Endo Seeking Missile

Just a quick update about a potentially interesting piece of research I noticed today.

Researchers have identified a protein (called z13) that selectively binds to and is absorbed by, endometriotic cells. In a way, finding this protein has been like the child’s toy where you have a box with different shaped holes in it and you have to find the right shaped peg to fit in the hole, except imagine you have a box with tens of thousands of different holes and tens of thousands of accompanying pegs, not an easy task. Now that this protein has been discovered it means we have a way to target endometriosis specifically and ignore all other tissue and organs in the body.  

What the researchers then did was attach other proteins to z13 which would induce cells to die. Effectively, what they now had was an endo seeking missile. So far the researchers have tested this on peritoneal endometriosis in baboons and found that the targeted proteins caused the endometriotic cells to die whilst leaving the surrounding tissue unharmed.

One of the best things about this approach, from a patient perspective, is that this is completely non-hormonal; no messing around with the ovaries, no pumping the whole body with hormones, just targeting the disease itself.

Cautious optimism aside, it may be a while before we see this approach translated into humans and there are still many more tests to be done to make sure it is safe. Nevertheless this shows that research is not continuously bogged down in the old ‘hormone therapy’ mindset and people are exploring new and exciting possibilities and, whilst this may not be a cure, it is a step in the right direction.

Highlights from WCE 2014 - Part 3

Carrying on with our WCE 2014 highlights, let’s have a look at some of the research into fertility issues and endometriosis. Reduced fertility is one of the major problems faced by women with endometriosis, yet there are still many mysteries surrounding how endometriosis affects fertility.

In order to shed at least some light on the issue an Italian research team investigated how ovarian endometriosis (endometrioma) can affect the viability of ovarian follicles in women undergoing IVF. What they found was that follicles closer to endometrioma showed higher levels of iron. Iron, of course, is important for your body but in endometriomas iron accumulates in high amounts, probably due to blood filling the inside of the cyst. These high levels of iron can be toxic to anything close by, in this case, ovarian follicles. This leads to impaired development of the follicle and perhaps partly explains why so many women with endometrioma/s find it hard to conceive.

If you have an endometrioma, chances are you’ll want surgery to remove it, but you’ll also want to know what the risk of recurrence is and what factors influence that risk. A team from Brazil looked at the records from 202 women undergoing laparoscopic excision of endometrioma between and 2003-2012 and analysed those records to see what influenced endometrioma recurrence. They found that the overall rate of endometrioma recurrence was 16.4% and that factors such as age, race, symptoms, exercise, number of children and type of surgical procedure had no effect on recurrence rates. However, they found that having a cyst larger than 6cm (which is pretty large) and stopping medical therapy after surgery significantly increased the chance of endometrioma recurrence (although the abstract didn’t specify which medical therapy was used). Because of the side effects associated with some of the medical treatments for endometriosis, it is unsurprising some women need to stop treatment. However, if stopping treatment means an increased risk of disease recurrence, then more work needs to be put into ensuring other, more tolerable medical options are made available.

Speaking of IVF, some women who suffer with fertility issues may consider IVF as a means of conception. It is therefore important for women with endo to know if their condition may affect their IVF outcome. A group from France compared 291 women with endo to 1316 women without to see what the effects, if any, endo made to the delivery rates after undergoing IVF. What the researchers found was that, in the women who had good ovarian stimulation response and high quality embryos, the total cumulative successful delivery rate for fresh and frozen embryos was 52.3% for women with endo and 45.8% for women without. Although women with endo had lower rates of good ovarian stimulation, the overall outcome was no different between women with and without endo. This suggests that having endo (regardless of stage) may not impact the success of IVF.

Although it appears that endo doesn’t affect the success of IVF, it would still be good to have some way of improving IVF outcomes. A group from New Zealand has been conducting a randomised, controlled trial to see if a drug called Lipiodol has any benefit on IVF outcomes, as their initial tests showed this treatment improved the fertility of women with endo much more than women who couldn’t conceive but didn’t have endo. Lipiodol can normally be used for hysterosalpingography (a procedure used to determine the shape of the uterus and fallopian tubes) and is injected into the uterine cavity so comes into contact with the endometrium. The authors of this study think that Lipiodol ‘bathes’ the endometrium, making it more receptive to a fertilized egg. Their results are still very preliminary so should be met with cautious optimism, but are still encouraging. The women who received IVF alone achieved a live delivery in 22.7% of cases, but the women who had Lipiodol treatment plus IVF achieved a live delivery 43.8%. These results are encouraging, but we’ll have to wait until the clinical trials have been completed and the results properly analyzed before drawing any firm conclusions.

Highlights from WCE 2014 - Part 2

Let’s continue our exploration through the World Congress on Endometriosis 2014 and we’re going to delve into some of the research about what makes women with endo different from those without and how this could give us clues as to what causes endo in the first place.

A team from Australia made an interesting discovery regarding stem cells and endometriosis. You have probably heard about stem cells before, but why would they be of interest in endometriosis? Stem cells are the precursors to the different types of cells in your body and are mostly of use during the very early part of your development when you were a foetus growing new organs. But they still have some use as an adult, for example, inside the uterus there are a population of stem cells that your body uses to regrow the endometrium after each menstruation, which are unsurprisingly referred to as endometrial stem cells. If these cells can grow endometrium and endometriosis is endometrium-like tissue, it becomes clear how these stem cells could play a role in endometriosis. Some researchers believe that genetic changes associated with endometriosis result in some endometrial stem cells becoming displaced during embryo development, which go on to produce endometriotic lesions as a girl approaches adolescence. Others believe these stem cells are shed into the pelvic cavity by retrograde menstruation (where the menstrual blood goes into the pelvic cavity) and implant around the pelvis and then develop into endometriotic lesions.

This investigation by the Australian team looked at the number of endometrial stem cells in the blood, menstrual blood and peritoneal fluid of women with and without endometriosis. What they found was that, although the amount of peritoneal fluid was similar between the two groups, the number of viable endometrial stem cells in the peritoneal fluid was massively higher in women with endo. So how did those cells get there? Retrograde menstruation is a likely explanation, but they found no difference in the amount of stem cells in the menstrual blood between women with and without endo.  It could be that the immune system of women with endo doesn’t clear the refluxed stem cells and they just accumulate or maybe there is some other way these cells are getting into the pelvic cavity, at this moment nobody knows for sure.

Speaking of peritoneal fluid, a group from the US and Brazil analysed the peritoneal fluid looking for inflammatory factors that are related to endometriosis associated pain. What they found was that dyspareunia (painful sex), non-cyclic pain and infertility were not related to the inflammatory factors they were studying. What they did find though was that certain inflammatory factors were associated with dysmenorrhea (excessively painful periods). This has some potentially very interesting implications, particularly as dysmenorrhea is the most common symptom of endometriosis. This suggests that dysmenorrhea is caused by areas of chronic inflammation around the sites of endometriosis regardless of stage or location. If it were possible to find out how these inflammatory factors are being produced and find a way to reduce the level of these factors, in the future this could be a new way of treating the pain associated with endo. 

More highlights on the way soon...

Highlights from the World Congress on Endometriosis 2014

It’s that time again, that time when the best and brightest in the field of endometriosis gather together in one place to share their collective experience and figure out where the future of endometriosis research and treatment is going; all whilst enjoying a caipirinha on the sunny beaches of Sao Paulo (us science types know how to multitask). Although I managed to go to the previous WCE in France, unfortunately I couldn’t make it this year, so instead of enjoying the glorious heat of the Brazilian south I was enjoying the drizzly rain of the English northwest, oh well. However, thanks to a friend, I did manage to get the book of abstracts (which is basically a summary of all the talks, presentations and posters at the conference) so I can give you a rundown of what’s been going on in the field of endometriosis research now and in the future.

Before I continue I must mention that the information I’ll be presenting here is taken only from the abstracts, which as basic summaries of the research and not in depth discussions and may or may not be taken from completed or peer-reviewed research. Also because these are conference papers I can’t provide links to source material as I normally would.

To start with, just looking at the book is encouraging, over 400 pages of research into all the many and varied aspects of endometriosis, which is broken down into different subject matters, so I’ll start with genetics and endometriosis.

Genetics is an important factor in endometriosis, mainly because we don’t really fully understand how genetic changes contribute to endometriosis risk. A team from Sweden aimed to examine indirectly the role genetics play, by looking at the rate of endometriosis in twins. There are two different types of twins: monozygotic (where both twins come from the same egg and are essentially genetically identical) and dizygotic twins (where each embryo comes from a different egg and can so each twin can be very different from the other). Of all the female twins this research looked at they found that there was a much higher risk of endometriosis if your monozygotic twin also had endometriosis. That certainly seems to suggest that genetics plays a role in the origin of the disease. Of course there are other factors at play too in determining endometriosis risk. This team, after doing some calculations, found that in the women they studied, genetics accounted for around half of the risk associated with endometriosis and environmental factors accounted for the other half. Finding out what the specific genetic and environmental factors are and how they increase or decrease the risk of endometriosis, is an ongoing challenge for the future.

Several other studies presented at the conference aimed to find out what these genetic factors are. Our genetic material (our DNA) is a funny thing, it can change in many different ways, some bits can swap, duplicate or be deleted all together and sometimes specific changes can be associated with specific diseases. Other research identified some of these specific changes associated with endometriosis which may, in the future, might allow us to identify women at risk of the disease with greater ease and hopefully give us to better understand the way in which the disease works.

Of course there are problems to consider, for example, are the genetic changes we see the same across all women? One of the presentations from an international team found that the genetic changes we know of so far are very similar between women of European and Japanese ancestry, but we still have no information on women of African, Chinese, Indian etc ancestry to compare them to. These types of studies though require a great deal of time and money invested in them, so it may be a while before we see a complete picture of the genetic risk associated with endometriosis for women across the world.

Another point to consider is the difference between types of endometriosis. One piece of research from a Danish team found genetic alterations specific to deeply infiltrating endometriosis. Therefore it could be that peritoneal, deeply infiltrating and ovarian endo all have different genetic alterations (and different genetic risks) associated with them. It’s good to know though there are people actually looking into this and one day, maybe soon, we’ll have that complete picture.

More to follow soon.

Endometriosis: Improving the wellbeing of couples

Whilst this blog is mostly concerned with clinical and lab-based research into endometriosis, there is other research being carried out that it equally informative and deserving of our attention.

In point of fact a new piece of research has been published from my old alma mater about the impact of endometriosis on relationships, with viewpoints from both the male and female perspectives.

So if, like me, you are in a relationship with someone with endo, or are a woman with endometriosis in a relationship (or even if you're not), this will be a very interesting read.

To read the full report click on this link

Endometriosis Awareness Month – Part 3

Endometriosis awareness month marches forward, quite literally. As you may have seen there have been awareness events taking place in many countries. Women with endometriosis and their supporters have been marching through major cities all over the world to help raise awareness for endometriosis and they have done an exemplary job.

Unfortunately I couldn’t make it to the UK event, but seeing the great turnout in all the cities and all the people who talked about it on Twitter/Facebook/blogs/forums etc, really showed just how much endometriosis awareness has changed for the better in the last decade. It certainly makes me hopeful for the future wellbeing of women with endo.

Speaking of the future, let’s have a look through some of the current research that will hopefully contribute to better prospects for women with endo everywhere.

We start then with a study from Denmark, which assessed the long-term reproductive status of women with and without endometriosis. To do this investigators examined medical records from tens of thousands of women across four national registries from 1977 to 2009.

 What they found was that, over the time course examined, women with endometriosis had around 7% fewer childbirths and 8% fewer naturally conceived children than women without endo. Not a massive surprise there; it’s well known that women with endo can find it difficult to get pregnant. Interestingly though the researchers found that as time went on (from 1980 to 1998), more women with endo had children, suggesting that it takes a long time for women with endo to conceive naturally (of course we must also remember that assisted reproduction wasn’t introduced until 1980). What is quite interesting is that they found that women with endometriosis were more likely to get pregnant with ART than women without by a small percentage.

This study also found that, for women with endo, the risk of ectopic pregnancy was twice that of women without. In addition, there were 21% more miscarriages in the group of women with endo. The reasons as to why this was the case remain unclear, it may be that the presence of active endometriosis in the pelvic area negatively affects pregnancy outcome somehow. Although, as the authors point out, there are other studies that have shown no increased risk of ectopic pregnancies in women with endo, so the jury is still out. In addition this study found that women with endo undergoing ART were at an increased risk of miscarriage, however another recent study found no increase in miscarriage risk. So whilst these studies are informative, they only represent the experiences of a certain population of women. 

One of problems with this study was that some of the women said to be diagnosed with endo, were only suspected to have it, not because they had laparoscopic diagnosis, meaning they may have had endo, or not, or another condition. Another issue is that this study wasn’t able to follow women throughout their entire reproductive life, so they didn’t have a complete picture of all the women’s reproductive history.

Nevertheless, what this study does tell us is that women with endo may require special prenatal care. If results such as these are the same in other countries it certainly suggests that additional provisions need to be made for women with endo (such as better monitoring of foetal and maternal health) and the medical community needs to be aware of this.

Moving on then, from the problems women with endo have to suffer with, to the ways in which the medical community is trying to solve those problems. Laparoscopic surgery is considered the best way of surgically removing endometriosis, but you need a good surgeon at the helm. Another problem is that not all endometriosis can be found and removed easily. One of the most troublesome forms of endo is deeply infiltrated endometriosis (DIE). This type of endo is very commonly associated with the most painful symptoms, such as chronic pelvic pain, painful sex, painful urination and painful bowel movements (depending on where the DIE is and how deep it has infiltrated).

Removing DIE is quite a challenge then, even for a skilled surgeon, which is why some surgeons are now trying robot assisted laparoscopy. Using ‘the robot’ does offer several advantages, such as better precision, better visualisation and more freedom to manoeuvre the instruments. Of course the downsides are that a surgeon will have to learn to use the robot and it is very, very expensive. Another point raised it that using the robot lacks a ‘tactile response’, that is, surgeons cannot feel the resistance or tension of some organs/tissues that might give them an idea of how to proceed with the surgery.

Therefore studies are needed to assess how well robot assisted surgeries fair in removing DIE. That is the subject of a recent paper from centres across the world.  This study looked at robot assisted operative results from 164 operations on women with DIE in different places to see how well the surgeons and patients faired.

Overall the average time for surgery was 180 minutes and the average hospital stay was 4 days, which, given the low rate of complications, seems like a long stay to me, but that may be due to different approaches to post-operative care in different centres/countries. 113 patients were followed up after an average of 10 months and 86.7% were found to be pain free, which is a god result by anyone’s standards.  

Other studies have shown that while robot assisted surgery takes slightly longer and is comparable in outcomes to conventional surgery with respect to stage I and II endometriosis, it may be beneficial for advanced stage endometriosis and has a lower risk of needing laparotomy.  

At the moment then the current evidence suggests that robot assisted and normal laparoscopy perform equally well in some respects, but that robot assisted surgery may be beneficial for women with advanced stage disease. However, more studies directly comparing the two surgical approaches are needed.

I will leave you then with an unusual case of endometriosis. A 52 year old man was sent for a CT scan after complaining about pelvic pain. What the doctors found was an inch long ‘cyst’ that, upon closer examination was found to be a tube like structure, with a muscular layer on the outside and an endometrial layer on the inside. Essentially this was a small uterus, but as it is displaced endometrium it still classifies as endometriosis (or endomyometriosis, to be technically correct). Unlike other male endometriosis cases, this patient hadn’t been undergoing any hormonal therapy and the man in question had no genetic or hormonal abnormalities that could account for this finding. In addition the patient had previously undergone surgery for a hernia near the area in which the ‘uterus’ had been found, so one would think this area of the body would have been examined thoroughly previously, indicating this problem may have arisen quite recently.