During this session, Dr Kristýna Frühaufová, PhD, Head Physician of GYNEM Fertility Clinic, Czech Republic discussed implantation failure in IVF. She explored the causes and talked about prevention strategies and how to overcome it.
Yes, I didn’t cover this because it’s a tricky question. The lining itself, the thickness, is not well defined. What is the minimal thickness? We usually consider anything above 7 mm okay for planning the embryo transfer. We were speaking about the thickness of the endometrium in the first phase of the cycle because when we add progesterone, the endometrium changes in its pattern and thickness. What is also crucial is the appearance of the lining because we should get a well-defined triple lining to the endometrium.
There are still debates about whether the appearance or the thickness of the endometrium is more important, and there’s no consensus even within the IVF community. Both aspects matter, and you also have to consider the patient’s history. Some women can grow the endometrium and get pregnant even with a 6 mm thickness. If a patient has had a successful pregnancy with a thin endometrium, and you’re using quite high doses of medication, there is no need to cancel the cycle just because the endometrium is thin.
Yes, exactly. We have to consider the patient’s history. When the lining is thin and the patient is not responsive to medication, the first step before doing an embryo transfer, in my expertise, is to look inside the womb with a hysteroscopy. If the lining is thin and doesn’t develop the pattern you want, it’s important to rule out adhesions before proceeding with the embryo transfer. However, if the cavity is normal, pregnancies can still occur. A thin endometrium reduces the chances a bit because you need sufficient endometrium for proper placentation, and the patient may be at higher risk for complications like placenta accreta or other pregnancy-related issues later on.
It depends on the pattern. We don’t usually plan a transfer if the endometrium is above 13 or 14 mm, but I’ve seen patients with naturally thick endometrium having successful pregnancies. If this thick endometrium is their usual pattern, we follow it accordingly.
This is a difficult question. We know that most abnormalities come from the egg. Women are born with a set number of eggs that age with us; we don’t create new ones. The DNA within the egg becomes unstable due to being held in the division process for a long time. There are protective proteins that cover the DNA, but these wear out over time. External factors, like free radicals, also damage the DNA. This is why as we age, DNA damage becomes more frequent, and during fertilization, this can lead to abnormal embryos.
We still don’t have enough data on this. We know age shouldn’t harm implantation, but we’re not certain if it has a significant effect. Any medication added to a cycle without proven benefit could potentially be harmful. Each embryo and attempt is different, like flipping a coin. Even with added medication, it’s unclear if success was due to the treatment or just chance.
Most likely, we don’t know. Some women are prone to repeated polyps and need to undergo repeated hysteroscopies and polyp removals. It is most likely due to some benign mutation in the cells within the endometrium, causing the endometrium to overgrow in one spot, leading to a polyp. So most likely, genetics are the cause.
When it comes to fibroids, it’s more likely because of genetics. Most of the time, it’s something that runs in families. That’s the case here as well.
As I said, DNA fragmentation of 20% is not that high, but it may play a role in implantation failure. The sperm is equally important in fertilization. We know that sperm usually doesn’t contribute as much to chromosomal abnormalities as the egg, but it’s still a factor. You had the embryos tested, so you know the ones transferred were genetically fine. It’s the way the embryo interacts with the important womb. Some women have a certain immunological phenotype, making them less prone to implantation, while others get pregnant more easily. It’s like how some people get sick more often when exposed to germs. It might take more attempts for these women, even when transferring good embryos.
You mentioned the septum—was it removed? If not, the septum should be removed before the IVF attempts. A septate uterus can cause anatomical distortion. Even if the uterus is ill-shaped, it can be reconstructed using hysteroscopy and laparoscopy, depending on how much the septum affects the uterine cavity. The septum itself might be the cause of the failures.
Regarding the microbiome, we still know that a lactobacillus-dominant environment is more favourable for embryos, but even healthy women with less lactobacillus can still get pregnant. It’s difficult to define the perfect microbiome environment within the uterus because it changes throughout the menstrual cycle. More research is needed, but having less lactobacillus reduces your chances—it doesn’t mean you have no chance at all.
There is no clear answer. The most effective probiotic for colonizing both the vagina and possibly the uterine cavity is lactobacillus rhamnosus. To ensure probiotics work properly, you should take them vaginally, as most oral probiotics are killed in the gut. What we usually suggest to patients is a 10-day round of probiotics after finishing their menstrual bleeding, before embryo transfer. But it’s safe to continue taking probiotics during pregnancy if needed.
It depends on whether you want to go for IVF with your own eggs or egg donation. If we’re talking about IVF, we would start with a hormonal profile and an ultrasound, which is usually sufficient, including a semen analysis to assess the male factor as well. I don’t think doing preventive tests to cover all possible aspects is necessary because most patients do get pregnant just by repeating embryo transfers, provided the quality of the embryos is good. Only a small percentage of women have additional issues like immunogenic factors. Too much data can be difficult to interpret, so I would begin with basic examinations to see if everything is anatomically fine. A 2D or 3D ultrasound can rule out most pathologies. After age 40, we might expect fibroids or polyps, which need to be ruled out first. If you’re trying IVF, we’ll also look at ovarian capacity, but keep in mind that at this age, we need more eggs and embryos to be successful.
Different countries have different brands, so it varies. However, lactobacillus crispatus should be part of the probiotic. Probiotics usually contain several strains of lactobacillus, but the brand names differ by region.
If possible, a natural cycle is always preferable. However, with ageing, women often face luteal insufficiency, making it difficult to carry out natural cycle transfers. If the cycles are too short, the endometrium may not build up properly, or ovulation may not be trackable. In general, for women with regular cycles, the natural cycle is the best option.
Yes, I participated in a clinical trial for this medication a few years ago. Unfortunately, it didn’t show any efficacy. The same clinical trial was recently repeated by the Chinese, and they came up with the same results. It was proven twice that it doesn’t work.
Endometriosis affects the immune system and is a chronic inflammation, but it’s not treated with antibiotics. It’s better to downregulate endometriosis, which means reducing estrogen production before the IVF cycle or embryo transfer. The treatment depends on the stage and whether the endometriosis is active. If active, sometimes surgery can also be helpful.
That’s a tricky question, depending on how many embryos we get from the cycle. To start, I’m not a huge fan of PGT-A, so I don’t push for it in all cycles. We need a good quality blastocyst to test, as we want to ensure the embryo can handle the biopsy, freezing, and thawing process. There are many things done to the embryos to get results from genetic testing. If the woman has a sufficient level of AMH and responds well to stimulation, producing multiple oocytes, then PGT-A can shorten the time to embryo transfer by identifying healthy embryos.
However, if we’re obtaining eggs from natural cycles, the question is whether to test each embryo or to accumulate several embryos over multiple attempts before testing. We must also consider the age factor for both getting embryos and achieving pregnancy. You don’t want to spend two years gathering embryos and only then get pregnant.
It depends on what tests and checks you’ve done. If you’re referring to immunological testing, sometimes we also perform a hysteroscopy to assess the uterine environment. However, the effectiveness of some tests is still questionable. If everything comes back negative, you may just need the right embryo, even though it’s demanding and frustrating.
Our knowledge of the microbiome is still limited, and we need more research and data to understand its role better. Unfortunately, it’s one of those areas where we need to wait for more results.
Age doesn’t affect the uterus as much as it does egg quality, but the whole body changes with age. We know that vascularity changes and anatomical issues like adenomyosis and fibroids become more common, which can affect implantation. We also need to consider how the endometrium responds to stimulation, as it becomes less receptive to medication with age, making endometrial growth more difficult.
Since you’ve only had two blastocysts, the endometriosis might be affecting your ovaries, reducing ovarian capacity. I’d recommend ruling out other genetic factors, like Fragile X syndrome, which can cause premature ovarian insufficiency. As for PGT-A testing, both adenomyosis and endometriosis don’t increase aneuploidy rates. Statistically, your euploid rate should be the same as any healthy woman your age. I’d focus on addressing endometriosis and adenomyosis rather than pushing for genetic testing right away.
Surgery for adenomyosis is demanding for both the surgeon and the patient. It’s often reductive surgery, meaning it won’t remove all the lesions but will reduce the majority. The most important part is reconstructing the uterus afterwards. There’s a risk of uterine rupture during pregnancy after this surgery, so it has potential complications. It’s usually a last resort, but skilled surgeons can operate effectively.
In cases of adenomyosis, I prefer frozen transfers. I use a combination of downregulation, which works on a central level, and a combination of letrozole, which inhibits estrogen production in the myometrium. This treatment can be done before or during the frozen embryo transfer, showing better outcomes, though not as good as in healthy patients.
Just be optimistic, that’s the main thing. There are a few things to avoid: don’t overheat your lower abdomen, so avoid saunas and jacuzzis. Other than that, behave normally—eat what you usually do, and stay positive. You don’t need to lie down and wait; staying moderately active might even help.
Any anatomical abnormality can reduce implantation chances, but there could be other contributing factors. It’s worth looking into more details.
The slightly polycystic ovaries might be contributing to lower egg quality, as we often see reduced quality in such cases, even in younger women. The male factor issues also suggest PGT-A testing may be a logical next step, especially after several failures. If there’s no mention of genetic testing for you as a couple, it might be worth exploring possible genetic factors. Considering your history of miscarriages, genetic testing could help determine if that’s the cause. Testing both partners is recommended.
After 3 failed transfers with a young donor, it’s reasonable to assume the embryos were likely euploid. I don’t recommend PGT-A testing on embryos from a donor cycle. However, it’s important to look into other contributing factors, like uterine anatomy, sperm analysis, or even factors like obesity, which is often overlooked but can play a big role in implantation failure. Some basic immunological testing, like NK cell function, or a biopsy to assess NK cell activity in the womb, might also be helpful.
High anti-TPO antibodies usually indicate chronic thyroid inflammation, which can lead to hypothyroidism. If you’re not already on thyroid medication, adding it may help lower the antibodies. This is something your endocrinologist should manage by reviewing your thyroid panel and deciding on appropriate treatment. We try to avoid corticosteroids unless necessary, as they can increase the risk of pregnancy complications, such as preeclampsia, by affecting placental formation. It’s unlikely to harm the embryo directly, but it could have an indirect effect. Leave the treatment decision to your endocrinologist.
Yes, as I mentioned, it might. Some studies show that a higher DNA fragmentation rate might negatively impact implantation, but we still don’t know exactly why this happens or what the exact cause is. When there’s lower sperm quality, the ICSI method was developed to overcome that issue, so it’s the method of choice for poor sperm samples. The genetic information from the father plays a role in how the embryo is presented to the immune system, so we can’t leave the malefactor out. However, we still don’t know how much it directly affects implantation failure.
