSI technique, we can further investigate it. We can check genetics, and DNA fragmentation, we also need to ensure that the endocrinology profile of the male is normal and check that the embryos are capable of producing healthy blastocysts. If we genetically check these embryos and they are normal, we can be fairly confident that the male side of the equation is normal before moving on.

Egg donation

There’s always a moment in time when we will start thinking about using donated gametes. It usually refers to egg donation, especially in females of advanced reproductive age, with repeated implantation failures or miscarriages who have thoroughly explored the possibility of IVF with their own eggs. After 4,5 or 6 embryo transfers in a female in her early or mid, or late 40s, it’s probably time to move on to egg donation. It’s never an easy decision, it has to be made by the couple, it’s a huge crossroad that the couple has to move on together empowered by knowledge and psychological support. If they do, the tables are turned. In egg donation, we are looking into an accumulative success rate of more than 90% per embryo transfer. That means that 9 out of 10 couples after 1, 2 or maximum of 3 attempts with an embryo created by a young egg donor and a healthy sperm of the partner, will achieve pregnancy. There is a small proportion of the population, less than 10% that will still fail. IVF can never be 100%, unfortunately, whether we use own eggs, egg donation, or embryo donation, it will never be achieved worldwide. What happens if we use egg donation and we’re still unsuccessful in 2 or 3 attempts? Then again, we open the cards again, we will review the whole file again, and ensure that all investigations have been made. It’s so important for all patients to always question whether they have been fully investigated and ensure that you challenge the doctors before you move on to any important next step.

Embryo donation

After the egg donation, we have the embryo donation, and it is indicated when there have been failures with egg donation and own sperm. In particular, it is associated with bad quality sperm that has been known beforehand, unfortunately, the same way women age, men age as well, perhaps a bit later in terms of genetics, but it is a common thing to have men attending the clinic in their late 40s, early or late 50s, early 60s, and it’s very common to have abnormal sperm parameters, and abnormal sperm sometimes produces abnormal embryos which may not be seen under the microscope, not even after the genetic biopsy. In those cases, after many unsuccessful attempts, embryo donation might be an option for those couples to move forward. When we use embryo donation, we work in the area of more than 90% overall success rate after a couple of transfers embryo transfers, we insist on the single-embryo transfer of the top quality embryo.

Surrogacy

The question always remains: how much do you want to be a parent? When the answer is very much, the next question would be: how far would you prepare to go? If a couple or single woman are prepared to go all the way, then all the way involves gestational surrogacy. In this case, we can have a child with or without the use of genetics of the parents or the single mother and the use of a gestational surrogate who would carry either a genetically linked child with intended parents or a genetically different child from a third donor or donors. There are various options, you can use your own eggs and a surrogate, egg donor and a surrogate or embryo donation and a surrogate. The overall success rate of this program is nearly 100%. Take-home messages are that as long as the couple understands their odds, and that there is a specific percentage of success related to the type of IVF we perform for each one of them and as long as they understand that we know what to expect from the treatment, and we know when to move on to the next treatment and as long as they are prepared to accept those options, probably more than 95% of the couples or single women will eventually achieve a pregnancy within maximum 3-5 embryo transfers overall. After own eggs IVF, egg donation, and embryo donation are exhausted, the vast majority, perhaps 95% of couples if not more, will achieve pregnancy with a maximum of 3 to 5 embryo transfers.

How likely are you to have a baby after one, two or three IVF cycles? - Questions and Answers

What about patients with only one ovary and poor response who get just 1 embryo for transfer and do not want egg donation?

I would keep going as long as patients produce at least 1 embryo, we can keep going. The good news is that if there is a poor response with 1 embryo with 1 egg or with 1 or 2 follicles, we don’t even need to do any major stimulation. Doing a natural cycle can be very successful, or using a mild stimulation cycle either with Clomid or Letrozole plus or minus a small dose of FSH could successfully give us 1 or 2 follicles and 1 embryo. Anyone at a reasonable age, for me using own eggs, is under 45 who is willing to keep going, and as long as they produce an embryo, I would just keep going. That depends on the age and how many unsuccessful implantations they’ve had so far. There’s always the option of PGT-A testing the embryo or the embryos to ensure that at least we transfer a healthy embryo. Egg donation is not obligatory, and to be honest, it’s not that widely available. There is a misconception about egg donation, the patients do understand when they need egg donation. They ask for it when they’re ready psychologically, physically and when they understand they have explored the chance of using their own material fully. In our clinic (Embryoclinic), we would always mention that egg donation may be an option for somebody with multiple IVF failures, especially if they’re in the early 40s, we would always mention that as an option, but as long as someone is producing eggs and it is safe to proceed with the egg collections and transfers, we would like to explore that fully, before resorting to egg donation.

Is it true that the embryo itself plays the most crucial role in 80%, and all other factors account for the rest 15-20%?

The embryo is important, I’m not sure about the figures, I have seen some figures similar to that, but I’m not sure where they came from. I had a case today I had a request from a patient in her late 40s with 20 years of infertility, she had 10 or 12 IVF failures with her own eggs, she had laparoscopies, ectopic pregnancies, pelvic infections, multiple IVF failures including embryo donation, that patient clearly should go for surrogacy. Yes, the embryo is significant, but let’s not forget the endometrium, the recipient, the health of a female, a big component is the uterus, the endometrium, but there are other factors. There are women in their late 40s who are fit as a fiddle, and there are women in the late 30s who are seriously overweight, who have diabetes, adenomyosis, scarring in their uterus, fibroids and so forth. It is important to be clear about the value of a good embryo, that’s why we need to ensure that we have top-quality embryos. If we’re unsure about the embryos, it’s better to either wait until we become more certain or don’t transfer. I think every clinic have their own standards, and thankfully most clinics don’t transfer embryos that are not of good quality. I think it’s very important to understand that every single factor is important.

What do you mean by a healthy endometrium? Hysteroscopy, check for endometritis and lactobacillus?

You can never be 100% sure about the health of the endometrium, but in my opinion, the minimum level of investigation of the endometrium includes a very good quality ultrasound scan performed by somebody who is an expert in vaginal scanning and with using very high-tech equipment, and that has to be coupled with some sort of hysterosalpingogram test whether it’s X-ray or HyCoSy perhaps that’s a big question. However, a scan is not enough, some sort of imaging of the uterus and the tubes, the endometrium is needed. Keep in mind that hysteroscopy is part of the essential assessment of the endometrium in the majority of cases. For me, these 3 are the absolute minimum. If there are multiple failures or if there are any abnormal findings, then again, doing a biopsy of the endometrium to check for histology and microbiome may also play a role. Since it’s still March, which is endometriosis awareness month, let’s not forget about it. Endometriosis is very common, especially in infertile patients. The more we have advanced IVF technology and science, the more we have forgotten the importance of endometriosis and the fact that endometriosis may only be diagnosed by laparoscopy. We don’t want to do laparoscopies, our patients don’t want to have laparoscopies done, but let’s not forget the endometriosis factor associated with inflammation and infertility and IVF failure.

Me and my husband have no problem making euploid embryos in 2.5 years of trying followed by 7 euploid transfers, I have not had a single positive pregnancy test. After exhausting all evidence-based investigations (autoimmune screen, thrombophilia screen, HSG, hysteroscopy, ERA, EMMA, ALICE, karyotyping), we just had immune testing, I have high NK cells and complete DQ alpha match with my husband. I have been advised to try LIT and then a transfer cycle with steroids and intralipids. Realistically, what is the chance that I will get a positive test followed by a live birth? I am 36.

I would keep going, it sounds like a long shot, but you’re still young, you have high-quality euploid blastocysts, you seem to have done all the things. I would consider a laparoscopy in your case to exclude endometriosis that is not visible on scans or other tests to ensure that you don’t have any inflammation factors in your tubes or your pelvis. I would get the most senior person in the unit to do the embryo transfer, let’s not forget that embryo transfer is like shooting a penalty, you have the whole team working for 90 minutes, and then somebody has to hit the penalty, and somebody has to score. There’s a lot of stress, for me, the embryo transfer is a penalty because it will give us success or failure, but it has to get there, it has to be perfect, and the more I look around, the more I discuss with my colleagues all over the world, I understand that there’s a huge variation of the embryo transfer technique. Unfortunately, even after 7 embryo transfers, there are still some areas that may go wrong. I would probably suggest a laparoscopy to ensure that the pelvic area is normal. I’m not a huge fan of intralipids, but they probably don’t do any harm. I would use steroids, possibly Aspirin, and Low Molecular Weight Heparin (LMWH) to ensure that at least I have covered empirically all the areas that may affect. I would very carefully monitor the progesterone levels, I would be very careful in monitoring the frozen embryo transfer cycle, there’s a huge variation in how people manage the embryo transfer cycles. I would get perhaps a second opinion on how to do that on a natural embryo transfer, frozen embryo transfer, medicated with or without down-regulation, there are so many variables. After having so many transfers, I would like to be sure that they’re done perfectly.

I went for a hysteroscopy and was told my uterine lining is thin. What can I do so I have success for pregnancy and implantation?

This is tricky and difficult as it depends on how thin is thin. Thin is 7.5-7.7 millimetres after adequate estrogen priming, thin is 5 millimetres after priming, and again endometrium is not just about thickness, it’s also about the shape and the way it looks. It’s also about the stage during the cycle and whether there are adhesions or not in the uterus. In my opinion, if there is a concern about your thin endometrium, there is a risk that this may be associated with adhesions with scar tissue, unfortunately, there isn’t any magic wand to treat adhesions and Ascherman’s syndrome of the uterus as we call it. This is the time when you probably would need to consult your fertility specialist. If your fertility specialist is also a fertility surgery specialist, they would be able to advise whether that is something that could be treated by hysteroscopy. This is something that can be managed by medical treatment, which would achieve an adequate thickness of the endometrium and In my opinion, the minimum that the endometrium has to go to for a fairly good chance of success is more than 7 millimetres with a fairly normal shape. If that can be achieved, then various protocols can work in that direction, medical protocols may be repeated hysteroscopies, and if this is the case, then move on to implantation. If that’s not the case, or if you’re far below 7 millimetres and you’ve had lots of failed implantations, then maybe you should start thinking about surrogacy. The uterus mainly consists of 2 components: the wall and the lining, so it is not uncommon to have a very normal wall, and this is what most people refer to as the uterus looks good, but then the lining can be bad. They’re both important for successful implantation and successful pregnancy. The most significant is the lining, it’s more important than the wall. An abnormal wall can be a result of previous surgery for fibroids or adenomyosis, Caesarean scars, ectopic pregnancies involving the uterus, etc. It is an issue, it is the factor that gives a chance of a successful IVF and a successful pregnancy by 20-30 %, but the most crucial factor is the endometrium.

What about a 41-year-old with a 24 AMH level?

That’s probably good news, but that probably means that there is some sort of polycystic ovaries. I prefer polycystic ovaries at 41 than not. Why? Because I get many eggs, of course, many of those eggs are not of good quality, but usually, we can work with some of them, the good quality ones. If they’re not polycystic ovaries, then they probably behave like that. This is a potential for good stimulation and the production of a lot of mature, probably good quality eggs. In my opinion, it’s probably a good factor to move on with your own eggs.

Does ICSI have a positive/negative impact on the success of embryo transfer?

It depends is the answer. There’s a lot of literature on ICSI, there’s also a bit of controversy about it. Some reports are saying that maybe if the sperm is normal and if the eggs are of good quality, maybe ICSI does not produce better quality embryos than conventional IVF. I’m not sure about that because there are a lot of factors that may affect the quality of fertilization. To have a successful embryo transfer, you have to have good quality embryos and to have good quality embryos, and after you’ve had good quality eggs in the egg collection, you need to have good fertilization. Sometimes we have fertilization surprises, and sometimes, we have bad surprises, so I think the big question is how do we differentiate whether to use ICSI or standard IVF on our patients. There are a lot of factors that may produce abnormal fertilization even when it’s least expected. For example, if we have a young female in her early 30s who’s having IVF for tubal factor and if we have a young male in his mid-30s with normal sperm, we would probably use standard IVF. In that case, I don’t think ICSI would make a huge difference. However, a small proportion of those patients may have a hidden sperm factor or a hidden female factor affecting the oocyte quality, and we may have a bad surprise of very poor fertilization. We collect 10 eggs from a 32-year-old, we have normal sperm on the day of that collection and then out of 10 eggs, we have 2 fertilize, it’s not common, but it happens. We end up using ICSI more and more. In my practice and what I would probably suggest to my patients, firstly I think it’s important to make it clear to the patients that what we do in the lab is to give you the best possible success. That’s why in my unit, we don’t charge extra for whatever we do in the lab to achieve better results and better fertilization rates and better top quality embryo creation rates. There’s no such thing as IVF plus ICSI, assisted hatching, time-lapse, EmbryoGlue, etc. We disconnect all those extras that we can do in the lab for any additional costs to patients because this is giving us the freedom to do whatever is necessary to achieve the best possible embryos for patients. From a mid-30s couple, I collect 10 eggs, and if I have a perfect sperm, maybe I will do 5 IVF and 5 ICSI. By doing this, I don’t risk having a very low fertilization rate of an unknown factor that would influence the conventional IVF success rate. The older the female, the more I would use ICSI and the older the male, the more ICSI I would use versus conventional IVF. Then you have the frozen sperm that we use quite often for various reasons, in which case I would use ICSI and not standard IVF. ICSI is giving us more standardized fertilization results and rates than conventional IVF, and it’s securing some good fertilization rates for our patients for either the majority of their eggs or not all of their eggs. I think ICSI, whether we want it or not, is becoming the norm for the majority of our patients nowadays.

I’m using a sperm donor as a single woman. I had 4 failed transfers, I have 1 embryo left. I have been advised to do an endometrial scratch. Is this effective? I just turned 40.

After 4 failed embryo transfers, I would probably suggest hysteroscopy as soon as possible. It should be done close to the embryo transfer time, not just a scratch, a hysteroscopy, and a scratch. Then the embryo is transferred by the most experienced person, and the full luteal support afterwards, so good doses of progesterone, adequate estrogen and maybe empirical aspirin steroids, and Low Molecular Weight Heparin (LMWH), just to cover all the other possible areas of failure.

Do multiple IVF cycles have an accumulative negative impact on the woman’s health and on how many healthy embryos she could create? Could the process mean quality decreases?

I wouldn’t go indefinitely for embryo transfers, and as I mentioned, I would not use the same recipe if I found that this is unsuccessful, even if I cannot explain the failure. IVF is a wonderful opportunity for a thorough female checkup, we insist on thorough cervical screening, a formal breast screening using either a breast ultrasound scan or mammography, even that’s not part of the guidelines in many countries offered under the public health guidelines. I don’t think that the quality fails with the number of IVFs we perform. The quality is hugely related to age, so if we do 2 or 3 IVF cycles within the same year, I don’t think the quality is affected by the IVF cycles. However, if we do 1 every cycle this year and 1 next year and 1 third year, the later we do it, the quality perhaps will be a bit less, but that’s related to the female age.

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Authors

Elias Tsakos, FRCOG

Dr Elias Tsakos, FRCOG, is a Medical Director of Embryoclinic - Assisted Reproduction Clinic in Thessaloniki, Greece. He has received extensive and certified training in the United Kingdom and is a Fellow of the Royal College of Obstetrics & Gynaecology. Dr Tsakos is also a Board Member Representative of the Royal College for Greece and Cyprus and a Board Member of the Hellenic Society of Assisted Reproduction. He is a Member of the British, European and American Fertility Societies (BFS, ESHRE, ASRM). Dr Tsakos has been living and working in Thessaloniki, Greece, since 1999.

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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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