How many IVF cycles do I need for a successful pregnancy?

Dr Miguel Ángel Checa, Fertty: I work as one of the founders of Fertty Clinic in Barcelona, and I am a Professor at the University Pompeu Fabra and Director of the Master of Assisted Reproduction at the University Autònoma in Barcelona. We have published more than 100 papers, and we have been doing lectures in ASRM for many years. Particularly, I specialize in advanced maternal age and egg donation.

What is a successful pregnancy? A successful pregnancy is normally when you have a positive result, and finally, you see a sac in the uterus and finally have a baby at home. Normally, in our clinics, we follow these patients until we reach mid-pregnancy. Most of our patients go outside our country, but for us, a successful pregnancy is when we see the evolution to 21 weeks because this is part of the pregnancy. The other are complications of the pregnancy.

Dr Violeta Fodina, PhD, IVF Riga: I‘m a reproductive specialist and Medical Director of IVF Riga. I am a PhD doctor from the University of Latvia and the author of 3 original papers; 1 is on failed implantation in IVF cycles.

The answer to your question is: IVF success is the results we are getting after the embryo transfer. The embryo transfer can happen several times, and if we are doing the treatment more successfully and getting positive results, we need to focus on the most important examinations we can do before the embryo transfer. Our focus in the clinic is on treating difficult patients, especially those with failed implantation. In our clinic, we have 3 laboratories that combine activities to help one of the patients. This includes the embryo laboratory, genetic laboratory, and immunologic laboratory. The specialists in all these fields can combine their expertise to decrease the chances of pregnancy and achieve positive results.

Prof. Dr Ana Teresa Almeida Santos, Eugin: I’m a professor at the University of Coimbra at Eugin Clinic in Portugal. We are a fertility clinic that is well known in Europe, but in Coimbra, we have only been here for 1 year. I have been doing Reproductive Medicine for 30 years now, and we perform a lot of egg donation treatments with non-anonymous donors, which is not very common in Europe. Therefore, we specialise in this type of treatment.

The most important determinant for the number of IVF attempts is the age of the woman because it is the main influence on the quality of eggs and embryos. Nothing is more important than age, indeed age matters a lot. If we have several failed IVF cycles even with own eggs, we must try to discuss egg donation.

Dr Miguel Ángel Checa, Fertty: Age is the most important determinant for success rates in IVF. We always work with preimplantation genetic testing (PGT) when a woman is over 37 years old because it helps ensure the transfer of a healthy embryo, reducing the chances of failed attempts or miscarriage. For a 45-year-old woman, if three attempts have failed without pregnancy, the next step is usually egg donation. In our clinic, if three IVF cycles don’t result in pregnancy, the best approach is to switch to egg donation.

Dr Violeta Fodina, PhD, IVF Riga: Pregnancy results depend not only on embryo quality but also on other factors. One important factor is the status of the uterus and its ability to support implantation. We can test the endometrium for its receptivity, the timing of implantation, and the activity of the endometrium. Additionally, factors like coagulation disorders, hormonal levels, and immunological conditions can affect the chances of success. If the patient has had long-term unsuccessful treatment, I would recommend focusing on these factors. We could also explore immunological treatments, such as the injection of a partner’s cells, which could increase the chances of pregnancy. This is a newer procedure, and I plan to publish a paper on it soon.

Prof. Dr Ana Teresa Almeida Santos, Eugin: The first thing I will tell you is that in Portugal, IVF is not allowed over 50, and this is a reason. It’s because of the risks of pregnancy in women over 50. This patient must be aware of the higher risks of pregnancy at that age. Once she is aware of that, she must, of course, try to find a centre in a country where it is allowed, and where egg donation is done with quality, meaning the donors are screened for infections and also more frequent genetic diseases. This is what I would say to her because the treatment is the same everywhere. IVF is not very different from one lab to another. So, the main question would be the type of gametes that she will use and the main risks of pregnancy at this age.

To prepare for egg donation treatment, it would be important to check if the uterus is okay if there are no problems in the uterus, and if the endometrium grows as it should. We also need to check if there are no other pathologies, such as cardiac issues, that would be dangerous for pregnancy. She should have, in Portugal, mandatory screening for heart diseases and also a general check-up to ensure that everything is okay for her to get pregnant and not worsen any health issues she may have.

Dr Violeta Fodina, PhD, IVF Riga: When I see patients over 40, I usually start by discussing the possible pregnancy outcomes using the Poseidon criteria. I explain to my patients that the results of the treatment depend first and foremost on ovarian reserve, which we check through the Bologna criteria—this involves three points: AMH, FSH, and AFC. When we know how many eggs we can retrieve, we can recalculate the possible chances using the Poseidon criteria. The results are completely different for a 40-year-old patient with approximately 15 eggs after retrieval versus someone with only two eggs retrieved.

There was an interesting publication in Fertility and Sterility that showed the percentage of viable embryos from patients of different ages. Women over 40, for example, showed a starting point of about 20%. This gives us a rough idea: if we get 10 blastocysts, the chances of having a normal embryo and a successful pregnancy are high. But if the response is low, unfortunately, the percentage is not as high.

In general, the average chance of a woman over 40 getting pregnant is around 15-20%.

Dr Violeta Fodina, PhD, IVF Riga: I think if we examine the patient well and know what is wrong, it’s easier to address these factors. The factor V Leiden mutation is not too concerning; we would use low molecular weight heparin and compensate for this factor. If we talk about the KIR (killer immunoglobulin receptors), we focus on this question as well. In just two minutes, I can explain that our previous strategy involved examining the embryos for the CAA receptors. Now, we’ve shifted to using the lead procedure for this patient because patients with KIR mutations have a higher risk for non-implantation, early miscarriages, and, if pregnancy does occur, the risk of placental insufficiency, leading to problems in the third trimester. Knowing these factors, we can try to address them during the preparation phase. In terms of ovarian reserve, this patient has the same chances as other women over 40. I would focus more on ovarian reserve and the possibility of getting a good embryo.

Dr Violeta Fodina, PhD, IVF Riga: In Latvia, we have had a very liberal law since 2006. You might be surprised, but we don’t have an age restriction for egg donation. However, we do have clinic-specific rules. I completely agree with my colleagues from Portugal and am also very sceptical about pregnancy after 50 due to the high risks associated with pregnancy at that age, including gestational diabetes, placental abruption, arterial hypertension, and other complications for both the mother and child. If we talk about egg donation, I’ve answered the question already. But for using one’s own eggs, we try to do the maximum we can, but we aren’t gods and don’t have magic pills to change the age of the eggs. My personal opinion is that we need to focus on analysing each patient before starting IVF treatment, and if we see that the chances are very low, we need to explain that to the patient and provide a realistic picture.

Dr Miguel Ángel Checa, Fertty: In Spain, there is a recommendation, not a law, that we don’t perform IVF after 50. Our clinic restricts IVF to patients under 50, and we don’t go beyond 45 because, after years of practice, we’ve seen no pregnancies in patients over 45. We are a serious clinic and don’t want to give false hope to patients for treatments that haven’t yielded results.

Regarding the KIR AA question, I don’t want to scare patients, but there have been many papers published recently showing that KIR AA mismatching is not an incompatibility. It only increases the risk of miscarriage and preeclampsia, but it’s not an obstacle to implantation. We should be cautious about over-treating patients with unnecessary immunological tests that don’t improve pregnancy chances. These tests should only be applied to patients with specific issues like implantation failure or repeated miscarriages.

Dr Miguel Ángel Checa, Fertty: We started using endometrial receptivity tests many years ago, and I’ve published research on this. However, it’s not a good tool to use for every patient. We’ve seen that for most patients, endometrial receptivity testing doesn’t significantly increase pregnancy chances. In fact, we’ve recently shifted our approach to using a natural cycle for embryo transfers, and the pregnancy chances are equal to or even higher than using hormonal replacement therapy. I think these tests should be restricted to patients with clear issues like multiple embryo transfers with no success. With good embryos and a good clinic, the chances of pregnancy are high. We need to focus on obtaining good embryos to achieve a pregnancy, as doing tests for marginal improvements isn’t helpful in most cases.

Prof. Dr Ana Teresa Almeida Santos, Eugin: Yes, I agree that PGT-A is a good tool for women who have a high risk of aneuploidy, which is typically over the age of 41 or 42. But, of course, we need to have enough embryos that reach day five to perform PGT-A. The issue is that women over 41 or 42 often do not have many embryos. But if they do, I would counsel them to undergo PGT-A because it helps us transfer the euploid embryos, saving time, and money, and increasing the possibility of a successful pregnancy. Even if we use time-lapse monitoring to select embryos based on morphology or morphodynamic characteristics, it is not enough at that age. As far as the embryo’s ability to self-correct, even though it’s been described in papers, I don’t think it’s something we should rely on. If we can select the best euploid embryo, that is the best course of action for the patient at that age.

Dr Miguel Ángel Checa, Fertty: I recommend PGT-A for all my patients after 37 years old. It’s the best way to avoid failed transfers and to achieve a successful pregnancy as soon as possible. I know we can transfer all embryos and eventually find the viable one, but it comes at a high emotional and financial cost. PGT-A allows us to explain to the patient what’s happening. Sometimes the problem may come from the man, not always the woman. Nowadays, we can analyze the origin of aneuploidy to be more successful, whether it means considering egg or sperm donation in the future. PGT-A is the key to success.

Dr Miguel Ángel Checa, Fertty: It depends on the age of the woman. If there’s only one embryo, I usually recommend embryo banking—collecting more embryos—so that we can choose the best one after PGT-A. But if there’s just one embryo, I would be more cautious.

Prof. Dr Ana Teresa Almeida Santos, Eugin: If the patient agrees, yes. I think it’s the best way to have a diagnosis. But normally, patients prefer to do the transfer if they only have one embryo. It’s more often a psychological decision.

Dr Violeta Fodina, PhD, IVF Riga: Regarding the first question about the lady with 3 aneuploid embryos, from my experience, in many cases, we are not just dealing with aneuploidy but with mosaic embryos. It’s important not to discard them without understanding the type of mosaicism. We need the help of clinical geneticists to determine whether the embryo can develop properly or if there’s a higher risk of implantation failure or miscarriage.

For the second question about having just one embryo, I agree with my colleagues. I would recommend embryo banking to have more options and perform PGT-A before transferring to increase the chances of a healthy pregnancy.

Dr Violeta Fodina, PhD, IVF Riga: First of all, it’s a question about the quality of the eggs at 42 years old, so what I would do is examine the patient deeply for hormonal status. Of course, we need to exclude hypothyroidism and check for elevated testosterone. That’s the first step. The second is excluding factors that affect egg quality, like anti-ovarian antibodies. We also need to assess the quantity of eggs, and based on that, we can suggest what the chances are for producing high-quality embryos. We must not forget about the man’s role, either. One option we typically perform is a DNA fragmentation test to assess sperm quality, as monosomy can also be a result of male factor issues.

Prof. Dr Ana Teresa Almeida Santos, Eugin: I would do double stimulation because it’s the fastest way to retrieve a high number of oocytes in this patient. If there are follicles that can be stimulated in the second round of stimulation, that would be ideal. If not, I would suggest another round later on. It’s important to get a good number of eggs to ensure we obtain euploid embryos. I often recommend double stimulation, as sometimes the luteal phase stimulation response can be better than the initial one. I think it’s worth trying.

Dr Miguel Ángel Checa, Fertty: Yes, we do, but it depends on the moment in the cycle. Sometimes I see antral follicles in the luteal phase and start stimulation then. But not always—we tailor it based on the cycle. For a woman at 43 with these numbers, I would likely need at least 4 or 5 cycles to achieve 1 euploid embryo.

Dr Violeta Fodina, PhD, IVF Riga: The 35-year-old patient still has a good chance of producing high-quality embryos. Even with one failed attempt, it doesn’t mean she won’t succeed next time. The chances of success are still over 50% in our experience. To improve embryo quality, I would recommend a full examination to rule out any contributing factors, but her chances remain good overall.

Prof. Dr Ana Teresa Almeida Santos, Eugin:  That’s not a difficult question. If everything checks out—thyroid function, vitamin D, prolactin, and other hormones—then I would simply recommend folic acid and a healthy diet.

Dr Miguel Ángel Checa, Fertty: Probably diet is better than supplements. Mediterranean diet has been demonstrated to enhance pregnancy chances. So, I’d recommend folic acid, vitamin D if levels are low, and sticking to a Mediterranean diet—vegetables, seeds, fruits, white meat, avoiding soft drinks, minimizing coffee, no alcohol or tobacco. That approach can help more than taking a lot of supplements like CoQ10.

Dr Violeta Fodina, PhD, IVF Riga: Yes, I agree with my colleagues. Patients shouldn’t take too many supplements. They often come in with a bag of them! The key is folic acid and inositol, which can help with cell regeneration during stimulation. Another important factor is managing weight—overweight patients may benefit from weight correction before starting IVF, as it can improve egg quality across all ages.

Prof. Dr Ana Teresa Almeida Santos, Eugin: The IVF laboratory is fundamental for the success of IVF. Of course, if you have a good lab, you have higher chances of pregnancy. For recurrent implantation failure, I don’t think the lab will directly affect the rate of implantation, but it can determine the quality of the embryos, especially the blastocysts. It is very important to check your results weekly to ensure that fertilization rates and blastocyst rates are consistent. If not, you need to adjust something. So yes, the lab is a very important part of IVF treatment for me.

Dr Violeta Fodina, PhD, IVF Riga: If I saw a patient who has experienced multiple pregnancy losses, especially with genetic issues like trisomy, the first step would be to do a karyotype for both partners. There’s a high chance of finding something like a Robertsonian translocation from either the woman or the man. Depending on the results, we can decide on the next steps. From what I understand from the question, the egg donation was done using the husband’s sperm, so it would make sense to do a karyotype on him and then proceed based on those results.

Prof. Dr Ana Teresa Almeida Santos, Eugin: Yes, I agree. We always do a karyotype before PGT-A, so if they haven’t done it yet, it’s essential. If there’s no chromosomal abnormality, I would consider moving to a double donation. It’s a simpler step before considering more complex treatments.

Dr Miguel Ángel Checa, Fertty: I completely agree. We perform karyotyping in all our patients, and probably, these particular patients are out of our scope of reproductive medicine because, based on the failures, it’s likely more related to advanced age, and the issues are beyond our expertise. There’s space for immunology, thrombophilia, and all the complications related to pregnancy. The focus should be on achieving a pregnancy, and this woman has achieved many pregnancies, so the problem might be beyond our initial treatment focus.

Dr Miguel Ángel Checa, Fertty: We do DNA fragmentation testing because recent studies with 300 donor egg cycles have shown no difference in pregnancy rates whether sperm analysis is done or not. For a donor aged 22 and a male aged 49, I wouldn’t recommend PGT-A. Studies show that the pregnancy rates with or without PGT-A are the same for younger donors. The clinical pregnancy rate in our program for egg donation with one attempt is around 79%, which is what we expect in our clinic.

Prof. Dr Ana Teresa Almeida Santos, Eugin: We don’t use sperm analysis anymore because it’s not useful clinically. Even though we pioneered some of this research, we now know that sperm analysis doesn’t provide actionable information. Testing that shows 50% of sperm cells are defective is not helpful, since we can’t select them for use. It’s interesting for research, but not for clinical practice.

Dr Violeta Fodina, PhD, IVF Riga:  I agree with my colleagues. We don’t use sperm analysis anymore. Both methods are expensive for the patient. I would also recommend genetic counselling to discuss potential risks for older men, but there’s nothing to be overly concerned about.

Dr Violeta Fodina, PhD, IVF Riga:  Every case is individual, so there is no one-size-fits-all answer. If a patient has had negative results in previous cycles, they shouldn’t lose hope. It’s important to consult with a specialist who will carefully review their history. Unfortunately, reproductive age is limited, and sometimes we must stop treatment due to age. However, we always hope that, even after setbacks, the patient will eventually have a successful pregnancy.

Dr Miguel Ángel Checa, Fertty: For patients over 40, it’s essential to carefully select the right IVF protocol. Pregnancy rates are higher in women under 35, but for older women, small adjustments, such as optimizing stimulation, culture, and overall care, can make a difference. If you find good-quality embryos, the chances of success are high. However, if you don’t get viable embryos, it may be time to consider alternatives like egg donation.

Prof. Dr Ana Teresa Almeida Santos, Eugin: I would advise reviewing everything done in previous cycles, and paying attention to the details of each cycle’s success or failure. The decision to continue or change strategies depends on the patient and the embryos. If viable embryos are available, I recommend continuing, as both the embryo and the endometrium are key for implantation. If not, alternative methods, such as egg or embryo donation, may be necessary.