Cases infer transcript — SMP305 lecture transcript

I. I. I. I. Nice. I was wet. It. He still ill. I see. I But. yeah I So then he's not. So it's just like one name and like 50 responses. that I it's not. I get. too. I was so I was like. It. I. Right. Yeah. Yeah Yeah, I'm somehow the most graffiti. It might be OK Yeah. Attitu who actually took the thing. Right, good morning. Hi. I'm, I'm Jonathan Scott, I'm one of the consultants here in reproductive medicine. And uh I'm gonna talk to you about infertility. What I'm gonna cover is how common the problem is, the causes of it, and how we go about investigating it and give you an overview of treatments. I'm also gonna direct you to some of the nice guidance and talk a little bit about NHS funding cos it's uh interesting although not on your curriculum. So fertility problems are quite common if we define. Infertility, according to the WHO criteria, which is failure to conceive after a year of trying, it affects about 15% of all couples. A lot of people try and conceive more than once in their life, though, so actually about a quarter of all couples experience some conception delay. It doesn't mean a quarter are infertile and don't get pregnant at all, but they experience some conception delay. There's some evidence that fertility problems might be increasing, and there's various reasons for that. It could be environmental factors, and as a species, we are less fertile for all sorts of reasons. There's also the effect of the women leaving it longer before they have children, which we will talk about in a minute. So there's certainly some evidence that we are becoming less fertile and more people are seeking help. Possibly because we've got more options as well, we've got more treatments, more investigations, and there's a greater awareness of fertility problems and a bit less stigma than there used to be, but certainly, you know, we're seeing more and more patients and it causes a lot of distress. But remember, of course, about getting pregnant naturally, not everyone gets pregnant straight away, there's a cumulative conception curve. So this is why the WHO define infertility as or subfertility as a year because most of your pregnancies occur in the 1st 6 months, but there's still a. Reasonable pregnancy rate up to a year after that point, it slackens off a bit, although given another year, another 10% of those patients would conceive, so after 2 years of trying, if there's nothing wrong with you, about 95% of the patients will get pregnant, so. What about the causes? Now, just to, just to mention before we go too much further is obviously this talk is aimed at a heterosexual couple presenting with fertility problems. Of course in the fertility clinic we do see a wider variety of patients. We see single women, same-sex couples, both male and female, transgender patients, all those sorts of things, but that's not the. The main aspect of this talk is really about fertility problems, so it's about heterosexual couples trying to conceive, but the principles apply to those other groups as well. So if you've got a couple having trouble getting pregnant, about 25% of them are due to an ovulatory problem, about 20% are a tubal problem, and about 10% a uterine problems, so. That's anatomical, so about 30% are anatomical and about 30% are male. So you know, because you need tubes, you need eggs, and you need sperm to get pregnant, so anything can go wrong with those three things. But there's a piece of pie missing there, and that's the unexplained group. So about 25% of our couples have all the tests are normal and they unexplained infertility. Now those of you that have done a bit of quick maths will realise that's not 100%, right, it's more than 100%, and that's because about 40% of our patients actually have multiple problems, they combined male female factors or an ovulatory and a tubal problem, so it's not uncommon for. Couples to have more than one fertility factor, and it might be that there's a mild male factor, a mild ovulatory problem, but cumulatively that has more effect. One on its own with a more fertile partner may have less effect. And there's very few things that are an absolute cause where you don't get pregnant at all unless you've got no tubes or no sperm. Now, the other thing to bear in mind when you're always considering a fertility patient or a couple is age and fertility. So that unfortunately is a graph that shows how fertility declines with age and there's nothing you can do about it because you're born with a. number of eggs, they gradually decline throughout your life and by the age of the menopause, you've got none left. You'll also note that that decline in fertility happens more rapidly from 35 onwards. So this is all related to the number of eggs that decline and the quality of eggs that decline. That also leads to higher rates of miscarriage, so miscarriage rates increase dramatically as you get older, and most of those are due to chromosome abnormalities. Some chromosome abnormalities of course result in Down syndrome, Edwards syndrome, things like that. You don't need to remember those figures, it's just purely to demonstrate that quite a significant increase from mid-thirties onwards.

The other. Influence of age is not about just getting pregnant and holding on to that pregnancy, it's the fact that pregnancy itself carries more risks as well. So you've got every pregnancy complication that can occur occurs more frequently if you're older, particularly hypertension, diabetes, growth restriction, you're more likely to end up with an operative delivery, thromboembolism, blood clots more common, and. Unfortunately, maternal death also increases, so the maternal death rate over the age of 40 is 5 times that of under 40. Fortunately, the number under 40 is a very small number, so 5 times a very small number is still a small number, but it is still 5 times the risk. Why is this important? Well, it's because of huge population changes that have occurred over the last, you know, 2030 years, well, possibly a bit longer. What you see on that graph there, this is data from the ONS that shows how the age, average age of having a baby has increased. So, particularly in the over thirty-fives, and 2015 was important because that's the age where more babies are born. To women over 35 than under 25, and that's not because we could become more fertile, that's socioeconomic changes that have led to that. Biology hasn't changed, and, and the average age of first birth now is actually more than 28.5, I think it's up to about 30 now. Interestingly, when I was a medical student at your age. Go along to the antenatal clinic and if somebody was having their first baby at 28, the midwives used to write on elderly prima gravida on the notes and that would pretty much applies to everybody now. I hope you haven't seen that written anymore. We don't tend to, and if it was over if you're over 35, they would write geriatric mother. They don't do that now either, but it did recognise the risks. So when we've got a couple, as I say, we're concentrating mainly on a on a heterosexual couple here that are presenting with conception delay, it is important that we see them as a couple and see them together, and they should be seen in a dedicated clinic. Unfortunately, that doesn't always happen in particularly in district general hospitals that don't have specialised services. It might be just a woman. He's booked into a general gyne clinic. The man's sort of forgotten about. He may or may not have an appointment. He may not be encouraged to attend, but it is, that's, that's not ideal at all. It should be seen as a couple because this could, this does affect both of them, and we have to accept, you know, you have to understand that because of the stress and, and, you know, uh, anxiety and everything else that. Associated with fertility problems, this can often cause a lot of distress to those couples, can cause relationship relationship difficulties. That in itself can lead to more fertility problems because if you've got stressed, it's quite difficult to have intercourse on a regular basis, but it is really important that patients are seen in a specialist clinic, and that's been in the nice guidance for years and years and it still isn't happening.

So, often the first thing though is if you maybe you're a GP and you're presented with a, a, a woman, it tends to be the woman who goes to a GP first and I'm having difficulty getting pregnant, she may or may not take her partner at that point because the partner might be registered with another GP. But the first thing we're gonna do is give them some initial advice and see whether there is a problem. Referring, so sometimes it's just a little bit of reassurance that they might just need a little bit more time. You know, a lot of patients will turn up to the GP after maybe only 3 or 4 months of trying and saying I'm not getting pregnant, what do I do? Obviously take a quick history, establish whether there's likely to be any underlying problem, but if everything seems all right, you can reassure them that they just need to try keep trying a bit longer, you don't. Generally recommend investigations until they've been trying for a year, but take into account age and also every time you see a patient, it's a good opportunity to give preconceptual advice, make sure that they're doing everything possible to improve their chance of pregnancy, but also improve pregnancy outcome, and I'll come on to what we tell them in a bit. And as I said, after a year, refer, but if you suspect there's a problem. And she's older or or she's older, you might want to think about referring early and the current NICE guidance actually says that anyone over 35 should just be referred if they think they've got a problem. But if they're not having, um, so yeah, basically, early referral uh criteria are over 35, not having periods, obvious menstrual disorder, she's probably not ovulating. She gives a history of.

Pelvic surgery, PID, sexually transmitted infections, that's more likely to lead to problems. Again, a reason to refer. And on the male side, this is at least an indication to get an early semen analysis. If he has a history of testicular torsion, maldescent, some sort of testicular problem, at least it's a reason to get a semen analysis. If it's abnormal, then you prefer. If it's normal, perhaps reassure. So as I said, preconceptual advice is really important, and this isn't just when they're first starting to get pregnant, we try and reiterate this every time we see them because sometimes situations change. Obviously give advice over intercourse. The current advice is because sperm lives for quite a while, it's not necessary to time intercourse absolutely with ovulation, we just suggest 2 or 3 times a week. Um, and that gives you as good a chance of any, and it gives the sperm a little bit of time to recover. Make sure your patient's on folic acid because that reduces the incidence of spina bifida. You'd be amazed at how many patients start off with good intentions. They're taking their preconceptual vitamins every day, but because they haven't got pregnant, they stop taking them, but obviously that's not ideal. Well, it didn't help me get pregnant, so I've stopped taking it, that's not. The purpose of it, the purpose of it is to reduce the risk of spina bifida. Make sure they're up to date with the smears, not because it'll help them get pregnant, but because we don't want them to have a problem during pregnancy. Ensure they're really immune to rubella, because we don't again want congenital rubella. It is rare, but this is an opportunity to ensure that they are all, um, immune before we start.

And if they're smoking, give advice over smoking because that's obviously not good for pregnancy, and again, give advice over alcohol. And ensure their weight's normal. The other thing is ensure that if they've got any medical problems, that those are optimised for a pregnancy. Both the the condition itself is optimised, but also any medications they're on are safe in pregnancy. And of course one of the other problems we have as women are older before they're getting pregnant, they've had time to develop other medical problems, which might mean that they're on medications that are not actually safe in pregnancy. So again, another, another problem with ageing is that. Now seeing many more complicated patients who have complex medical issues that we never used to see before. The other thing we've seen a lot more of is weight, weight-related issues. You know, we know that obesity is increasing and that causes all sorts of reproductive problems. It exacerbates problems with polycystic ovaries, it increases the risk of miscarriage, decreases your fertility, and lowers success rates. IVF success rates are lower. In patients who are overweight and they're more likely to run into obstetric complications. So again, if they're overweight, gives us an opportunity to manage them.

So yeah, we'll skip that. So when it comes to investigations, we want to look at whether they're producing an egg, whether the sperm's all right, and whether the anatomy is normal. Those are the three things that we're gonna look at. So let's look at ovulation first. Now, I'm not. I'm going to give you a lecture on the physiology of the menstrual cycle. I take it that you've already had that at some point and you should know that and that graph there showing all the hormonal fluctuations should not be new to you. But just to recap, to ovulate, you need an intact hypothalamic pituitary ovarian axis. Everything has to work properly. So at the start of the cycle, pituitary releases some FSH that recruits follicle, continues to release some FSH. Follicle grows, that produces oestrogen, and in the middle of the cycle, you get an LH surge, which causes ovulation. After that, the follicle becomes a corpus luteum that releases progesterone, which changes the endometrium into a secretory phase to allow implantation. So those are all the hormonal fluctuations. So if we want to check ovulation, what can we do? Well, many years ago, and still sometimes, patients would check their temperature. Because progesterone causes a rise in basal body temperature, and in the past we used to get patients to take their temperature with a mercury thermometer every morning and record it on a piece of paper and they'd come in with reams of charts, but it wasn't very reliable, and only about 30% of ovulatory women can detect that basal body temperature rise. It's very difficult to do because it's very subtle. You need quite a sensitive thermometer. You need to take. Temperature before you do anything, so it's really difficult to show. Interestingly, with the advent of more technology, there seems to be a bit more interest in basal body temperatures again because you've got various devices. I think Apple watches even measure your temperature overnight and things like that. There are also other devices that can measure your temperature and record it on an app. So I've now got patients instead of coming in with pieces of paper showing me their phone with their temperature charts and things on, but it's not very reliable. And we just think it causes a lot of stress and anxiety. The technology might be slightly more accurate than a mercury thermometer, but it just generally causes lots of stress. So we, we don't currently think that's particularly reliable, and I wouldn't encourage patients to to do that. The other thing you can do, and you can buy these over the counter is check for your LH surge. You've probably seen in the chemists, there's there's uh shelves and shelves with clear blue urine testing kits. That will pick up that LH surge in the middle of the cycle, so you pee on a stick every day, picks up your LH surge, you know you're ovulating. I, but that surge can go up and down quite quickly, you can miss it. Um, if you've got a very irregular cycle, you don't know when to start taking it, so you might end up using an awful lot of clear blue tests which cost a lot of money. And so it's, it's again whilst it's accurate if it picks up the LH surge. The absence of it isn't particularly helpful. No study has ever shown that that makes more babies, and in fact it's counterproductive because again it causes more stress and anxiety if you're using the LH surge to time intercourse, well, if you miss it, you've missed that opportunity that month completely, and the first ejaculation might have been that, you know, stored up sperm for days and days, it might be quite old, not particularly good sperm, which has less chance of making a pregnancy, so. Oh, timing intercourse around LH surges is not particularly helpful and just causes more stress and anxiety. It's better just to have regular intercourse. Of course in the IVF unit we do scans, we can pick up the follicles, when we want to really time something for an insemination, we, we do ultrasound to monitor it, but that's not practical for routine diagnosis. For routine diagnosis, all we need to do is pick up that progesterone surge that occurs a week after ovulation. So it's often called the day 21 progesterone because most cycles are 28 days, but. It should really just be called midluteal because you have to take into account the length of the menstrual cycle. So if somebody tends to have a longer cycle, you'll need to do that day 21 at a later stage. So if it's a 28 day cycle, we'll do it day 21. If it's a 35 day cycle, you do it day 28, so it's in that mid luteal phase. Now, patients who have got sometimes slightly irregular cycles, maybe they vary between 25 and 35. That's still within the bounds of normal and you might have to do progesterone series on 2 or even 3 occasions during the cycle to make sure you get that peak and we're looking for a level of over 30. If you've got a level of over 30, the chances are she is ovulating and everything's fine. If it's between 16 and 30, it's equivocal, it might just be that you've got the timing not quite right. It's very simple to do and and it just involves, you know, one blood test. So as I said, don't test temperature, don't do urine testing, don't do other hormone testing if it's not, you know, if they're actually ovulating. It's not necessary. The other thing we do as part of the workup though is we think about ovarian reserve testing and that's particularly important because of that decline in fertility with age. Working out ovarian reserve can be useful. Measuring it, we do measure FSH on day two, because that goes up as you approach the menopause. It's, it's very useful for determining causes of an ovulation, but actually in terms of. Predicting pregnancy, predicting outcome is not particularly useful, but we do ask the GPs to do this before referral. Um, an actual follicle count done on a scan again is useful in the context of of uh of assisted conception because it will tell us how many follicles are there and give us a guide to ovarian reserve, but there can be intracycle variability um and. Operator variability as well, it's quite difficult to do accurately on a scan, you can miss follicles, so it's not as reliable as AMH so anti-Mullerian hormone is a hormone produced by the growing follicles in the ovaries, and the more follicles you've got, the higher your AMH level will be. The AMH is actually a better guide to ovarian reserve testing, however, it does not predict pregnant. See, it does not predict when you're going to go through menopause, it's only useful in the context of predicting response. So it's, it's useful for us in the fertility clinic because if we've got a patient with a lower ovarian reserve, we know we're going to give a higher dose of drug to stimulate them for IVF. Also, we might not want to waste too much time because if their ovarian reserve's going to drop, then that's going to affect their IVF success, so. For us to know that, however, in routine workup in general practise or initial appointments in fertility clinic, knowing AMH is not that helpful, and one thing I would enco discourage you from doing is going around and checking your AMH. Now you can buy tests now. You can send off, you used to be able to just get these, you know, get someone to take your blood and send it off, get it done privately. I think yeah, now you can go into um, last time I was in the chemist, I noticed there's a whole load of home testing kits, so you can get. All sorts of testing now on a little finger prick. You get your thyroid done, you get your vitamin D, all sorts done, it's great, it looks fantastic. Someone's making loads of money out of that. You can also get your AMH done on the finger prick and then you send it off and it'll come back with a report saying your AMH is average, above average, lower than average um for your age. Now that's, that's great because you might think, oh well, you know, my AMH is good. I can uh put off having a baby for a little while. Or my MH is really poor, oh my God, I need to have a baby now, um, and it causes lots of stress, but of course it doesn't predict pregnancy, it doesn't tell you what's gonna happen in the future, and no one's ever shown that actually that's helpful, so. Whilst you can go and spend some money and do these tests, I would discourage you from doing so. On the male side, it's quite easy, you just do a sperm count and we're looking for how many there are, how fast they move and whether. You don't need to remember the figures in an exam, you would always be given the reference ranges. They do change every so often. We're currently on the 2021 methodology, but no doubt in a couple of years' time it'll change again and those figures will change slightly, but the principle is you need lots of them and you need to swim well. They need to also look normal, but not many of them need to look normal, and morphology actually isn't that useful, um. It's only done by assessing um 200 sperm out of all the millions and we only expect 8 of them to look normal, so you know you can see that you know sometimes you've got 6 of them look normal, so you've got 3% morphology and the patients get really anxious about that and you say well actually it doesn't really matter, it doesn't predict pregnancy, it's the number and how fast they move that's most important and. Generally we only do one semen analysis, if it's normal, that's fine, but if it is abnormal, we repeat it because the spermatogenesis cycle takes 3 months and you could have something that knocked off your sperm count temporarily, if you had a flu-like illness, raised temperature, maybe a stag weekend or something like that, that's gonna knock your sperm count off for a bit and so. We repeat it 3 months later if it's abnormal. So we have a pathway agreed with our ICB and for referrals to the fertility clinic, and this doesn't apply to all areas, but it encompasses all those initial investigations. So we agree that patients should be referred after a year. Sooner if they think there's a problem, and we ask the GP to do those initial tests, so when we see a patient in a fertility clinic, we know whether they're ovulating, we know the sperm count's all right, we know that they've all their preconceptual stuff's been done, they're immune to rubella, smears are up to date, etc. So they come to the clinic and then we've got some basic information and we can direct their further tests accordingly and we have an electronic referral system and it works reasonably well.

But when we first see them when we've seen the patient in the clinic, we might think, well, we need to check their tubes. We don't do it on everybody because if there's an obvious sperm problem, we might not need to know the tubes are open because we might be thinking about treatment that bypasses the tubes anyway, might be referring to IVF. We don't need to know about tubes for IVF, but in the. Patient where all the tests are normal, we want to know is there a tubal factor now that's stopping you from getting pregnant. If there's no risk factors for tubal problems, not had surgery, not had infections, we do a hysterosal bingogram in most cases. Some units use HOSI, which is a an ultrasound based test, so HSGs, X-rays, Hyosis is an ultrasound based. So there's pros and cons to each, and both are probably just as good. It just depends on, uh, the hospital's individual setup. Most places use IOsy though uh uh HSG because it's a bit easy. It's a bit more reproducible. It's easier to arrange with imaging. But if you think that a patient's likely to have tubal problems, we would want to do a laparoscopy because it gives you more information and HSG. Or Iosi might miss subtle things. A laparoscopy will pick up, it's the gold standard. It'll pick up everything and also gives you the opportunity to treat any problems that you find. But of course it's an operation, it carries some surgical risk, it's more expensive, so you don't do it for

everybody. And we also do some swabs before we instrument the uterus because we don't want to spread chlamydia around. So on the left there is a an HSG that shows that the right tube is blocked but the left tube is open. So that's the sort of image you get back on an HSG. So you can see there, the left tube filling and spitting quite nicely, the triangular thing in the middle is the uterine cavity, but on the right side, the dye has gone into that tube, but it's blocked at the end, so it's a distal block, it's not going anywhere, so that suggests there's a problem. We also tend to do ultrasound because we want to know the uterus is normal, we want to know the. Yeah, ovaries are normal. An ultrasound may also pick up a hydrosaline as in that case, but it doesn't always pick them up, so HSG is better. But we would do an ultrasound scan for everybody. Oh, yeah. It's also the scan allows us to look for uterine abnormalities. So we might see the polyps, we might see poor endometrial development, which might suggest adhesions. We might see fibroids or a congenital abnormality of the uterus like a septate utes. So knowing that the uterus is normal is really important, even if we're not testing the tubes. Now, sometimes the association between the abnormality you see and fertility is difficult to be, you know, difficult to be absolutely sure. There is some doubt as to whether polyps really cause infertility or not, but they probably do. And again, fibroids, it depends on where they are, which we'll come on to. So this is a polyp that you see on scan. Scan will pick up most polyps and you confirm it. By hysteroscopy and that gives us the opportunity to remove it. There's no randomised trials to show that removing a polyp improves results because it's actually very difficult to do a randomised trial in that context. There was an attempt a few years ago to do that, but once patients knew that they've got a polyp and they knew removing it was very easy, no, no one would be randomised to the groups which would leave it alone, so you know, it, it makes sense that if you see a polyp, remove it because it could act as a foreign body and prevent implant. Plantation. If you've got fibroids, now, here's a picture here of a patient here with massive fibroids, but they're mostly pedunculated fibroids that are on the outside of the uterus, they're not actually enlarging the uterine uterus itself, and that makes it a little bit unclear as to whether those will affect fertility. And the actual effect of the fibroid depends more on where it is than on the size of it. So a small fibroid within the cavity of the uterus, a submucous. Fibroid's going to distort the uterine cavity, reduce places for a pregnancy to implant, and probably have more effect than a fibroid on the outside. However, if a fibroid gets to around about 5 or 6 centimetres, it starts to divert blood supply and things and may have more effect. But there are plenty of women with fibroids that do get pregnant naturally. So before we go around surgically treating fibroids, we want to be sure that that's actually going to benefit them and not cause more harm, because removing fibroids is not, not easy.

When you look at, again, it's impossible to randomised trial in this situation, but when you look at IVF results on patients with fibroids, if they have a submucous fibroid, you have much lower pregnancy rates. If you have an intramural fibroid above 5 or 6 centimetres, again, about halves your pregnancy. So it probably is worth removing large fibroids or anything that distorts the cavity. But my and myomectomy has been shown in retrospective studies to improve results, but again, no RCTs and myomectomy is quite an invasive operation. It carries some risk. You have a separate talk on fibroids, so I'm not going to go into that. Occasionally we might find a patient who's got adhesions within the uterus and again that's going to reduce the number of places a pregnancy can implant. It's not common, but it can occur if you've had over vigorous curettage. Usually then it's associated with not having regular periods. We can treat it hysteroscopically by little scissors to just divide the adhesions and try and restore anatomy, but it's very difficult to completely remove every single adhesion, and it's, you might restore menstrual cycles, but fertility is still compromised in lots of these patients and ongoing pregnancies are still complicated by growth restriction, preterm delivery because it just doesn't implant so well, so those are high risk pregnancies if you've had hysteroscopic. Sometimes we find congenital abnormalities. Again, I haven't got time to go into all the different congenital abnormalities. You can have a double uterus, uterus didelphus in various different forms. You can have a unicornate uterus where only one half is formed, but the thing we sometimes see in the fertility clinic is a woman with a septate uterus, so that's that, that middle one there on the left, and that's what it looks like a hysteroscopy. So you've got a septum coming down into the uterine cavity, and you can see that that's going to again. Impair implantation if the pregnancy wants to implant on that septum, it's not gonna get such good blood supply, it's not going to do so well and we, we know that these patients have higher rates of recurrent pregnancy loss and miscarriage and whether it affects fertility or not is difficult to to know, um, but it certainly is associated with recurrent recurrent miscarriage, so if we find a septum in a patient with a fertility problem, we will often offer resection of that septum. Because they might have another fertility problem that we're offering them IVF for, so it's a couple coming for male factory fertility. That's the reason why they're not getting pregnant, but you correct that with IVF and then you turn them into a recurrent miscarriage patients. So we would often suggest resecting that septum, and it can be done hysteroscopically. We use a little diathermy like that, or we can use a little scissors to try and restore the uterine anatomy, but again, we've weigh up the pros and cons. No randomised controlled trials because it would be very difficult to do. Occasionally we'll see a patient with a unicorn uterus, so this is only one half of the uterus is formed, it's not, not that uncommon. She will have both ovaries, but she'll only have one tube. The uterus itself actually will support a pregnancy satisfactorily, slightly higher rates of miscarriage and premature delivery, but not, not too bad, slightly higher rates of abnormal presentation like a breach because it's not got room to move around, but other than that, they do quite well. But we would regard that as a sort of unilateral tubal disease because she's only got one tube, so half the time she's going to ovulate on the left side, not the right, and and there's no tube on the left, so she's gonna have difficulty conceiving, but if she ovulates on the right side, she's got just as good a chance as anybody. So it's associated with fertility problems just for that reason, although it may not actually be an absolute cause.

So that's how we investigate patients. We're looking at the tubes, we're looking at anatomy, we're looking at ovulation and male factor. When it comes to treatment, it depends on the cause, and that's why it's really important to establish a cause, uh, before, so that we do the most appropriate treatment. So I'll go through all the different types of treatments that we do for different causes and then give you an overview of IVF. When it comes to a male factor, again, we have to interpret that semen analysis in the light of his history. Is there some. that he might have a low sperm count and might it be temporary? So again repeat it if we need to. If he's got a very low sperm count, we do want to examine him to look for secondary sexual characteristics and testicular size. Testicular size is a good indicator for fertility. Small testes would suggest that they're not working so well. And, and then we might do some further tests. If the count's less than 5 million, we'd want to look for. Hormonal problems, they're quite rare, and you can get some men with delayed puberty which who have hypogonadotrophic hypogonadism, they have low FSH levels, low LH levels, low testosterone, they usually have delayed puberty. It's very unusual for us to pick them up in the fertility clinic because they've usually presented to endocrinology first, you know, they've noticed that things aren't changing when all their peers are changing and they will go to endocrinology and be diagnosed as a problem. So we tend to see patients who've already had that diagnosis. They may have been on testosterone, um, to induce, you know, secondary sexual characteristics, but when they want to get pregnant, their testes will work. They just need gonadotropin stimulation and the endocrinologists do that. We'll check the carrierty because there's an association between carrier type abnormalities and male factor infertility. One that's most common is something like. Klinefelter's, but there are other chromosome abnormalities as well, and we'll do a cystic fibrosis screen because there's an association between being a carrier for cystic fibrosis and congenital absence of the vas deferens, which is an obstructive azo spermia. Um, I need to add one thing onto that which I haven't yet because it's only recently been added on. We also do Y chromosome deletion testing now as well. So for a man who's asospermic, we will do a testicular biopsy to see if his testes are making sperm. So if you're aospermic, it's either because there's a blockage, so it's obstructive, or a sperm production problem, non-obstructive. But if it's obstructive, we can find sperm directly from the testicle, so if you've got an absent vas, we can find sperm within the testicle or the epididymis to use for treatment. If you've got a non-obstructive. There still might be some spermatogenesis in the testes, it's not enough to ejaculate any sperm, and so we can retrieve sperm from the testes in about 40% of cases there to use in treatment. But of course in that situation, we want to be able to freeze any sperm we get so we don't have to repeat this testicular biopsy too often because surprisingly, men don't like needles put in their testicles willy-nilly. I don't know why, I mean, you know. You know, it is done under some anaesthetic, but only a local. and very occasionally we might want to do some imaging for patients. Occasionally we might ask a urologist to see patients. There's always been a bit of doubt as to whether things like varicoceles affect male fertility. That sort of comes and goes depending on the evidence. The current evidence is that actually a varicocele that causes symptoms and is clinically apparent may cause the lower sperm count, and so those patients might benefit from seeing a urologist or. Having that embolized um but again you have to take into account other things like women's age. You, if a woman's older, you might just get on with treatment anyway.

So I said, in terms of treatments, well if your sperm count's only marginally low, you might think, well, can I, uh, concentrate on that, do intrauterine insemination, and then still, still get pregnant sort of fairly naturally, but that's very debatable. There's really a lack of evidence to suggest. That that helps in mild male factor for moderate or beyond, you need IVF. Alright, for severe problems you might need ICSI where we inject the sperm into the egg, and as I said for azospermia we might offer surgical sperm recovery, and if we can find sperm, use that for IVF. If we can't find sperm, offer donor sperm treatment. And I said, very occasionally we might offer surgery and the varicocele is a little bit there, you know, um. Debatable, um, but the current nice guidance that came out this year suggests benefit for patients who were symptomatic, but no benefit if it's asymptomatic. In cases of hormonal problems, these very rare cases of hypogonadotrophic hypogonadism, we might offer gonadotrophics. Now there is one other group that we sometimes see men who've got low FSH and LH levels, but high testosterone levels, which of course doesn't happen with high. Gonadotrophic hypogonadism that happens with steroid abuse, and we're seeing more and more men who are taking steroids. It seems to be a common problem and it causes profound testicular suppression. It does wear off, but it takes a while to wear off. We don't give hormones to induce spermatogenesis. We just let it wear off and you have to stop the steroids, but we are seeing more and more of that. It seems to be an increasing problem.

So I say other things we're going to always look at environmental factors as well. Is there anything that a man can do to improve his sperm count? If he's overheating his testicles, that can affect sperm, so sedentary occupations where you sit down a lot. If you sit for more than 2 hours, testicular temperature, scrotal temperature increases enough. Of effects of hematogenesis and so long-distance lorry drivers, taxi drivers who just sit around all the time do overheat their testicles, so it's important to cool them off. There's some evidence that men who wear boxers and loose-fitting underwear have have slightly higher fertility than those who wear tight underwear, but There's no randomised controlled trials that show that changing your underwear habits improve your sperm count, um, but again, all linked to overheating, smoking obviously not good, alcohol excessive alcohol, not good, but drinking within the sort of government safety limits of 14 units a week is fine. Some men are exposed to chemicals in their occupation. It's quite rare nowadays, but occasionally you'll get somebody that is exposed to hydrocarbon solvents in the course of their occupation, and reducing that exposure may help, but it is quite uncommon. I had one man that he sat on the machine that lays tarmac, you know. Just breathing in bitumen fumes all day. He had a very low sperm count and it suggests that maybe he had a chat with his boss and do a slightly different job, and his sperm count did improve once he was no longer sitting on top of molten bitumen. So, uh, again, difficult to study, but, um, but you know, it's a good idea to take it, take him to a. Account somebody's environment supplements, improving diet may help. The evidence is contradictory and it's very difficult to do a study to show that a supplement improves sperm counts. If you look on the internet or TikTok or whatever, there's no doubt somebody is trying to sell you some supplement that's going to improve your fertility. But the evidence that it does so is lacking. Uh, we did a study recently where we were looking at lycopene supplements to see if that improves sperm counts. Um, spoiler alert, it didn't. But interestingly, part of that study, we were looking at men's dietary habits to see whether it changed at all during the course of the study, so we were taking a detailed dietary history of them. And it was surprising how appalling some people's diet is. We had men that were having half to 1 portion of vegetable a day, you know, and it's terrible. Not surprising they had sperm problems, but, you know, healthy diet, healthy lifestyle is important, and if they're overweight, losing weight may also improve their sperm count.

So we'll quickly deal with an ovulation, so we're done, we're done then, but I say about a third of our women have ovulatory. Problems and that can be split into three sort of areas where things can go wrong. You can go wrong with the hypothalamus or the pituitary or the ovary. So the WHO split that into 3 groups which would make it helpful, and I always start from the top down. So we, we think of WHO group 1, hypo hypothalamus and pituitary's got to work, so the WHO call that group 1, those patients are gonna have. Low FSH, low LH, low estradiol, they're gonna have absent periods. Causes that might be stress or excessive exercise, so professional athletes sometimes find that their periods stop because they're overexercising and they're underweight. You have to be doing an awful lot of exercise though to suppress your periods, but obviously that's not good. The treatment for that would be correcting that and patients who are anorexic, eating disorders. Because again, that will stop your periods and obviously you know we don't try and correct the hormonal problem, you correct the underlying problem and there are conditions like Calman's syndrome where you don't have the the gonadotropes that make the hormones, but that's quite rare. So WHO group one accounts for a few percent of our patients, but it's not, so it's not common. Um, treatment if you've normalised their weight and everything they're still not ovulating would be FSH and LH injections. Um, you cannot use the GNRH pump, but it's quite complicated to use. Things that can also go wrong with the pituitary. The most common thing that goes wrong with the pituitary is a pituitary adenoma that releases excessive pro pro prolactin. Treatment for that would be bromacriptine or cabergolin to lower prolactin levels, and it's very effective. It's not particularly common, uh, and if we diagnose the problem, we tend to send them to an endocrinologist to treat the underlying problem, but usually it restores. Ovulation in the majority of patients, but it's not a common problem. And there's also a condition called Sheehan's syndrome, which is where you necrose your pituitary. If you are pregnant and you have a massive postpartum haemorrhage, because the pituitary is grown in pregnancy and it's got a poor blood supply, it's very sensitive to drops in blood pressure, and you can actually necros your pituitary. After that, it is uncommon. I've only seen it once in my career and I was very excited when I saw it because I'd only seen it once and I haven't seen it again, um, because most women don't have such a massive postpartum haemorrhage that necrosis of the pituitary or you deal with it, but you know it is something that's reported. The next thing is we come down to the ovaries, so we dealt with the pituitary and hypothalamus. Next thing we come down to the ovary. Now, so WHO group 2 is polycystic ovarian syndrome. Those patients are gonna have normal FSH. They're gonna have an ultrasound scan that suggested they may have raised androgens, and it accounts for about 85% of the causes. Treatment for that would be ovulation induction. They've got eggs, just need to make them release them. We'll come on to PCOS in a minute. The other group is WHO group 3, where you've got no eggs at all, and that might be, that's the menopause, it might be physiological or it might be a premature menopause. Because there's no eggs, your pituitary drives hard and you get high FSH levels. Unfortunately, you can't make new eggs, the only treatment is donor eggs. Then other endocrine disorders can also affect ovulation, so in particular, thyroid or adrenal causes. Now, polycystic ovarian syndrome is the most common condition. Now you may be aware, I haven't changed this slide yet because there's been a recent name change. It's now called PMOS Polyendocrine metabolic Ovarian syndrome. The two things are interchangeable. We're only just getting to grips with the new name change, and the name was changed because polycystic, Ovaries sort of implies that the problem is just with the ovaries, and it's not. It's a metabolic problem. It's a polyendocrine problem. It affects all sorts of things glucose metabolism, all sorts of things, so it's a much wider syndrome than just the ovaries. So the new name change is welcome, but I'm not quite sure how it's going to affect your exams, but I'm sure we'll accept both answers at the moment. The criteria for diagnosis though hasn't changed even though the name has changed. You have to have two of the three criteria, which is an ovulation or irregular periods, polycystic looking ovaries on scan, and raised androgens. You do only need the two of those, so you can have polycystic ovarian syndrome and not polycystic ovaries on scan, because you could have irregular periods and raised androgens as long as it's not an adrenal cord, and that's why PMOS is better because. It doesn't require the ovarian um aspects of it. Treatment is now a lot of these patients because of that underlying glucose metabolism, insulin resistance, do have a habit to put on weight, although you can still be a slim PCOS, but a lot of these patients will struggle maybe with weight loss and be overweight. If their BMI is over 30, often just losing weight will normalise ovulation, um, and generally we would not induce. Population until their BMI is normalised because it's less likely to work and initial treatment, the licenced treatment is clomiphine, although nowadays we tend to use letrozole, it's unlicensed but it works in the same way. It's possibly a bit more effective and has lower risk of multiple pregnancies, so that's why we tend to use that now and we use it to do it for up to 6 cycles and then you monitor ovulation with day 21 progesterone levels and ultrasound scan. One study. showed that if you took Klonopin for more than 12 months, it slightly increased your risk of ovarian cancer. That study has not been done with letrozole, and it wasn't a particularly good study, but most of the pregnancies occur in those 1st 12 months anyway, so you wouldn't really use it for longer. You tend to only use it for 6. If clomiphene isn't working or letrozole is not working, we sometimes add metformin, again, drug used for diabetes, not licenced for ovulation induction on its own, it's less effective than clomiphen. It's also less effective in the obese patients, which is unusual, but we tend to add it in if clomiphene or letrozole is not working. It seems to help in that situation. It has a lot of GI side effects though that limit its use, and a lot of patients don't like being on it. I've had some, some patients with polycystic ovaries that find that when they, you know, when they're perhaps not trying to get pregnant, that metformin helps with some of their other symptoms of PCOS, maybe helps them normalise their weight. But on the whole it's not that effective, I think again because it's such a wide spectrum of disease, you'll find some patients where that's helpful and some where it isn't. When you do a study, there's so many different types of patients, it doesn't show a benefit, but sometimes individualise it, it might, it might be worth a try. Now going back to our normal cumulative conception curve, if you treat them with clomiphen, you can see it mirrors exactly the same thing and actually it it gives you almost the same chance of getting pregnant as if you had nothing wrong. With you, most of those pregnancies occur in those 1st 6 months, so we tend to give 6 months of treatment and then think about moving on to other things. So if it is working, um, do it for 6 months and then move on to assisted conception. If it isn't working, and there are still some patients that won't respond to clomiphine, metformin, letrozole, we've got options of ovulation induction with gonadotropin injections, which is a bit complicated and quite expensive. It's also. Technical laparoscopic drilling of the ovaries and this is where we just drill 4 or 5 holes in the ovary using diathermy. We don't exactly know how it works, somehow it affects androgen inhibiting production within the ovary and allows the ovary to ovulate spontaneously. The exact mechanism is unclear, um, but it actually is quite effective for clomorphine resistant patients, um, and of course that laparoscopy also allows you to. Look at the tubes as well. So we used to do quite a lot of it, but now because we're using letrozole and letrozole seems to be better than Klonopene, and actually we don't do it very often, we do it a couple of times a year. It's very easy to do and it's great fun because you're just buzzing little holes in the ovary. It's like popping bubble wrap, it's really sort of satisfying and it does work quite well, but there aren't that many patients that need it, but it is, it is quite effective. So, just quickly talking about tubes, I showed you that. HSG earlier, which showed a distal block, but you can also get a proximal block where the dye doesn't go into the tube, and if your HSG is abnormal, we're then going to want to do a laparoscopy to identify what the problem is and see whether we can treat it. So the block can be distal, it could be due to due to adhesions or it could just be proximal block. The causes of it, the most common cause is sexually transmitted infections, sometimes also due to endhesions from surgery or endometriosis. Again, we're seeing more. And more sexually transmitted infections nowadays than we used to, unfortunately and so inevitably that's gonna lead to a bit more tubal disease, again, one of the consequences of having children later is that if you don't start trying till you're 35, you may have had more sexual partners, that's gonna increase the risk of you picking up a sexually transmitted infection during that time, so, um, be careful if

we find tubal problems. You've got an option, well, can we correct that surgically or do we just bypass the tube completely and do IVF? When you look at studies, you show pregnancy rates with IVF of 30% or so, and some studies have shown that you can get quite good pregnancy rates with tubal surgery. You don't need to remember those figures, it's just to show that actually studies often show really good results with tubal surgery, because what you've got to remember is that people publish studies who are interested in tubal surgery. And are probably quite good at doing it and good at selecting their patients, those figures may not be achieved in real, real practise, the real world might not achieve such good pregnancy rates and so you have to be very careful when you look at those figures, and also if you're doing tubal surgery yourself, you need to collect your own figures to be sure that you are actually helping. So, tubal surgery is not dead in the era of IVF, it still has a role, but um. IVF might be considered if tubal surgery doesn't work or the tubes are not suitable. Now this is a case of adhesions around the tube caused by chlamydia. You can see there the tube itself, the fimbral end looks quite healthy, there's dye coming out. Her HSG would have been normal and you would have missed the adhesions, but the ovary is covered by adhesions, the tube's tethered. She's clearly going to have problems getting pregnant. That's quite a nice case for tubal surgery because you can free it up quite nicely. You can divide all the adhesions. Restore anatomy and that gives her, you know, 40% chance of pregnancy, so that's quite good. You can though find something like a hydrosalpinx, so this is the hydrosalphinx from the HSG you saw earlier, massive tube there full of dye, doing surgery on that to restore anatomy is going to be very difficult, it's too damaged. We might find endometriosis, we might find just a few spots of endometriosis. We might find severe adhesions and endometriosis all over the show, and you can see how that would affect fertility. It's difficult to see how the small spots of endometriosis would affect fertility though because anatomy is not distorted. When you look at medical treatments for endometriosis, it doesn't improve the chance of success, so suppressing the endometriosis for a couple of months medically doesn't improve your chance of pregnancy, so we don't do that anymore. But we might be tempted to laparoscopically treat it, so this is where we buzz it. Way laparoscopically with diathermy and treat the endometriosis. Now, there was a lot of debate as to whether that improved the chance of pregnancy. Obviously, in the more severe cases where you're restoring anatomy, that's going to potentially help, but does just buzzing a few spots of endometriosis diathermy improve the chance of pregnancy? Well, the only way to answer that is a randomised trial, and those have been done and the randomised trials show there is benefit to laparoscopic treatment. So there's been a number of studies done. The biggest one was done in Canada in '97. And it randomised patients like as I showed you earlier to treatment or no treatment and the group without treatment, it doubles your chance of pregnancy. So now if we see endometriosis, we treat it. If a patient has painful periods, we might think, well, they might have endometriosis and doing a laparoscopy in that situation to treat it might improve things. It might improve the chance of natural pregnancy. It doesn't affect their chance of IVF working though. So I said, now in a number of studies, it's Cochrane. Reviews, nice guidance, all showing that treatment of endometriosis surgically improves your chance of natural conception.

So we've dealt with those physical things, but we've got still got about 25% of patients with unexplained infertility, which is very, um very frustrating for them. Now some of those will get pregnant, given a bit longer, but you can't just say to a patient, oh well, you've got unexplained infertility, go away, you carry on trying it might eventually happen. After two years of treatment, we started thinking, well, the chances of it happening are quite low, we'll start offering them treatment and the treatment has been variable. Now in the past we used to use clomorphine to boost a few egg production, double their chances, buy more lottery tickets, increase their chances, but actually the randomised trials suggest that clomiorphene doesn't really significantly improve your chance of pregnancy, so now in the 2013 NICE guidance that came out there. Intrauterine insemination used to be used, so we used to just concentrate the sperm, stimulate the ovaries, and think that that would help. Now that went out in the 2013 guidance because they said randomised trials showed no benefit, IVF was more effective, but in the current 2026 guidance that came out a couple of months ago, they're now saying, well, actually it could be considered for four cycles. They're sitting on the fence there. The European guidance suggests we could do intra uterine insemination. And we're currently part of a study here, uh, where we're randomising patients to IUI for 3 cycles or IVF, um, and that's part of a national study run in Birmingham, and that might help us answer the question. So I think IUI may have a role, but, um, the best treatment for unexplained infertility is IVF, which we tend to recommend after 2 years. So anyway, it keeps going one way or the other, the pendulum keeps swinging, and because it keeps swinging, you probably won't get asked about that in an exam. When it comes to assisted conception, this is what we do in the IVF unit. Most of what we do is IVF, but we do do ovulation induction, we do do some intrauterine insemination, and sometimes we're using donor eggs and sperm, and the majority of what we do is licenced by the HFEA Human fertilisation and Embryology.

Authority. So I'm gonna quickly go through an IVF cycle with you. We call it an IVF cycle because it takes about a month. In the early days of IVF, it was just done in a natural cycle, but of course had very low success rates because we know that a lot of eggs are not normal, we stimulate the woman to produce lots of eggs and that way we we improve results. And the way we do that is to give her FSH and. Injections, these are self-administered subcutaneous injections, very easy to do now, and we monitor her response with scans and blood tests and what you see is the ovary starts to grow, produces lots of follicles, and, and then once you've got enough follicles, she's ready for egg collection. The egg collection is done transvaginally and it doesn't require a general anaesthetic, um, some places use general. But most of the time it's just the sedation and local anaesthetic. It's a very quick procedure, takes 1015 minutes and we just pass a needle up to the top of the vagina into the ovary, use ultrasound there, you can see that on there, needles in the follicle, drain out the fluid and that hopefully has the egg in it. Very simple, small risk of bleeding or infection, 1 in 2000 is pretty low. So it's um it's easier to do. In the old, originally, of course, the eggs were collected. Laparoscopically with Steptoe and Edwards back in '78. Um so yeah, it's uh, fortunately we don't have to do that very often now. There are the odd odd time we do do laparoscopic egg collections if you've got inaccessible ovaries, uh you can't access it vaginally, you can do a laparoscopic egg collection. There aren't many units that can do laparoscopic egg collections because most IVF units are standalone units not attached to hospitals, but because we are attached to the hospital, we. We do have the facility to do laparoscopic laparoscopic egg collections, and I do maybe one every couple of years, but it's quite fun, but, um, fortunately, not necessary, and I'm glad I wasn't, uh, stepped out because he was doing them at like 3 in the morning because it was a natural cycle, he had to do it when they were ovulating and they would be on call and come in and do the laparoscopic egg collection for the one follicle. Um, and that wouldn't have been a good job.

So once you've got your eggs, we've got to fertilise them with the sperm. So the man produces a sperm sample. If we're just doing IVF, we are taking the mature egg and just inseminating it with about 100,000 sperm around it and letting that sperm still fertilise naturally. But if you've got severe malefactor, we're gonna do ICSI where we inject a single sperm into the egg to achieve fertilisation. The eggs go in the incubator and the following day, see if they're fertilised, so they're gonna form a. A nucleus embryo the following day, and then we've got to watch them grow for a few days. So on day 2, they're going to have about 4 cells. Day 3, they're gonna move up to 8 cells. But we're trying to go longer now to blastocyst on day 5, because an embryo has to get to this stage to implant. Some embryos will stop growing, so there's no point putting them back, so we only put an embryo back if it gets to the blastocyst stage. That still doesn't guarantee it's going to implant, but it's got a much better chance. So it's like, uh, you know, athletic trials. Or extended test drive to try and find the best and the fittest embryo to put back.

The embryo transfer procedure is very easy. We just put a little tube through the uterus, we use ultrasound to pinpoint the tip in exactly the right place and then just gently expel one or two embryos back into the uterine cavity. You've still got to carry on growing, you've still got to implant, um, uh, and carry on growing. It doesn't guarantee it's gonna achieve a pregnancy. Any spare embryos can be frozen. for future use of liquid nitrogen and then you do a pregnancy test 2 weeks later and then pregnancy scans if they're positive. So I'd say the whole process takes about 1 month. Now we used to put in the old days, 3 embryos back um and then it went down to 2, but now it's often 1. This is old data because we don't put 3 embryos back anymore. I used to think well, putting more embryos back improves the chance of. Pregnancy, but actually putting 3 back over 2 probably doesn't make any difference. All that happens is you increase your risks of multiple pregnancy. Now when pregnancy rates were low, you know, patients accepted the risk of multiple pregnancy, you know, it's better than not being pregnant at all, but multiple pregnancies carry risks, there's, you know, low birth rate, increased perinatal mortality. So as pregnancy rates improve the treatment, multiple. Before pregnancy rates became more of a problem and so we started to think about doing something about that, so we started just putting some restrictions on three embryo transfers back in the early 2000s and then from about 2010 onwards there was a move to a single embryo transfer, so now a lot of the time we're only putting single embryos back because actually in a good prognosis patients, you can achieve just as good pregnancy rates putting one back as two back. But you can almost eliminate twins, the only twins that occur from that are identical twins. So now, again, NICE produced some guidance in 2013 and it hasn't changed in the latest guidance suggesting that we should do single embryo transfer in our good prognosis patients, you don't need to remember the figures, it's just the principles are young patients, first few cycles, put one with good embryos, put one back, older patients, repeated cycles, poor quality embryos, put two back. And we're monitored on that, the HFEA monitor us, so we have to achieve a multiple pregnancy rate of less than 10%. When the guidance and the one at a time sort of uh guidance came out, pregnancy rate, multiple pregnancy rates were about 30%. So it's this big, big reduction and initially some of the, some people in the industry were quite reluctant to adopt that, but now it seems to be universally accepted that we should avoid multiple pregnancy because that's our biggest. Risk and actually currently now the national multiple pregnancy rate is 6%. So our special care baby unit used to be full of our babies with twins, now there's there's none from us or not so many.

So I said the risks of IVF, the main risk is multiple pregnancy, which we're trying to do something about. There's no greater risk of miscarriage, there's a slightly greater risk of ectopic. We don't think there's any greater risk of foetal abnormality with conventional IVF. ICSI, the jury is still out there may be slightly higher rates with ICSI, and we're not too sure about longer term fertility of ICSI conceived children because they've just really not been around long enough, and we may be passing on some male factors possibly. There's a condition called hyperstimulation syndrome. I haven't got time to go into that. That's where the ovaries get very large and cystic and leak fluid into the tummy. It's, it's uncommon nowadays. The modern regimes we use, uh, we have an adopt, if you've got an over response, we can. cycle or freeze the embryo so they don't get pregnant because that makes it worse, so actually it's quite rare to have a patient admitted with hyperstimulation nowadays, but it is one of the risks, as I said, egg collection carries small risks because it is a surgical procedure and we don't think that there's any increased risk of ovarian cancer, although the du is still out on that one. When it comes to success rates, IVF is not 100% successful, it's about 25-30% successful overall. Success rates have improved as the number of cycles have improved over the years, but it's still, well, that's, it's a little bit out of date, it's probably nearer 30% now. The thing that affects success again is age. The cause of infertility, number of attempts affects things a bit, but the most important thing is age, and that just shows you there, the graph there just showing how pregnancy rates decline with age, exactly the same as natural.

So NICE guidance, I say 20,130, I haven't changed the slide yet because I haven't had a chance. There's a, but the, the, this hasn't really changed in the new guidance. It's still suggested that we do IVF up to 2 years of trying. NICE also suggests that three cycles should be funded for women under 40 and for women over 40, single cycle if they've got good ovarian reserve. Now, the problem is that most ICBs that fund the treatment haven't got enough money, haven't got enough money to do what they're currently doing this, and they don't have enough money to fund the full 3 cycles. There's very few areas that fund the full 3 cycles of IVF. I think you get 3 in Newcastle, you get 3 in Scotland, um, but most ICBs in England fund only 1 cycle. We used to get two in South Yorkshire until the 31st of December, and now we only get one. Um, and there are often other restrictions if you've got children already, uh, being overweight, things like that also restrict funding. So, um, it's not ideal, it would be nice if we had 3 cycles.

So just to quickly. summarise, take home messages, fertility problems are common, they may be increasing for various reasons, perhaps environmental factors more and certainly demographic factors. We've got sound evidence-based management that should be done in a dedicated clinic and it should be as a couple. Always maximise their chances by good preconceptual care, try and encourage healthy lifestyle and everything to, both improve their chances of getting pregnant, but also improving pregnancy outcome and get the men to eat more than one vegetable a day. It's important to thoroughly investigate somebody because the cause of infertility will determine your treatment and you can't just think, oh well, everything needs IVF. There's a tendency to think, well, Everything needs IVF, let's just not cut out some of the investigations and just do IVF, but it is important that you investigate thoroughly because the treatment does depend on the course, but also the desire of the couple. You have to accept that some, some patients will not want to do IVF. It's too invasive for them, or they may have ethical objections. Again, we can't go into those today too, not enough time. And if you've got pre-existing problems that might be affecting you getting pregnant, but also affect IVF outcome like uterine. Almatis, it's important that those are investigated and treated before they have IVF. IVF itself is effective for many of those different causes. It may be a first line treatment for male factor, it may be where other things we use IVF where other things have failed, but the main risk of IVF is multiple pregnancy. Hopefully we've largely dealt with that, we don't get too many now and but your chance of. Pregnancy both spontaneously and naturally decreases with age, the number of successive cycles, and other environmental factors like being overweight, smoking, alcohol, caffeine, jury's out on that one. The odd cup of coffee, I, I say patients can have the odd cup of coffee. The current suggestion is that as long as you have less than 200 milligrammes of caffeine a day, it probably doesn't affect fertility any more than that might. Uh, 200 milligrammes is 2 espressos.

Not very much. So, uh, in terms of guidance, sorry, I haven't updated that, there is now the 2016 guide, the 2026 guidance for for NICE. It is worth a read. There's a nice executive summary and a bit for patients. Don't read the 297 new guidance. It's, uh, it'll take you too long. Um, HFEA has got some nice information actually. Um, again, it's directed to patients. It is quite, it's quite easy to read, gives you a bit of an overview. Our own website has quite a lot of information about IVF and also has some videos about what happens in the cycle and what happens in the lab if you're interested, um, I think there's some quite reasonable videos. One of them has me on it. The one with embryology is better. So, um, any questions? I think we're just about. OK, have you got another, another lecture now? What time? Hmm, 10:30. Yeah, OK, so, um, I won't lock up but I'll give the key back to, uh. Good. Anything else anyone wants to ask? Right, I'll leave you to it. I I Yeah Let me give. Mm. Yeah. I Me And Let's see what. Yeah 1111. Yeah. I want. Because if you come at 1:30 then. shadow. It's just like. No Oh did you? time. You're good at getting in fights with just. Yeah, because I was just like, we're in universities have to grow and we just yeah you can. Is this the guy yeah, why don't you get past. The I Mhm. I. So it's up so. I. They I I Yeah, too fast, it does. I basically have the worst job. The SAQ is always probably I just, I, I also got. I take a break and this is it's not complicated. So it's just. That's the one I wanted to finish with this house on my oldest sister like shes sorry. fine. OK Oh, I haven't even, I feel like that's good. Sorry. And it was just kids. it was just. feel like I mean yeah like yeah. I it's it'll be right. That's it's but I'm not. To. Yeah. for Right. I. Yeah, well, you're doing fine. Yeah, no, I think. I get, I get loads and I'll go. Where I You know, Oh I But it's like even um. That, yeah, that's the worst. Like we might not, like you might not call you when we know. especially is It's not. It's fun. It's really. Yeah. That's really good. I like that uh. Anything like that yeah. I Oh What I that But I just it's like. I just you do want competition. And this is like. Oh. Yeah. Oh Oh All right, People Yeah OK, I really don't, but that's just because it's sitting there and watching the dog. It'd be much more interesting for you my face like I literally didn't, yeah. I I was like oh I hate and I. You do like. I it's just. you get How But like you're trying to do. And you've been good in like women. Yeah. I so. but Yeah. Yeah, um, I. I would like, but I hadn't had to um. you Yeah, I think that's what it is and all the social things as well like. Yeah, yeah. That's very good. I don't want that. Sorry This is Yeah. As part of bond field. Yeah Yeah, we did have a, we had like a, it's like a friend I met one of the guys. Yeah. rice, but this is the. Yeah. Yeah it's like really like at the end of it, yeah, they've not really. Yeah Yeah, it's. I And I was like he was always the person and you could see like he tried to get the place and like they didn't, and then he end up like for 3 months and then it happened it was like. But like so Yes I know it's The Or should I just Would But I don't think I did that. I I know, I do actually buy everything. I I what this is phone number. It's like if you get the same. Like like family children so like. situation. Yeah. Correct. Not Yeah, I don't mind. I don't actually want that a lot, but I, I like it on. to I I like. So my mum's like if she drops out. Isabelle, Isabella. Oh, Isabella. Uh. Yeah. So I just google. Again, not good at all. Also I think that this is just very. A lot of the time I draw random. Yeah Like on paper and it's kind of striped and I'll shade it round there and then as it's like over like runs over I'll start to like see I dispatch. It's. OK. Yeah, I'm I can't. Oh Yeah Oh. Yeah. This you OK. Are there, are there more people? Are you expecting more, or is the crowd? Good and like that. So the um the last topic was on uh infertility, isn't it? This one, OK, so.