WHAT IS THE ‘IMPLANTATION WINDOW’ IN FERTILITY TREATMENT AND HOW TO IMPROVE IT?
SIGN UP AND GET ANSWERS LIVE >

Hysteroscopy before IVF: can it improve outcomes?

Elias Tsakos MD, FRCOG
Medical Director , Embryoclinic

Category:
Reproductive surgery

hysteroscopy-ivfwebinars-Embryoclinic-r
From this video you will find out:
  • Can you explain the technical details of hysteroscopy and how it is performed?
  • How does diagnostic hysteroscopy differ from operative hysteroscopy, and when is each type used?
  • What uterine abnormalities can hysteroscopy detect and treat, and how might addressing these issues improve IVF outcomes?
  • Are there specific cases or conditions where hysteroscopy is particularly recommended before undergoing IVF?

Hysteroscopy before IVF: can it improve outcomes?

During this event, Dr Elias Tsakos, Fertility Expert and Medical Director of Embryoclinic, shared his expertise and insights on how hysteroscopy can potentially enhance IVF success rates.

Hysteroscopy is a very simple instrument, fairly inexpensive. What you need is a camera, a lens, a light system, and an irrigation system for the water. How does it work? A direct visualization of the cavity directly is needed by using a special instrument and infusion of saline. The hysteroscope is equipped with a camera, flashlight, and a working channel for the insertion of surgical instruments. The advantage of this is that you can use it without anesthesia, without even a speculum, and you can control the bending of the instrument to go straight into the uterine cavity.

Types of hysteroscopy

There is a diagnostic hysteroscopy, which is basically when there’s nothing visible in the fertility context. At Embryoclinic, a diagnostic hysteroscopy is performed even if the scan is normal. Why is that? The scan is unable to diagnose details in the endometrium, which may include infections, endometritis, adhesions like mild Asherman’s syndrome, small polyps, or polyps located in a weird location, sometimes hyperplasia, and all of that. So we may embark on a diagnostic hysteroscopy even when we expect that it may be normal.

In my experience, we find that, especially in women over the age of 35, even more so if they’re over 40, the chance of diagnosing pathology that has been missed by ultrasound is probably as high as 30%, 1 in 3. The importance of diagnosing this pathology depends on the pathology and the age.

Another type is operative hysteroscopy, which means that it is operated on at the same time. Sometimes it’s known beforehand, sometimes it can be discovered during the procedure. According to Dr Tsakos, outpatient diagnostic hysteroscopy is very easily done and should be set up.

The advantages are:

  • It’s a minimally invasive procedure with minimal if any, complications or morbidity ( less than 1 per 10000).
  • No scars, no incisions,
  • It remains the gold standard for the diagnosis of endometrial conditions.

Uterine cavity assessment

Hysterocopy can be used for various reasons including uterine cavity assessment is very important for every patient, especially those of advanced reproductive age, but even more important in cases of recurrent miscarriages and unexplained infertility:

  • polyps – hyperplasia
  • myomas or an uterine septum
  • submucosal fibroids
  • adhesions

Uterine fibroids & Myomas

The restoration of normal uterine anatomy via metroplasty in another application. Metroplasty in Greek means restructuring the uterus. Before the existence of hysteroscopy, this was performed and it created significant collateral problems, such as adhesions and infections. These days, we can very easily correct congenital anomalies with diaphragms through hysteroscopy operations. Nowadays, we can treat fibroids, central anomalies, polyps, and adhesions.

Uterine fibroids are a fairly common pathology. Around 50% of women in the Western world will develop fibroids during their lives, and about 80% of women of African origin may have fibroids in their lives. Tumors that grow within the uterus, outside the uterus, or sometimes in the cavity are common. The ones in the cavity, called submucosal fibroids, are associated with negative outcomes. If there is a pathology of this type, it must be sorted out before IVF.

Congenital uterine abnormalities (CUA), uterine didelphys. This is more uncommon compared to diaphragms, which can be sorted out nearly 100% with hysteroscopy and sometimes with the combination of laparoscopy. There are several different types of Congenital uterine abnormalities including septate, arcuate, unicornuate, etc.

Managing uterine anomalies, the congenital anomalies, by hysteroscopy provides up to 50 times better outcomes compared to controls, compared to just watching and proceeding with IVF. Studies show there is a reduction in miscarriage rates by 98%. Most of these conditions can be diagnosed by a scan and then followed up with hysteroscopy. The same applies to premature labor, which is associated with these conditions.

Fertility improvement – post-hysteroscopy

The next application of hysteroscopy is the improvement of fertility independent of other factors. Hysteroscopy may have a fertility-enhancing effect, which may be due to the procedure itself, a little bit of dilating the cervix and ensuring that the cervical canal is not narrow, bent, or full of adhesions, guaranteeing an easy embryo transfer.

Does pre-hysteroscopy improve fertility outcomes? The evidence is that it does, it improves overall fertility outcomes by 44%. Even more importantly, there’s a 30% improvement in live birth rate. With all the pre-IVF testing, investigations, drugs, costs, traveling, and stress, the addition of hysteroscopy is minimal compared to the rest, with a very significant contribution to the overall success rate.

Miscarriages

Another aspect is the removal of retained products of conception post spontaneous miscarriage. Miscarriage is a very common form of pregnancy loss, with about 1 in 4 pregnancies ending in miscarriage, the majority of which happen in the first 12 weeks.

How do we manage miscarriages? There’s medical management and surgical management. A good proportion of miscarriages end up requiring surgical management, which is a blind procedure in most places. According to Dr Tsakos, globally more than 90-95% of evacuations of retained products of conception are done blindly.

I believe we should move on to using hysteroscopy in this context to remove the retained products of conception. The advantages are both theoretical and proven by evidence. Firstly, we target and remove the sac with precision. Sometimes the sac is here, sometimes it’s there, so we target the specific area of the abnormal gestational sac. By doing this, we achieve minimal injury to the surrounding area, preserving the healthy endometrium for the future.

Additionally, with the management of retained products of conception, a diagnostic hysteroscopy is performed, which is valuable for future planning. There is evidence that the complete resection rate is 91%, a very low 2% complication rate, and a low negative findings rate. It’s a very safe procedure. The outcomes show a clinical pregnancy rate near 90%, with an increase in live birth rates and a decrease in pregnancy loss.

At Embryoclinic, there is a dedicated research and development department that constantly reviews new evidence and literature in our practice areas. Recent meta-analyses show an increase in pregnancy rates after hysteroscopic evacuation, faster time to conception, 5 times fewer complications, and almost 0% needing reoperation for retained products of conception. Additionally, there is a reduction in significant bleeding because if there is significant bleeding, it can always be cauterized and managed through the hysteroscopy.

Take-home messages

  1. Hysteroscopy is a very valuable diagnostic and therapeutic tool in assisted reproductive technologies.
  2. It’s very important because it’s safe, incisionless, and minimally invasive.
  3. It’s a solution rather than a procedure or surgery.
  4. It can treat several conditions, and even in the absence of an abnormality shown on the scan, there is a good chance (20-30%), which in the context of fertility is very important, that hysteroscopy may improve fertility on its own.
- Questions and Answers

Are there any risks or discomfort associated with hysteroscopy?

There’s no procedure nor intervention without risks. Even sitting here on my computer has a risk—it may blow up or, I could get electrocuted. However, the risk is minimal. I would say serious risk is less than perhaps 1 in 10,000, and mild risk is less than 1 in 1,000. Like everything in medicine, we try to balance risk and benefit.

Regarding hysteroscopy, the benefits still significantly outweigh any potential risks. Regarding discomfort, it depends on whether it’s just diagnostic or what I call micro-operative. If it’s a small pathology, then the discomfort is minimal. We all know that comfort is a very personal trait, so some people react differently. But overall, women after diagnostic or mildly invasive hysteroscopy, walk out of the clinic within a couple of hours maximum, and they go back to their normal activities on the same day.

After an operative, extensive hysteroscopy for huge fibroids or big thick diaphragms or combined pathology, in that case, it may be a bit more uncomfortable, but they don’t require any more than just simple painkillers.

Are there any risks or discomfort associated with hysteroscopy? Is there a limit to how many hysteroscopies you can have?

That’s a difficult question. I don’t know the answer. I’m trying to think, how many have I performed on the same person? Probably 5 or 6, depending on the indication. The most challenging pathology to treat hysteroscopically is adhesions or Asherman syndrome. All the other pathologies usually require 1 or 2 procedures. I would say 9 out of 10 uterine pathologies can be treated with 1 procedure, and perhaps 10% may require a repeat procedure in a month, 2 months, or 3 months.

If there’s a huge polyp, or if there’s a massive diaphragm, or if there’s a fibroid, sometimes we remove them in two steps. The more experienced we are, the less this becomes the norm. In my practice, I think it probably happens once every couple of years that I have to go back very quickly for a repeat procedure for those indications: polyps, fibroids, diaphragms.

With adhesions, it’s a different ball game. In those conditions—polyps, fibroids, diaphragms—we can be confident that we can cure them 100%. We can confidently say to our patients, “It’s going to go away.” With adhesions, we do not have this confidence because adhesions effectively are the replacement of normal uterine tissue with scar tissue. As we all know, at least with superficial scars, there’s no surgery without scars. Even if we try to remove a scar, there’s still going to be a smaller scar replacing it. Endometrial adhesions, which may be caused by infection, surgery, or both, are the most challenging pathology that we are called in to treat. In those cases, we may need to do 3, 4, or 5 procedures.

If the hysteroscopy is done and things are sorted, and we’re happy, it is valid for a year, maybe 2 years, depending on the age. If a young woman has a hysteroscopy at the age of 36 and there’s no pathology found, I would feel confident not to repeat it for 2 years because, you see, pathology changes. Someone may not have a polyp or adhesion infection, endometritis, at 36, but they may acquire it at 38. For standard patients, I quote that a normal hysteroscopy is valid for maybe a year, or a year and a half. Then, of course, if I need to repeat it, it doesn’t cause any harm. We usually don’t dilate the cervix. We don’t touch it. It’s a bit of a “no touch” technique. I would say there’s a limit.

Is there a limit to how many hysteroscopies you can have?

No, is the answer. It doesn’t always improve it. When we suspect adhesions, it’s the most challenging part. It’s like trying to grow grass around the goalpost. It’s always very difficult. I think it’s important to partner with your patients. We sit down, have a cup of tea, and just discuss and say,” I suspect adhesions” Why? Because I see the very thin lining, because you had a couple of D&Cs or because you had an infection in the past, or you had a difficult birth with a placental abruption or whatever during birth. There are a lot of reasons why someone may have adhesions—because you’re having a very small amount of bleeding every time you have your period.

There are various types of adhesions. They could be fine, they could be dense, they could be massive, they could be local. Let’s do a diagnostic hysteroscopy to see what’s going on. My first hysteroscopy for adhesions is always diagnostic, to be honest. Then I sit down with the patient. I say, “Okay, fine. You have Asherman’s syndrome type 2. This is a bit challenging. Your uterus is never going to be perfect, and I will try to make it as near perfect as possible and improve it to maybe 80% or 90% or enough to sustain a pregnancy.”. Sometimes, we can’t even start. I have done diagnostic hysteroscopies where there was no cavity. In those cases, the prognosis is not very good. We may perform 5 hysteroscopies, and we may still not be able to be effective.

At the moment, I have 2 patients with severe Asherman’s. One of them has severe Asherman’s, but it was fairly localized, so we managed to navigate through some pockets of unhealthy endometrium. It took us about 6 to 8 months for the first embryo transfer. She had the first miscarriage, unfortunately. We managed that with a hysteroscopy. That’s a good case to be published. To cut the long story short, then we did hysteroscopic management. There were still adhesions but mild adhesions. She got pregnant again, the second time, very difficult IVF with PGT-A for various anomalies because of advanced age, and miscarried again. Second miscarriage, again hysteroscopic management. We had one more embryo. We did an HSG on her because I was very concerned about the very thin uterine wall and there was a bit of, sometimes when the uterine wall is very thin when you inject the dye, it goes through it. There was that phenomenon. However, it was very localized. We did the diagnostic hysteroscopy to see. Long story short, the lady is 16 weeks pregnant now, a normal and complicated pregnancy.

My biggest fear is that this myometrium going to withstand the pregnancy, so I’m planning to admit her to the hospital at about 32 weeks for observation in case we have any sort of worry about the integrity of the wall. We delivered a similar case with a very big and thick diaphragm where she had a very fine fundus of the uterus and all that, it can be very tricky. To be honest, sometimes I ask one of my colleagues to have a look as well. One of them, I actually asked them to travel to Athens, 1,000 kilometres, I don’t know, 500, and back just to get another opinion. They’re challenging cases.

 At the moment, I have another case, a medical doctor, with a very difficult uterus with multiple, multiple fibroma surgeries. We managed to get an endometrial lining of 6.7, and on her, we performed PRP, platelet-rich plasma, on the endometrium. This is something that has been around for over a decade. My team and I hadn’t been convinced about the evidence. Some people are not convinced even now. Having said that, there are some very good meta-analyses, and very good studies published in 2023 that indicate that for those patients, there may be a benefit. We performed PRP treatment on her. We haven’t seen the result yet. Furthermore, we haven’t dared to do an embryo transfer yet.

These are the weapons: hysteroscopy, hysteroscopic surgery, and perhaps PRP if we want to fight for that uterus. I have a big passion for the uterus because most people believe that it’s all in the embryo. Yes, the embryo is important, but the uterus is also important. It’s like trying to decide what’s more important for a vineyard: is it the soil or is it the seed? I think it’s both.

Let’s not forget that 1 in 5,000 women of reproductive age has what we call absolute uterine factor infertility. This means that the endometrium is not treatable. Even for those women, in the fertility context, there are 2 solutions. One is very established and standardized, which is surrogacy, and the other is uterine transplantation. My team and I have been very fortunate to be involved with the first people in the world, the pioneers, the Gothenburg group, Professor Brännström and Dr Mölne. We’re even looking into that because sometimes there’s nothing you can do for a damaged uterus apart from perhaps transplantation.

Is hysteroscopy always suggested before like is it suggested before every transfer ?

No, of course not. Our team, like most teams, is very aware that there is a lot of medical “ammunition” on the shelf, and we don’t pick it up every single time. It depends on the situation. If we have a straightforward case with a young couple, say 34–35 years old, with unexplained infertility, with a normal scan, and a normal history, we wouldn’t do it.

For women over 40, I tend to do it. I’m also very much aware, because I’m a gynaecologist with a background mainly in surgery, that there are risks associated with endometrium. Endometrial cancer is more common than we think, as is atypia, which is a precursor to cancer. One of the risk factors for these conditions is obesity, which is not uncommon in women in their 40s, and polycystic ovary syndrome (PCOS), which is not uncommon in women with infertility.

In our fertility unit, we see 1 or 2 cases of endometrial atypia or cancer a year, and these are invariably in women over 40. Sometimes, we identify associated pathologies. For example, we might see a polyp, decide to remove it, and it comes back as cancerous. We see thickened endometrium, diagnose hyperplasia, and it comes back as hyperplasia with atypia. We don’t suggest hysteroscopy for every transfer, but we are cautious and use it when we think it might reveal significant issues, especially in older patients or those with certain risk factors.

In my opinion, before starting IVF, we must ensure the safety of our patients, especially those over the age of 38 or 40. We need to ensure thorough screening, particularly for breast health. I am very aware of the screening protocols in various countries, and they are often not sufficient. Some countries start breast cancer screening at 45, but 1 in 7 or 8 women will develop breast cancer, and 15% of those cases will be in women under 40.

How can we justify proceeding with IVF if a woman later discovers advanced breast cancer because she was never screened? In my department, no one goes through IVF without proper screening. IVF has a near 50% chance of success, and the cumulative chance of pregnancy with 2 efforts is around 75-80%. If a woman has an undiagnosed cancer, even if the chance is small (1-2%), that could still mean 5 to 10 women in my clinic every year.

The most gratitude I’ve received is often from women for whom we insisted on thorough screening. Recently, a wonderful woman from Serbia was found to have breast cancer during our pre-IVF screening. She underwent surgery and chemotherapy and continues to thank us regularly because she understands that we saved her life. Similarly, with hysteroscopy, we diagnose about 2 to 3 cases of atypical hyperplasia or endometrial cancer annually in women over 50. Last year, I performed a total radical hysterectomy on a 42-year-old woman who came for IVF and was found to have endometrial cancer.

Fibroids are another concern. While most are benign, about 1 in 500 are malignant. Given the large number of women with fibroids, it is crucial to be vigilant. I am very conscious of this risk, and I am strict about ensuring both breast assessments and hysteroscopies are performed. To date, I have been fortunate not to have had an undiagnosed cancer case a year after IVF.

My passion stems from a deep commitment to patient safety. By being diligent with screenings, we can prevent life-threatening conditions from going unnoticed and provide our patients with the best possible care.

If a hysteroscopy is done, when should IVF be performed? Is it possible to do it in the same cycle?

It depends on why the hysteroscopy was performed. There are 3 primary indications for using Platelet-Rich Plasma (PRP) in this context. First is unexplained implantation failure, which occurs when we have good-quality embryos and have done multiple transfers, yet there is no success. The endometrium looks fine—good shape, nice Doppler results, and a trilaminar appearance. In this scenario, the theory is that there might be something functional that PRP could improve. In such a case, where everything looks fine by scan or even by hysteroscopy, I would perform the PRP injection 4 to 5 days before the embryo transfer. This involves just 1 PRP injection through a uterine catheter, similar to an embryo transfer catheter, 4 to 5 days before the embryo transfer.

I’d like to note that it took me 5 to 6 years of investigation before I decided to use PRP. There are many areas we still don’t fully understand, and many unknowns remain. One of the biggest unknowns is that we don’t know exactly what we are injecting. I found, through interviewing and interrogating dozens of my colleagues, that most of them were not entirely sure what their PRP injections contained.

In my practice, we always perform quality control. We aim to achieve a platelet concentration of 1 million per microlitre. We conduct quality control on every single specimen for each patient because the ability to produce this specimen depends on the concentration of platelets in the patient’s blood and the amount of blood we have worked on. In summary, yes, it is possible to perform IVF in the same cycle as a hysteroscopy, depending on the specific circumstances and the reason for the hysteroscopy.

During my interview with my colleagues, I was very surprised to see that some of them are using 5 ml of blood, concentrating down to 1 ml, while some are using 30 ml. What is the optimum volume of blood we need to draw? It took us about 2 years of working with my team in the lab to standardize the procedure so that we ensure the right concentration. We need 1 million platelets. Most PRP applications in other specialities, such as facial or vaginal rejuvenation or even cartilage orthopedics, require 300,000 to 400,000 platelets. Thus, most labs that prepare PRP for those uses don’t have the right equipment, tubes, bottles, or proper positioning of the tubes. There are a lot of tricks of the trade involved.

The second group includes those with an okay endometrium but not brilliant—endometrium on the thin side (7.5 to 8.5 mm), not-so-good trilaminar appearance, not-so-good Doppler’s, perhaps a bit of irregularity on the surface on the scan, or visible defects on the hysteroscopy. For those patients, depending on where they live, I would probably do 1 injection perhaps a month before and then another injection during the treatment cycle. If they don’t live locally, I would probably perform one injection at the beginning of the stimulation, maybe on day 7, or if it’s a frozen embryo transfer, a bit later, on day 10, and then the second injection a bit before the embryo transfer.

Then there’s the third category, which includes the ladies I described with terrible endometrium, less than 6 mm, many adhesions, multiple hysteroscopies, Asherman’s syndrome, and just one spot of period every month indicating a very small amount of healthy endometrium. In those cases, we just don’t know. I would do 1 injection every month and assess the score of the endometrium each time to determine the optimum time for the actual treatment.

When is PRP advised for the ovaries, and how long should it be done before, for example, egg collection?

PRP for the ovaries and endometrium—there’s enough evidence for endometrial PRP. It depends on how stringent you are. Recently, there was a study, and they were quite strict in their assessment. It’s very difficult to set up a good study, especially in fertility, where there are so many factors involved. It’s very difficult to match the patients and to find controls. For instance, what about the embryos? They all have to be PGT-A tested if you are to match, so it’s very difficult. A lot of it has to be empirical; there’s no other way, and we accept that.

Having said that, for endometrial PRP, to my mind, there’s enough evidence to apply it clinically. There is enough evidence in the literature, especially in the two big meta-analyses that came out last year. For ovarian PRP, the evidence is just now being accumulated, so it is not as strong as it is for the endometrium. My team and I are gathering all the data from our practice, and we’re hoping to understand a bit more and hopefully publish some results. Hopefully, those results may contribute to the general scientific knowledge.

For the ovaries, we know that they need a little more time. The growth factors in the PRP injection need more time to work. There are beautiful ways to monitor it, one being the antral follicle count (AFC) and the AMH. I would probably wait 2 to 3 months before egg collection, sometimes even more. If I see that the ovaries are responding and that something is happening, I may repeat the injection after a couple of months.

I learn from my patients before I learn from books, journals, and conferences. A very good protocol that was suggested by one of my patients many years ago, which I didn’t do at the time but has since incorporated into my practice, is to do PRP on the day of the egg collection. This will not work for the current cycle, but it will be beneficial for the next cycle.

We have quite a few patients with very poor ovarian reserve and very poor response to stimulation, even women undergoing natural cycles. I find it very useful to inject PRP into the follicle when you do the aspiration for one or two precious follicles. The target is there, the needle is there, and the procedure is under the same anaesthetic. It doesn’t take much longer to complete. The effect of that may be evident in the next month or a couple of months ahead.

Can someone who is not an IVF patient at your clinic have only a hysteroscopy as a procedure? On which day is the best to perform it?

The answer is, of course, yes. However, I apologize that some of my colleagues may be a bit restrictive towards other patients. Even if we contribute with a phone call and good luck to any of our patients or viewers, that is very positive for us. Anything we can do to contribute a little bit to anyone’s journey by any possible means aligns with our ethos. By all means, you’re very welcome if you want to attend just for that or if you want to get a second opinion. Just drop me a line, and I would be delighted to offer it to you.

Do you do sub-endometrial PRP via hysteroscopy? Is it more beneficial for a thin lining in comparison to normal PRP?

To be honest, in theory, yes, it is more beneficial. But I don’t do it as the first line. I would only do it for the third category of patients—very difficult patients with significant adhesions. But again, not as the first line because it is invasive. So, I wouldn’t do it easily. I would consider it as a second-line treatment for very difficult patients in whom the injection of PRP fluid into the endometrium hasn’t worked or hasn’t worked significantly.

Can Endo-PRP (endometrium rejuvenation) treatment improve your endometrial thickness?
Do you trust your clinic? Building, training and tuning your BS detector
Fertility preservation & egg freezing: understanding your options
Advanced maternal age & egg donation in Spain: exploring your options
Diagnostic evaluation & management of male infertility
Personal boundaries in your fertility journey: what are they,  how to put them in place, and why you might need them
Authors
Elias Tsakos MD, FRCOG

Elias Tsakos MD, FRCOG

Dr Elias Tsakos, FRCOG, is a Medical Director of Embryoclinic - Assisted Reproduction Clinic in Thessaloniki, Greece. He has received extensive and certified training in the United Kingdom and is a Fellow of the Royal College of Obstetrics & Gynaecology. Dr Tsakos is also a Board Member Representative of the Royal College for Greece and Cyprus and a Board Member of the Hellenic Society of Assisted Reproduction. He is a Member of the British, European and American Fertility Societies (BFS, ESHRE, ASRM). Dr Tsakos has been living and working in Thessaloniki, Greece, since 1999.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
Have questions about what factors will affect your IVF success?
Join our live event to directly ask your questions to three IVF experts.