Pregnancy, fertility and MS

Jodi: Good morning, everybody. Welcome to the last day of Women's Health Week. We've had a fantastic week, and I am really excited about today's webinar to finish the last day of Women's Health Week, a topic that is just so important for women with MS. When MS is diagnosed commonly between the ages of 20 to 40. So, pregnancy, fertility and MS is such an enormous area of research, an enormous area of understanding and great, great importance. So welcome to everybody. We want to make it clear that when we say women in this discussion, we mean people who are assigned female at birth. We also understand and acknowledge that people who don't identify as a woman can still experience pregnancy or have questions about fertility and family planning.

In the spirit of reconciliation, MS Plus acknowledges the traditional custodians of the country throughout Australia and their connections to land, sea and water. and community. We pay our respects to their Elders, past and present, and extend a respect to all Aboriginal and Torres Strait Islanders peoples today.

It is an absolute pleasure to introduce Associate Professor Vilija Jokubaitis. I have had the absolute privilege to be working with Vilija in many different ways for the last 20 odd years. And Vilija is an absolute powerhouse. She is the group head of the Department of Neurosciences Central Clinical School at Monash Uni. She leads neuroimmunology genomics and prognostic groups. She is a clinical and translational neuroscientist with skills in molecular medicine and bioscience statistics. Her research interest lies specifically in the intersection of biology and clinical outcomes research. Now that all sounds like a lot of words that are really hard to get your head around.

But what Vilija has managed to achieve is really integrating neurosciences and understanding genetics into how clinical practice is delivered. And that I know has been Vilija 's passion for the many years that she's been in the research space and has achieved an enormous amount of publications and work leading up to now leading the International Women's Health Pregnancy and Neonatal Outcomes Registry, which is integrated in an enormous international registry called MS Space. And one thing to understand pregnancies in MS, the outcomes in pregnancies, we really need to understand a lot of information from a lot of women, and this is one way and an incredibly important way of doing that, as well as understanding some of the biological mechanisms. Vilija also heads the or is part of the international women in MS mentorship program. That's a really important program when we're talking about women's health because the focus is enormously on women's health and the areas of research particularly about empowering women neurologists, which is really important, and women in neurology science, which is equally important, and also doing women's health.

So, I could go on and on about Vilija 's achievements. She's extraordinary, but we are very delighted for her to cover Pregnancy and Fertility and MS today. So thank you, Vilija.

Vilija: Thank you very much for that amazing introduction, Jodi. very privileged. So yeah, it's my absolute privilege to be able to speak to you all today about an area that's a great passion of mine, which is really empowering women to be able to understand that pregnancy and fertility in the context of their multiple sclerosis and to be able to ask informed decisions of their clinical health care teams to help them make the best decisions for themselves.

So as Jodi said, I'm an Associate Professor of Neuroscience at Monash University and my contact details are on this slide as well for anyone that's interested. So as Jodi already mentioned, I am the chair of an organization called the MS Base Registry. Now, MS Base is an absolutely incredible tool that we use for a lot of our research. And it's really powered by the generosity of people with MS that allow scientists from around the world that are affiliated with this to analyze their anonymized data. So, we don't know any individual or personal details of the people that allow us to analyze the medical records. But what it does allow us to do is to do a lot of analyses that help us to understand a number of different questions and in my context, it's to understand how pregnancy impacts multiple sclerosis. But also, to understand how we can use medications to make sure that women remain healthy throughout their pregnancy and also have healthy babies. And so, this is just a slide to show where some of our data comes from and Australian women are, women are incredibly generous and so we have a lot of data from Australia and it's just a bit of a slide also to show the types of information that we collect.

Okay, so why focus on women's health and pregnancy? And I think Jodi really already touched on this, but basically women are typically diagnosed, or people are typically diagnosed, I should say, with multiple sclerosis between the ages of 20 and 40. And we know that that's the age when a lot of people are thinking about having families. Now it's not for everybody, not everybody wants to have a pregnancy or a baby. But it is the age when a lot of people would be considering that. And so that's why it's really important. I think the other thing to note is that multiple sclerosis is becoming more prevalent. And so, a couple of years ago, we thought it was about one in a thousand Australians had MS. But the latest data now shows that it's one in 700. So, it's really affecting more and more people and more than that. It affects more women than men. So, it's about three women to every man that has MS. And so therefore family planning considerations are really important.

Okay, so I've been privileged to be part of a number of international panels that have put together consensus statements or advice for doctors and clinical health care teams about how best to manage women through pregnancy. And so, this is just a bit of a summary of the topics within which we have generated advice. So, there's advice on pre pregnancy counselling, prenatal advice, pregnancy, and then also how to manage postpartum. And so, I thought today what I might do is go through each of those in order to give you a as well, so that you know what sort of questions you might want to ask in the future of your own healthcare teams if you're planning a pregnancy.

Okay, so the first one is, you know, thinking about what should women know in terms of pre pregnancy counselling. And so, we advise that if you're diagnosed with MS, even if it's really early on and you've just got a very new diagnosis, all women who are of childbearing age should have pre pregnancy counselling as early as possible because there's a lot of things to consider. And Women should also advise their health care teams if they're considering a pregnancy, particularly in the next 12 months, because that's going to have implications in terms of what sort of medications you might go on. Now, I know that there's a lot of questions in and around whether or not MS affects fertility, and so what we can say with the best of the knowledge that we have at the moment is that having MS does not affect fertility. And so that, you know, if you're worried about getting pregnant, you know, and, or you don't want a pregnancy just yet, that you should be using contraception.

Now, there have been a number of studies that have been done to try and understand and fertility in the context of MS. And so, some of these studies have looked at a hormone called anti malarian hormone. And anti malarian hormone is a hormone that is used to measure basically your ovarian reserve, how many eggs you've got left. And so, the largest of the studies that have been done looking at this, comparing with this, Women with MS and women without MS have shown that women with MS have roughly the same concentrations of this AMH hormone as age matched non MS controls. So, this is the evidence that we're using to suggest that fertility is not affected by having MS. Now having said that, there is evidence that women with MS tend to have fewer children. And so, the best evidence of this came from a study in Denmark. And so, in this study the Danish are amazing they're able to link all of their medical registries together and get really in really detailed information that helps all of us in the MS community understand things better. And so, in this particular study they identified 9, 000 women who had multiple sclerosis. And they matched them to 37, 000 women who did not have MS that were of the same age. And so, what the research showed comparing these 9, 000 women with MS to the 37, 000 women without MS was that even before women have a diagnosis of MS, women who are destined to develop MS tended to have fewer children than women who did not have MS. Now, this a lot of reasons why this might be the case, and it's not necessarily to do with fertility.

There's a lot of research that's been done over the last few years talking about this concept of the MS prodrome. And so that basically talks about having sort of non specific symptoms that, you know, might be niggling health concerns that don't necessarily indicate that you have MS at all. But, you know, if you're generally not feeling very well, maybe you're just not in a position to consider having a family just yet. And so, they did show that women destined to develop MS did have slightly fewer children, but men who are destined to develop MS did not have a reduced fertility rate. The interesting thing that happened was after the diagnosis of multiple sclerosis, there was a massive decrease in the number of women who had children. And so, you can see that highlighted that number 0. 63. And so what that 0. 63 tells you is that women who then had a diagnosis of MS on average had fewer children. So, if you imagine for every one child that a woman without MS had, women with MS had 0.6 it's a kind of a strange concept, but it's basically showing that the rate of having children was massively reduced by about 40%. And the same thing happened with men. So, men previously, prior to a diagnosis, didn't have any differences in the number of children that they had, but after the diagnosis that also dropped. And so, what this really tells us is that it's more, not a fertility issue, but more likely a decision making issue. So that once somebody is diagnosed with MS, they might then start to consider things like, will I be well enough to look after a child? What happens if I can't work anymore? Will I be able to afford to support a family? And things like that. So, it's not necessarily fertility so much as lifestyle considerations. So that’s what the data show us. So, no concerns around fertility. It's more about decision making. Having said that, I think it's also really important to note that infertility is really common in Australia. And so, these are some statistics that I got from the Australian Bureau of Statistics, well, Australian and New Zealand bureaus, actually. And it shows that infertility affects about one in six Australian couples. And so, it's not, you know, necessarily, if you do have infertility issues, it's not likely to be MS related. It's just the fact that infertility is relatively common.

And so back in 2019, the ABS study, statistics showed that across Australia and New Zealand, there were almost 89, 000 IVF cycles that were undertaken. And of those, about 16, 000 babies were born through IVF. So that's a success rate of about 18%. So again, it's just something to consider that may or may not be an issue. But again, it's not MS related. Sometimes, you know, we just wait a while to have children and so forth. And so that can affect fertility as well.

Now, historically, there was also a lot of concern that undergoing, if you had fertility issues and that women with MS would have relapses in and around the IVF period or certainly shortly after undergoing IVF. And that's because historically a lot of women were withdrawn from their disease modifying therapies in order to undergo IVF. But the latest research is really reassuring. So, this is research from America and I know that it's a bit of a complicated squiggly graph here, but basically what this graph shows us is that it's measuring the number of relapses that women had before undergoing IVF. With the zero to 90 days being roughly when they underwent IVF, and then the blue shaded area being post IVF relapse rates. And even though there's a little bit of movement up and down within this graph, overall, it's fairly flat. So, any sort of historical data that you might have heard about saying that if you undergo IVF, if you do have fertility issues, is likely to result in a relapse. You can be really reassured that these days with the way that women are being managed by their neurologists and their IVF specialists, that IVF is no longer a risk factor for having any additional relapses.

So, another question that people are often concerned about is whether or not their child is likely to develop MS if they themselves have multiple sclerosis. And as Jodi mentioned, some of my research also involves genetics and it's something that I'm very interested in. And so just to reassure you that the risk of your child having MS is very low. From what we understand at the moment in terms of the genetic inheritance patterns, is that your child, it has about a two to three and a half percent chance of developing MS if one parent has it. And it's about a 20 percent chance if both parents have MS. And that's because MS is not highly heritable. So, it's not highly dependent on your genetic code. And we know genetics does play a role. So, we know that if it's one in 700 people in Australia in general have MS. And then it becomes 2 3%. That's about, you know, 20 30 percent higher risk if you have a parent with MS, but overall it's still very low. And we know that the environment and lifestyle are really important as well. So, some things to consider in terms of environmental factors that you do have some control over is to make sure that, for example If you are a smoker, that you quit and don't smoke around your children because we know that smoking increases the risk of developing MS. There's also a lot of literature to show that childhood obesity can be associated with MS. So again, things like exercise, healthy diet, all those sorts of things can also play an impact on the risk.

Okay, so continuing to go through the pre pregnancy counselling one of the other things that I think women need to know when considering it, and this goes back to that study showing that numbers of children dropped significantly after a diagnosis of MS in the Danish population, is that you should be reassured that pregnancy does not increase your risk of your disability worsening.

So, this is some research that my research group has done and also some research by some Italian and Spanish groups. And so, what we've shown in terms of the short term post pregnancy, so talking about a year or so after giving birth, the risk of having any measurable increase in neurological disability after giving birth these days is only about, well it's a bit under six percent. So less than six percent of women will see a measurable increase in their disability progression in the year after giving birth. Now that has dropped significantly. So, there was an Italian study that was published several years earlier that suggested it was up to 13 percent of women. And the drop in the increased disability rates really just speaks to the fact that to better at being able to manage women postpartum and knowing which medications are safe to give them and how soon. So, the risks have really dropped. In terms of the long term effects of having pregnancy our work in a study using data from the MS based registry that included almost 2, 000 women showed that women that had relapse onset multiple sclerosis and a pregnancy actually accumulated less. disability over a 10 year period than women that didn't have pregnancies. Now, that's not to say that you should have a pregnancy to prevent disability accumulation. Disease modifying therapies work really, really well as well, but it was more so just to show that there is something that is protective immunologically about having a pregnancy, so you shouldn't be concerned about it.

Now there are other studies that suggest that pregnancy doesn't have any protective effects on the accumulation of disability. And I guess, you know, the thing is that we all use slightly different methods to measure these things. But overall, the Spanish study also certainly found that there was no increase in disability.

So, at the end of the day, if you choose to have a baby, in terms of the long term outcomes, there You may accumulate less disability, but it certainly won't make your MS worse. And so, I think that's really important to know.

Now, what about women that have progressive MS and want to have a baby? There's really not a lot of data about this in the literature, and that's because there aren't a lot of women that have progressive MS that have babies. Now, again, I know this probably looks like quite a complicated squiggly graph. But basically, this is again data from the MS Base Registry and that thin grey shaded line that you can see is the time when a woman had a pregnancy and this tracks nine different women. So, this just shows you how few women we've recorded that had progressive MS and had pregnancies. But, you know, the squiggly lines look like they're all over the shop. And basically, what that tells us is that for these women, their MS was going to continue to do whatever it was going to do. And having a pregnancy made no material impact on that. So, some women's MS got worse, some women's MS got better, some women's MS remained stable. But again, it just shows that pregnancy didn't impact their disability outcomes. So, I think that's really reassuring as well.

Okay, so what about relapses whilst you're pregnant? So again, women should know that when you're pregnant, your relapse rates may reduce although they may also increase in the three months postpartum. So, this is a study that was originally done by a French group back in 1998, but it's also been repeated numerous times now by ourselves, by groups in the States, by groups in the US, and it's always the same reassuring story. This grey box that you can see here is the pregnancy period and the squiggly line represents relapse rates. So basically, it shows that about a year before pregnancy there's a level of relapse activity and that's fairly stable up until the pregnancy period. Then at the start of that grey box, you can see that relapse rates drop, and they're lowest in the third trimester. But then after giving birth, so you can see this little delivery arrow here, you can see that there was a spike in relapse rates, and then relapses went back down to the normal. Now, that's not to say that, you know, that's going to be you. Every woman is different, and every woman's disease is controlled differently. But regardless, it's reassuring that for most women, when they're pregnant, their MS symptoms do subside, and their relapses do reduce.

Okay, so some really important things. If you're newly diagnosed and you're thinking about having a baby, the advice is that you should not defer from beginning a disease modifying therapy. Again, it's all about talking to your neurologist and your healthcare team, your MS nurse, telling them that, you know, this is in your near future or your future planning, and that'll help them to advise you as to the best disease modifying therapies that you should perhaps take. And so, when you have these conversations, the teams are likely to consider the timing of your planned pregnancy, the safety of the various disease modifying therapies that are out there, and think about the risks of relapses if you withdraw from a therapy or after we give birth.

Okay, prenatal advice. So, you know, you've decided that you want to have a baby and you've had some discussions in and around, you know the timing of that with your clinical health care team. What else should you know? At the end of the day, women with MS are no different to all other women. They should be following exactly the same prenatal advice, stop smoking, have a healthy lifestyle and diet. And, you know, make sure you are taking all of your normal prenatal supplements such as vitamin D and folic acid and follow all normal obstetric advice. It's all applicable to everybody. So, if you are currently on a disease modifying therapy, and I apologize, I've used the acronym DMT throughout this entire presentation. So DMT refers to disease modifying therapy for MS. So, if you are currently on a disease modifying therapy you know, you should have a discussion with your neurologist about whether or not you should stop it, or whether or not it's safe to continue it, or whether or not you need to switch that therapy to something else, depending on the safety profile of that drug.

And women who plan to stop using their disease modifying therapy if you know, they're concerned about foetal impacts and so forth. You also really need to consider very carefully how long it might take you to get pregnant. You know, some women fall pregnant very, very easily. And for other women, it can take, you know, a year or more to fall pregnant. So, it's really important to consider your MS and your health. As well as any sort of risks when you're thinking about withdrawing from therapy if that's the way you decide to go.

Okay, so, I think, you know, the other thing that we encourage healthcare teams to do is to consider the whole person when counselling women about pregnancy and so forth, including you know, mental health.

So, as I said, a lot of women do find that their MS symptoms improve during pregnancy, but there are some symptoms that may worsen, and particularly in the later stages of pregnancy. So, we know that when we're pregnant, often, you know, we have a lot of urinary urgency just because the baby's pressing down on the bladder or the bowel. And so, you may, particularly in the latter stages of pregnancy when your baby's getting larger, have some bowel and bladder symptoms. It might also exacerbate fatigue. Fatigue can already be quite great in the first trimester and also in the third trimester, but these might also be exacerbated as one of the MS symptoms as well. Another thing to consider also is balance. You know, your balance might be thrown off just by having a pregnant belly out in front of you, but also if you already are a woman who experiences balance symptoms with your MS, that might also be a concern.

Now, of course, the other thing that we need to think about is depression. So, we know that depression affects a lot of people with multiple sclerosis. It's hard to know how many exactly, the statistics vary quite greatly, but somewhere between, you know 20 to 60 percent of people with MS also have depression and we know that things such as if, for example, you do have fertility problems and you're trying to conceive and it's taking a while to get there, that might be also exacerbated. So, it's another symptom to think about as well. If any of those symptoms occur, again, talk to your healthcare professional and they'll be able to advise you the best strategy going forward.

Okay, so there's also a lot of people that believe that pregnancy for women with MS is high risk and I just want to reassure you that that's certainly not the case. We know that women who are well and well treated with disease modifying therapies for their MS should not be considered as high risk. And so, you know, you can still choose to have your baby in whichever way you'd like. Obstetric management shouldn't be influenced by that. It is okay to have an epidural and it's going to be different for everybody. If you do have quite disabling disease or spasticity, maybe you might need to go to a higher risk clinic just to help with issues around pushing and so forth. But for the vast majority, it shouldn't influence your obstetric management at all.

So, I think now moving on to pregnancy itself, it's really important to say that some disease modifying therapies are actually safe to use in pregnancy. And I'll show you a bit of that data as well. And in particular continued use of disease modifying therapies in pregnancy should be considered if you've got highly active MS. Alternatively, when you're planning a pregnancy, you can also consider the use of long lasting disease modifying therapies that provide really effective long term control and this includes certain medications like Ocrevus and Mavenclad as well. So, something to talk to your doctor about.

Now this is a photo of my son when he was one day old. So, I'm biased, I think he's the most beautiful baby in the world. And I just wanted to put it there because, you know that's the reward you get at the end of the pregnancy. But it's, there's a lot of difficult decision making. And I think, you know, a lot of the concerns that people have in and around pregnancy and choosing which disease modifying therapy to use really stems from the fact that pregnant women are excluded from clinical trials. And, you know, that makes sense. When clinical trials are being performed, we don't necessarily know the safety of the drug for a fetus because most previous studies are to have occurred in animals and humans are not necessarily rodents and so forth. And so pharmaceutical companies, of course, have to ensure that you know, they're not going to inadvertently harm a fetus. And so, when women are trying to decide, you know, what to do in terms of access to disease modifying therapies, they often feel forced to choose between themselves is in taking a disease modifying therapy to control their MS or their child and feel like they need to perhaps stop taking their disease modifying therapy during pregnancy and breastfeeding.

So, there is a lack of data from clinical trials, but the really good thing is, is that we do have large real world clinical registries such as MS based. There's also the German pregnancy registry and then a number within the U S. And so, what these registries do is again, thanks to women who have kindly agreed for us to analyse their anonymised data. Is that we basically get to study pregnancies that occur in women who either A, got pregnant whilst under disease modifying therapy unintentionally or B, with increasing confidence from doctors and patients about the use of disease modifying therapies that they have used these. And we've been able to study what happens and as I said some disease modifying therapies are actually or have been shown thanks to these clinical registries to be safe and we know that now. And so that's where we get our evidence from.

And this is just a slide to show you, it's from a paper that we published back in 2019, and slightly older data. But I just want to direct your attention to the orange bars. And the orange bars show the number of women that were exposed to a disease modifying therapy throughout their, or at least, for part of their pregnancy. And you can see between 2006 through to 2016, the proportion of women that were being exposed to or using a disease modifying therapy when they became pregnant has been increasing. And its sort of about 60 percent of women these days are actually using a disease modifying therapy when they become pregnant. I actually think that the probably understating it a bit. A lot of this data is from Europe where they're a lot more conservative than we are in Australia and so it has it that it's a lot higher in Australia. Probably closer to about 80 percent of women would be using a disease modifying therapy of some sort.

So, I think this is probably the information that a lot of you are keen to know and understand. And this is really, you know, which medications can you use, or should you not use when you're having a pregnancy. And this is data that we've put together that we published earlier this year in the Lancet Neurology. And this is based on advice from pharmaceutical companies, based on real world evidence from registries and so forth. And so this is a general consensus and I probably don't have every single medication listed here but I've got the big ones.

Now I know that most Australian women don't use interferon beta or Copaxone anymore but regardless these are safe to use in pregnancy. So, there's no evidence of any increased rate of malformations or abortions within women who use those drugs. There's also Tecfidera, and that's been used for a number of or different formulations thereof, but basically the same drug has been used for a number of autoimmune diseases over many, many years.

And so, we also know in the context of MS that it's safe to use Tecfidera. Some say that you should stop using it once conception has been confirmed, although the EMA, so that's the European Medicines Agency, has also said that you may be able to continue to use it in your pregnancy if the benefit outweighs the risk. And so that basically means that if your MS is quite active, if you're somebody who has a lot of relapses, then, you know, perhaps consider that. But I think in Australia, the most popular medication that's being used at the moment during pregnancy is actually Tysabri. So Tysabri is the infusion medication that most people would have once a month. Some people extend it out to once every six weeks. And so, this is safe to use up until the third trimester. So up until about week 34. And if there are concerns that can be stretched out, as I said, instead of four week infusions to six week infusions. Now the reason why it needs to be stopped after week 34 is that the placenta does become more permeable to larger molecules and that can go through. And so there have been shown to be some blood related anaemia and thrombopenia in women that have been exposed beyond that, but it's completely reversible as well. But even so we recommend that women stop taking their last dose around week 34.

Now the other one is Ocrevus, and I know that there's been quite a lot of controversy around Ocrevus, and you know how you should and shouldn't take it and when you should conceive. And so again so the FDA here refers to the Food and Drug Administration so that's the American agency and the FDA recommends a six month washout but as you know, Ocrevus is taken every six months so it basically means the advice from the FDA and from the pharmaceutical companies is basically to have a dose and then start trying to become pregnant when your next one is due. The problem with that is that your B cells might return and therefore you're at increased risk of disease activity reoccurring. And so, the latest advice and a lot of neurologists are really comfortable with this, is to attempt starting to conceive within about one to three months after the last dose of our purpose. So that protects you against disease reactivation, because again, we don't know how long it's going to take to become pregnant, but it also mitigates the risk of the drug transferring into your fetus.

Kesimpta, which is kind of similar. Again, FDA has a really conservative washout. But what people are recommending these days is that you time your monthly injection with your period. So that, you know, you have your period, you have your injection, and then you start trying to conceive, such that if you do conceive, then you just don't take that next dose.

Now, with the others, there are much more strict warnings, and they shouldn't be used during pregnancy. So, with Lemtrada, they say that it should be a minimum four month washout period and to check your thyroid function. With Gilenya and all of the related drugs that have got a similar mechanism of action, there are nuances around that. But generally speaking, it's a two month washout. Mavenclad this one, it affects both men and women and you shouldn't try to conceive for at least six months after the last dose. And with Aubagio, if you do accidentally become pregnant, there is an accelerated washout that you can do to eliminate any sort of harmful exposures to the fetus.

Okay, so relapsing pregnancy. So, this is some of the data that we produced. And again, a lot of squiggly lines here. So, I've just summarized the different drug names. Nat refers to Tysabri or Natalizumab. Fin refers to Fingolimod or Gilenya. DMF is Tecfidera. Lo refers to Copaxone and Interferon Beta. And none is obvious. And so, this really shows relapses before pregnancy, during and after, in women who have taken these various medications. So, within this box here, we can see relapse rates during pregnancy, if women have been on any of these drugs.

So, we know these days that Fingolimod is actually contraindicated, which means that, again, you should wait at least two months before trying to conceive after stopping the drug, because there have been some risks of harm for the fetus. Having said that, though you can see the green line, Natalizumab, that relapses appear to be going up in pregnancy.

Now, this is kind of counter to what I've said before, but if we go to the next slide, there we go, that's better. I'll explain what's going on here. So basically, we know that these drugs stop your immune cells from entering into your central nervous system. And so, if you stop taking them, all of the sudden these, your immune cells have the opportunity to enter your central nervous system and cause a relapse. So, the reason why we recommend that women continue to use Natalizumab is your relapse activity reoccurring after withdrawal of the drug is related to the timing of that withdrawal. So, if women with the green line withdrew from Natalizumab before their pregnancy, they were likely to have relapses during pregnancy. With the orange line, if women were taking Natalizumab or Tysabri and they withdrew from medication in the first trimester, so that orange line, they were likely to have relapses in the second or third trimester. But if women continue to take their Tysabri up until the 34th week, of their pregnancy, you can see that they didn't have any increase in relapses whatsoever. And in fact, their relapse rates were the same as women who were on low efficacy drugs, such as the interferon betas and Copaxone. And so, you know, that should be really reassuring in terms of taking those medications and being able to reduce relapses in pregnancy.

Now, a couple of other really quick things are that if you do happen to have a relapse in pregnancy, during pregnancy, it is okay to have corticosteroids, so to have some prednisolone or methylprednisolone. And, if you need an MRI, it's okay to have one, you just should not have contrasting agents, so none of that gadolinium.

Okay, in terms of care postpartum, it's really important, I think, to engage with the physiotherapist, particularly for your pelvic floor rehabilitation after delivery. And also, be aware that you are at a higher risk of having a postpartum relapse. And this is true for women, particularly who were on higher efficacy drugs such as Natalizumab. And so, it's really important to consider the timing also of reinitiating with these disease modifying therapies.

Okay, so talking about the postpartum risk. There we go. So, this is now looking at the postpartum relapse risk. And so, this is going back to that sort of original breakdown of being on Tysabri in general in green, Gilenya in orange Tecfidera in purple, pink was low efficacy and green is none. And so, what our research showed is that just under 14 percent of women are likely to experience a postpartum relapse. And we mean that as in a relapse within the first three months of delivery. But what you can see again if we look at Tysabri in particular here, is that if women withdrew from their Tysabri very early on in the piece, they're more likely to have a higher risk of having a postpartum relapse. But if women re initiate their Natalizumab really soon, so if they continue to use it up to the 34th week and then re initiate their Tysabri within a week or so of delivery, then their risk of having a postpartum relapse is really low as well.

Now, what if you were to have an abortion, a miscarriage, or a stillbirth? Unfortunately, these can happen. In fact, miscarriages affect about 20 percent of pregnancies. So, we also had a look at this, and our research showed that just under 10 percent of women who had an abortion or a miscarriage or a stillbirth still had a postpartum relapse. And so, I think it's really important to communicate with your healthcare teams just to let them know if that does happen to be the case. So again, you can make sure that an eye is being kept on you and your MS. Now, this is some research that was done in Austria, and the other thing that they showed was that women who had an elective termination were at slightly higher risk of having a post pregnancy relapse than women who had a spontaneous miscarriage. So again, if you do for whatever reason need to have an abortion just be aware again that you should communicate that with your neurologist health care team, just in case there is an increased risk of relapse in that circumstance.

Okay so talking about breastfeeding and reinitiation of disease modifying therapies. So, we do really recommend that you reinitiate with your disease modifying therapy quite quickly after you've given birth. And again, the choice should be discussed with your healthcare team. And there are some DMTs that are safe to use during breastfeeding. So, if you want to breastfeed, you should be encouraged to do so. There are a lot of benefits for yourself and your baby. If that's not for you, that is totally okay as well, and I don't think that women should be placed under pressure to breastfeed if that's not something that they're able to do. Okay, there is some evidence that breastfeeding might be beneficial, but it seems to be more so in terms of reducing relapse risk. But that's more so it seems now with new evidence coming out that it's in women who have slightly less active MS. If you have very active MS, it appears that breastfeeding perhaps does not protect against relapse risk as much as we originally thought. And as I said some are safe to use.

So, again, there's been a number of studies looking at the various disease modifying therapies and which ones are safe to use in breastfeeding and which ones aren't. Generally speaking the ones that are large molecules, so the monoclonal antibody therapies, so we're talking about Tysabri, Ocrevus, Rituximab, Kesimpta. They're the ones that are okay to breastfeed on, as well as Copaxone and Interferon Beta. But small molecules, so Aubagio, Tecfidera Gilenya Mavenclad, they're not safe to breastfeed on to the best of our knowledge at the moment.

Now I've got a list here that says transfers to breast milk tick or question mark. What's happened here is that women have been pumped and donated breast milk for scientists to analyze. And some of these drugs do transfer across into the breast milk, but there are tolerances that are allowed. And according to the various EMA and FDA type agencies, it's okay for up to 10 percent of these molecules to transfer into the breast milk. And with all of the ones that have been studied to date, it's about 3 percent or less of the dose that you're receiving transferring into the breast milk. Now it's also infants who have been breastfed by mothers taking these drugs have been monitored for safety. And the reason why we say it's still safe to breastfeed, even if it transfers into the breast milk, is that all of the studies to date don't show any developmental delays, no growth restrictions, or anything like that to babies that have been breastfed. And that's why we say it's safe. safe to breastfeed on these drugs. And there's more information in those papers as well.

Okay. So, we're getting towards the end now. An important thing to note as well is that, you know, you may experience increased fatigue postpartum. And so, some advice that we would say is that if you do have extra milk that you should pump and store it so that if you are having fatigue or relapse, that you can defrost breast milk and that can be used to feed your baby. If you do have a relapse and you need some methylprednisolone, that's totally fine, but you just need to pump and dump, and you should wait at least four to eight hours before breastfeeding your baby after a dose of prednisolone.

Okay I just wanted to finish up so there's maybe some time for questions but some of the take home messages that I just really wanted to leave you with was that MS does not affect fertility and that your child has a very low risk of developing MS.

Now, if you do decide that you do want to have a pregnancy, you should start planning for that really early on so that you and your healthcare team can start thinking about which disease modifying therapies might be the right one for you to be on through that period of time. Follow standard obstetric advice unless you have particularly well, follow it regardless. But you know it's, if you have particularly severe MS, it's only then that you need to worry about any sort of high risk situations. Pregnancy is not going to be harmful for your disease course. It may be beneficial. We're still doing more research on that. Relapse rates are likely to reduce during pregnancy, although you might still continue to experience some symptoms that I went over before.

Although pregnancy is still a time of disease risk activity for some women, and so that's why we talk about using different disease modifying therapies for some women throughout their pregnancy, just to make sure that we look after your health as well as your baby's health. Exclusive breastfeeding may be beneficial, but that's mostly for women with more mild disease. And there's lots that we don't yet know about the effect of disease modifying therapies on neonatal outcomes. But the medications that I've highlighted today seem to be the ones that we know the most about, and we're continuing to do more and more research on these topics.

So, some of these guidelines you can also find on MS Brain Health and there's the web link there if you're interested in those. And then very finally, I do need to, on the last slide, just thank everybody that I work with. So, I'm at Monash Uni and I work with Alfred Health and the amazing MS Neuroimmunology unit there. And in particular, I want to highlight Anneke van der Walt, who is the lead there, and Louise Rath, our amazing clinical nurse. And Francesca Bridges one of my PhD students, who you might have heard talk about metaphors, although maybe it's too early for you to be thinking about that just now. So, we're part of the women's health research team there. And of course, lots and lots of collaborators that allow us to do what we do and of course thank you to all of the women with MS who, you know, very generously share all of their information with us so that we can hopefully come back and give you some good advice as well.

Thanks.

Jodi: Thank you, Vilija. Wow, what an enormous amount of information that you captured there so well. That's, it's so much to cover because it is such a complex area. And we had some questions come in earlier. So, thank you for the people who put forward their questions earlier. Most of them were answered. We were able Vilija so most of them were answered already within the presentation. But yeah, certainly is a often needing to be individualised as well too, the discussions about whether you, about what treatment it is and where your treatment switches. And it can be quite challenging because neurologists do have different opinions and that can make it really hard, that can make it really hard in terms of. But what you've done is give, give the evidence, which is just so important for women to be able to have. This is what we know that empowers women to say this is the evidence, this is the current knowledge, and you can feel informed when you go into your discussions with neurologists if you are thinking about pregnancy planning. But there's also the many unplanned pregnancies and they always require fun, fun times as well too and fun discussions as well too, but generally it's all manageable. You know, we get through, you know, we can get through and most of the time there's solutions and options, that's for sure. Jess, did we have any other questions?

Jess: Yes, we did just have one question which was really good. It was around if there's any known issues with switching DMTs to fall pregnant.

For instance, this person is on Ocrevus, and they've been told that once they're stable, we'll stop using Ocrevus so we can try. And so, would it be a good idea to then start on another DMT that's safe for pregnancy and whether there's any complications around that?

Vilija: Yeah, so again, it's a very personal question and I think it's important to talk to your doctor. And as Jodi said, lots of doctors have very varying opinions on this. I know that some neurologists MS would be happy you know, if you had your last dose of Ocrevus, just started trying to conceive within one to three months, if you fall pregnant fairly soon after that. I haven't shown it now because it's research that we're going to be presenting at the largest MS conference in Europe next month looking at Ocrevus, what we've seen is that women that become pregnant fairly soon, like within, you know, three months of their last dose, that actually keeps them quite stable throughout their entire pregnancies. We actually didn't observe any relapses in pregnancy at all and very few postpartum, so you may not need to go on anything else. It really depends on how long it takes you to conceive. It also depends on your B cell counts. Some neurologists might suggest going on to Tysabri. Some might be happy to re dose you with Ocrevus. Some might have another opinion altogether as well. So certainly, something to talk to your doctor about.

I think also, I forgot to cover, but one of the questions I believe from the audience previously that Jess and Jodi passed on to me was how soon you should have your next dose of whichever medication after delivery. And I conferred with my clinical team to make sure that I'm giving all of the right advice. One of them was specifically around Ocrevus. And so, checking with the neurologist that I work with, if you are on Ocrevus after delivery, they suggest that you should get your B cells checked within about a week of giving birth. And if they're sitting at zero, you're probably okay to wait for your next infusion. But if they're anything above zero, they would like you to get a new infusion ASAP. And likewise, if you're on Tysabri, they want to they want you to get back on the drug within about a week. So, in terms of planning and timeframes, that's sort of what you're looking at for those.

Jodi: Thanks. And that can be tricky too, because when you've just had a baby, it can be there's a lot of things going on, and so I think one of the things is having that planned already before, you know, alright, I know I need to do that, and that's when you can rely on your team around you and the people around you to say, don't forget to remind me that I'll that I'll need to, I'll need to be having those tests done and I'll need to be able to organise my treatment and definitely your neurologist and MS nurses can help book those treatments in.

I just want to thank you, Vilija. And I do want to just mention the fact that Vilija was one of the people who helped contribute to, and the rest of the Alfred's Women's Health Team were contributed to the preventative health tests for women checklist that we developed in collaboration with Alfred and these are tests that women help, specifically for women with MS .We developed this checklist because we know that it's hard to remember all the tests that you need and sometimes it's also hard to bring up the topic with GPs if you wanted to. So, we hope that this checklist helps women know what tests they need, be organised when they go to the GP to have all the tests done and also as a prompting tool to have discussions with your GP or neurologist if you need to have these checklists, these health test done so that's available on our MS Plus website. If you need any other support, there's all the support available to you at MS Plus.

Will be available on our resource hub. And if you need someone to speak to, if you've got a question many pregnancy discussions, as Vilija has highlighted, do require a one to one discussion because it can depend on so many different factors as to what the decisions are. And it's really important that you have enough information to feel like you’re part of an informed decision making and one that also respects your wishes. And so, if you want to get any more information about you and your particular case, you can always call Plus Connect. And they can put you through to one of the MS nurses who will give you again a bit more information and talk to you about what your needs and values and desires are.

So, thank you everybody. And if you could stay on for a short survey, that would be great. And thank you again, Vilija. That was absolutely fantastic overview. And after all that talking, you absolutely need to go and have a rest now. So, thanks so much for your time today. We really appreciate it.

Vilija: Thank you for having me.