During this live session, Dr Elias Tsakos, MD, FRCOG, Medical Director of Embryoclinic, Greece, discussed endometritis, how it affects fertility, how it’s diagnosed, and explored the latest treatment options.
Endometritis is not endometriosis, it’s an inflammation of the lining of the uterus, the endometrium. It can be caused by infection, and it is associated with infertility. It can be caused by infection. These infections may be clinically evident—in other words, a woman may realize or may not that she is suffering from it. Like any other infected organ, it may exert impaired function. The dysfunction caused by endometritis could lead to infertility.
How common is endometritis? It remains unknown. Presumably, it is more common than we think. This is simply because it is hardly ever investigated. To investigate endometritis, we need to do what we usually do not perform—either an endometrial biopsy or hysteroscopy, or both. If an endometrial biopsy is performed, we do not usually request to look for endometritis unless we specifically ask for it. A biopsy report may not be relevant to endometritis. Most biopsy reports focus on conditions like polyps and myomas, excluding malignancy, and they do not look for markers of endometritis.
This may manifest as a failed implantation or a miscarriage. Looking at some percentages, we see that endometritis is more common in women with infertility. Approximately 1 in 5 women with infertility suffer from endometritis. Usually, endometritis causes no symptoms, or the symptoms may not be severe enough to be reported. 1 in 3 women who keep failing to get pregnant after IVF may have endometritis. It is very common in women with fibroids, adhesions, or polyps. Why is that? The reason is those anatomical features—those benign tumours, can create a tendency for infection and inflammation. This may be one of the mechanisms through which fibroids and polyps cause infertility.
Endometritis can be caused by IUDs, polyps, myomas, infections, miscarriages, and abnormal uterine bleeding. Which pathogens or microbes are associated with endometritis? They may already exist in the vaginal region, such as Staphylococcus, E. coli, Streptococcus, Ureaplasma, or Candida. Sometimes, other abnormal organisms like Pseudomonas or Klebsiella produce this inflammatory effect.
The most common symptom is no symptoms. Instead, endometritis presents with indirect symptoms such as infertility, implantation failure, or miscarriage.
How does it affect fertility? If organisms cause infection, then this area becomes unfriendly for implantation. There is an indirect mechanism related to the immune response to inflammation, which disrupts the endometrial cavity’s receptivity to implantation. Sometimes, as a result of inflammation, we see micro polyps. On the slide showing the associations between endometritis and infertility, it is evident that the rate of infertility is much higher in women with endometritis. The same applies to recurrent pregnancy loss.
Endometritis decreases the chances of a clinical pregnancy. It decreases the chances of an ongoing pregnancy rate. This is the reason why, some units, routinely prescribe a short course of antibiotics to most, if not all, women undergoing IVF.
This is a bit of a blind procedure, but the theory behind it is that if there is some sort of endometritis—my theory is that there’s always mild endometritis. So I don’t hesitate to cover with antibiotics, especially if there’s an associated procedure like egg collection, for example. Invariably, in all my egg collections and fresh embryo transfers, I give a short course of antibiotics.
Observation 1 is that the presence of confirmed endometritis has a definite adverse effect, and it decreases the implantation rate.
Observation 2 is that the presence of endometritis reduces IVF outcomes, with a much lower chance of implantation.
Observation 3 is that the severity of chronic endometritis affects its impact on IVF/ICSI outcomes, highlighting the existence of the disease spectrum and the need for diagnostic investigation.
How is endometriosis diagnosed? There are all sorts of different diagnostic methods, but the most reliable is immunohistochemical (IHC) staining for plasma cells. That’s the most reliable method. Most histopathology colleagues—most of the biopsy experts—unless they’re prompted, unless they’re alerted to look for endometritis, would only look for malignancies. There has to be a good laboratory and good collaboration with the laboratory, especially when sending samples for endometritis diagnosis.
How is it done? There is a pipelle biopsy, which is very simple and has those amazing advantages. Hysteroscopy is the gold standard because we have a visual of the lining. We may be able to provide a clinical diagnosis if we see micropolyps or even proper polyps, which sometimes may be missed by conventional ultrasound scans. More rarely, they’re missed by the 3D scan, but this is the gold standard. However, it remains a bit of an intervention with a slightly higher cost.
The standard treatment option is antibiotics—doxycycline for 2 weeks. Some non-compliance may be an issue here. The second-line treatment is Metronidazole and Ciprofloxacin. Some people suggest a ‘test-of-cure’ endometrial biopsy, which can confirm treatment effectiveness. However, Dr Tsakos mentioned that he is not very keen on that because it increases intervention.
There have been a lot of discussions about the role of probiotics. Dr Tsakos added that he’s a big fan of probiotics in general—not just for fertility, but also for general well-being. Gut flora is very important to be healthy, and equally, the endometrial flora.
One of the studies presented from 2024 showed a trend toward improved pregnancy rates after co-treatment with probiotics and antibiotics. There’s the emerging role of the endometrial microbiome. A molecular examination and typing of the microorganisms in the endometrium provide reliable information regarding the flora and its constitution, which could assist in defining prognosis and optimizing treatment. However, it is important to add that the research is ongoing.
What is the effect of treating endometritis on IVF outcomes? The effect is positive. It’s proven through some meta-analyses and pooled research data, which show that treating endometritis increases the ongoing pregnancy rate and live birth rate by 5 times. It also reduces the miscarriage rate by 80%. Clearly, this is something that needs to be addressed.
The answer is possibly no. Endometritis is usually chronic, although it can be acute or chronic. Invariably, acute endometritis becomes chronic, and then you may have an acute phase on a chronic background. But no, it is not cycle-dependent in my opinion. It can be diagnosed at any phase of the cycle. To be honest, we even try to culture to avoid a pelvic biopsy. We try to identify plasma cells in the menstrual flow, but it hasn’t been very successful. We tried to correlate the findings with pelvic findings, but we didn’t come to any amazing conclusions. It’s not cycle-dependent. It should be kept in mind, especially when talking about unexplained infertility, particularly in cases with additional pathologies like polyps, myomas, miscarriages, or failed implantations, especially with good embryos.
That’s a very difficult question. The answer is yes, but in your case, thin lining equals one thing: endometrial adhesions. There is no other cause for thin lining than that, and endometrial adhesions are caused by a combination of mechanical injury and inflammation. Thin lining (thin endometrium) is most likely the effect of endometritis caused by either a microorganism, surgery, or both.
I don’t understand why they struggled to take a biopsy because you either take a biopsy or not, and it shouldn’t be that difficult. This makes me suspicious of the potential presence of Asherman’s syndrome. If your uterus is blocked with adhesions, we may not easily access the endometrial cavity.
In your case, you need a thorough investigation. I would start with a 3D ultrasound scan and then perform hysteroscopy in a surgical theatre environment, by someone highly experienced, while performing an ultrasound scan. That’s how we approach Asherman’s syndrome, so we know where we are. Sometimes, we don’t. Also, prepare for laparoscopy in case we suspect perforation, which is one of the risks of Asherman’s syndrome or to diagnose other conditions. Always remember endometriosis—it can cause an inflammatory reaction around the uterus, even if not necessarily in the endometrium.
Most people, especially when dealing with a thin lining, are already halfway through their IVF preparation, having booked flights for embryo transfer. Many of us feel trapped and unsure of what to do. The reflex is to increase estrogen levels and give more estrogen. If we measure the estrogen level in the blood, it could be in the hundreds, yet the lining is still 5 mm. As many of you may know, especially seasoned IVF patients, we speak about endometrial lining characteristics like thickening, shape, size, location, flow, contractility, and the presence of plasma cells, among others. Unfortunately, the medical community, including myself, has not communicated this properly. You don’t keep giving estrogen when there are adhesions in the endometrium, as there’s no tissue to react. Unless you remove the adhesions to create a cavity or use treatments like PRP to promote healthy tissue growth, increasing estrogen is just wasting time and potentially risking complications, such as thrombosis.
In my opinion, this needs a thorough assessment.
It’s very difficult to comment but trust me, yes, it can happen. You can have adhesions, and for some reason, they can be missed, or the endometrium can be filled with scar tissue that, with inappropriate lighting or no proper lighting, can resemble normal tissue. At 42, for example, it makes a huge difference whether it’s your own eggs or not, and if your eggs are tested or not with PGT-A. It’s a complex issue and beyond the scope of this discussion. However, I always try to simplify it for my patients. All you need is a good embryo, and then you need a good uterus and surroundings.
The uterus isn’t just the endometrium, it’s also the myometrium and the surrounding peritoneum around the uterus and the tubes. Many IVF doctors now are trained to believe that the uterus is all about the endometrium, but that’s wrong. The environment around you matters too, such as blood components, vitamin levels, the quality of your blood, your general health, etc. What’s a good embryo? It’s hard to say. In my opinion, a good embryo for any woman over the age of 35 is of good quality and PGT-A tested. At 42, the chance of an abnormal embryo, even if it looks normal, is higher than 60 or 70%. That’s an issue.
What I’m trying to do in my mind and also explain to my patients is that we try to optimize all these factors. We use the best technology and knowledge to obtain top-quality embryos. That’s why we use AI in the lab to help us identify the best-quality embryos morphologically. We also perform PGT-A with the newest techniques, especially for women over 35, definitely for women over 40, and for women with more than 2 or 3 miscarriages or implantation failures. In terms of the endometrium, yes, plasma cells are important. If you’ve had a biopsy that came back normal, ask if they specifically looked for plasma cells. 9 out of 10, they don’t—perhaps 9.5 out of 10 they don’t—unless you specifically ask the histopathologist.
Histopathologists are trained to look for cancer, not endometritis. Unless you ask them for that specifically, and unless you sit down with them, check the protocols, and check what’s written down and how they quantify it, you will never get the right answers. The problem with medicine is that we only get answers to the questions we ask. It’s like having a blood test—you have to ask them to check for specific things, like vitamin D or iron levels or tumour markers. If you don’t ask, they won’t do the test. I think that’s the confusion.
Not just that, but I’m very passionate about polyps and fibroids. It’s not easy—it takes me hours to think about individual patients with polyps and fibroids. Unfortunately, it’s not easy to quantify the effect of these on implantation. There’s a myth. I had a relative of mine in Canada, a first cousin, who came for IVF with a 10 cm fibroid, and some doctors there said it makes no difference because it’s not in the cavity. I know that’s not true. We have to be pragmatic and very experienced. Some of us are fortunate to be trained in fertility medicine and fertility surgery, but that’s not the case anymore. In my time, in the ’90s, when I was getting trained, it went without saying that you should do laparoscopies and hysteroscopies to be an IVF specialist.
Now, that’s not a prerequisite. Most IVF-trained doctors from 2005 onwards have only been trained in IVF. It’s a long discussion—at which point do polyps adversely affect implantation, and after how many failures do we address polyps and fibroids? That’s something I ask myself every day. I can’t answer specifically because I don’t know the size, shape, or location, and we must also consider malignancy. I don’t want to scare anyone, but it’s extremely rare. We mostly see women under the age of 50, and malignancy in this group is very small, but it’s not zero. In my practice, we diagnose perhaps three or four cases of malignancy in women in their 40s with a fibroid or polyp. I’m not going into detail, but I always thank God for diagnosing it before they got pregnant, because if they got pregnant and then received the diagnosis, it would be too late. The diagnosis would be delayed by at least a year and a half.
I’m passionate about this and would love to give you my opinion and perhaps some helpful information. You can send me scanned pictures or scan reports, along with a short history, including your age and previous attempts. I would be delighted to help you. In my opinion, the best way to map fibroids is through a high-resolution ultrasound machine, performed by an expert in mapping fibroids—not just in terms of location but also vascularity. 3D reconstruction of the uterus, along with elastography, gives us a lot of information, especially for identifying potentially dangerous fibroids or adenomyosis, which we often confuse with fibroids.
Fibroids are common—about 50% of women in the reproductive age group have one or more. In African races, this is even more common. We should address this properly and consult experts when necessary. If you’re not trained in fertility surgery and don’t have access to high-resolution ultrasound, I suggest seeking the expertise of specialists in multidisciplinary meetings. We don’t know everything, and if we don’t, our patients deserve to have other specialists work with us to find the best solution for them.
I think it depends on what we’re treating, the severity of the condition, the clinical situation, the laboratory results, and the history. However, I believe three months is a little bit too long. In my practice, 6 weeks is usually more than enough. During that time, I also ask patients to be very careful with sexual intercourse, perhaps using a sheath to help maintain their health as much as possible before the embryo transfer.
I learn about diets from my patients every day. Yes, an antioxidant diet would be very helpful, but you don’t need a highly specialized diet—just a standard biological vegetable diet, time outdoors in the sun and countryside, a healthy lifestyle, a bit of exercise, and avoiding smoking and alcohol. As for probiotics at a low dose, I agree with you 100%. I was suggested this by one of my amazing patients, a complementary therapist from the US. In my practice, I give low-dose probiotics to everyone, just like I give them prenatal vitamins. It won’t harm anyone, and it has fertility benefits as well as general well-being benefits. I take them myself as well.
