How many IVF cycles are needed for a successful pregnancy?

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.