Episode 8: Ectopic Pregnancy

Transcript

Speakers:

Host - Olivia

Guest – Dr. Annie Solangon

00:00:04 Olivia Moir 

Hello everyone and welcome back to It all starts here. This is a podcast focusing on the communication and education of topics in reproductive science and Women's Health. I am your host, Olivia Moir, and we are back here today at the Institute for Womans Health here in London at UCL, and today we are going to be talking about a pregnancy condition that is called ectopic pregnancy.  

00:00:31 Olivia Moir 

Just to get this out there in the beginning of the episode, ectopic pregnancies, as we will cover today, often do end in pregnancy loss. So, this is a podcast episode dealing with a subject that might be sensitive to our listeners. So of course, if this is something that you are not comfortable listening to today, don't continue. It will have some good bits of information, and just remember that there are important resources that if you are dealing with pregnancy loss that you can reach out to and different clinics in your area, if you are based in the UK, examples of these will which will be linked in the shownotes.  

00:01:09 Olivia Moir 

So with that being said, I have with me Dr. Annie Solangon, who is an obstetrician and gynecologist specializing in early pregnancy, gynecology, and advanced ultrasound at UCLH. Presently, she is undertaking a PhD in ectopic pregnancy and pregnancies of unknown location under the supervision of Professor Jurkovic here at UCL.  

It is such a pleasure to have you here with me today, and why don't we just really just jump right into things? Let's talk a little bit of background on maybe what ectopic pregnancies are if you were going to sort of broadly explain this field to a listener.  

00:01:54 Dr. Annie Solangon 

Yeah, sure! First of all, thanks for having me on this podcast. So yeah, an ectopic pregnancy for those who don't know is a pregnancy that's not implanted in the cavity of the uterus or the womb. So that's sort of the inner part of the womb. And we'll just go a little bit back to basics in terms of the womb structure. So you've got the outer layer, you've got the middle layer, which is the main muscle, and then you've got the sort of lining inside which is where a pregnancy you would normally implant. So that's what I mean by cavity and an ectopic pregnancy is any pregnancy that essentially isn't implanted within that cavity. So you can get generally two sort of broad classifications:  

1. You've got utrine, ectopic pregnancies   

2. And you've got extra uterine ectopic pregnancy. 

The most common is extra utrine, so that's in the fallopian tube, and that's the tube that carries the pregnancy from the ovary and transports it into the cavity of the womb. So if you were to get an ectopic pregnancy, you would most likely get it in the fallopian tube. 

00:02:57 Olivia Moir 

OK. 

00:02:58 Dr. Annie Solangon 

You can also get ones like on the ovary. You can get some implanted in the abdomen. You can get something called a rudimentary horn pregnancy. So there's lots of different types and then the uterine ectopic pregnancies are ones that are found kind of within the the muscle of the womb. So you can get one called intramural, which is essentially within the muscle of the womb. And actually you can get one on the caesarean section scar. So if women have had a caesarean section before you can get pregnancy implanting into the scar, you can also get one called cervical ectopic pregnancies. That's well, yeah, You can get them lots of different places. Most commonly they are found in the fallopian tube.  

And the significance of an ectopic pregnancy. I mean, it happens in about 1% of pregnancies. If it's not found early enough and it's allowed to, you know, continue to grow in some cases it can lead to the woman being quite unwell, pain, bleeding, etcetera, things like that, which is why we're we want to pick it up early. And we want to make sure that the women's well from it. 

00:04:15 Olivia Moir 

OK. Interesting. Wow, it's. And you said abdomen – how does that happen? 

00:04:24 Dr. Annie Solangon 

Yeah. So it just means, yeah, outside of the uterus. And you've got this cavity called your abdomen and your pelvis, which is usually where things like your gut stay. You know, that's where your gut is so you can get the most common reason why you might get an abdominal ectopic pregnancy is actually if you get pregnancy that was in the tube. Yeah, that has fallen out of the tube. And then it kind of implants and then starts growing from there. It's really rare. Really, really rare. And yesterday actually I just gave a teaching presentation about this and yeah, it's it's an interesting phenomenon, I think. 

We are seeing it slightly more with caesarean section pregnancies that grow outside and then they, you know, there and get their blood supply from outside of the womb. But yeah, on the whole is it's a rare ectopic pregnancy. 

00:05:23 Olivia Moir 

Interesting. OK. So in terms of why this happens, ectopic pregnancies, I know you mentioned that previous pregnancies, whether it was caesarean section delivery or potentially scars. Are there other kind of risk factors that are involved or I you know how does this come about really? 

00:05:46 Dr. Annie Solangon 

Yeah. So from the studies that have been done, so about 2/3 of women with an ectopic pregnancy may have a risk factor. And the most common ones are things like having had a previous ectopic pregnancy naturally increases the risks of that having another one and feature also things like problems of the fallopian tube. So if you've had a previous infection before, that means that you know the pregnancy can't travel down the tube. If you've had things like previous surgery and what that does is it can cause scar tissue inside the pelvis, which just means that some things might get stuck to each other that can hinder things like the fallopian tube transporting the egg Into the womb, things like assisted reproductive therapy, so most people commonly know about this in terms of IVF pregnancies that can also increase the risk. Smoking increases the risk maternal age over the age of 35 also increases the risk. And another thing that might increase it is certain types of contraception. I want to stress on the whole that contraception, by the way it works, you know, reduces your chances of conceiving. So that means on the whole, your chances of having ectopic pregnancy are also reduced. But in some cases where it hasn't worked and we know not all contraception is 100% effective. It may be that the woman is at risk of having an ectopic pregnancy. So, for example, when when women get their tubes clipped, tubal ligation. If that doesn't work in terms of preventing pregnancy, sometimes it can get stuck in the flopping tube and develop into an ectopic pregnancy  

00:07:41 Dr. Annie Solangon 

The important thing as well, actually, is that I've said 2/3 have risk factors about 1/3 of women will not have any risk factors, and it will just be, unfortunately, one of those things that comes out of the blue. 

00:07:55 Olivia Moir 

Wow, OK. So then let's say you know a woman presents with in a topic pregnancy, which also to cover that sort of like I guess this would be diagnosed pretty early on hopefully in pregnancy. 

00:08:10 Dr. Annie Solangon 

Hopefully yes. So as long as you know, as long as generally women with ectopic pregnancies will have symptoms, so we always advise women, you know, if you're having pain or bleeding in early pregnancy, go to your local early pregnancy unit and just get checked out just to make sure everything's OK, and nowadays with advances and things like our ultrasounds, our imaging, we're actually able to detect ectopic pregnancies at a much earlier stage. I think historically, it always used to be one of those things that were diagnosed at surgery and quite late on, and we've definitely moved away from you know, diagnostic surgery for ectopic pregnancies now for for most cases. So with the, you know, advances of ultrasound sound, that also means that less women are becoming severely unwell because we can pick it up early. We can monitor them. We could offer treatment as well, so yeah, interesting. 

00:09:11 Olivia Moir 

Interesting. OK. So then in terms of the management, so sort of brushed over this, but your PhD you are focusing in different parts of ectopic pregnancy, but also looking at the management of ectopic pregnancies and the different ways that this can be done. So maybe you can talk a little bit about this. 

00:09:31 Dr. Annie Solangon 

So yeah, lots of different projects on my PhD, but one of them is looking at and comparing the different treatment options for ectopic pregnancy and I'll just tell you about the three broad treatment groups for ectopic pregnancy and I'll I'll just focus on tubal ectopic pregnancy at the moment. I think I think for most ectopic pregnancies these treatments are are, you know, this is how you would treat those other topic pregnancies. But there's a few sorts of certain cases where these may not be. So let's just say because 99% of ectopic pregnancies are in the fallopian tube, let's just talk about treatment of that. 

00:10:10 Olivia Moir 

OK. 

00:10:11 Dr. Annie Solangon 

So one is 1) surgery, where you remove the ectopic pregnancy, and that's usually done through keyhole surgery. Nowadays, back in the past it used to be a a smaller cut in your tummy, but now they're very small cuts in sort of your belly button on one maybe either side of your lower tummy and we do that to remove the ectopic pregnancy and it's reasonably straightforward procedure and hopefully if everything's well, then the woman can go home the next day and for most ectopic pregnancies, that's the way to treat it, and there are certain criteria as to when you would think that's more appropriate as opposed to the other two options. So, for example, you know, if there's a large ectopic pregnancy or the pregnancy hormone levels are quite high or, you know, the woman has lots of pain. Or if there's blood inside the pelvis as well, then you definitely would want to do surgery. Some women may say I don't actually want to do the other two options. I'd rather go for surgery as well. And that's that's a reasonable option. 

And then the other two is. 2) let's talk about medical management, which in most places in the UK in the world, they use something called methotrexate. And this is an injection that's given usually as an initial dose. You may need other doses afterwards and what it does is it essentially stops fast dividing cells, so that's the rationale for using it on a on a ectopic pregnancy. 

00:11:42 Olivia Moir 

OK. 

00:11:48 Dr. Annie Solangon 

There are side effects to methotrexate, so things like an upset tummy sometimes in rare cases, it can affect things like your white blood cells or your lungs, etcetera, things like that. So you need to be reasonably fit to have it. It won't be appropriate in some cases, for example very high pregnancy hormone levels. 

And also afterwards you'd want to say try not to get pregnant for three months once treatments finished, because it can impact a new pregnancy in the future. And in terms of effectiveness, range studies range between 60% to 90% just depends on what the study is  

And that that's part of the interesting thing that my research highlights is you know. It's more why is there such a disparity in terms of effectiveness of methotrexate? And it really depends when you look deep down at the studies, it depends on things like patient selection, like what are the groups that they've, yeah, chosen, what do they define as treatment success, what Methotrexate regimen, have they used, you know, what's the diagnostic criteria for an ectopic pregnancy.  

So there's lots of different things that come out. Yeah. And then you realise, actually, it's really hard to compare, and to definitely say that this one's more effective or not. 

00:13:18 Dr. Annie Solangon 

But I'll talk a little bit more about that I think at later stage, before I forget the last treatment option, 3) Which is expectant management. So it's essentially waiting, watchful waiting and monitoring. So what you do is you do regular blood tests to make sure the pregnancy hormone levels are falling, right? You advise the women when to come back, you know, give a strong safety net of, “here, if you're worried, please go to your local hospital or you can come to us during daylight hours. Symptoms to look out for, etcetera. And. And so the woman needs to be compliant with that and by that I mean sometimes people will say I, you know, I just don't want to keep coming back into hospital. I've got a job, I've got children, etcetera, things like that. So it may not be appropriate for everyone. And also it's it's not appropriate for very high pregnancy hormone levels or if there's lots of blood in the pelvis, you know things like that. So similar to methotrexate and expectant management, they're generally reserved for more clinically stable women. 

00:14:22 Olivia Moir 

Right. 

00:14:36 Dr. Annie Solangon 

And yeah, so the expectant management I think has been around for a while in the UK. But still a lot of people depend on things like methotrexate. Yeah. So if you look at, for example in the US, I'm sure there's people in the US who use expectant management. But what struck me before was looking at social media, when a US doctor was like, ohh, you know, how about this expectant management? Maybe we don't need to use methotrexate and then? One of our UK doctors is like, yeah, we've been doing this for years. So I think, yeah, it's, you know it, we're we're becoming more aware of it and we're realising that actually sometimes you don't have to do anything like as a pregnancy that ectopic pregnancy may resolve by itself. But as long as you've found it and you know what you're dealing with and you've got the resources around you to be able to monitor someone closely. 

00:15:35 Olivia Moir 

Yeah, I guess, I guess that's true. And I feel like we're finding that out about more about different conditions because I feel like it comes from a good place. I think, right? You know, as someone who is, you know, a doctor or practices medicine you want to be able to help your patient, they're coming in. They're looking for care. And I think you know particularly, you know, in the US, there's like a high output and generation of you know we need to do this and this and this and this is you know and I feel like here sometimes it's more, Well, let's just take step back and evaluate before jumping in to treatment.  

That's my perception at least, but I it is important to do that. It's important to to look at the patient and give them sort of what we're getting at as the individualized care towards. 

00:16:23 Dr. Annie Solangon 

Exactly. And some treatment options will be better for some people, and it's really about having that discussion and action reviewing all of your information that you have and then having that one to one discussion with the patient to say you know these are treatment options of course as a healthcare professional you are allowed to advise them on what you think is the best thing for them. But essentially I think you know as long as. 

If the patient has the information, they're also empowered in their own care, and I think that's really important. Yeah, so that they're not sort of fed through the system, not really understanding what's going on. It's good to. It's good for them to understand the process. 

And think what you said earlier about healthcare professionals just wanting to do something. And and it's very true and it does, it does come from a good place. You know we're supposed to help people. So if something has been said that it can help people, then why wouldn't you want to do that? 

00:17:23 Dr. Annie Solangon 

But what we're trying to say is actually, you know, it used to be done like this, ectopic pregnancies used to need surgery all the time which is probably why there's this sort of huge fear around it. Because because women did, you know, unfortunately, women do still become unwell, but in the past it was a lot more, right. But now we've had advances in surgery, advances in imaging, things like blood tests and protocols and research we can actually say, OK, well, we don't necessarily need to do that anymore and then we can just keep doing that with the different management options and say, OK, well, this does work. Why don't we try and see whether it works more or? You know, if methotrexate really is that great, then why are the studies around it? Saying that it's not better than expectant management for for a certain subgroup of of of women. Yeah, with low hormone pregnancy levels, et cetera, but yeah. It's just this and I think that this is what we always need to do with research is to continue questioning. 

Why are we doing things in a certain way? Can we do something in a better way? And yeah, that I think that's, you know, one of the most important things is to constantly evolve, constantly challenge our old views as well to say, yeah, to find new ways to to do something. 

00:18:50 Olivia Moir 

Yeah, absolutely. 

Yeah. And I think sort of just as you were saying, it's it's not, it's and it's not even necessarily that as you know, a clinician you're not then treating them because watchful waiting I think is where the term was, you're still, you're still involved and you're still doing something and you know, even though it may not be a physical intervention that's, you know, that's still sort of like it provides care to the patient. So I think that's good to lean on. 

00:19:21 Dr. Annie Solangon 

Yeah. Yeah, absolutely.  

00:19:24 Olivia Moir 

OK. So in terms of the studies in your research, we've highlighted a lot kind of in this podcast the importance of having evidence based research and different types of analysis that can be done and you sort of talked about how in your research you've found that the inclusion criteria can be different and then they will make concluding remarks based off of different inclusion criterias in terms of ectopic pregnancies and the management of that, we've already touched on this a little bit, but what is your main kind of like output from this and a future directions for research, looking at the management of ectopic pregnancy. 

00:20:05 Dr. Annie Solangon 

Yeah. Yeah. So yeah, my research, a lot of what what I'm doing as we covered earlier is comparing the different management options for ectopic pregnancies for tubal ectopic pregnancies. So one of the studies that I did, we're very interested in this whole expectant management versus methotrexate debates to answer the age-old question of you know which one is better and does methotrexate actually work. 

So it's a study called an individual participant data meta analysis. Very long term for essentially what I've done, is collected raw data from various studies and pulled them to have a bigger data set and then to undertake further analysis from a bigger data set. So, we looked at all the studies that compared expectant and methotrexate for ectopic pregnancies tubals. And we only found four studies and we could only include two. 

One study was quite old and they used oral methotrexate like tablet form which we now know isn't effective for anything. It's essentially placebo. 

And then another study part of their inclusion criteria was the hormone pregnancy level. Had to be already falling before they could be included in the study. So yeah, that that kind of means. Well, that probably means that the pregnancies, ectopic pregnancies were already resolving, right. So whether you use expectant methotrexate, you're not really going to get that answer that you want. 

And then so we included two studies, one with a Dutch team and one in the UK, which was from Prof Jurkovic study and we had 152 cases and when we combined them and we analyse them, we still found that neither was was more effective than the other. There's no sort of significant change in things like surgical intervention as well. 

So that was one study. And then I did another study with Doctor Altair's team again with Prof Jurkovic that looked at all the treatment options, including surgery, but also other medical treatments that I use possibly around the world or maybe they were used historically but aren't now anymore. 

And when you compare all of them, surgery is the best because you know it's removing the pregnancy, so it's always going to be the most effective, but actually when you look at conservative treatment, so again looking at methotrexate and expectant mostly there, there still wasn't a difference. And when you're really looking down at these studies a lot of them are comparing methotrexate to methotrexate, so there's no placebo, there's no control which would be expected.  

So I think the question is, how can you certainly know that methotrexate is better than not doing anything, umm, if you're not really comparing it to to your controlled. 

00:23:03 Olivia Moir 

The alternative, yeah, yeah. 

00:23:04 Dr. Annie Solangon 

And this is where all the older studies came from. So I mean, I was doing a little bit of a dig around in terms of where did methotrexate come from? And I think it was started being used for ectopic pregnancies in the 80s because it was historically used for gestational trophoblastic disease, which is like an abnormal sort of growth of pregnancy cells, right? So it doesn't result in a normal pregnancy. 

And then they said, well, why don't we try that on ectopic pregnancy. So they did a few case series and they said Ohh it resolved right. And then in the 90s someone did a cohort study, so they just only looked at women who were treated with methotrexate and they said, oh, look, it works. And actually, that's where a lot of the methotrexate sort of regimes come from. Now from that study in the 90s and then based on that more and more studies were were made but essentially apart from the four that I spoke about. 

Comparing methotrexate and expectant, which is placebo control, all the other studies were comparing it against a different type of methotrexate or different regimen of methotrexate or methotrexate and something else. And then they've said yes, it works. But OK, yeah, yeah. It could just be that it's resolving. Yeah. And instead of saying actually this definitely works.  

Why aren't we challenging that and saying, OK, well, if if you really do think it works and maybe it does, maybe it does for a certain group of women for a certain pregnancy level hormone level, then why don't we do more studies, larger studies looking at that and a control and then we can finally hopefully answer that question. But so far, everything that's been out there says that it's not you know, statistically more statistically significantly different. Yeah, different, better, et cetera. 

00:25:24 Olivia Moir 

Yeah, interesting. So I guess this highlights sort of your research and your PhD, probably the focus of it, but in this episode, really just the importance of kind of taking a step back sometimes in the different treatment options that we have and also the research as you said, that's been done. It's important to keep questioning and it's not to say that methotrexate isn't helpful because it potentially is, yeah, but maybe we don't have the data to back this up. Yeah, properly. So it's important. I think it highlights the bigger point of making sure that we have this kind of evidence based research because otherwise it's kind of like, Yeah, we're not really sure. 

00:26:05 Dr. Annie Solangon 

Yeah. And then 40 years later, you're still using that treatment, and you dig around. You're like, why are we using this right. And you find this information, you're like Oh yeah, OK. And I think it's very easy to get led by something that's been around for such a long time, it's just the way that things were done. So let's just continue it because it's working for us, whereas actually, I think the whole point of research is to kind of say is to, you know, let’s go beyond search elsewhere and say actually I think this and I'll do some research to prove or disprove it. It's just a challenge the way that we're doing things because essentially at the end of it is what is most beneficial for the patient so that should be. That's at the heart of all of our research is what is best for the patient. And that should really be the core of it all, and we need whenever we're doing any form of research, we need to say, you know, how is this beneficial for for the patient, how is it going to improve their their quality of life, how is it going to save them etc. 

00:27:16 Olivia Moir 

Mm-hmm. I love it. You've really. You've highlighted, I think what I think a lot of researchers share in common is that sort of drive behind it really well, which I think is great.  

So going just sort of forwards in this field and closing off this episode thinking about kind of the future of the management of ectopic pregnancies and you know, you practicing clinic. You're also doing your research on this. What do you hope to see going forwards? I mean also are there certain things that you really want to stress that in clinics, sometimes you have patients where it's a common misconception, like what are certain just bits that you want to maybe. 

00:27:59 Dr. Annie Solangon 

I mean in terms of improving where you know where we want to go in future, I I always say more research. I think everyone says more research. But behind that more funding as well and particularly in Women's Health research and I think it's Women's Health funding and Women's Health research has gained a lot of traction this year and I think we need to keep pushing that forward. I'm always going to see more research into expectant versus methotrexate because that's that's what you know what my PhD is based on and I think also sort of emphasizing in in pregnancy, I think there's a lot of emphasis, and rightly so. On the 2nd and 3rd trimester, but lesser on the first trimester, which is usually when things like ectopic pregnancies get picked up. So and it's associated with, you know, significant pregnancy loss and it's something that a lot of people just don't talk about because they think it's a taboo subject or, you know, it's not as important because it's just first trimester. But it's hugely important for so many people. It impacts people in so many different ways. So I think a lot more research on the early pregnancy, a lot more emphasis on that as well, because that's really where you can provide quite a lot of support. You can provide, you know, optimize someone's pregnancy from the very early stages. I mean that should be like pre pregnancy. But you know first trimester as well is really important. So I think a bit more focused on that. 

00:29:31 Dr. Annie Solangon 

Another thing that I keep advocating for is better quality ultrasounds. Working in an amazing scan unit at UCLH Hospital, I've seen how transformative a good quality ultrasound is. Not just an early pregnancy but gynaecology, and I think the reason why a lot of the studies in the past, haven't you know they're not as good quality as there's, there's this lacking in a good quality ultrasound? 

So what is the? What is the patient population that you're studying? Is it truly an ectopic pregnancy or is it something called pregnancy of unknown location? Mm-hmm. Which is when you have a positive pregnancy test, but you can't see it on scan at UCLA at UCLA Hospital because the scanning is of, you know, high quality. 

We know that POL's most of them are resolving pregnancy, so like miscarriages that are too early to pick up on ultrasound, whereas in other parts of the UK and around the world these, you know, these get confused for things like ectopic pregnancies as well, and and are all too common. They're lumped into the same groups, but they're very different disease entities that you're that you're looking at. So how can you do your study that kind of crosses all of that together and then say Yep, this is good for ectopic pregnancies and what we found in this meta analysis of 31 studies that we did is that half of them didn't even have a diagnostic criteria for ectopic pregnancy half of them said yes. We saw an ultrasound scan and then the other. I think there were 1/4 that were non specific and then another quarter didn't say anything. So like well, what what were you? You know, who were you? Including what? What was happening with these truly ectopic pregnancies or actually just resolving pregnancies? And that comes down to better imaging. And that's just early pregnancy. And there's so many benefits and gynecology with a good quality ultrasound scan, so yeah, that's another thing.  

And I suppose the last thing that I want to emphasise and highlight is that management plans have to be very patient centered. Yeah, and tailored to the patient, to her medical history, their presentation, how they are. Who? You know, what's their family unit? What? Their expectations or their, you know, it's based on so many different things. And one thing may not necessarily fit another. So it's really important to have, umm, that sort of way of of treating anything actually. For it's not just ectopic pregnancies, but for everything in Women's Health is to make sure that the patient is at the centre. And yeah, advise them. 

00:32:36 Olivia Moir 

Agreed. Yeah. And I think that's a common concept that we've had. Like I said here on the podcast, is sort of that end of shifting more towards as as best as we can with the resources we have available to us, is the individualized sort of patient care and management. 

00:32:53 Dr. Annie Solangon 

Yeah, yeah. It's so important. Yeah. 

00:32:55 Olivia Moir 

Hmm, well, this has been so interesting and I have absolutely loved speaking with you about this. So thank you so much for joining me today 

00:33:03 Dr. Annie Solangon 

Thanks for having me.