 Okay, good afternoon and thank you for joining us today for listen to your gut living well with IBD. Today's topics are focused on women's health and IBD. I am Grace Purse with the University of Maryland Medical Center. Presenting today is Dr. Lauren George, assistant professor of medicine at University of Maryland School of Medicine. She will present Beyond Pregnancy, Women's Health and IBD. Dr. Seema Patil, associate professor of medicine at University of Maryland School of Medicine will be presenting Birds and the IBD's Sex, Fertility and Pregnancy in IBD. Before we begin, I have a few housekeeping items. Please submit your questions during the presentation and the physician will answer them at the end of the presentation. This seminar is being recorded and an email with this recording will be sent out next week. Thank you everybody for tuning in. I will now turn this over to Dr. George. Thank you Grace and welcome everybody. I'm going to start this webinar off by talking about everything except pregnancy. There's a lot of things that happen in a woman's life and we should be aware of each stage and how IBD affects that stage of life. So this is just an overview of what I'm going to talk about today. We're going to go through a little impuberty and menstruation and then menopause as well as some important preventative health measures that are specific to women and especially our women who are on immunosuppressants. And then we'll talk about some conditions that can occur with IBD that more commonly affect women and need to be addressed at your medical appointment. So as we know puberty is the start of a woman's reproductive life cycle and it occurs in the early teen years. And there's not much known about puberty in IBD as the majority of patients are diagnosed beyond the age of puberty. However, we do know in our pediatric patients who have IBD if their disease is poorly controlled it can delay the onset of menstruation. And this certainly can be from multiple factors. If you have poorly controlled disease and you're underweight or have failure to thrive, if these girls are on steroids, if they're having active flares and diarrhea and having poor eating habits or if they have nutritional deficiencies, all of these can delay the onset of menstruation and puberty. However, we do know that once disease is controlled and inflammation is controlled, girls will undergo a normal menstruation. And then the menstrual cycle itself, many women will have changes in their symptoms during the menstrual cycle and indeed many healthy women without IBD will have GI symptoms or changes in their GI health during their menstrual cycle. Many women will complain of looser vows or more frequent vows at the time that they're having experiencing menstruation. And specifically in women with IBD they can also have these cyclical changes in their IBD symptoms. And it has been shown in some studies that women with IBD do have this more frequently than women without IBD. And unfortunately changes in bowel habits can always be mistaken for active disease flares. And these women can have unnecessary prescriptions of steroids, unnecessary changes in therapy or symptoms that are due to hormonal changes and not truly active inflammation. This is a little bit of controversial, but sometimes if a woman with IBD is having significant cyclical GI symptoms, they can be managed with hormonal contraception. 20% of the time these can be managed with an estrogen-containing contraception in another study about 50% of the time an IUD was successful in managing these cyclical symptoms. And so there is an option and some treatment decisions to be made if you know you're experiencing a large change in your bowel habits during your menstrual cycle. Additionally, about 25% of women with IBD can have changes in their menstrual cycle itself. So they can have a longer or shorter cycle or they can have change in the amount of days between cycles. And so it's not completely unexpected if you notice that since you've been diagnosed with IBD, you have had some differences in your cycle. And then go into the other end of the spectrum with our reproductive life cycle is menopause where women undergo hormonal changes that lead to the cessation or the stoppage of the menstrual cycle. This is defined if you haven't had a menstrual cycle in about a year. You're considered to be in menopause. The good news is there's no difference in the age of onset of menopause. Women with IBD and without IBD tend to experience this at the same time, which averages late forties to early fifties. Again, somewhat controversial, but women with IBD who are on hormone replacement therapy after they undergo menopause may have less disease flares than those not on hormone replacement therapy. And there was some promise for this previously. However, in a larger national study, we've learned that hormonal replacement therapy does carry its own risks, including blood clot, heart disease, breast cancer, and stroke. So I'm certainly not saying this is a treatment option for your IBD, but it has been examined in the past. I think most importantly with women's health, we need to be considered of the special health maintenance that we must undergo as females. And cervical cancer is a large concern. As we know, all females should be undergoing screening for cervical cancer throughout their life cycle with a gynecologist. And cervical cancer is caused by a virus in the majority of the time, the human papilloma virus or HPV, which you may have all heard about. And about 70% of all cervical cancers in all women are due to two specific types of HPV, type 16 and type 18. And we can easily identify these on a traditional pap smear. And a pap smear is a scraping of the cervical tissue performed by a gynecologist on a pelvic exam. And this is how we screen for cervical cancer. Now, this is extremely important in our IBD population because we do know that women with IBD do have higher rates of abnormal pap smear compared to women without IBD. And this can be anywhere from three to six times the risk of having an abnormal pap smear. And once you have an abnormal pap smear, there's further testing and procedures that must be done to determine if there are pre-cancerous changes. Women with IBD are also at risk of having more severe lesions. Again, there's a whole grading system for cervical cancer and our patients tend to have higher grade lesions or more significant lesions. This is increased even more if you're a smoker. So again, another plug for working on stopping smoking if you have IBD. And in these studies that show that our patients have increased rates of abnormal pap smears, all the patients had these two strains of HPV 16 or 18. So it's really imperative that we're following with a gynecologist and identifying these strains of HPV and abnormal pap so that you can have the appropriate follow-up and care to prevent a cervical cancer down the road. Additionally, many of our patients are on immunosuppressive therapy and immunosuppressive therapies include Remicade, Humera, Simsia, Stalara, Antivio, all of these steroids, all of these medications, can increase your risk of developing these abnormal lesions in the cervix. So it's more important that you visit a gynecologist regularly and we would recommend usually, annually, you should be seeing a gynecologist and being screened for cervical cancer if you're on one of these medications. And that gets me to screening. So normal screening for cervical cancer in women without IBD or healthy women is to start with pap smears at age 21. And then based on the results of those pap smears will determine how often you need a repeat, similar to how we perform colonoscopies and look at polyps. However, in women who are immunocompromised, which again includes any of our biologic medications, it is recommended by both the American College of Obstetrics and Gynecology and the American College of Gastroenterology to start at age 21 but give annual pap smears. Additionally, all women should be avoided to counsel to avoid tobacco. And all women should be counseled on safe sex practices with a barrier contraception since we do know that HPV can be sexually transmitted. We also have another option for our younger patients and that includes vaccination. We do have a vaccine called Gardasil that works against HPV. It is safe and effective. It has been on the market for a few years now. And it prevents nine types of HPV virus including those types 16 and 18 that I talked about on earlier slides. And it targets the types of HPV that can most commonly cause not just cervical cancer but also oral and anal cancers. So this is an important vaccine in our armamentarium. The Advisory Committee on Immunization Practices, which gives guidelines and recommendations on vaccinations, currently recommends the HPV vaccination in all females between the age of 9 and 26. And more recently, societies have come out and recommended using a shared decision-making process, which means having a discussion with your doctor to determine if you should be vaccinated for HPV if you are between the ages of 27 and 45. And during this conversation, your doctor would talk to you about your risk factors. Are you a smoker? Do you have one of these types of HPV already? And what type of clinical scenario you have on to help make a decision on should you be vaccinated? There are multiple series of the vaccination. There's two shots or three shots. If you are on a biologic medication and immunosuppressed, you should receive the three dose series. And moving on to another important topic in women's health is bone health. As we know, women in general are at increased risk of having osteoporosis, which is low bone mass or low bone density. And that can lead to fractures or broken bones, hip fractures, spinal fractures. And a lot of complications as we age. And in addition to that, patients with inflammatory bowel disease are known to have increased risk of having reduced bone mineral density or osteoporosis. In certain studies anywhere between 14 to 42% of patients with IBD have osteoporosis. We know that certain patients are at increased risk. These include females. If patients are underweight or have a low normal BMI or weight, patients on steroids are at very high risk for it to their bone health. If you have uncontrolled inflammation and active disease, if you have a low calcium or low vitamin D, and if you have malnutrition, if you haven't been eating, if you've been losing a lot of weight. So in general, when a patient comes to an IBD center or our clinic, we assess a vitamin D level in all patients. And we give you vitamin D to replenish you if needed. And traditionally all women over the age of 65 should undergo a bone density scan or a DEXA scan, which is a radiology test that screens for osteoporosis. Additionally, many patients who come through our clinic who have been on chronic steroids or are underweight or have malnutrition, we will also perform a screening bone density scan. And this helps us identify if you either have osteoporosis or if you are starting to have low bone density, which may lead to osteoporosis in the future and allow us to make appropriate recommendations and referrals. So multiple conditions can occur in patients with IBD that are not related to inflammation and can cause similar symptoms. And a lot of these can happen more predominantly in females. So many patients with IBD, even when their inflammation is controlled will continue to experience abdominal pain or diarrhea or constipation changes to their bowel habits. And patients with IBD can be up to four times more likely to develop these chronic symptoms than someone in the general population. Within IBD, women are more likely to experience ongoing GI symptoms. And this is true in a general population as well where women are more at risk to develop irritable bowel syndrome. And certainly women who have existing anxiety or depression are at increased risk as well. An important take home point from this talk is that if you have a history of trauma or PTSD or anxiety or depression, you are at increased risk for developing irritable bowel syndrome overlap. And you should be talking to your doctor about these issues in addition to your inflammation. And we know that there's a strong connection between the nerves that supply the brain and the nerves that supply the bowels. This is called the mind-gut connection. And many symptoms that continue after your inflammation is controlled on a medication for IBD is due to this connection of the nerves. And when you have anxiety or depression, you can have even more sensitization of these nerves. So it's really important to identify these triggers. And we know that patients who have irritable bowel syndrome in addition to their IBD, again, present with symptoms and have increased use of steroids or narcotics. They get more imaging scans or go to the emergency room. And this has a huge impact on utilization of resources, but also quality of life for the patient. And so it is always important for your doctor to perform studies to make sure you don't have inflammation and that can include labs, stool tests, imaging or colonoscopy. But then it's also important to recognize that if these studies are negative, a treatment focus should be moved to treating irritable bowel syndrome. And there's multiple different options for irritable bowel syndrome. There's dietary therapies. There's a strong connection with the use of psychological therapy, such as cognitive behavioral therapy or hypnotherapy. And there's also multiple medications, including antibiotics or antidepressants or things that control the input of the nervous system that can be used to improve symptoms not due to inflammation. And finally, another condition that commonly occurs in females and especially females with IBD is fecal incontinence. And the pelvic floor refers to the muscles that make up your pelvis and are involved in having bowel movements, urination, childbirth. It's a large connection of muscles. And when you have a disorder of your pelvic floor or a problem with these muscles, you can develop multiple symptoms, including fecal incontinence, which is the loss of the ability to control your bowel movements. And this is common in IBD. Up to 75% of patients with IBD will have experienced fecal incontinence in the past. And sometimes certainly this is due to inflammation, but at other times it can be due to a pelvic floor disorder. And it's certainly under reported because our patients feel discomfort and embarrassment telling their doctor that they've had an episode of fecal incontinence. This is increased in women, and especially as women age, it is more common. And there's many other causes that are not related to your IBD. If you've had trauma from childbirth, if you've had inflammation in the past, if you've ever had a surgery involving the anus or the rectal area, certain medications, and just overall physical conditioning, because these are muscles. And patients with fecal incontinence have decreased quality of life. So again, just like having irritable bowel syndrome overlap, the first step is always to investigate for inflammation. But once inflammation has been ruled out, it's important to really test that pelvic floor and do further evaluations for the structure of the muscles, the sensation, the function. And there are again, alternate therapies. There's dietary therapies. We use ways to bulk up the stool, and there's actually a type of physical therapy called biofeedback that can strengthen the pelvic floor. And all of these are really important for providing a comprehensive evaluation and treatment of these incontinence disorders. And with that, I hope that was a nice overview of some conditions and concerns that affect women throughout their life with IBD. I look forward to a great presentation from Dr. Patil next about pregnancy, but I'm happy to take any questions you have at this time. Thank you. We'll go ahead and give everybody a minute to get their questions in. Okay. The first question we have might have two parts to it. So the question is, sometimes it's difficult to find information regarding women first diagnosed with Crohn's after age 65. So first I was going to stop there. If there's any beyond the doctor, is there any recommendations you have or finding more information or should women really head to their doctor's office? Do you have any comments on that certain group? Yeah. So that's a great question. There have certainly been an increasing rates of diagnosis of IBD in general in our older patients, and we are seeing that trend. And so it's definitely a group of interest. I would say that the most common age is still younger and a lot of our information is related to that. But you can certainly, I would recommend ask your doctor questions. Again, as we age, the more important things that we're going to think about are going to be things like bone health, maintaining immune health and what the right medication is for someone as they age based on if they have other medical conditions or how healthy they are or what kind of immune status they have. And so I think it is a special population and I think going to your doctor is important. I also think the Crohn's and Colitis Foundation has great patient resources and a great network of peer support. And so certainly always going on their website or reaching out can help you find others who have been diagnosed over the age of 65 as well. But I would say, you know, your doctor is still going to be the primary resource. Great. The next question is, my gynecologist says, I don't need a pap smear yearly. I have panohistorectomy. Is this correct? Should I insist on this? So that is another great question. I will give the best answer I can. I'm not a gynecologist, but I believe, you know, the hysterectomy itself and the details of the hysterectomy are important. You know, usually when they do a hysterectomy, I believe the majority of time they take the cervix out and they leave just the vagina sewn off. And if that's the case, there's really no cervix left. I know there are instances where part of the cervix can be left. And I would say I would definitely trust your gynecologist that they would make the right recommendation. And it may be that you no longer have a cervix, in which case that is true. You do not need annual pap smears. This question is looking for information. For women with IBD, are rates of colorectal cancer different for men? Or if you could just speak to colorectal cancer and IBD in that relationship? Yeah, no, another great question. So certainly in general, our patients with IBD and specifically inflammation of the colon, so either Crohn's colitis or ulcerative colitis are at increased rates or increased risk of having colon cancer. And that's why as you'll know that as you get further and further into your diagnosis, we're going to start doing more frequent colonoscopies. To my knowledge, there's no significant difference between men and women with IBD of the colon in the rates of colon cancer. And you should still be screened as per our recommendations, which is usually every one to two years after a certain time period since your symptoms or diagnosis. Thank you. One more minute. If there's any last questions, hand it over to Dr. Patil. Okay. So I am going to start with just welcoming everybody as well. Glad you could be here. Dr. George gave us a great background on many different topics of women's health and IBD. And so I'm going to focus on the so-called birds and the bees, sex, fertility and pregnancy and IBD. So I titled this sexuality and impaired sexual function. There's often the term sexual dysfunction used. I feel the word dysfunction can sometimes be a loaded term, but we'll use them interchangeably. But sexual dysfunction is really defined as persistent, recurrent problems with many areas of sexuality and sexual activity, including response, desire, orgasm or pain, and significantly that distress you or strain your relationship with your partner. Studies show that up to half of women with IBD can experience sexual dysfunction. It's very common. And while they overall report average rates of sexual activity, they also report less satisfaction. This issue is really inextricably tied up with body image. That can be greatly impacted in women with IBD depending upon corticosteroid use like prednisone and other steroids, as well as prior surgeries. And depression and anxiety often play a role. And impaired sexual function and body image have a real significant impact on quality of life. So it's really important despite the discomfort to talk to your doctor if you're experiencing any issues with this. The next topic I'll talk a little bit about is contraception. And Dr. George mentioned some of these issues in terms of hormone replacement therapy. One of the couple things that I wanted to emphasize with contraception is when you have a small bowel involvement with Crohn's disease, your contraception absorption can be impaired. And that is also true when you've had extensive resection of the small bowel. And finally, talking about estrogen or the kind of contraceptives you have is really important if you have a personal or family history of blood clots. As Dr. George mentioned before with hormone replacement therapy, similarly estrogen containing contraceptives have been found to increase this risk. So moving on to fertility. Now overall, women with IBD who have disease in remission and have no history of surgery really have fertility rates that are similar to the average population. But it is thought that active IBD may decrease fertility. This may be for a lot of different reasons, not least of all because when you're sick, you may not be engaging in sexual activity as much. What is clear is that our medical therapy for IBD does not decrease fertility. Now surgery is something to be considered. Patients with ulcerative colitis who undergo J-Pouch procedures or patients with both kinds of IBD who undergo proctectomy or permanent ostomies can experience decreased fertility. And the main driver behind this is really thought to be the generation of scar tissue from a pelvic surgery, which can really affect many areas of the reproductive organs and impact their ability to function normally. Laparoscopic surgery may improve fertility rates in some studies, so that is also something to be considered. Overall, we do recommend that at any age, any woman with IBD who is unsuccessfully trying to conceive for over six months should consider fertility treatment or evaluation for such. The next issue at hand is something we frequently get asked is what is my risk of passing on or increasing, what is my child's risk of developing IBD? So the risk of Crohn's disease in offspring born to a mother with Crohn's disease is about 2.7%. And for ulcerative colitis, that risk is thought to be about 1.6%. This is important because while genetics can play a role in the development of IBD, it's certainly not the whole story. Now we do know that if both the mother and the father have IBD, the risk to the child is about 30%, so increases significantly. And unfortunately at this time, there are no genetic tests that are able to predict whether your offspring would be born with IBD. It's something to take into consideration, but the risks again are still quite low. So one important thing to consider when possible is planning, thinking in the preconception time period about setting yourself up for so to speak in the process, we recommend shooting for three to six months minimum of remission prior to conception. And the reason is this really reduces the risk for flare during pregnancy and the postpartum period. In addition to other issues to deal with the pregnancy, which I'll discuss in a few minutes. This may require kind of evaluation with multiple modalities endoscopic evaluation, biomarkers, et cetera. And then as with any pregnancy with or without IBD, ceasing smoking, alcohol use and drug use, including prescription opioids as possible is an important thing to consider before trying to conceive. What will happen to your IBD during pregnancy? Generally, overall, it seems to follow the rule of thirds. A third of women will feel better. A third will be stable and a third can experience a flare of their disease. We know that women with active disease at pregnancy are twice as likely to flare and also have a significant increased risk for preterm birth. When flares do occur and evaluation is required, there are certainly considerations for the safety of the pregnancy in terms of endoscopic evaluation, unsedated, unprepped flexible sigmoidoscopy overall is very safe. And then colonoscopy can be considered, if we need to do it, we're looking to perform after 24 weeks of gestation with fetal monitoring. So it's certainly something we are very cautious about, but can be done. One huge area of interest for most women with IBD who are pregnant or planning pregnancy is their medical therapy and their greatest tools in thinking about this issue has been a large registry study called Piano. The full title of the study is a multi-center national perspective study of pregnancy and neonatal outcomes for women with inflammatory bowel disease. It's currently in its 11th year and it's in three sites nationwide. In case you are interested in looking into this more, the website below will take you to details about that study. These 1600 women have been followed for years through pregnancies and have been on a variety of medications for inflammatory bowel disease and the amount of information we've gleaned from this has been incredibly useful in guiding our patients and the treatment of their IBD during pregnancy. Here is a quick chart with some of the most important lessons I think we have learned from this. Misalamine products like misalamine, misalazine, balsalazide, there are a lot of different trade names that go under, in general are continued. Sulfa salazine is a little bit of a special consideration. It can impact folic acid metabolism in our bodies and that is especially important in pregnancy because of the neural core development of the baby. When people are on sulfa salazine, when women are on sulfa salazine during pregnancy we recommend that they take an increased dose of folic acid. Corticosteroids we typically try to taper off. It has been associated with increased risk for preterm birth, low birth weight and gestational diabetes and it's overall not an appropriate method for maintenance in IBD. Azethioprine monotherapy or treatment alone with that medication is typically continued. We do recommend avoiding starting it as a new medication during pregnancy and the main reasons for that is that it can be associated with a small increased risk for pancreatitis, low blood counts and there is a delay in time to affect. If it is being started for significant symptoms it's not going to be effective for a long time as we'll talk in a minute that has a big impact on the pregnancy. Now methotrexate is the one medication that is unequivocally contraindicated in pregnancy. In fact it should be stopped at least three months longer before conceiving. Biologic therapy and this is a category that includes anti-TNF agents like infliximab, adelimumab, the trade names of those may be include remicade, humera, as well as betelizumab or antivio, and eustachinumab or stilara. These medications have been shown to be in pregnancy in that they are safe and have not been associated with adverse pregnancy outcomes. We do continue these medications throughout pregnancy. We monitor levels to ensure they're within a tight range and not deviating too much during pregnancy. We do recommend using them as the only medication in other times of life. These medications can be combined with other immunomodulators, but during pregnancy if at all possible, we do recommend trying to just stay on one medication. There are some specific factors to consider. These medications do cross the placenta with the exception of sertilizumab or simsia. As I mentioned, they have not been associated with adverse pregnancy outcomes. This study, the piano study, has also shown that they have not been associated with any increased risk of infection in infants to one year. That's an important piece of data to know. Tophacitinib is a newer medication that we are using in all sorts of colitis in some patients. There is very little data regarding the use of this medication in pregnancy. We really recommend if at all possible to avoid this, especially in the first trimester. Overall, this class of medication biologics to include Tophacitinib, there are newer recommendations about possibly adjusting the intervals to try to minimize or increase the distance between placental transfer or transfer of these medications across the placenta and the time of delivery. That's a really nuanced area to discuss in detail with your doctor. Finally, antibiotics are really something that we consider stopping, particularly superflexus and metronidazole and tetracycline. Prenatal care, in terms of the OB team, every pregnant patient with IBD should have at least an initial consultation with a maternal fetal medicine specialist. These are obstetricians who have increased or additional training in high-risk pregnancies. That can be reasons for mother's health or the baby's health. You may sometimes hear them called high-risk OBs. MFMs and primary OBs can then decide upon subsequent appropriate monitoring and delivery plan. In some patients and depending upon the OB, they may just need distant monitoring or monitoring as needed. In other cases, it may require regular follow-up with MFM. What should we be thinking about in terms of nutrition in pregnancy? One thing we can certainly target is to look for and correct common vitamin deficiencies that we can see in IBD, particularly B12 iron and vitamin D. Folate administration, as we briefly discussed before, is important in all pregnancies and in sulfasalazine, or if you are on a significantly modified low-residue diet because of narrowings or strictures in your gut, if there is significant, active, really considering an increased dose of folate in those cases is also beneficial. Finally, women with IBD are at higher risk for inadequate gestational weight gain or not gaining enough weight during pregnancy. That is often associated with active disease. An inadequate gestational weight gain is also hand-in-hand with increased risk of preterm birth and small for gestational age infants. What should we be thinking about in terms of delivery? It is certainly well-proven that women with IBD undergo C-sections at a higher rate than most women. But what is not true is not that all of these C-sections are necessarily medically indicated. In fact, most deliveries in women with IBD can be vaginal. We consider C-section to be indicated in only a couple of instances. We consider C-section to be indicated in only a couple of instances. Active inflammation in that area, draining fistulas, abscesses. That is because there is a ten-fold increased risk of high-degree perineal laceration in the setting of active perianal disease and vaginal delivery. In particular, in the setting of surgical repair, it should be a case where C-section is considered. Finally, J-pouch history. Patients with ulcerative colitis who have undergone a colectomy and J-pouch should be considered for a C-section. What we are cognizant of is that women with IBD who undergo C-sections have been shown to have higher rates of blood clots. So, really considering prophylaxis against that, which can be done with medication, should be highly considered and discussed with your OB. Finally, after delivery, and after a few years after an uncomplicated C-section, you can resume your medications safely. Just a few notes about lactation or breastfeeding. In general, following standard nutritional recommendations for the lactation period is recommended. That generally means taking in 400 to 500 more calories a day, making sure you have Omega-3 fatty acids and that you stay very well hydrated is important for optimal breastfeeding. Fenugreek is a commonly recommended herbal medication to increase breast milk production, but that's something we generally advise avoiding because it frequently causes diarrhea and it can increase bleeding risk, so that's something to be a little bit cautious with. None of the IBD therapies that we use suppress lactation. However, we do recommend avoiding sulfasalazine, methotrexate and topocitinib in the lactation period. These have been shown to enter breast milk and either are unsafe or have not been proven to be safe in the newborn. Other IBD medications are either undetectable in breast milk or present in very low concentrations with no negative impact on infant health outcomes, including developmental milestones and infection. Other medications really no need to, as they say, pump and dump. And infant consideration, so what does this mean for the baby? If the mother is on a biologic therapy, particularly during the third trimester, but truly it's a consideration I consider for all women who are on biologic therapy at any time of pregnancy, the infant should not be receiving live vaccinations and in the US vaccination schedule, the only consideration is the rotavirus vaccine. So aside from that, all other vaccines can be received on schedule. And the live vaccination restriction is true for six months. There are additional live vaccinations, particularly the MMR, which is given at a year and is safe to administer to the baby. And IBD medications, as we know the Piano Registry, do not affect infant developmental milestones. Some of these babies actually have been followed into toddler hood without any impact on developmental milestones. However, the effect of inflammation is actually a very important area of study looking at in utero, baby's exposure to mother's inflammation does it affect brain development. So that's still something we are staying tuned to figure out. So in conclusion, these are just some of the main points that I wanted to get across today, that sexual functions an important part of quality of life. It can be uncomfortable to discuss, but when it is impacting your quality of life it is important to bring it up to your gastroenterologist, your gynecologist, just reach out for help. Overall, a healthy mom is the best chance for a healthy pregnancy and baby. When you are considering pregnancy, even if it may be in the distant future, bring it up with your GI and your OB or GYN at that time, bring it up early and often. And when you do become pregnant, assemble a team. It should consist of your GI, your primary OB, and maternal fetal medicine specialist. And finally, staying healthy during your pregnancy and the postpartum period really does include maintaining your medications as well as close GI monitoring. Thank you. At this time we can take any questions. Please leave them now. We'll give everyone a second to get caught up. The first question that's coming is, is there a connection between IVD and polycystic ovarian syndrome? So to my knowledge, I don't know a significant increase in risk, although there are some certainly clinical considerations that would complicate things. Certainly some of the symptoms that you can experience with polycystic ovarian disorder and Crohn's disease can, or IBD in general, can overlap. And in terms of thinking about management, some of the issues in terms of surgical options may be further complicated by a polycystic ovarian disorder. Thank you. Oh, can I, sorry, I mentioned one other thing. The fertility issues also, certainly with PCOS, can also become a little bit complex, particularly in the setting of surgery for IBD. Thank you. This is a specific medication question. And if we need to, if you think the recommendation should be to follow up with the doctor or yourself, we can do that too. So the question is, I've been on as a feely prime, I'm not going to say this correctly, as a feal prime. As a friend. Thank you. And mesolamine. Mesolamine, yeah. Okay. Mesolamine for several years with great success. My GI has warned me for years, however, that when I'm ready to get pregnant, I can't stay on as if the, as a feal prime, but you mentioned it can be used during pregnancy as a mono therapy. Does that mean I'd need to stop the mesoline or keep that and stop that as a feal prime? So in general, what I would say the general approach and not being too specific about the details of your specific disease is, if a medication was required to put you into remission and manage your inflammation with the exception of methotrexate or TOFA-sittenin, that medication should really be continued during pregnancy. When I spoke about mono therapy, I was mostly referring to other medications that may impact your immune system specifically, things like biologics. So the addition of mesolamine is, doesn't have a significant impact. Overall, certainly for simplicity, if the mesolamine is something that has not been shown to be necessary for management of your inflammation, that can be discontinued. Now, there used to be an older or a previous thought that azathioprine may not be safe in pregnancy. This was primarily based on studies in rats. In those studies, rats were given what would be equivalent to about 80 times the dose that we would use the corresponding human dose of azathioprine that we use in IBD. And in those rats with 80 times the dose, they were seeing increased risk of congenital abnormalities. But when, now that we are decades upon decades out from those kind of studies and with a lot of help from literature studies from, for example, other populations that use this medication, like transplant patients, rheumatologic patients, we have not seen the same issue with humans. There is no increased risk of congenital disorders or any other adverse pregnancy outcome specific to azathioprine monotherapy. And we've seen that in that piano registry I've mentioned as well. So the general recommendation is if someone is doing well on azathioprine, that that should be continued. Thank you. Looks like we have time for one last question. If Crohn's is entirely within helium and not reachable of typical colonoscopy, are there non-invasive techniques that can be used to determine muscute mucosal healing? So in general, other things that can be considered and this is all first speak sort of globally outside of the realm of pregnancy and specific, but we do use non-invasive tools like blood and stool, what we call inflammatory markers or biomarkers. Those can be elevated in the majority of patients with active IBD. And that is true of ilial involvement as well. In addition, there are other ways that we can reach the helium outside of a classic colonoscopy. There are extended sort of a little bit more complex endoscopic procedures and there is also capsule endoscopy. Now, if you talk specifically about pregnancy we're generally not recommending those procedures either capsule endoscopy or balloon endoscopy in the setting of pregnancy. But the other non-invasive tests definitely can be employed blood tests and stool tests to get a sense of activity. Thank you. So that's all we have time for today. Thank you to Dr. George and Dr. Patil from the University of Maryland IBD Program at University of Maryland Medical Center. If you'd like to make an appointment you can do so today by calling 410-706-3387. Thank you to everyone for tuning in.