During this event, Dr Harry Karpouzis, Founder and Scientific Director of IVF Pelargos Fertility Group, shared expert insights into how patients can optimise their chances of a successful embryo transfer, covering: what to do before embryo transfer, the ideal conditions for the endometrium, and Fresh vs. frozen transfer: which is better? Common reasons for failed transfers: The role of timing, medication, and lifestyle. Evidence-based protocols used.
Whether you’re preparing for your first IVF cycle or have experienced unsuccessful transfers in the past, this session offers practical, science-backed guidance to help you feel more informed and empowered.
Embryo transfer is often described as the final step of an IVF cycle. Still, as Dr Harry Karpouzis emphasised in this webinar, it is also one of the most critical. While the procedure itself may only take a few minutes, its success depends on careful preparation, correct timing, and a highly individualised approach. Drawing on clinical experience and evidence-based practice, Dr Karpouzis explained how embryo transfer should be planned and performed to maximise the chances of implantation and a healthy pregnancy.
Dr Karpouzis explained that embryo transfer is a deceptively simple medical act. Compared with ovarian stimulation or egg retrieval, it is technically straightforward and short. However, the emotional and clinical importance of this step cannot be overstated.
By the time patients reach embryo transfer, they have already undergone weeks of injections, monitoring, and often invasive procedures. In many cases, there may be only one viable embryo, sometimes genetically tested and confirmed as chromosomally normal.
At that moment, Dr Karpouzis explained, the entire IVF cycle is concentrated in a very small catheter in the doctor’s hands.
Because of this, both patient and clinician experience significant pressure. Even a small technical error or poor preparation can compromise the outcome of the entire cycle.
According to Dr Karpouzis, the vast majority of IVF cycles today involve frozen embryo transfer rather than fresh transfer. Advances in vitrification mean that frozen embryos now have implantation rates that are equal to, or in some cases better than, fresh transfers.
Fresh embryo transfer is still possible when conditions are ideal, but it has become the exception rather than the rule. Hormonal stimulation during fresh cycles can negatively affect the implantation window, which is why many clinics prefer to freeze all embryos and transfer them later in a more controlled environment.
Dr Karpouzis outlined several protocols for preparing the endometrium before frozen embryo transfer. The choice of protocol depends on menstrual regularity, medical history, fertility diagnosis, and whether the patient is travelling from abroad.
A natural cycle embryo transfer relies on the woman’s own ovulation. It can be a good option for women with regular cycles and predictable ovulation. The advantages include avoiding medication, fewer side effects, and lower costs.
However, Dr Karpouzis highlighted important limitations. Even in women with regular cycles, identifying the exact moment of ovulation requires close hormonal monitoring. Missing the LH surge can result in cycle cancellation. From a practical perspective, natural cycles are difficult to coordinate, especially for international patients, which is why they are often avoided in medical travel cases.
In a modified natural cycle, ovulation is triggered with medication, most commonly hCG. This improves scheduling and reduces the risk of missing ovulation. Progesterone support is still required after ovulation.
Dr Karpouzis explained that success rates are generally comparable to hormone replacement cycles, with the benefit of using fewer medications. Importantly, modified natural cycles have lower cancellation rates than fully natural cycles because ovulation timing is more predictable.
For women with irregular cycles or inconsistent ovulation, ovulation induction using medications such as letrozole may be used. Clomiphene is generally avoided because it can negatively affect endometrial thickness.
This approach helps ensure ovulation occurs and may improve the endometrial lining in some patients with thin endometrium. Luteal phase support with progesterone is still required before and after embryo transfer.
The most commonly used protocol, especially for international patients, is hormone replacement therapy with oestrogen and progesterone. Dr Karpouzis explained that this approach allows maximum control over timing and eliminates the unpredictability of ovulation.
Typically, oestrogen is given for 12–18 days, followed by progesterone. For blastocyst transfer, around five full days of progesterone exposure are required before transfer.
There is no clear evidence that oestrogen doses above 8 mg per day improve outcomes, but in patients with thin endometrium, higher doses may be necessary. Even with high-dose oestrogen, spontaneous ovulation can still occur in a small percentage of patients, although the risk is significantly reduced.
In selected cases, ovarian downregulation with GnRH agonists may be used before starting oestrogen and progesterone. Dr Karpouzis explained that this approach is particularly useful in women with endometriosis, adenomyosis, or fibroids.
While downregulation can improve receptivity in some patients, it also increases treatment duration, cost, and side effects such as hot flushes. In women with a history of thin endometrium, it may be avoided unless clearly indicated.
Endometrial thickness is important, but not the only factor. Dr Karpouzis explained that an endometrial thickness above 7 mm is generally considered acceptable, with better outcomes seen above 8 or 9 mm. Very thick endometrium, however, may also be suboptimal.
Equally important is the appearance of the lining. A trilaminar or “triple-line” pattern is associated with better implantation rates. Pregnancies can still occur with thinner linings, but success rates are reduced.
When the endometrium does not respond adequately, the first step is often to cancel the cycle and adjust oestrogen dosing or administration route. Further investigations may include hysteroscopy, biopsy for chronic endometritis, and targeted antibiotic treatment.
In cases of recurrent implantation failure or miscarriage, additional testing such as implantation window assessment, immunological evaluation, or endometrial receptivity testing may be considered. Adjunctive treatments discussed by Dr Karpouzis included sildenafil, G-CSF, aspirin, PRP, and, in selected experimental cases, stem cell therapy.
Lifestyle factors also matter. Dr Karpouzis advised optimising thyroid function, stopping smoking, managing stress, and considering acupuncture as supportive measures.
The embryo transfer should always be performed under ultrasound guidance, which is now considered the gold standard. Dr Karpouzis explained that the type of catheter used depends on cervical anatomy and previous transfer history.
Anticipating difficulty is essential. Patients with previous cervical surgery, HPV treatments, or difficult prior transfers may benefit from a mock transfer. When a difficult transfer is expected, performing the procedure under sedation can reduce uterine contractions, stress, and discomfort, improving the chances of success.
Bladder filling should be individualised depending on the uterine position. Both overfilling and underfilling can make the procedure more difficult.
Dr Karpouzis concluded by stressing that embryo transfer is not a “one-size-fits-all” procedure. Protocol selection, endometrial preparation, and transfer technique must be individualised.
A perfect embryo can fail if the transfer is not done correctly.
He explained, adding that experience is especially critical in complex cases.
Embryo transfer is a short but decisive step in IVF
Frozen embryo transfer is now standard practice
Endometrial preparation must be individualised
Thickness, structure, and receptivity all matter
Anticipating and managing difficult transfers improves outcomes
Experience and planning can make or break an IVF cycle
By combining careful preparation with expert execution, embryo transfer can be optimised to give patients the best possible chance of success.
I haven’t understood completely if we are talking about embryos that are already frozen from the age of 38, or if we are talking about doing a new stimulation now and doing PGT-A at the age of 43 before freezing the embryos. The answer is easy. There is data that says that if we have already frozen embryos, to defreeze them, to biopsy them, to freeze them again, and then defreeze them, this compromises the quality of the embryos.
It is not clearly associated with changes in the chances of implantation, but it is clearly associated with increasing the miscarriage risk. So you compromise an embryo when it is already frozen, to defreeze it and biopsy it. The answer is no, especially if we are talking about embryos frozen at the age of 38. Transfer them.
Now, if you are 43 and you are thinking about doing a new IVF and you want to freeze the embryos, PGT-A the embryos before you freeze them. The answer is yes, do it. The documentation of the PGT-A results is very important. You need to know, in the unit that you will be going to, what exactly their thresholds are. Yes, when you take a biopsy for PGT-A, it’s from the outer part of the embryo. It doesn’t always correspond to what it is inside.
But when you have less than 30% aneuploid rate, it’s considered to be euploid. The embryo has very good chances of success. When it is more than 80%, it is an aneuploid embryo, and the truth is that it gives you close to zero chances of success. When you have a middle category between 30% and 80%—I’m saying now the percentages in our clinic, okay? It can vary. That’s why you need to ask—it’s mosaic.
When you have a mosaic embryo, some of the mosaic embryos maintain some chances of implantation when they are low mosaic, from specific chromosomes, etc. What do you need? Genetic advice. We offer a geneticist to advise you. You need to know that if you transfer an embryo of low mosaicism, we will not throw it away. It will not give you 70% chances.
If you don’t have a euploid embryo, and you transfer a low mosaic, it might give you 30% chances or 20% chances. So you take the risk and you transfer it, a consented decision. Yes, at the age of 43, I would do PGT-A. If your embryos are from age 38, I wouldn’t do PGT-A.
I don’t agree with that. We don’t do day 3 transfers in our unit. In a laboratory that respects itself, if an embryo has got chance of reaching day 5, it will reach day 5. If it doesn’t reach day 5, it means that 99% of the time, if you transferred it on day 3, it wouldn’t have worked. As I told you before, it cannot really eliminate good embryos.
It can create mosaic embryos that, under the best consultation and after talking to a specialist who is a geneticist, you get a consented decision on which embryo is transferable and what embryo is not. An aneuploid embryo, which means more than 80% mosaic rate, gives you almost 0 chances of implantation.
These are good questions. First of all, we need to know that the ERA test has less and lower evidence behind it. Of course, new ERA tests might be coming. The knowledge behind the implantation window might be changing. Nowadays, we use ERA testing in unexplained failures of implantation, after investigating everything else and if they are still not working. In such cases, we consider whether the implantation window is an issue. Yes, the timing can change, and someone can be pre-receptive or post-receptive. But the truth is, usually, it doesn’t change.
In cases like yours, and I had this question before, if it is your only precious and only embryo, and you have checked everything else and found nothing wrong, then by the book, repeat it and do it again. But the chances are small that the pre-receptive or post-receptive timing will change later on.
Regarding the second part of your question, PGT-A with medium blastocysts, the number of blastocysts that you check depends on your age, to increase the chances of finding even one that is chromosomally normal. If you ask me, I have seen euploid embryos in BB grading, which came back euploid, and I have seen aneuploid embryos in AA. I have seen pregnancies with BB embryos that are euploid.
The truth is, if you have 9 or 10 embryos and you are 40 years old, you can choose to biopsy the best ones that give you better chances. Hopefully, you will get the embryo that you want among these. If you don’t, you can either decide to analyse the remaining ones as well, or choose not to.
We usually take biopsies from all the embryos in our unit. Whether you choose to analyse 5 or 6 of them, 4 of them, or all of them depends on your age and also on the cost, as it goes per blastocyst. But we usually take biopsies from all of them.
PGT-A is usually done in cases of recurrent implantation failures or recurrent miscarriages. My theory behind not transferring an embryo that has not been checked for chromosomes is this: if it fails again or miscarries again, I will have to tell you, “It might have been the embryo.” And this answer, if I were a patient, would not be good enough for me. That is the reason why I say, when you have the history and you do PGT-A, transfer embryos that you know are healthy. Otherwise, if they fail again, you will not know what the reason was.
It’s not much different. What I’m trying to say is that this is a very conflicting issue, and there are different theories behind immunology. We consider it more accurate to take a biopsy at the time after endometrial preparation from inside the womb rather than from the blood. We think that what happens in the blood does not always correspond to what is happening in the uterus, and that is what we are mostly interested in when planning treatment.
Generally, if you do blood tests, the treatment will be more or less the same. If natural killer cells are high and the TH1 to TH2 ratio is over-suppressive, you will give steroids, intralipids, or Plaquenil (Hydroxychloroquine) if needed. So, it doesn’t change dramatically in terms of treatment. What changes is what you believe more, the blood tests or what is happening inside the uterus.
Most probably, I would recommend a frozen embryo transfer. I might have investigated possible endometriosis. There are some specific tests that you can do if you don’t want to check with a camera. Many times, there is endometriosis, and you don’t suspect it. I might even consider down regulation with Arvekap, with the active ingredient Triptorelin, a GnRH agonist used in IVF treatments to prevent premature ovulation, injections or Gonapeptyl injections, since your modified natural cycle did not work on a euploid embryo.
If you have another embryo, and we don’t know the grading of this embryo, which plays a role, I would change the protocol, either to an HRT cycle or a cycle with HRT and downregulation if we suspect endometriosis. We are one of the units that measure progesterone levels before embryo transfer. The lower threshold is usually 12. We don’t have an upper threshold. In women with endometriosis, there is progesterone resistance, so many times we target higher levels rather than lower.
As for the dominant follicle, it depends on the endometrium as well as the timing. We usually trigger with at least 14–15 mm. Some units trigger even at 12 mm if the endometrium is okay. We also measure blood tests to make sure there’s no unexplained early luteal surge that might cause premature ovulation without realising it.
Prolutex, for example, has a very quick lifespan. It acts quickly. It is a muscle relaxant and can help in cases like that. Many times, it’s not really associated with cramps — it might even be related to bowel movements, and you think it’s from the womb.
Cramps are generally a sign. So when someone complains, at least in our practice, we give them Prolutex, Lentogest, or progesterone, which are muscular relaxants, to help a bit with that.
Not really. Retroverted uterus is present in 15% of patients. They are born like that. If you do the transfer properly and leave the embryo properly, it shouldn’t affect anything. Sometimes a retroverted uterus is associated with endometriosis, adhesions, and scar tissue. In cases like that, endometriosis itself reduces the chances.
It cannot enhance receptivity. It is used in a specific category of patients: those with adenomyosis, those with endometriosis, or when we strongly suspect endometriosis. It is also used in women who have fibroids of average size close to the cavity and want to reduce the size before embryo transfer.
All these patients are helped by Arvekap and GnRH analogues because they reduce the disease of endometriosis or adenomyosis, or the size of the fibroids.
Most probably, it’san additional medication to make sure you will not ovulate prematurely. For example, you might have a follicle slightly bigger at the beginning of the cycle. If you start Progynova with that, it might not be enough to prevent ovulation. Most probably, your doctor is trying to prevent the follicle from ovulating early. Cetrotide helps with that. We do it as well in some cases.
Crinone is a vaginal medication that contains progesterone. Many times we give luteal support, progesterone support, after ovulation and before embryo transfer. Usually, we don’t do this in natural cycles, but sometimes in modified natural cycles or letrozole cycles, we use this medication to provide luteal support before transfer.
You can use Crinone or other medications like Cyclogest, Utrogestan, or Prolutex. Each clinic has its own protocol.
Yes, I mean one of these follicles, if it keeps growing, it might cause ovulation, so check the progesterone to make sure that ovulation hasn’t happened. If it has happened, you need to cancel. Also, a 7 mm endometrium is not an ideal thickness. It’s doable, but not ideal. It depends on how many days you take estrogen. If you take estrogen only for 7, 8, or 9 days, increase the dose and push more because the endometrium might get thicker. We usually give between 12 or even up to 18 days of estrogen. This is usually the implantation window, so that we can keep pushing to increase the thickness of the endometrium. Now, if in the meantime a follicle grows and ovulates, then unfortunately, you need to start again from the beginning.
Yes, there are some studies about these things. We use relevant tests as well, either through blood, period, or biopsy. We don’t use it on everybody. We use it in people who have recurrent implantation failures or recurrent miscarriages. If you have chronic endometritis, then yes, you need to take some antibiotics. Even though the latest data from the last congress shows that antibiotics in chronic endometritis, compared to a placebo, might not really be doing the job. But it’s still early. If you have failures of implantation or miscarriages, and you identify something, you treat it or take probiotics. There is some data that you need to have a good flora inside the womb or vagina to improve implantation chances.
Yes, it’s not ideal. A traumatic transfer with more manipulation causes more problems. Contractions might be caused. The ideal thing is to be smooth, but it’s not always easy. Sometimes it’s impossible to be smooth.
Most probably, it’s a question regarding techniques of embryo transfer in an anteverted or retroverted uterus. Sometimes you have an anteverted uterus, and it’s very easy to pass the catheter. Sometimes, a retroverted uterus is also easy. In acute situations, it might be tricky. There are techniques, as explained in the presentation, that can help make the embryo transfer smoother and help pass the catheter.
We do check mainly for minimum threshold levels. We use a combination of vaginal progesterone together with Prolutex subcutaneous injections.
There is some evidence. There are some studies. We don’t use IVIG because it’s very difficult to find and administer in Greece. Instead, medications like Plaquenil, Tacrolimus, combined with steroids or intralipids, more or less do the same job.
We don’t do it. It’s not allowed in Greece by law. I don’t think there’s a benefit. It’s a traumatic procedure. Even with experienced embryologists, the risk of injury to the embryo is minor, but still, you remove cells. You need to balance the advantages versus the disadvantages. When someone has recurrent implantation failure, miscarriages, or is over 38, the advantages are greater. But if the donor is 20, checked for karyotype, chromosome analysis, and other conditions, then the advantages are not more than the disadvantages.
I would start with the best one, most probably the 6AA. But it depends. You need to discuss with your embryologist and the laboratory. Are both day 5 embryos, not day 6? If both are day 5, AA is the best. We usually start with the best embryo. Now, one or both—it gives good chances if you transfer a euploid embryo. But if you are 45, you need to consider all risks from a possible twin pregnancy. I would try one. But again, it’s a discussion between you and your doctor.
