During this live Q&A, our experts explored the challenges of good embryos leading to poor outcomes, discussing: possible reasons why high-quality embryos fail to implant, the role of the endometrium and immune factors in IVF success, advanced strategies to improve implantation rates.
Featuring experts:
The event was hosted by: Professor Alan Thornhill, Fertility Expert & Coach, Founder of The Fertility Guy.
Dr Jon Hausken, Klinikk Hausken: I’m from Norway. I started with IVF in ’93 because my father was one of the founders of IVF in Scandinavia. I was raised with him and IVF from when I was a child, and I’m still here. I do everything. I talk to the couples, and I do everything personally, so I’m not only the CEO.
We use the Gardner grading system for blastocysts, but we also use timelines. We know that timelines may not necessarily increase the success rate in the general population, but they provide a lot of information about how the embryo develops and its cell division. We use timelines and, in the end, a morphology grading of the blastocyst. I would say that anything less than 4AA is not a good embryo.
Dr Zane Vitina, EGV Clinic: I’m Dr Zane, a gynaecologist and reproductologist from EGV Clinic, one of the biggest— I would say the biggest—reproductive clinics in Latvia. We are a private clinic working with infertility and infertility treatment. We have an andrology centre, a tissue cell centre, and an embryology laboratory. We are the only ones who perform microsurgical sperm aspiration. I’m not only the CEO but also the medical director as well as a gynecologist and reproductologist. Therefore, I’m not the embryologist who evaluates embryos.
A good embryo is selected morphologically, and that is the job of the embryologist. We use a time-lapse incubator as well as artificial intelligence for assistance. There are three main factors for embryo evaluation:
Then, of course, we assess how the embryo develops—how cells divide, whether the cytoplasm is good enough, and fragmentation. However, if a patient is over or close to 40, a good embryo is not evaluated only according to morphological features but also based on the presence of euploidy.
Dr Raúl Olivares, Barcelona IVF: I’m the medical director of Barcelona IVF, based in Barcelona, as the name suggests. The clinic was opened in 2010, though we all come from another clinic. I’ve been working in infertility since 1994. We are lucky that in Spain, we can perform almost every treatment. We have a state-of-the-art laboratory where we use time-lapse incubators and AI to identify the best embryos in terms of morphology. We also use the Gardner classification to select and classify embryos. But in my opinion, even in the best possible scenario, the only good embryo is euploid.
We know that even with egg donation and PGT-A, around 30% of embryos will still be aneuploid. Recent studies published with data from hundreds of thousands of patients suggest that if you transfer euploid embryos, the live birth rate—which is the only outcome that matters for patients— is good. If not, you may need many transfers. This leads to the concept of implantation failure, which is very controversial.
How many embryos do we need to transfer before considering that someone is experiencing implantation failure? In my opinion, 90% of success depends on the embryo, so true implantation failure is not that common.
Dr Raúl Olivares, Barcelona IVF: Two large studies from the Lorenzi group in Italy suggest that once the embryo is euploid, morphology is no longer relevant.
They have the same implantation rate. This study is based on more than 2,000 embryos. A better-looking embryo is indeed more likely to be normal, meaning it has a higher chance of being euploid.
Once an embryo is euploid, implantation rates do not change, regardless of morphology. On top of that, we sometimes have really good embryos, but if the time-lapse data has not been perfect, it may indicate issues in embryo evolution. Time-lapse tends to provide negative rather than positive information, meaning it helps to identify problems. We may have AA embryos that are transferred after a BA embryo, simply because the BA embryo performed better in time-lapse. There are multiple criteria, not just morphology.
Dr Zane Vitina, EGV Clinic: The answer is very easy—yes.
Dr Jon Hausken, Klinikk Hausken: Yes, of course. We have all seen that. There are embryos that we think will never work, but that’s the only option the patient has. We discuss it with the patient and say, “Okay, we have this. It’s still available and alive, so we will transfer it.” They say yes, and then we see pregnancies. Morphology is, of course, not 100% accurate. You will always choose the embryo that looks best first.
You can’t start with the bad one. But yes, we have seen unexpected successes. That’s the amazing thing about IVF. You have couples who you think will never have a child, and then they succeed on the first attempt. Then you have young, fresh couples who seem like an easy case, and they need 10 attempts.
Dr Zane Vitina, EGV Clinic: Yes, it is allowed in Europe. In Latvia, for sure. It is not allowed to choose gender or do gender selection. We are asked to choose the best embryo for the first transfer. There is no problem with PGT-A at all. It is not government-funded, but yes, for sure, it is allowed.
Yes, sure. This would not be the only thing I would perform. But yes, I would offer PGT-A.
Dr Raúl Olivares, Barcelona IVF: We are allowed to do all kinds of PGT. It’s true that, depending on the type, we may need government authorization, especially for monogenic diseases. But when it comes to aneuploidy screening or translocations, there are no issues. We can do it in any case.
For a patient who has had recurrent failed transfers, or even egg donation failures, I would probably check the sperm. I think sperm quality is underrated when assessing embryo quality. Unfortunately, just as having a normal AMH doesn’t guarantee fertility, having a normal sperm analysis doesn’t guarantee fertility either.
Dr Jon Hausken, Klinikk Hausken: Yes, it’s a big question. We are not allowed yet to do PGT-A in Norway, but it will come, and I think it’s a good idea. We all know about a big study in the U.S. involving about 4,400 couples attempting IVF. They only had top-quality embryos transferred with normal PGT-A results, and in the end, after 3, 4, 5, or 6 transfers, not all, but 95% got pregnant.
What about the 5%? Couples also think about implantation, and there is much to say about implantation. You need a healthy embryo and an implantation window that will accept the embryo, so we need to discuss that a little bit. It also depends on the patients. I tell couples that PGT-A is a good idea, and I will help them because there are clinics outside this country that offer it, but it’s all about the patient.
Let’s say we have a woman aged 42. She probably will not have a top-quality embryo at all. If she has 1, we are happy. So, I always say it’s all about the number of eggs needed to create one top-quality embryo. You should cleverly use your money. Why test an embryo if she only has 1? Should we put it back or do PGT-A? It’s all about cost. If the cost is low, I love PGT-A.
Dr Raúl Olivares, Barcelona IVF: I think embryo quality is mainly related to the chances of success and implantation likelihood, but not to long-term issues in the babies. We have limited information. The first baby born after IVF is now 46 years old, and the first baby born after PGT-A is probably around 19 or 20 years old. That’s all the data we have.
So far, no evidence transferring lower-grade embryos leads to unhealthy babies. The main difference is that the chances of success are lower.
Dr Jon Hausken, Klinikk Hausken: I can follow up. I agree with you, Raúl. Children are not affected by morphology grading. The grading is not a perfect tool, but it is the best we can do when we look under a microscope. PGT-A is helpful because, for example, if a young woman has 6 top-quality embryos, it is really important to do PGT-A. Instead of transferring all 6 embryos one by one, she can do PGT-A and find out that only 1 is normal. That saves time and money.
However, some couples do not have many top-quality embryos—perhaps only one. In such cases, we need to discuss whether PGT-A is necessary or if we should transfer the embryo and see if it works.
Dr Raúl Olivares, Barcelona IVF: PGT-A does not fix anything; it just gives us information about the real quality of the embryo. It depends on how important that information is for the couple. If all 4 embryos are abnormal, they may consider egg donation rather than continuing with the same treatment. However, if they only have 1 embryo, we can offer them the option of transferring it and checking during pregnancy if it is normal.
This is particularly difficult for patients who have experienced miscarriages because they don’t want to go through that again. But in cases where there is no choice, transferring the embryo is still a valid option.
Dr Jon Hausken, Klinikk Hausken: You have to know that we want to help couples, and IVF today is very expensive. There are so many tests available, and couples don’t always know what they need, so they trust the doctor. We should be open and honest. Some tests are not necessary for everyone.
We need to keep costs down because many couples cannot afford IVF at all. We have to be responsible, not just offering test after test. I’m not against PGT-A, but are we also going to test if the tubes are open, check the implantation window, test for bacteria, or do more and more tests? Of course, patients follow the doctor’s advice, but we need to stop and ask: Is this necessary for this couple?
Dr Zane Vitina, EGV Clinic: If we determine the embryo quality is good and implantation fails, we start investigating potential causes. In Latvia, we tend to act quickly due to our reimbursement system. Reimbursement covers only two unsuccessful attempts or as many successful cycles as necessary.
We usually proceed with the first IVF cycle and transfer. If it fails, we recommend a second attempt with the patient’s own funds. If that cycle is also unsuccessful and the embryo appears to be of good quality with no obvious implantation barriers, we begin exploring possible underlying reasons. One of the first evaluations is sperm DNA fragmentation analysis. Elevated DNA fragmentation in sperm is a leading cause of male-factor infertility, affecting embryo development and potentially leading to early miscarriage up to the ninth gestational week.
Then we usually evaluate both partners’ karyotypes if it has not been done already before. We always do karyotyping for ladies over 40 or if there are situations or pregnancies where there is trisomy or in the first relative generation. For those who are with unknown reasons for infertility, if it has not been done before, then we do it at the moment.
Then we usually recommend seeking coagulation factors to screen for thrombophilia, congenital or acquired thrombophilia. Yes, we do hysteroscopy with an endometrial scratching if it is good enough, or we seek chronic endometritis—morphological or immunohistochemical. We also do microbiome analysis as well as endometrial receptivity tests. We do not believe—we always inform how much evidence each of these tests has. Not always is the patient ready to pay, or according to our knowledge, ready to wait. But at least after the second ineffective cycle, we speak about all these add-ons and treat if we find anything, then move forward.
Dr Raúl Olivares, Barcelona IVF: The Spanish Fertility Society recently released a book assessing the clinical evidence for various IVF add-ons, and the findings were discouraging. We lack strong studies to support many of these interventions. I often say that in assisted reproduction, we follow trends. Unlike Jon, who has patients who trust him, I often deal with patients who bring stacks of research papers they’ve found online. Dr Google complicates things.
Patients frequently reference treatments that friends have undergone, leading to a desire for multiple tests and interventions. However, we believe in very few tests. Over the years, we’ve seen trends come and go—tests that seemed promising initially but were later ineffective. For example, HLA typing, uterine receptivity assays, and even the ERA test have not demonstrated significant benefits.
I’ve always believed that if an embryo can implant in a fallopian tube, it doesn’t require a perfectly optimized endometrium. The embryo is the key factor.
We primarily test for thrombophilia and antiphospholipid syndrome when indicated. In some cases, we empirically prescribe anticoagulants. We are also assessing whether the microbiome plays a meaningful role, though we remain critical of this area due to the risk of contamination in sample collection.
There is significant debate surrounding microbiome studies, and we don’t routinely recommend hysteroscopy unless uterine abnormalities are detected via ultrasound. Multiple studies, including subsequent meta-analyses, confirm that hysteroscopy does not improve live birth rates if the uterus appears normal. Since hysteroscopy is an invasive procedure, we reserve it for cases where polyps, abnormalities, or poor endometrial development are suspected.
Ultimately, I spend a lot of time explaining why certain tests or treatments are unnecessary. Immunology is another controversial area—we do not believe in natural killer cell testing, TH1/TH2 cytokine analysis, or many other immunological markers. Studies indicate that the treatments associated with these tests, besides being potentially unsafe, do not significantly increase live birth rates.
Dr Jon Hausken, Klinikk Hausken: That’s a great question. We know that implantation can be affected by these conditions.
Adenomyosis, in particular, is associated with lower implantation rates. The underlying cause is inflammation and immune system involvement. While we don’t have all the answers, we sometimes use immune-suppressive medications to address potential implantation issues.
However, if it’s the patient’s first attempt, I wouldn’t introduce any additional treatments. But if we’ve conducted two or three cycles with high-quality embryos and implantation still isn’t occurring, we discuss available options with the patient and adjust our approach accordingly.
