Women’s Health: Pregnancy, Fertility & Polycystic Ovary Syndrome (PCOS)


Two expert clinicians in obesity explored important clinical areas in women’s health: pregnancy and fertility. First, attendees learned about the interplay between fertility and obesity, with a special focus on PCOS, and how GLP-1 agonists can support treatment. Next, the links between obesity and pregnancy, including associated complications and unique challenges for patient care were presented. More information here.


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Hi everyone, I'll get started. I'll just go through quickly the house rules for the EASO comms network webinar. This is actually the final webinar of year 2023, so thanks very much for joining.

So before I hand over to the chair and the expert speakers, I just want to welcome everyone to the comms webinar and just let you know while you're listening to the presenters, if you have any questions, there will be time for the Q&A at the end, so please do use the chat function to ask questions as you think of them and we'll make time at the end to have a discussion about these with the presenters. So please, please do follow EASO on social media. I will add the links to the chat as well so you can access them and I'll also drop information about the webinar in the chat.

Just one final note from me, I am going to share a feedback survey with you as well, so please, please, please take the time to complete this because it also asks about your ideas and your ideas on what would be useful to learn in future webinars, so I really appreciate that so we can develop the future webinars. I'm going to hand over to our chair Barbara McGowan now and I'll let you introduce yourself Barbara, thank you. Thank you Lisa, good morning, good afternoon everybody.

My name is Barbara McGowan, I'm a professor of endocrinology and diabetes at Guy's and St Thomas' in London and I'm an obesity physician and it is a great pleasure to introduce today two excellent speakers. It's all going to be about women today, of course, very popular, I understand. So without further ado, I'd like to introduce our first speaker, that's Dr. Amelia Houbinen, who's a specialist in gynecology and obstetrics and she's affiliated with the University of Helsinki, where I understand it's snowing right now, at the Helsinki University Hospital in Aava, at the Aava Clinic and she's going to present on obesity and fertility with a special focus on PCOS.

So Amelia, over to you, thanks very much. Thank you so much, let me share my screen. Okay, I hope you see my slides now.

Okay, great. Well, good morning, good day and good afternoon and greetings from Helsinki. Yes, it's snowing here and thank you EES for inviting me to this exciting webinar.

So my name is Amelia Houbinen and I'm a gynecologist and I did my PhD on gestational diabetes. I still continue research among these women, obesity, lifestyle and diabetes, but also do clinical work in gynecology and treat women with obesity. Here are my disclosures, which are basically lecture fees and participation in some scientific groups.

I know that many of you might think, what on earth is a gynecologist talking about obesity? I get that question quite often, but for me, my PhD was my gateway to the world of obesity and lifestyle. After that, I continued my residency in gynecology and I started to see how obesity actually impacted women's health in so many ways during their life cycle. There was heavy menstrual bleeding, there was endometrial hyperplasia, infertility, pregnancy complications, and all that we could do was say, well, eat less and move more.

So I started to think, maybe I could combine my scientific background with my clinical work. And so I found my passion. And now I've started in pregnancy and I've now moved to the period before that, because I think that the earlier that we can help these women, the better impact we have on fertility and pregnancy.

So during this talk, I want to share with you my passion. And specifically, I want to answer three questions. How does obesity challenge fertility? What does PCOS, so polycystic ovarian syndrome, have to do with fertility and with obesity? And how could we help these women? Specifically, could we use GLB-1 agonist to help women with PCOS and obesity? So let's start with obesity and fertility.

For us to have a successful pregnancy, we actually need many pieces of a puzzle to fall in together perfectly. So we need functioning ovaries, we need ovulations, we need a receptive endometrium, we need mobile, good quality sperm, and we need a good implantation and a dividing embryo. And unfortunately, obesity can affect all of these individually.

Of course, if you have, if you're trying to study one person, it's very difficult to disentangle them. But there've been studies on ovum donations and surrogate wombs, and they've found out that actually all of these are affected. So as Barbara said in the beginning, today we're talking about women, so just keep in mind that obesity also impairs male fertility, but today we focus on women.

So when we think about the background features, in studies we've seen that women with obesity have a lower level of luteinizing hormone, so LH, and also the follicle stimulating hormone, FSH, that are secreted from the pituitary gland. Also the progesterone at the end of the cycle is lower, and these lead to the fact that follicular phase is typically longer and luteal phase is shorter. I'm sure we don't know even half of the mechanisms that lie behind all these changes, but just to name a few, we know that at least high leptin levels, free fatty acid levels that are higher, and the low-grade inflammation do interfere with female fertility.

When we think about the clinical manifestations, one of the most important features is, of course, ovulatory problems. And as you've seen this figure, they start to rise already after BMI 25, and when we cross 30, they are already three times more common. The other thing that's very important in this figure is the fact that actually we can have an ovulatory failure also with a regular cycle.

The other clinical manifestations include miscarriages and congenital malformations. So unfortunately, in spontaneous pregnancies, the odds for getting a miscarriage is 1.2 to 1.9 when there's obesity. And the special feature is that the chromosomes are more often normal, so it just implies that there are some other features, probably in the endometrium, inflammation, insulin resistance, that are the cause of the miscarriage.

In congenital malformations, we see more neural tube defects and cardiovascular malformations, and it seems that the heart defects increase by increasing BMI. Again, thinking about what's behind this, it could be, of course, in the early pregnancy, you have a higher glucose level, but it also can be something related to folic acid or so, but we don't know. We just know that it is a higher risk.

But could weight loss help? Which is, of course, a very important question. And fortunately, we can say that yes, it does. So if we are looking at lifestyle intervention, aiming at weight loss, we see an improved pregnancy rate, improved live birth rate, we have more ovulations and less pregnancy complications.

So definitely, we should help these women with weight loss. But as you are obesity specialists, you know that weight loss is not easy to achieve. And if you want long-lasting lifestyle changes, you need time.

And therefore, I think that if we would start as early as possible, we would have time enough before the pregnancy is really wanted to help and reach a better, a lower weight. Okay, so we know now obesity challenges fertility in many ways, causing ovulatory problems, miscarriages, and malformations. But then how about PCOS? What is it? And what does it have to do with fertility and obesity? Well, polycystic ovarian syndrome, PCOS, is actually the most common cause of ovulatory problems.

And it's very common. It ranges, of course, based on population and diagnostic criteria from 5% to 25%. But it's approximately, let's say 1 in 10 women have PCOS, which is quite a lot.

And it is very much associated with obesity. So 74% of women with PCOS also have obesity. PCOS also has a strong association with the genetic background and or intrauterine conditions, because we know that we look at monozygotic twins, there is a 70% concordance rate.

Luckily, we just have received an international evidence-based guideline for managing and diagnosing and treating PCOS from the Helena Tiede and her associates. There's plenty of information, go and check that out. They also modify the diagnostic criteria slightly.

So we need two of these three criteria. We need ovulatory dysfunction. Previously, it was irregular menstruation.

But nowadays, as you remember from the figure, you can have also a regular cycle with other problems. So ovulatory dysfunction. Second, we need symptoms of hyperandrogenemia or a clinically in a lab test measured high androgen levels.

So biochemical hyperandrogenemia. And the third criteria is multifolicular ovarian ultrasound. And in this updated version, you can use a surrogate marker high AMH level.

So two of these criteria, and you can diagnose PCOS. When I think of PCOS symptoms, I divide them into four categories in my mind. There are the metabolic symptoms that are related to the high androgen levels and high insulin levels.

So there's this parasitism and acne. There is type 2 diabetes and metabolic syndrome, insulin resistance, high cholesterol. And of course, there are the gynecological symptoms.

We have irregular periods, infertility, pregnancy complications. There are also psychosocial symptoms. There's more depression and anxiety, and also sleep problems in the form of sleep apnea.

So very, very diverse symptoms. But although the name implies two ovaries, and for ovaries somehow being wrong or sick, actually what is in the middle here is the big villain, and that is the hyperinsulinemia. So it is the insulin resistance and the high insulin levels that are at the background of PCOS.

So it's the high insulin that goes to hypothalamus and interferes with the GnRH production, therefore interfering with LH and FSH levels, giving a very mixed signal to the ovaries, which leads to the polycystic appearance and ovulation problems. The insulin also goes straight to the ovary, stimulates the thicker cells to produce more androgens. So there, it's causing the high androgen levels.

Also, the insulin resistance causes high glucose and therefore in the liver, decreases the levels of the sex hormone biline globulin, again, adding to the amount of free androgens in the blood. So there we have this circle, and when we have high androgen levels, again, then it will increase insulin resistance, and we have the circle ready. Actually, despite the woman's BMI, based on studies, we suspect that 95% of women with PCOS have insulin resistance.

But how about obesity? So is it obesity causing PCOS or PCOS causing obesity? So what is the hen and what's the egg? At least we know, based on studies, that obesity increases the risk of PCOS. So each BMI-ST increase increases the odds of PCOS by almost threefold. But mentally and randomization studies have confirmed that there is a causal role from obesity to PCOS, but not necessarily from PCOS to obesity.

But we have to remember that, yes, indeed, women with PCOS do report difficulty in losing weight. So, but this is what we know based on research nowadays. And the difficulty of obesity when we think of PCOS is, of course, the fact that obesity also increases insulin resistance.

So obesity increases inflammation, increases adipose tissue malfunction, which in turn increases insulin resistance, and therefore adding up to this cycle. It also has an impact to the long-term health of this woman. So we know that PCOS is associated with hypertension in the future and threefold risk of type 2 diabetes.

But when you put obesity into the picture, it increases the risk even further. So we know obesity challenges fertility, and we know that obesity also increases the risk of PCOS, which is the most common cause of under-ovulation. But how can we help these women? Just to remind you, yes, we know that lifestyle interventions aiming at weight loss are good for fertility.

So they do increase the pregnancy rate and life birth rate, improve ovulations, and decrease pregnancy complications. But when we think of PCOS, typically, you know, as doctors, we want to help the patient, and we are very symptom-driven. If a woman has irregular cycles, we want to give oral contraceptives to give regular cycles to her.

Or if they have acne, we give acne treatments. If they have obesity, we give lifestyle advice. If there's depression, we give SSRIs, and so on and so on.

Of course, I have to admit, yes, we do use metformin, which is for insulin resistance. And yes, combined oral contraceptives do increase sex hormone binding globulin, so they help to decrease the androgen levels. But the more I think about the pathophysiology of PCOS, I think that we should be focusing more on the fundamental goals of treating hyperinsulinemia and obesity.

Because we know from studies, actually, that if we help women with weight loss, it improves both the clinical features and long-term health of women with PCOS. It decreases insulin levels and insulin resistance. It lowers androgen levels and the symptoms related to that, so hercystism and acne.

It also improves psychological well-being, menstrual cyclicity and fertility, and also metabolic health in the long term. However, as I told you before, this is not easy for women with PCOS. It was actually a consumer survey.

They asked women, what do you need help with? And the number one concern for a third of the women was weight management. So this is what they need help with. So could we use GLB1 agonist for women with PCOS? Well, as obesity specialists, you are for sure familiar with GLB1 agonist.

And when we think about PCOS, of course, we welcome the fact how they decrease weight and food intake, improve satiety. But also, I'm very interested in the way that they work in the liver by increasing insulin sensitivity and decreasing gluconeogenesis, how they work in the muscle and improving insulin sensitivity, and in the pancreas, increasing beta cell function and biosynthesis of insulin, and also decreasing secretion of glucagon. You are probably all aware of the studies showing that with increasing BMI, there are lower levels of GLB1 in creatine.

So that is probably common knowledge. But interestingly, there are a few, yes, very small studies of just, you know, 14, 12, 20 women among women with PCOS and normal weight, and they seem to tell the same story. In this study, again, women with PCOS and normal weight compared to normal weight women had lower levels of GLB1.

And in this study, they did an OGTT, and then they saw similar levels of GLB1 in the beginning, and then it dropped faster. Yes, these are very preliminary, very small studies, but it just gives the suggestion. If we think of what we need to treat when we're treating women with PCOS, we want to treat, of course, help them with their adiposity.

We want to help with insulin resistance. We want to help with the high androgen levels, and also with the gynecological symptoms, so irregular periods and infertility. Here, I focus now on loractazide because it's been longest in the market with the indication for weight loss, and it's been used in most of the studies among women with PCOS.

Unfortunately, there is one RCT, which used the three milligram dose, which is the one that we use for weight management. This was 32 weeks, so not even a year, I would say. It's a short study with a bit more than 80 women, and they found that, yes, loraclitazide was better than placebo for weight loss, improving free androgen index, and improving menstrual cycle frequency.

Of course, there's been several other studies before that. They were mostly, you know, one or three months maximum. They used a very low dose, 1.2, maybe 1.8, but typically a lower dose, short period.

But just to summarize what we know from them, it seems in adiposity, yes, loraclitazide is superior to placebo, decreasing weight and fat percentage. Insulin resistance, yes, loraclitazide is definitely superior. Improving hyperandrogenism, yes, better, and also menses occurrence.

Of course, the one drug that we have been using until now for PCOS is metformin, so we need to also compare for that. It seems to be loraclitazide, especially when you use the three milligram dose, it is superior in adiposity and insulin resistance. In the others, the results have been inconsistent.

Of course, when we're treating women in their fertile age, especially concerning their fertility, we need to think about the safety during pregnancy. So these are like safety periods calculated from the T-half-life times seven. So for an alpha-Xenobarbapine, five days, there are some metabolites, so maybe two weeks is at least safe.

For loraclitazide, four days. Semaglutide, seven weeks. Phentermine topperamide extended release for four weeks, and tirazepatide, five weeks.

Because we don't have safety data on any of these during pregnancy, nor during breastfeeding. Special notice, of course, to phentermine topperamide, because we know that topperamide does increase the risk of congenital malformations, possibly autism, so that is like the most severe that we know, but from the others, either we don't have any safety data. So especially when we think about that, I mean, if we use anti-obesity medications, we need to be not trying to get pregnant, so we need time enough before the one in pregnancy.

So again, it kind of highlights the need that we need to start early, so we have a possibility to benefit the women for fertility and pregnancy. Before my conclusion, I want to just give a quick shout out and welcome you to Helsinki in the beginning of February to enjoy the Nordic meeting in Helsinki. And to conclude, obesity impairs fertility in many ways, but treating obesity in young women improves fertility and decreases pregnancy complications.

PCOS is the most common cause of anovulation, and weight loss improves symptoms and underlying features. And the GLB-1 agonists do offer a promising tool for helping women with PCOS and obesity. Thank you, and I'm happy to answer questions after the next talk.

Thank you very much, Amelia. That was a really wonderful and informative talk, and I'm sure there'll be lots of questions after that. So if I can invite just our visitors to put questions in the chat so we can address these at the end of the next talk.

So thank you very much, Amelia, and I would like to introduce our next speaker, Professor Finula McAuliffe, and she holds the position of Director at the University College Dublin Perinatal Research Centre. And she's also the Head of Women's Children's Health at UCD School, and she serves as the Chair and Professor of Obstetrics and Gynaecology in Ireland. So there's no better person to talk to us today about obesity and pregnancy.

And so, you know, Professor McAuliffe, the floor is all yours. Thank you very much. Great.

Well, thank you very much for the very kind invitation to speak. And can I just check that you can hear me and see my slides? Yes, we can. Thank you.

And thank you very much for Professor Amelia for setting the scene. And of course, what happens when these women get pregnant? What does the future hold for them? So this is a common enough scenario that I would see in my clinic, a first time mother. Her BMI is 58.

She has essential hypertension, for which she's on labetalol, which is a beta blocker. She has sleep apnea, for which she has CPAP at night. She has depression, anxiety, for which she's been treated with sertraline.

And what complications might she develop and what are the issues for her pregnancy management? So you can see she's got many of the comorbidities that that we've already heard about. So what about obesity? Well, obesity is the most common condition of women of reproductive age. And this is the most recent data from Eurostat.

The darker the color, the higher the rates of increased BMI. And you can see here that many countries in Europe indeed have high rates. You can see the numbers there ranging in around sort of 50 to 60 percent.

Looking in more detail at overweight and obese and Ireland is here very much one of the countries with the higher rates. The blue line refers to those with BMI over 30. And the orange is the BMI over 25.

So you can see that a majority of women in Europe have high BMI and quite a number up to 30 percent have BMI over 30. So what does this mean for the woman? And Professor Amelia has touched on this already. Obesity across the life course is a huge issue.

And any of us really interested at preventing chronic disease, we need to take a life course approach. And of course, no better time to consider intervention, which, of course, will happen all the way along the life course is before and during pregnancy. If a woman enters pregnancy with a high risk trajectory, similar to the case I've just presented, she's at increased risk of pregnancy complications and chronic disease in later life.

And also her infant is also at increased risk of chronic disease. So if we can intervene in before or in during pregnancy to lower her risk trajectory, well, then there will be benefits both for mother and baby. So we really need to think about the perinatal period as a crucial time to address chronic disease.

Now, when I discuss with my patients who have a higher BMI, what this might mean for them, decreased fertility, increased miscarriage, gestational diabetes, cesarean section hypertension, they might think, well, yes, I thought some of this might be appropriate and might pertain to me. But when I go on and explain to her that the impact of high BMI could have on her baby, I find that she's often quite surprised. Stillbirth is increased twofold, congenital anomalies, particularly cardiac and spinal defects, twofold and increased and growth problems, both macrosomia and growth restriction.

And then, of course, those risks don't end at the end of pregnancy and increased chance that her child will have obesity, diabetes in later life. So really what we're trying to do in pregnancy care is for the woman maximise her health before and during pregnancy to reduce non-communicable diseases for herself and for her child so that good health is passed from one generation to the next. And of course, pregnancy is a unique time in the life course.

Nutritional requirements are increased. And of course, I've never met a pregnant woman who doesn't want to do better for her baby. So she's very engaged.

It's considered a teachable moment. Women who are pregnant often are very responsive to advice. And of course, we have two patients.

It's the only time in the life course where we have two patients and one. So fantastic opportunity to improve the health for her and her baby. And of course, pregnancy is a time in the life course where the woman is interacting with health care professionals every month.

So there's a huge intensity here for for health care delivery. And we should use that to improve her weight and nutrition. So I'm involved in the International Federation of Gynecology and Obstetrics, which has 139 country members.

And one of the initiatives that I developed together with Mark Hansen and Moshe Had was FICO Pregnancy, Obesity and Nutrition Initiative, really recognizing the challenges that we all face with higher BMI and poor nutrition. And our vision is nutrition and weight will be at the front line of pregnancy care for women globally and that we need to think nutrition and weight first at every contact so that we can give the gift of a life free from chronic disease. One of the ways that we're working on this is we produced a supplement, which is seven articles covering basic clinical research and guidelines.

And one of those guidelines is the care of women living with obesity before, during and after pregnancy. And the aim of this guideline, you have to remember that International Federation of Gynecology and Obstetrics covers all the world regions, including Europe. And even within Europe, there are many health systems that are better or poorly resourced than others.

So our aim is to consolidate a published clinical practice guidelines from professional colleges throughout the world into one document. So we focused on three time points before pregnancy, during pregnancy and after pregnancy. And we recommend that all women should have their height and weight measured.

And considering ethnic differences, we need to advise women that if their BMI is increased, that this will impact on fertility and pregnancy complications for them and their baby. And we should encourage and support them to lose weight through diet and adopting a healthy lifestyle, including physical exercise and if available and appropriate other interventions that have been mentioned already, GLP analogs, for one example, and including bariatric surgery where appropriate and available. And crucially, women need to take folic acid up to five milligrams for at least one to three months prior to conception, because you remember the increased neural tube defects twofold over and above women with a normal BMI.

As you can imagine, the recommendations for the care of a woman living with obesity during pregnancy are quite detailed. We should monitor her weight and height and give her appropriate gestational weight guidance and support to achieve that. There are specific issues in terms of antenatal health care facilities that may need to be considered.

And certainly in our hospital, we would have a multidisciplinary discussion. The patient that I started with here has multiple comorbidities, and these will need to be managed. She may need to see a physician, an anaesthetist.

And you also need to look at the facilities that you have. Do you have adequate facilities in terms of equipment and so on to care for women with a higher weight? So we would screen her for gestational diabetes, both in early and late pregnancy. Perhaps she has type two diabetes and is unaware of it.

We would like to know about that in early pregnancy. We need a large cuff for measurement of her blood pressure. And of course, she's an increased instance of preeclampsia.

So we would advise aspirin, 150 milligrams from early pregnancy to 34 weeks gestation. Up to 20% will have depression and anxiety, and we know pregnancy is a risk factor for anxiety in all women. And so these women, we need to screen for that and offer appropriate support.

And then we need to be aware of the increased risk of stillbirth and offer increased fetal surveillance in the third trimester. We would advise an anaesthetic consultation with a BMI over 40 and be aware of the increased risk of venous thromboembolism, both antenatally and postnatally. And many of our ladies with a higher BMI would be on antenatal and postnatal thromboprophylaxis.

In labour, she needs early venous access, and we would tend not to go beyond 41 weeks gestation due to the increased risk of stillbirth and electronic fetal monitoring in labour and obviously additional care for wound infection. The following is birth by cesarean. And then postnatal period, this is a time, I guess the postnatal period is also a pre-pregnancy period because you may not see the woman again until she's pregnant again.

So we need to support her in breastfeeding. And in fact, these women often have challenges for breastfeeding, but there are huge benefits to her personally to breastfeed. And we need to consider, did she develop any pregnancy complications that need follow up? For example, if she had preeclampsia, she needs a blood pressure check going forward.

If she had gestational diabetes, she needs a postnatal and regular check for the development of type 2 diabetes. And then this is an opportunity to review with her a potential weight loss interventions. And then of course, when we consider contraception, we need to consider higher BMI in our decision.

And I think we need to be aware of how we discuss weight with our patients. We need to avoid weight stigma and bias. We need to use weight inclusive language and images.

We need to be aware of how obesity is viewed in different cultures. In some cultures, it's very much desired. And in other countries, it's not.

And for some women, a trauma informed approach is required because they have been exposed to unpleasant experiences during their life course regarding to their weight. So I wanted to spend a few minutes on breastfeeding and some really exciting data about breastfeeding. Breastfeeding is simple.

It's free. It's available to everybody. And lovely data now to show that it can reduce the development of type 2 diabetes and cardiovascular disease for women.

So looking at breastfeeding, this study, and there are many that have come out in the last number of years, looked at women that had gestational diabetes and women with gestational diabetes have a 50% chance that they would go on and develop type 2 diabetes, which is very significant. So we looked at women in this study, whether they breastfed or didn't. And those that breastfed were their chance of experiencing type 2 diabetes within two years of follow up was halved if they breastfed.

And there was a very nice dose response observed in this study that women who breastfed for longer had more of an impact on that reduction in the development of type 2 diabetes. And then recent data last year, looking at breastfeeding and later life cardiovascular risk. Many of you may well be aware of this, particularly if you're interested in the impact of obesity across the life course, looking at over a million women recruited at the age of 50 and followed for 10 years, and they collected the lifetime breastfeeding.

So adding up all the months the woman spent breastfeeding a busy slide, but all of the findings were in the one direction that cardiovascular disease, coronary heart disease, stroke and fatal cardiovascular disease all reduced in women who breastfed compared to women who didn't. There was also that dose response effect, seeing those that breastfed lifetime for more than 12 months had further reduction. And these are just summarized here.

Of course, cardiovascular disease is the main cause of death for women, even though if a lot of women think it's cancer, but of course, it's cardiovascular disease and a big risk factor for cardiovascular disease, as we know, is higher BMI. And you can see a 10 to 15 percent reduction in cardiovascular disease in later life amongst women who breastfed. So what about our higher BMI women? How easy is it for them to breastfeed? So we did this study in Ireland.

I regret to say we have relatively low rates of breastfeeding compared to other countries. We're not alone, I have to say, within Europe, but lots of room for improvement. So we did a qualitative study of women with a BMI over 30 who had successfully breastfed for six months.

We were interested to know what helped them and what were barriers. And of course, it is it is more difficult. They often have insulin resistance, which we know reduce milk supply.

They have a larger breast size, so it's more difficult for the baby to latch on. Some women are very uncomfortable about breastfeeding in public with the higher, larger breast. But the enablers, interesting, were supportive partner and lactation consultant support.

So we took these two elements and designed a multi-centre randomised trial of women with a BMI over 25. Randomised to usual care versus this package that we had identified from our qualitative study, an antenatal class with the partner on breastfeeding and then a one to one lactation consultant and advice in the hospital with six weeks of online or drop in clinic support. And our primary outcome is breastfeeding at three and six months.

This is the latch on study, and we're looking forward to publishing this very soon. OK, well, what about the lady that has had bariatric surgery? So two previous cesarean sections. She's booked in your clinic.

She's lost 30 kilograms, which is fantastic. But her BMI is 55. What are the additional issues over and above those that I've mentioned for women with a higher BMI? And of course, it depends on the type of surgery that she's had.

Was it restrictive? Was it malabsorptive or a combination? And the reason we differentiate these is because when it's malabsorptive, well, then there's concern about her micronutrient status. Does she have vitamins and minerals on board? Often she doesn't, and she will need to take replacement. And these are just examples of the various types of bariatric surgery.

And I'm not sure about your countries, but in Ireland, there is a long waiting time for bariatric surgery and therefore a bariatric surgery tourism is is quite popular. Many women will go to other countries and come back with a sleeve gastrectomy usually is the commonest one that we have. So what are the fetal outcomes following bariatric surgery? I mean, is it just a case of reducing the weight or are there additional concerns? So these are this was a lovely review of 14000 pregnancies after bariatric surgery.

Compared with four million without bariatric surgery, and you can see that even after bariatric surgery, the risks are increased. You can see small for gestational age, perinatal mortality, preterm birth and congenital anomalies. And you might say, well, look, why? Why is this? The weight is less.

Those risks that you mentioned should be less. But we feel that these risks are there because she has a malabsorptive function because of her bariatric surgery, and therefore she is often deficient in iron, vitamin D, folate. And these need to be replaced.

And this is a very nice infographic that some of you may find useful. So when you're looking after a woman who has had bariatric surgery, these are the things you need to consider. She still needs fetal monitoring and she won't manage her usual oral glucose tolerance test.

So we need to measure her risk for diabetes with hemoglobin A1C. We need to keep an eye on gestational weight gain and we need to consider the surgical issues. So this is just a snapshot from the pathway that we have in our hospital for women with bariatric surgery.

And of course, some of these women will present with a normal BMI. So unless you have a detailed history, you may not capture the fact that she's had bariatric surgery or indeed she may not tell you that she's had it. So but of course, you can see here that we need to monitor her vitamins and replace them if they are deficient.

We need to be aware that she's had bariatric surgery because, of course, there can be late complications which may mimic some of the pregnancy symptoms. Oh, doctor, I'm vomiting. Well, yeah, you're pregnant.

So a lot of women have have vomiting. But of course, if she had bariatric surgery, we would need to investigate for potential surgical complications of her surgery rather than assume it's pregnancy related or if she's reflux, we need to consider has the band slipped? Does she have interception with necrosis and volvulus? So we need to have a high index of suspicion and a surgical opinion should be sought and imaging performed where appropriate. So there are many cases where women have not been picked up in a timely manner because there wasn't this awareness of potential surgical complications of bariatric surgery.

So what sort of tools could we offer women? And this is a smartphone app that was developed by our dieticians here in the National Maternity Hospital in Dublin with some recipes. It's free for download breakfast, lunch and dinner and snacks. And it's all appropriate for pregnancy called Holistic App.

It came out of a randomized controlled trial that we did recently on 500 women with a BMI over 25. We randomized them to a low glycemic index diet exercise and supported with a behavior change theory and a smartphone app. We've had multiple publications from the study.

We had many beneficial effects for the women in the study, less gestational weight gain, less large for gestational age infant, better insulin sensitivity. And those that engage with the app had a better diet quality. So we've taken this smartphone app and we've made it available.

It's free for download. Anyone around the world to use in your clinics. It's based on randomized control trial data, which is very robust and it's appropriate for pregnancy.

So something to consider for your patients. And then finally coming to health care professionals. I mean, we all know we should be talking about healthy diet, but a lot of many health care professionals, you know, I don't know where to start.

What what what should we do? And this is the work that has come out of a FECO committee that I've chaired looking at the impact of pregnancy and long term health and looking to see how can we make nutritional advice accessible for all health care providers who see women before, during or after pregnancy. This is the team that worked on this. And it's the FECO nutrition checklist.

And I've asked Lisa to share the link with you, if you would like. Again, this is free for download. What is it? The checklist? Well, there's four areas that we review special diets, food intake, micronutrients and weight.

And then the woman, it's designed that if she says no to any question, well, then she is at risk of nutritional deficiency. And then she received a tailored advice back, depending on her answers. So she goes on to the FECO nutrition checklist web page, enters her age, country and whether she's pregnant or not, answers the questions.

And then this is the sort of feedback that she will get. And that's the link there. So be delighted if you would go in and access some of the advice for yourselves or share it with your patients.

So the patient will enter the data and then she will get individualized advice back. And what's useful with this is then the patient can then say to the health care professional, I've done this checklist. These are the areas.

And in fact, the information is available to the health care professional on how to support the woman. So the health care professional doesn't have to go off and read up on what foods do I need to tell her to increase her vitamin D or her iron. The information is given there.

And what we found with the checklist is that if the output is supported by health care provider, she's much more likely to engage with us. So what evidence do we have on the FECO nutrition checklist? Ronald Ma in Hong Kong validated it against a food frequency questionnaire and found that it correlated very well. And these are the countries across the world.

And you can see there's a nice cluster there in Europe where the FECO nutrition checklist is used. And these are the publications from various groups that have used the FECO nutrition checklist and they've used it in pregnancy and before pregnancy. So if you're interested, it's very simple.

It takes a couple of minutes. At the present time, it's available in English, French and Spanish. We've just translated it now into 10 languages.

So hopefully your language would be available soon. And of course, you can adapt this checklist to your own dietary guidelines and typical diets as has been done in India. So in conclusion, managing obesity and pregnancy, addressing nutrition and weight are really the cornerstones of this management.

And we need to focus on women of reproductive age so that global health outcomes can be improved and the burden on health care systems reduced. We need to, outside of weight management, women with obesity require specific considerations for medical, surgical or other care planning. The specific recommendations will vary depending on the resource settings.

FECO nutrition checklist is a useful tool for pregnancy care providers and the holistic app is also a useful tool for women in pregnancy. This is some of my research team and I'd be delighted to answer any of your questions. Thank you very much.

Thank you very much for that really amazing talk. And thank you for taking us through all the clinical trials and the evidence and informing us a little bit more in this area. But clearly, the message is quite clear when it comes to sort of the managing weight, I guess, which I think can be so challenging.

But thank you. And I think there are lots of questions. In the chat.

So let me just try and pull back the chat, which seems to have disappeared. OK. And I think what we'll try and do.

I'm trying to pull that we go. We probably go back to the hundreds of questions. But if we go back to the beginning.

So I think the first question is for Amelia. And the first question was like, there's lots of interest about GLP1. So can you comment on whether they will be useful for women of normal weight with PCOS? And also, if you can comment on whether GLP1, the effectiveness of GLP1 across different maternal ages, you know, so are they less or more effective as women get older? Yeah, yeah.

Very good question. Well, I think that we, well, considering where the weight or the BMI, of course, there's the guideline and the indication that we should use it for people with BMI 30 or over or 27 and a comorbidity. And personally, I think the PCOS is a comorbidity that has very strong implications on the woman's health.

So I have been using it with women with a BMI of 27 and over. I don't have any experience on lower BMIs. Probably future we will have studies.

So we don't have now. It's all done in obesity, but I've had amazing results. BMI 27.5, start GLP1 and one month she had regular periods and she was like, she never had regular periods.

And that just started then. And so then about the age, the maternal age, I think typically young women are more flexible. They have metabolic flexibility, so they probably might respond better, but it's always based on whether you find the right switch or right key to the metabolic clock, whatever you are trying to open.

So at least I can show you for sure that it seems that when picking an anti-obesity medication, if there's any history of PCOS, GDM, family history of diabetes, any suspicion of insulin resistance in the background, then GLP1s do seem to work better. But for the age, I don't have any for sure secure data. Thank you.

I guess in terms of the age, the GLP1 will work probably as effectively across the ages, but that doesn't translate into fertility because age, obviously. Yeah, I'm not aware of an age difference in terms of weight loss, but that doesn't necessarily translate to fertility. Great.

So there's a question that says, what do you think, and this could be either of you, but what do you think about obesity in early childhood or adolescence and its effect on reproduction? There's a notion that adolescent PCOS is a post-pubertal central obesity syndrome. Either of you would like to comment on that? Well, I can say shortly that I think that yes, it is a continuum for sure from the pregnancy conditions to childhood obesity to probably early puberty PCOS. So very difficult to disentangle all the different effects, but on the continuum would be my answer.

I don't know. What do you think, Fionnuala? Yeah, no, I think absolutely. And of course, there's the intergenerational effect is there as well.

So if you look at children that are born at the higher end, higher rates of childhood obesity, and so there's the genetic component as well. So yeah, I think there's multiple etiologies for sure. Yeah.

Great. So I think this is a question for Fionnuala and from Sandy Evans. What weight gain advice is provided suggested during pregnancy of overweight and patients living with obesity? I think you've given us a bit of a taste, but do you have any more advice that can help us in our consultations? So I think if the BMI is over 30, five kilograms would be the maximum weight gain.

But in fact, she doesn't need any weight gain at all, but no more than five kilograms. If her BMI is between 25 and 30, well, then up to eight kilograms. But I suppose when you look at pregnancy weight gain, so the baby, the placenta, amniotic fluid and the uterus and the breasts and all of the baby part of it is probably about five kilograms.

And so the and the other weight then that happens in pregnancy is getting the mother's body ready for breastfeeding. So increased breast size and laying down of adipose tissue. So really, she doesn't need the anything more than five kilograms that covers the pregnancy piece, the extra bit laying down adiposity to cover breastfeeding.

She doesn't need that because she has that already. So a lot of people now are looking at if BMI is over 30, no weight gain, just keep it steady. Or there's some tantalizing studies recently on weight reduction, which all of us are concerned.

Will she get ketotic? What will be the harm? But some data coming out now that we could even consider weight reduction. But I would often say to women, and we have to be realistic, no more than five kilograms. I do find women are very receptive if I say at the beginning of the pregnancy, here's the number you are now at the end of the pregnancy.

Let's see if we can not go beyond this other number. That's helpful rather than at the end of the pregnancy, tell her, oh, you've put on 20 kilograms and that's too much. That doesn't tend to be helpful.

But I find the women are motivated and they do like the idea of a target. So five kilograms maximum, I would have thought. That's really helpful.

And of course, sometimes we get ladies who've had bariatric surgery and they get pregnant maybe in the first six to 12 months as they're losing weight when they shouldn't be doing that. And then it's always tricky, isn't it? Yeah. What do you do there? So, but yeah.

Okay. Yeah, I might just pull out the bariatric surgery piece because I see that's one of the questions. Often after bariatric surgery, fertility returns fairly quickly.

And of course, we all know that the woman is fertile once before her period. So there are concerns about getting pregnant within sort of six, nine months of bariatric surgery because she's in metabolic freefall. Her metabolic state is very unstable.

She's in severe micronutrient deficiency, folate, vitamin D, iron. And we are concerned about people getting pregnant. Ideally, she'd wait 12 months so that her weight is stabilized, but certainly wait six, nine months.

There's evidence that the chance of congenital anomalies are higher if she conceives very soon after bariatric surgery. So if we can, so I think with bariatric surgery, she needs to be given effective contraception before the surgery and that covers her for the six, nine months. And then she stops it to try and avoid a complicated pregnancies from unplanned, sooner conception.

No, absolutely. Completely agree. Yeah.

Sometimes they don't quite listen. That's one of the challenges, but yes, we actually normally say 18 months to two years, but it's good to hear that you're happy with, you know, even a shorter timeframe after bariatric surgery. So, you know, sort of nine months, nine to 12 months, I guess.

Very good. And, and there's a question saying when developing the figure guidelines, did you find any recommendations in the national guidelines you reviewed on preconception or pregnancy care for women who have had bariatric surgery? And I think we've sort of discussed that a little bit. Yes.

I think the key here is the micronutrient status. So she needs to be on folate five. She needs to be on vitamin D iron.

So I would check all of those before she embarks on pregnancy. Okay, fantastic. So we talked about that and then there's a really interesting presentation.

You touched on the potential impact of culture on weight, weight loss. And I'm wondering if the guidelines consider other wider determinants of health, people experiencing food insecurity may not have the means to eat as advised by the healthcare provider or in line with recommendations. This may also play a role in decision to breastfeed if they're worried about the impact of their own poor diet on their baby.

Well, I think in, in many countries, it's much safer to breastfeed than infant formula because there isn't access to, to clean water, et cetera. So that's always promoted. I mean, we need a very good reason not to breastfeed would be my view.

And I've already shown you data of that particular woman having a benefit over and above the usual benefits for her and her baby of type two diabetes prevention and cardiovascular disease prevention. But it is a challenge doing guidelines, global guidelines. And when you look at the guidelines, we have best practice advice, and then we have pragmatic advice.

And I think that's important for some countries. They just won't have the resources. But I think, look, we have to advise people as best we can.

Inevitably, if there are vitamins and minerals available, that might replace a poor supplement, a poor diet. So I think a lot of countries go down that route where they, instead of providing healthy food, it's cheaper to provide a multivitamin. So, you know, we need to consider the role of multivitamins if in countries where there is food insecurity, for sure.

Fantastic. And I think we're pretty close to 1230. I wonder if a final words from both of you to take a message for us.

Emilia first, and then Canula. Okay, great. Well, I think that it's been very lovely discussions.

And I do hope and it's it was very lovely also from Fionnuala to see that we would see this treatment of obesity as a life course perspective, helping as early as we can help those women, the more we can help fertility and pregnancy and then the future generations. So I definitely hope that anyone who meets women in their early years, I think that us gynecologists, we do have a big role when we give contraceptives. Help these women with obesity as early as possible.

Fantastic. And Fionnuala? Yes, well, I just finish with weight and nutrition first at every consultation for all of us to address women to improve women's health across the life course. So every time we see a woman, we need to talk nutrition and weight.

Thank you. Fantastic. Well, thank you both very much for giving up your time today.

And thank you to the audience for the really interesting questions. And with that, I'd like to like I said, thank everybody. Wish everybody a great day.

And yeah, hopefully we'll see you soon. Okay. Thanks very much, everyone.