IVF & FERTILITY TREATMENT FOR WOMEN OVER 40 - WHAT ARE YOUR CHANCES?

The value of hysteroscopy in fertility care

Elias Tsakos, FRCOG
Medical Director , Embryoclinic

Category:
Advanced Maternal Age, Donor Eggs, Endometriosis, Failed IVF Cycles, Fertility Assessment, Reproductive surgery

hysteroscoopy-its-role-in-fertility
From this video you will find out:
  • What Is a Hysteroscopy, how does it work, and when is it indicated?
  • How accurate is hysteroscopy?
  • How long is recovery after a hysteroscopy to remove polyps?
  • Does hysteroscopy improve IVF success?
  • What size fibroids can be removed with hysteroscopy?

The value of hysteroscopy in fertility care

How is hysteroscopy useful in infertility treatment?

In this webinar, Dr Elias Tsakos, FRCOG, Medical Director at EmbryoClinic, Thessaloniki, Greece, talked about the benefits of hysteroscopy in fertility treatments. Nowadays, fertility surgery has moved more into the hands of fertility surgeons or endoscopic surgeons. The assessment of female anatomy is part of the basic assessment, the use of ultrasound scans has evolved and is in standard use, but according to Dr Tsakos, the assessment of the female anatomy, such as the cavity within the uterus or the tubes, the ovaries have been hugely neglected. Therefore, fertility endoscopy should be considered to be applied for what is called unexplained infertility. What is fertility endoscopy?

Fertility Endoscopy

The majority of IVF clinics don’t require a tubal test before performing IVF on a basis. However, there are cases in which the tubes have hydrosalpinx, and they are not always picked up by scans, apart from the cases in which the uterine cavity has anomalies, which have not been picked up by the scan. Let’s not forget that the scan is not the panacea, it’s not the gold standard for anatomy assessment of the female reproductive tract. The gold standard is a hysteroscopy and laparoscopy. When is an endoscopy indicated? When there’s unexplained infertility, if it’s a tubal factor, endometriosis, fibroids, polyps prior, before IVF, after failed IVF, after miscarriages and after a mild male factor, which would not justify going straight for IVF. The fertility endoscopy includes hysteroscopy and laparoscopy, either the standard one or the da Vinci laparoscopy.

Fertility assessment

The first thing that is always checked and performed is hormonal testing, which includes the standard hormones, such as FSH, LH, estradiol, progesterone, prolactin, and TSH. It also includes advanced assessment, an AMH and some more specialized hormonal tests depending on the indications, for example, it’s best to perform more hormonal tests if there’s evidence of hormonal imbalance, like in the case of PCOS or premature failure. The next thing would be anatomy assessment, according to Dr Tsakos, this is something that is usually overlooked. These days the anatomy assessment tends to be limited to the ultrasound scan, but despite the advance of new technologies, not all IVF units have the skills and the availability to provide a 3D scanning or very advanced ultrasound scanning, including Doppler’s. In general, anatomy assessment should not be limited just to 1 scan, no matter how good the scanning facility or the scanning technology and skills are. It can only diagnose around 80% of the things we need to know about anatomy, and 20% of them are misdiagnosed or undiagnosed. Genetic assessment should include a blood group, but also a test for Cystic fibrosis, which is the most common gene amongst the white race, roughly 1 in 20 people are carriers of that gene. Also, Karyotype testing is important, another is electrophoresis, which is a genetic anomaly of the haemoglobin and this is related to the gene, it’s commonly known as Thalassemia, it is generally thought to be common in the south of Europe, in Italy, Spain, Portugal, Greece and France, it is a bit less common in Northern Europe, however, it’s not unheard of. Tests that are considered advanced assessments test should be performed on the indication, only if there’s a history of miscarriages or a family history of Thrombosis, for example, failed IVF cycles, etc. That includes Thrombophilia testing, which has become very popular in the last 10 years, it is fairly common in a large proportion of the general population, and even more common in infertility patients. It should also include autoimmunity testing, genetic testing and endometrial receptivity testing. These are still controversial, however, they may be considered advanced female tests. Male fertility assessment includes a semen analysis, semen culture, genetic tests should also be included as well as a blood group, and cystic fibrosis, whether it’s full cystic fibrosis gene testing or just a DF 508, this depends on the clinician’s protocols. Karyotype, serum viral testing is also very important for the benefit of the procedure and also the benefit of the unborn child, and a very simple hormonal assessment for the men is also important, men should also check their thyroid function, there is an association of thyroid anomaly and semen dysfunctions and the same applies with prolactin and some other tests like vitamin D and glucose. When we’re talking about advanced male fertility assessments, those are performed if there are some abnormal findings on the basic test. If there’s relevant history and that includes anatomy testing, referral to an andrologist, hormonal testing, DNA fragmentation testing and in some cases Y Chromosome microdeletion tests and so forth.  

How is hysteroscopy useful in infertility treatment? - Questions and Answers

Is hysteroscopy done under anaesthetic?

Generally, no, it’s not. I mean, there are 3 types of hysteroscopy. The first one is the office hysteroscopy, in which we use the flexible hysteroscope. Usually, we start with a flexible hysteroscope which is a very fine instrument, it has the size of a cable, it looks very much like a cable only that at the end it has a fibre optic ending, and of course, we use very high-quality cameras and lighting sources, so we just look inside and at the same time our patients look inside, it’s a little more uncomfortable than a vaginal scan. There’s no anaesthetic or priming of the cervix needed for that. Sometimes if the patient is a little agitated, we may give them a little of Panadol half an hour before, but that’s it. If there is pathology, we can always remove it again without an anaesthetic, but if there’s a big pathology, then we do it in the setting of the operating room, and we can provide an aesthetic state away and remove the pathology is treated during the procedure or at a later point.

When doing hysteroscopy, if anything is found, is it treated during the procedure or at a later point?

Invariably, we do a high-quality ultrasound scan before we do a hysteroscopy. When we see pathology on the scan, then we decide whether that pathology would be treatable with no anaesthetic or under local anaesthetic. Or whether it would require sedation or general anaesthetic. If on the scan, we do identify a small pathology, either a small polyp or a small adhesion, or if we’re not sure if the fibroid is distorting the cavity or not, we start with the diagnostic hysteroscopy.

Usually, we finish with the no anaesthetic hysteroscopy, of course, this has to do with the patient compliance and the patient collaboration, as well. More than 90% of patients tolerate diagnostic hysteroscopy with no problems at all. However, if someone becomes a little agitated or if for some reason they feel uncomfortable, we stop the procedure, we give them sedation, and then we move on, we try to complete everything as a one-step approach within the same session which usually doesn’t last longer than 20 or 30 minutes.

What causes the improvement in IVF after a negative hysteroscopy? 

There’s a lot of proposed mechanisms. Slight inflammation, not infection effect of hysteroscopy itself either through the water irrigation or through the little of scratching we may do by taking a small sample of the endometrium, this is the most proposed mechanism. In my opinion, it’s not just that it has to do with the fact that we ensure that the cervix is not stenosed. Performing hysteroscopy beforehand, we’re doing a very good mock trial transfer, so we ensure that the cervix is not closed.

Therefore, that would guarantee better embryo transfer. When we do IVF, it may well account for a good 10% increase in our success rate because we have ensured that the cervix of the uterus is normal, and if it’s not, we may do a small dilatation on the spot, which would facilitate the transfer. There’s a lot of mechanisms that may be implicated. The most popular one is the effect of scratching and causing this mild inflammation into the endometrium.

Is the same improvement also seen in natural pregnancy after hysteroscopy?

I don’t look at hysteroscopy as surgery, I don’t even look at it as an endoscopy, I look at it as the gold standard in ensuring that the endometrial lining, the implantation spot is normal. In my opinion, this is a very viable piece of information in a fertility workup. If we see an improvement in natural pregnancy or not, the answer depends on what patient we’re doing it for.

If we’re doing it for an unexplained infertility young couple with normal sperm and normal tubes, yes, indeed, that would improve their natural fertility chances. If we’re doing it for a mid-40s lady who was planning to undergo egg donation, perhaps the natural fertility chances are not going to significantly be improved, at least not in a countable way, so it’s very difficult to answer that, but in my opinion, it has a place in most of our fertility patients improving what could be improved. It’s not going to affect the egg quality if somebody is of advanced maternal age. It’s not going to have a serious impact on endometriosis if somebody has endometriosis affecting their fertility, but it would give us the confidence that at least it’s carefully evaluated and that we have eliminated any serious adverse involvement of pathology that has been undiagnosed.

I have performed hysteroscopies on many women with uterine diaphragms that have been missed by ultrasound scan, even performed by very experienced people with very high tech equipment. We all know this could be very well associated not only with IVF failure but with adverse pregnancy outcomes.

How big should septum resection be?

That depends on many things is the answer. It’s not just the size, it’s the location, whether it’s associated with other factors, previous implantation failures or miscarriages or preterm labours and so forth. Thessaloniki is one of the capitals of congenital anomaly classification, our professor Grigoris F. Grimbizis is the chair of the committee that evaluated and redefined all the congenital uterine anomalies, and he’s made a huge impact with his team, and of course, the ESHRE collaborators. In Thessaloniki, we do value the importance of classifying and designing what’s best for each patient.

Even metroplasty or septum resection doesn’t come with any potential consequences, but in my personal opinion and our team, we have a big series of hundreds of patients who’ve undergone metroplasty. To be honest, if it’s someone with failed IVFs and implantation failures or miscarriages, I don’t feel very comfortable if I don’t resect the septum, even if it’s a small one, touching just one-third of the uterine cavity.

You’ve mentioned that fibroids close to the endometrium may affect fertility? How close are we talking about?

I don’t like the lining, the endometrium to be malformed to be pushed to the side, or I don’t like the fibroid just underneath the mucosa. If it’s just underneath a mucosa and if it’s small, perhaps I would consider leaving it if it’s an intramural fibroid that is not distorting the cavity very much, I may allow it to be there provided that it’s not bigger than 3 centimetres. That again depends on whether that patient has had previous IVFs before or previous unexplained implantation failures, miscarriages.

In my practice, I think the most difficult cases are the grey area cases. If somebody has a huge submucous fibroid or a fibroid polyp, yes, it’s pretty straightforward that has to be removed. I recently had a relative of mine who came from overseas with a 9-centimetre intramural fibroid, I refused to do IVF on her, and then she went back to her home country, and then they refused to do the surgery on her and then eventually she had IVF, and they were successful. She had a fairly good pregnancy, she had a bit of pain, the fibroid became 15 centimetres during pregnancy, but then, she had a delivery, a caesarean section, everything went fine, she bled a little and so forth. There are always extreme examples of women with huge pathology doing very well without surgery, but in my opinion, it’s not just the outcome eventually, it’s the patient experience that is important.

I find it very hard to justify leaving a fibroid of 5 or 6 centimetres, which is perhaps in the muscular layer of the uterus. In case of a successful pregnancy, it would double in size. It would most definitely cause pain, would most clearly lead to a caesarian section and possibly a little of bleeding or a lot of bleeding. I find it very difficult to justify it, mainly it has to do with my training in the UK in the 90s. We were not just fertility specialists, we were also surgeons, and there were also situations where we were delivering our fertility patients babies. I’ve been fortunate enough to work with a wonderful team of gynaecologists here in Greece, and we still deliver babies for the patients, so it’s very uncomfortable even after a successful IVF attempt to have a 15-centimetre fibroid at 37 weeks of pregnancy and the woman in excruciating pain.

I try to individualize and discuss it with my patients, it’s not always easy to remove a fibroid, especially if it’s a small one. If it’s a 3 to 4-centimetre fibroid that is deep into the muscular layer of the uterus that may not be visible with laparoscopy, it’s not very easy to find, you can’t palpate the uterus to fill it. You don’t want to do an incision or use laparotomy. I’ve had patients who’ve been operated on twice through laparoscopy, and the intramural fibroid of 3 centimetres was not identified, so it was not removed. Then we had to do a robotic surgery which sounds a little of a joke using all this technology to remove a 3-centimetres fibroid, but yes, it may need to be done, and it may affect fertility, especially if it’s very close to the endometrium and in patients with multiple IVF failures. We may even need to use the robot the ‘Da Vinci technology’ with the amazing endoscopic ultrasound system to locate the deep fibroid into the muscular layer. Then we would know where to do an incision, remove the fibroid, which may sound ridiculously small at the time, but yes, it may affect fertility implantation and eventually the pregnancy outcome.

In which Müllerian anomalies do you recommend operative hysteroscopy?

I know the study is going on at the moment, I’m looking forward to the outcome. There is some preliminary data that perhaps small diaphragms or medium diaphragms may not be that important, I doubt it. I think they are important, and not only can they cause implantation failure, but also they cause miscarriage and potentially preterm labours.

In my gynaecology practice, I recently did a hysteroscopy on a postmenopausal woman who had almost complete uterus didelphys, she had a huge diaphragm of the uterus, and that was undiagnosed, and she had delivered through caesarean section children without knowing it, and she became 70 years old to find out that she had a diaphragm. I think this is the exception, for the majority of uterine diaphragms, there is a value, and there is a point in performing c to improve the chances of a successful pregnancy.

What is the optimal waiting time after hysteroscopy with fibroid removal before proceeding with egg donation?

The answer depends on the fibroid, on how big it was. You could have a fairly large fibroid with a small stem which means that the damage to the endometrium is minimal, or you can have a smaller fibroid with a large base and so forth. In my opinion, a couple of months, no longer than that, I think within six weeks, so, within a couple of menstrual cycles, the lining returns to normal.

Depending on the extent of the insult of the uterine lining, I would like or not to do a second hysteroscopy to ensure that all the healing has been perfect. There have been no adhesions before I move on to the egg donation. I must admit that in the majority of my egg donation cycles, especially with those over 40 years of age and those with previous IVF failures, I strongly suggest a diagnostic hysteroscopy.

I must say that the majority of the patients are very happy to accept it and request it before even suggestion, and it gives us huge confidence, it rules out quite a lot of pathology that otherwise we would be unaware of. Also, for women over 40, I always do an endometrial biopsy, not only to exclude endometritis and such factors but also to ensure normality. Sometimes we pick up atypia, we pick up endometrial hyperplasia, and atypia needs careful attention, which may need some progesterone treatments before we embark on the egg donation. For my egg donation cycles, invariably, I do suggest hysteroscopy.

Can you have hysteroscopy during the stimulation phase of IVF?

The answer is probably yes. In my opinion, you can do a diagnostic hysteroscopy. If it’s done in the early follicular phase, you may even proceed with the first embryo transfer if you haven’t done anything operative. If I have any doubts about the uterine pathology and if I’m not very happy with the fresh embryo transfer for any reason, I sometimes suggest and perform a hysteroscopy during the sedation of the egg collection. In my opinion, if we are to perform a hysteroscopy during an IVF cycle, the best time is to do it during egg collection, whether we do a fresh embryo transfer on that cycle or not. I don’t do a fresh embryo transfer when I’ve done an egg collection and hysteroscopy. Invariably when I do this, I have a strong suspicion that there may be pathology, and this is proven to be the case.

We had a problem during the hysteroscopy. We did D&C, it was performed properly. Our doctors were not able to get into the uterus to see if there is any problem. How should we go about this situation? We had 2 failed transfers. 

It’s difficult to comment on that, but if they fail to do a hysteroscopy, that probably means that you have some cervical stenosis or adhesions or both, and it’s a little curious as to how D&C was performed. D&C means that blindly an instrument goes into the uterus and takes a sample, so I cannot explain how that blind instrument went into the uterus and then an instrument with the light and deny at the end of it cannot go in.

In my opinion, I would probably suggest that you consider having a hysteroscopy at some stage to clarify whether there’s stenosis or adhesions or both. Try to optimize the conditions as much as you can. Optimizing both of them might have a positive effect on embryo transfer and implantation. If you’ve had a failed hysteroscopy, you are at a very high chance of a very difficult embryo transfer or a failed embryo transfer. I would suggest considering a diagnostic hysteroscopy before you move on.

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Authors
Elias Tsakos, FRCOG

Elias Tsakos, 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.
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