During this event, Dr Esther Marbán, Gynaecologist & Fertility Specialist at Clínica Tambre, explains how these advanced endometrial tests (ES-TIME & ES-META) can help identify the best timing for embryo transfer and boost your chances of IVF success.
In this session, Dr Esther Marbán explained that embryo implantation is one of the most complex and least understood stages of IVF. Even when good-quality embryos are transferred, implantation does not always occur.
Successful implantation depends on a precise dialogue between the embryo and the endometrium. The embryo must arrive at the uterus at exactly the right moment, when the endometrium is receptive and prepared to allow attachment and invasion.
Dr Marbán emphasised that implantation failure is not always related to the uterus. In many cases, especially in women over 40 or when embryos have not been genetically tested, the main limiting factor is the embryo itself.
The endometrium is not receptive throughout the entire cycle. Instead, there is a limited period known as the window of implantation.
Dr Marbán explained that:
around 70–75% of patients have a window of implantation that occurs 5 days after starting progesterone, which is why standard embryo transfer timing works well for most patients;
however, 25–30% of patients may have a window that is slightly earlier or later than expected.
In these cases, embryos may be transferred too early or too late, reducing the chances of implantation even when embryo quality is good.
The window of implantation can be personalised, Dr Marbán explained, and this is where endometrial receptivity tests may be useful in selected cases.
Dr Marbán presented 2 complementary tests designed to assess endometrial readiness more precisely.
The ES-TIME test is designed to evaluate when the endometrium is most receptive to embryo implantation.
It analyses gene expression in an endometrial biopsy taken after a specific duration of progesterone exposure. Based on the result, the endometrium may be classified as:
receptive,
pre-receptive (needing more progesterone), or
post-receptive (needing less progesterone).
This information allows clinicians to personalise the timing of embryo transfer by adjusting the number of progesterone hours before transfer.
Dr Marbán stressed that ES-TIME is not suitable for all patients and remains a controversial tool. It should be used selectively and only when there is a clear clinical indication.
The ES-META test focuses on a different aspect of implantation: the endometrial microbiome and the presence of chronic endometritis.
The endometrium contains microorganisms, and a healthy balance is essential for implantation. Dr Marbán explained that:
a healthy endometrial environment is usually dominated by lactobacillus species;
an imbalance or presence of pathogenic bacteria may interfere with implantation;
chronic, low-grade inflammation may be associated with biochemical pregnancies, recurrent implantation failure, or repeated miscarriages.
ES-META identifies microbial imbalances and signs of chronic infection, allowing targeted treatment before embryo transfer.
Dr Marbán was very clear that endometrial testing should not be applied routinely.
ES-TIME and ES-META may be considered in selected situations, including:
repeated implantation failure after transfer of good-quality embryos,
biochemical pregnancies,
repeated miscarriages,
cases where only 1 embryo is available for transfer after PGT-A, and maximising implantation timing is critical.
These tests are about personalisation, Dr Marbán explained, but they are not designed for every patient.
A key part of the presentation focused on clarifying misconceptions around implantation failure.
Dr Marbán explained that:
failure of implantation should not be diagnosed too early;
lack of implantation after one or two transfers does not automatically indicate an endometrial problem;
in women over 40, implantation failure is often related to embryo genetics rather than uterine receptivity.
If a non-tested embryo from a woman over 40 does not implant, that does not mean the endometrium is the problem,” she explained. “The embryo is often the limiting factor.
Endometrial receptivity testing should never replace a thorough anatomical evaluation of the uterus.
Dr Marbán described several diagnostic tools used to assess uterine structure:
3D ultrasound, which provides detailed information about the uterine shape and cavity;
magnetic resonance imaging (MRI), particularly useful for diagnosing adenomyosis or uterine wall abnormalities;
hysteroscopy, a minimally invasive procedure that allows direct visualisation of the uterine cavity and treatment of polyps, septa, or other abnormalities.
Not all patients have a perfect uterine cavity, and anatomical factors must always be assessed first.
Dr Marbán noted.
When ES-TIME identifies a displaced window of implantation, progesterone timing can be adjusted:
starting progesterone earlier if the endometrium is pre-receptive,
reducing progesterone exposure if it is post-receptive.
When ES-META identifies infection or microbial imbalance:
antibiotics may be prescribed to treat infection,
probiotics may be used to restore a healthy microbial environment.
These adjustments are made before the next embryo transfer to optimise conditions for implantation.
Dr Marbán concluded by emphasising that endometrial receptivity tests are tools, not guarantees.
They may help in carefully selected cases, but implantation remains a complex process influenced by embryo quality, uterine health, hormonal preparation, and timing.
There is no single test that solves implantation failure, she explained. What matters is a comprehensive, individualised approach that considers the embryo, the endometrium, and the patient as a whole.
In this case, we know that the patient achieved pregnancy before, which means the endometrium was receptive at that time. At 39, the most important factor is the embryo, particularly embryo quality and chromosomal abnormalities related to age.
If the patient plans to perform PGT-A, it may be reasonable to consider additional testing. However, because implantation has already occurred in the past, a receptivity test is not mandatory. An endometrial microbiome test could be useful to exclude infection, especially if only one embryo is available. Overall, this would be an option rather than a strict indication.
In this case, we know that the patient achieved pregnancy before, which means the endometrium was receptive at that time. At 39, the most important factor is the embryo, particularly embryo quality and chromosomal abnormalities related to age.
If the patient plans to perform PGT-A, it may be reasonable to consider additional testing. However, because implantation has already occurred in the past, a receptivity test is not mandatory. An endometrial microbiome test could be useful to exclude infection, especially if only one embryo is available. Overall, this would be an option rather than a strict indication.
Endometrial receptivity is not related to age. Being younger or older does not determine whether the endometrium is receptive. Receptivity depends mainly on the treatment protocol and the duration of progesterone exposure.
Testing is performed during a mock cycle, using the same protocol planned for the real embryo transfer. An endometrial biopsy is taken to assess the window of implantation and to detect possible chronic infections.
At this age, the chance of achieving pregnancy with one’s own eggs is extremely low. Most patients around 50 use egg donation. When donor eggs are used, age does not significantly affect implantation rates, but it can influence pregnancy development and obstetric risks.
If one or two embryo transfers with donor eggs are unsuccessful, it may be reasonable to explore uterine factors, including receptivity and clotting disorders. While egg quality is not the issue in donation cycles, maternal age can affect pregnancy outcomes later on.
Endometrial receptivity itself cannot be improved. What we can do is assess it. Tests such as ES-TIME or ERA provide information about receptivity.
Progesterone is what makes the endometrium receptive. If testing shows the endometrium is pre-receptive, more hours of progesterone are added before transfer. If it is post-receptive, progesterone exposure is reduced. In some cases, a repeat biopsy is needed to fine-tune timing.
We can adapt the timing of transfer, but there is no way to change the intrinsic receptivity itself.
Endometrial receptivity is not strongly linked to miscarriage. It is more closely associated with biochemical pregnancies. Recurrent miscarriage is more often related to chronic infection or embryo factors.
Tests that identify chronic endometritis can be useful, as infection may contribute to both biochemical pregnancies and miscarriage. However, miscarriage is usually multifactorial, and receptivity alone is rarely the sole cause.
ERA testing is controversial. It is not used for all patients. Some data suggest the window of implantation may vary slightly between cycles, even though laboratories state it remains stable if the protocol is identical.
The original studies were conducted in small patient groups. While some randomised trials show no benefit, this does not mean the test is useless. The key is patient selection. ERA is not valid for everyone, and implantation depends on many factors.
In our practice, we prioritise embryo quality and chronic infection assessment, which have shown clearer clinical relevance.
Different laboratories offer similar tests under different names. ES-TIME and ES-META are performed by DiNA Science, while ERA, EMMA, and ALICE are provided by Igenomix. The principles are similar, although methodologies differ slightly.
The catheter indeed passes through the cervix, but the tissue sample is taken from inside the uterine cavity. While some cervical contamination is possible, the analysed tissue comes from the endometrium.
In practice, results are considered reliable, and there is often a correlation between cervical and endometrial microbiota.
These treatments should only be used under the supervision of an immunologist. They are not part of routine protocols. They may be considered in selected cases of real implantation failure with a clear immunological indication.
However, the embryo remains the most important factor. Immune treatments are only considered after embryo quality and uterine factors have been fully evaluated.
If endometriomas are stable, not growing, not suspicious, and not causing significant pain, there is no indication to remove them before transfer.
However, patients with endometriosis may also have adenomyosis. In such cases, uterine treatment focuses on hormonal regulation rather than surgery.
Yes. Uterine surgery can damage the basal layer of the endometrium, which may affect lining growth. In these cases, different preparation strategies may be attempted.
If the lining remains thin, hysteroscopy may be recommended to ensure the cavity is normal.
In this situation, a receptivity test is not indicated because implantation already occurred. The pregnancy loss was related to cervical issues, not endometrial receptivity.
However, performing an endometrial biopsy to rule out infection could be reasonable.
A positive hCG means implantation occurred. However, implantation is only the first step. Receptivity and the uterine environment may still influence whether the pregnancy develops further.
Biochemical pregnancies can also be related to chronic infection or suboptimal endometrial conditions, even if initial implantation took place.
Chronic endometritis is defined as a chronic infection of the endometrium. Diagnosis often involves identifying CD138-positive plasma cells.
Thresholds differ between laboratories, which is why definitions vary. It is also important to perform bacterial cultures to identify the causative organism and select appropriate antibiotics. As with other immune markers, interpretation depends on laboratory standards.
