CASE NOTES 3: FERTILITY
RADIO 4
TUESDAY 20/04/04 2100-2130
PRESENTER: MARK PORTER
REPORTER: VIVIENNE PARRY
CONTRIBUTORS:
ALISON MURDOCH
SIARRON WEST
ZITA WEST
SIMON FISHEL
ROBIN LOVELL BADGE
PRODUCER: HELEN SHARP
PORTER
Today's programme is all about fertility - or rather infertility. Humans aren't the most fertile of species - a perfectly healthy couple in their twenties only has a one in three chance of conceiving in any one month.
The average age for having a first baby in the UK has now reached 30, meaning that more and more couples are leaving it later to start a family. But time isn't on their side - a woman in her mid to late thirties is already half as fertile as she was in her twenties and 4 out of 10 healthy couples at this age will take more than 12 months to conceive.
I'll be discovering what it feels like to know that starting your family isn't going to be anything like as straightforward as it seems to be for everyone else.
SIARRON WEST
The main thing I felt is I felt quite odd, I felt almost left out in some ways and I think you start to feel quite alone, you're not the only one but you do start to feel as though you must be the only person who isn't starting to think about having a family.
PORTER
And I'll be finding out more about a special type of IVF that allows a man to father a child, even if he can't produce any sperm.
FISHEL
Until the procedure was introduced in about 1992 only 5% of men that had a male fertility problem could have their own genetic child, now 95% of men can have their own genetic child.
PORTER
But could it have an unwelcome legacy for future generations? My guest today is Professor Alison Murdoch from the Newcastle Fertility Centre at Life and she joins us on the line from our Newcastle studio.
Alison, why is that fertility tails off with age?
MURDOCH
The problem that women have, of course, is that when they're born they have all the eggs in the ovaries that they're ever going to have for their whole life and they're gradually used up on a regular basis. And when they're all used up, which is the menopause, then I'm afraid that's the end of fertility. But sadly for the last 10, 15 years before the menopause the quality of the eggs that are released is actually very poor and that's why women are less likely to get pregnant as they get older, they're more likely to have miscarriages, they're more likely to have abnormal babies such as Down's babies.
PORTER
And that starts to become significant at what age - somewhere around mid thirties?
MURDOCH
We usually see fertility declining from about the mid thirties but as I said before you're only half as likely to produce a healthy child at 35 as you are at 25.
PORTER
Does age affect male fertility too?
MURDOCH
It does, but not quite to such the same extent. Men will go on producing new sperm all their life, so as they get older the proportion of sperm that they produce, which is genetically abnormal, will increase but of course any man is producing millions of sperm at any one time, so from their point of view, although their fertility's slightly declined, they usually still do remain fertile.
PORTER
We know that it can take a perfectly healthy couple 12 months or more to conceive, so how long should somebody wait before they seek help?
MURDOCH
Well of course this obviously very much depends on the circumstances for that woman, if we're already talking about a problem with age then the older the woman is the sooner that she should think about going to ask for help. Also if she's had - if either partner have had a problem in the past, say the woman has had a burst appendix and we'd therefore think there might be damage to her tubes, then she should go early and get it investigated. But if there's nothing wrong in their history and they're young still then we would usually not want to see them until they'd been trying for at least one year.
PORTER
And what about an older woman in her late thirties say, who's otherwise healthy?
MURDOCH
This gets more difficult, I mean officially we would say again you should wait one year but I think it wouldn't do any harm to start thinking about it when you're coming up to the year and talk about investigations at that stage, then at least we know that if there is a problem, such as a poor sperm count or problem with the tubes, then you're going to come and ask for treatment - IVF type treatment - at a stage when there's a more realistic chance that we can do something to help you.
PORTER
Well more about IVF later. Thank you Alison.
Zita West runs a private clinic where she and other midwives advise couples on how to use basic self help measures to improve their chances of conception. And one of the most basic, predictably, is to ensure that you are having sex at the best time in the menstrual cycle.
ACTUALITY IN CLINIC
ZITA WEST
So roughly how frequently are you getting periods and how long is a normal cycle for you?
PATIENT
They're fairly regular, they're anything between sort of 24 to say 30 days.
ZITA WEST
Okay, no that's good. So not always spot on 28 days though?
PATIENT
Not spot on, just a couple of days before and a couple of days after.
ZITA WEST
Well that's fine, that's still counted as pretty regular, so it shouldn't be too worrying at all there.
PORTER
Zita, what advice would you give to a couple who'd decided to start a family?
ZITA WEST
What I find here that the couples coming along - they can be working long hours, they can be quite stressful, the woman can just be deciding to come off the pill, so it's getting to know her pattern, her menstrual cycle, because having been on the pill for the last 15 years some women are very unaware of what a proper period is like.
PORTER
Of course they'll have regular periods the whole time that they're on the pill.
ZITA WEST
Absolutely. So I try and sort of do some basic fertility awareness to get them to understand what their cycle is doing. But the commonest thing I find, day after day, with couples coming through the clinic, they're not having enough sex and they're not having sex at the right time, so it's covering the basics.
PORTER
Well let's address those two now. They're not having enough sex - how often should couples be making love?
ZITA WEST
They should be making love about two to three times a week but again it's very difficult - when you first start and you want a baby there's a few months of excitement - will it happen, won't it happen - but that soon starts to wear thin. And you know six or nine months down the line women are getting very frustrated, they just want sex when they're ovulating, they're not interested at any other time in the month, there's a few psychosexual problems that come up as well because the men just feel that they're being a bit used, you know.
PORTER
For a change.
ACTUALITY - CLINIC
ZITA WEST
I mean the important thing is that the most constant length of the cycle, generally, is the time from ovulation until the next period.
PATIENT
I see.
ZITA WEST
And that will generally be around 14 days, so you've got a sort of average of about between 10 and 16 days, but it stays more consistent than the early part of the cycle. And the first part of the cycle, which is the time when the egg follicles are developing, can really be quite varied in length, anything from literally a few days, so if you were going to have one of your shorter cycles it's very likely that you'd be ovulating that bit earlier, whereas if you were going to have one of your longer cycles at 30 plus days then it would all be happening considerably later.
PATIENT
I didn't know that.
ZITA WEST
So the important thing really to recognise is the signs of fertility approaching. The best way to do that really is in the changes in the cervical secretions - do you know anything about the secretions or the mucus of …
PATIENT
I don't really, no I don't.
ZITA WEST
I don't know if you notice that after a period you may feel quite dry for a day or so and then sometimes you get something a little bit sticky, white - whitish type of secretion?
PATIENT
Yes, yes.
ZITA WEST
And other times a bit sort of wetter - do you sometimes feel a bit wetter or even seeing something that's a bit more sort of slippery. So anytime that you're noticing a wetter more fluid type of secretion generally it's meaning if you look at this illustration here what you see is that the mesh is much wider gaps at the time, so the sperm can get through - you see the difference between the two?
PATIENT
Yeah.
ZITA WEST
Many women are focussing on the ovulation kits, as opposed to what's going on in their bodies and for so many women they have a 28 day cycle, they count back, they think right day 14 that's it if we have sex around that time, lots of times, it'll be fine. But for some women their cervical secretions are at different times, they can be just after a period, they can be towards the end of the month - so they might be missing that window of opportunity. And that's the commonest thing I find - that women will focus on having sex bang on ovulation. The research shows six days prior to ovulation you stand a good chance of conceiving. And it's just going over some of the basic biology - that an egg can last up to 24 hours, sperm can last for five to seven days, so you need as much sperm up there waiting to pounce on that egg when it comes out.
PORTER
So if you wait for your day of ovulation you might be leaving it a bit too late?
ZITA WEST
You might be leaving it too late, absolutely.
PORTER
Zita West talking to me at her clinic in London. You are listening to Case Notes, I'm Dr Mark Porter, and I'm discussing fertility issues with my guest Professor Alison Murdoch.
Alison, whatever happened to the time honoured temperature chart for pinpointing when a woman releases an egg?
MURDOCH
Yeah we've really passed that now. The problem is that the temperature goes up by a hormone that's produced after ovulation, so by the time you wake up in the morning and you find your temperature's gone up you've actually ovulated and probably a day maybe two days later, so it's too late at that stage. So it's not a test now that we would recommend for anyone to do.
PORTER
Talking about whether a woman's ovulating or not - irregular periods are not a good sign are they.
MURDOCH
They aren't but I think we have to be careful what people mean. A lot of women assume that they should have a period every 20 days and in fact only about 50% of women will have a period bang on 28 days. So any periods that are up to six weeks we would probably consider being, within our definition, as being fairly normal. So it's only really women who have periods much less frequent than that that we would start worrying about in terms of ovulation. If you've got a period that comes every five to six weeks you're actually no less fertile than someone whose periods would come every four weeks.
PORTER
What about lifestyle measures and fertility, and we're always telling people to stop smoking, to cut back on alcohol, to lose weight if they're overweight, just how effective are those interventions?
MURDOCH
They are extremely important that we actually give this information to people because don't forget we're hoping that they're going to end up pregnant and then with small children and for the whole of that process you need to be fit and healthy, particularly as far as smoking's concerned. I think the only issue that really is important with fertility, with women particularly, is weight and we do know that women who are overweight are more likely to have a problem with their periods, they're less likely to get pregnant with treatment and that's in addition to all the general health issues related to weight. We use an index called the body mass index, which is the relationship between the height and the weight and we need that really to be less than 30 before we would want to treat someone with infertility.
PORTER
What basic investigations should be offered to a couple in the general practice setting, if they've been trying for 18 months, they're outwardly otherwise perfectly healthy and they're not getting anywhere?
MURDOCH
The GP's got a big role to play because in addition to getting these lifestyle issues sorted out and doing general things like making sure a woman's up to date with her smear tests and is not anaemic and has had a German measles vaccination, the GP can organise the basic tests of whether or not she's ovulating - doing a blood test before she has a period and doing a blood test when she actually has a period as well, to test how well the ovaries are working. And of course the GP can also arrange for the husband to have a sperm test done. So by the time they come to the clinic really the only investigations that should be left then to do are tests on whether the woman's tubes are alright.
PORTER
People are often surprised when I ask - I always - I mean women tend to come in and say look we've been trying for a year we've not had any joy or whatever and surprised when I want to see them with the partner because it does take two to tango, there's no point in investigating the woman unless you investigate the man from the outset.
What are the sort of most common problems that causes the fertility trouble?
MURDOCH
It's fairly well evenly divided I think between problems that relate to ovulation, male factor problems and tubal problems are relatively small, the big issue that we have as a major concern is those who have unexplained infertility and about up to about 30% of all couples - we do all the tests, the tests actually come back perfectly normal and that's a really - it's a difficult diagnosis for us to make because it means we're not clever enough to know what it is that's wrong with them. But clearly if these couples have been trying for two or three years and not achieved a pregnancy there must be something wrong but leaves them with the sort of limbo of not knowing whether they can get pregnant in the future and knowing what to do about it.
PORTER
You mentioned tubal causes there, these are the fallopian tubes which can be damaged and stuck together and of course things like chlamydia, the sexually transmitted disease, are an important cause of that.
MURDOCH
Yes it is and unfortunately as incidents of sexually transmitted disease increases I think we're going to see an increasing incidents of problems with fallopian tubes and that's a major concern to us.
PORTER
Well thank you for now Alison. You and Zita are both professionals used to dealing with infertility on a daily basis, but what's it's like to be on the other side of the desk. Siarron West and her husband have undergone several different fertility treatments in order to start a family. I asked Siarron what it feels like to realise that you may not be able to have a child.
SIARRON WEST
I don't think I really thought about it very much, I just assumed that we'd get married and have children. And I think I found it very difficult to understand why I was different from all of my friends, who were - within sort of four or fives years of getting married, were starting to think of starting a family. And I think the main thing I felt was I felt quite odd, I felt almost left out in some ways and I think you start to feel quite alone, you're not the only one but you do start to feel as though you must be the only person who isn't starting to think about having a family.
PORTER
Siarron you're talking there about yourself, you're saying I felt alone, but of course it was the pair of you that couldn't start the family, not you.
SIARRON WEST
Yeah it was the pair of us and my husband was - I wouldn't say equally as worried, I think he found it easier to deal with and easier to come to terms with, to be honest.
PORTER
And what was the actual problem?
SIARRON WEST
Right, my husband has progressive multiple sclerosis and so had several problems both in sexual function and with actually not producing enough sperm.
PORTER
So how did you get around that?
SIARRON WEST
Well initially we went for something called ICSI. ICSI is a relatively recent quite specific form of IVF where in men who don't produce enough sperm you can actually aspirate the sperm from the testicles and use those single sperm and push that one sperm into the egg to try and achieve an embryo. We felt it was really important to us that we had a child that was biologically related to the two of us. Unfortunately that didn't work and we then decided to go for donor insemination.
PORTER
That's using semen from an anonymous donor.
SIARRON WEST
That's right yes.
PORTER
How did you feel about your child not being genetically your husband's?
SIARRON WEST
To start off with I was the one who had the bigger problem with it, my husband said that a child that was half mine he would love it anyway and I was the one who felt quite strongly that my husband needed to have a child genetically related to him. But after going through a couple of goes of IVF we got to the stage where we really did start to think about what was truly important and what we really wanted was a child and it was a secondary issue what the genetic makeup of that child was.
PORTER
And how long after you started treatment were you successful because you have a baby daughter - not baby - she's four years old now isn't she?
SIARRON WEST
That's right, yeah. We were very lucky, it was probably only about two years, we had three attempts at various methods and the third attempt, which was our first attempt at straightforward donor insemination, was the one that worked.
PORTER
Well two plus years is still a long time, particularly when you have to go through those sorts of treatment regimes. Now you actually wear two hats because you're a part-time GP, just outside Cardiff as well, how have your own experiences helped you help your patients?
SIARRON WEST
I think I've appreciated what a sort of all encompassing thing infertility is - it affects the whole of your life. And no matter how well balanced you are I think you become quite obsessed with focussing down on one thing and that is having a family. And I think that once you get referred to a clinic I think you're on a bit of a roller coaster and it's quite difficult to step off and say right we've been through enough now. And so I think I can appreciate how difficult it is for my patients to make sensible decisions once they've actually started on treatment. And I hope that part of my role as a GP is to talk to people before they're referred and to give them some idea of what might lie ahead of them.
PORTER
Does that actually put some of them off - do some of them not realise quite what's involved?
SIARRON WEST
Yeah it does put some people off and it makes some people think that perhaps they would prefer to go for other options, such as adoption, because realistically not everyone who starts out on infertility treatment is going to end up with a child and for some people they would rather spend those years going through the adoption process and having perhaps a higher chance of ending up with a child at the end of it.
PORTER
Siarron West talking to me about her struggle to start a family.
Alison, Siarron talked there about ICSI and IVF - more of those later. I just wanted to ask you - do you see many people with secondary infertility - people who've had a child but don't have any joy the second time around or third time around?
MURDOCH
We do and they fall into two groups really. There are those who have conceived once and maybe just been lucky but there are a sub-fertile couple and they don't have that luck again. But then there are of course those people who have treatment and get pregnant and then want to have another child and come back for treatment again. That causes difficulties when we're talking about funding and whether the health service should fund second children as well.
PORTER
More about that later too. First of all what happens if I refer someone to a unit like yours - they've been trying for 18 months, their basic investigations are okay - what can we do for them to help them?
MURDOCH
A lot of people when they come to the clinic assume that there's quite a lot of things we do before we start advising IVF and that's not really the way it works now because for most causes of infertility eventually, fairly soon, the option we're going to talk to you about is going to be IVF treatment. Now for some couples that's too soon and therefore we need to spend quite a bit of time just going through whether that is an option, as Siarron said it's sometimes just a step too far for some people. But with the exception of those people who have a problem with ovulation and therefore need drugs like clomiphene or injections to make the women have periods, IVF is in most cases going to be the first line treatment for them.
PORTER
What's actually involved and how successful is it?
MURDOCH
In principle IVF is relatively straightforward, we need to give the woman a course of medication, which usually involves some injections for three to five weeks to make her produce more than one egg. We then collect those eggs by a very small operative procedure, put the sperm with the eggs to make the embryos and then put those embryos back inside the woman, just like having a smear test, about two days later. And then just wait two weeks to find out if it's successful. That makes a very scientifically complicated procedure seem very simple but in essence that's what's happening. We're looking on an average of achieving about one in four couples to take a baby home with one treatment each month, so if people seriously want to have the option of a good chance of a pregnancy they're going to have to have more than one treatment.
PORTER
So conventional IVF involves fertilising the woman's egg with sperm from the man and then re -implanting the resulting embryo back into the woman, but what if your husband doesn't produce enough sperm? Enter ICSI - a special type of IVF used to help couples where the man doesn't produce suitable sperm - either in terms of quality or quantity. All it needs is just one sperm, and even that can be taken by doctors from deep within the testicle - even men who apparently don't produce any sperm often have some hidden away.
ICSI's been so successful that nearly all men with these sorts of problems can now, in theory, go on to father their own child. But does fiddling with the natural processes involved in conception lead to problems later? It's a controversial area, but there could be at least one troubling legacy for boys born using ICSI, as Vivienne Parry discovered when she met Simon Fishel, one of Europe's leading experts on the technique.
FISHEL
It stands for intracytoplasmic sperm injection and what it actually means is the ability to pick up a single sperm and inject it into the egg itself. So it's literally - it's a one-to-one procedure.
PARRY
There seem to be slightly greater risks of problems at birth and in the early years for babies born as a result of assisted reproduction than there are for those born following normal conception. But this point is hotly debated and studies are conflicting. It might simply be because many parents are older which in itself increases the risk of a baby being born with a chromosome disorder like Down's Syndrome. Or because of the greater number of multiple births. One issue that isn't contested is the problems faced by men who have an inherited genetic cause for their infertility, as geneticist Robin Lovell Badge explains.
LOVELL BADGE
Normal women have two x chromosomes, normal men have one x chromosome and one y chromosome and it's the inheritance of the y chromosome from your father that makes you male. Now if you have an x chromosome from your father you develop as female.
PARRY
And some of the genes that cause infertility in men are carried on the y chromosome?
LOVELL BADGE
That's correct, so we know there is just one gene that determines whether you're male or female and there are a set of other genes, not a huge number but a set of other genes, which have several roles but most of them seem to be playing an important role in making functional sperm.
PARRY
So if you have an abnormality there and you use a sperm like that, that has that abnormality, then if you have a son by that technique he will also have that same problem?
LOVELL BADGE
Absolutely correct yes.
PARRY
Before ICSI these men's sperm would never have been able to fertilise an egg and they would have remained childless, a situation which causes intense sorrow and unhappiness for many of them. So how does Dr Simon Fishel, who introduced this technique to the world, feel about knowing that these men's sons will potentially go through the same trauma as their fathers?
FISHEL
That of course is a very important point and counselling these men is extremely important and as a couple of course, not just the men, they need to understand the potential implications for any offspring, some of which we may have a handle on - in other words we may have some knowledge about that we can inform the couple of the likely risks. Other situations are just at the moment a potential statistical relevance rather than actual information that we have. And couples must be informed about this relating to their particular condition, for example, a man with one type of sperm problem may have a very different risk to a man with another type of sperm problem, the chances of passing on his infertility condition might only be relevant in certain situations and it's very important we isolate that on an individual case basis and discuss it with the couple in as much depth as possible before they proceed with the treatment.
PARRY
If you know that you're passing on a problem to the next generation is there any way of screening sperm to prevent it? Robin Lovell Badge.
LOVELL BADGE
The only sort of abnormality we can have confidence about knowing is going to be there are those cases where the men have few or no sperm because of mutations on genes such as the y chromosome or in some cases I expect when they become better known mutations on other chromosomes that are affecting fertility. But it's going to be impossible to really screen sperm for any other types of defect because all the techniques you could use to screen them would destroy that sperm. Of course 50% of the sperm from a male are carrying one of these y chromosomal mutations, 50% of those sperm will be perfectly okay because they won't be carrying a y chromosome, so daughters of those individuals will be perfectly fine.
PARRY
Do you think then that there should be sex selection where ICSI is used for y chromosome abnormalities that cause infertility?
LOVELL BADGE
I personally think that's one good reason for considering sex selection as a technique. The idea of sex selection is a controversial one - many people don't seem to like the idea - but in this case perhaps it's a reasonable one to propose doing.
PARRY
Simon, critics of ICSI say that by using this technique for these men you're potentially significantly increasing the number of couples in the population that are going to need ICSI in the future - how do you feel about that?
FISHEL
Yes we can say that ICSI might beget ICSI. On the other hand we don't know what opportunities for treatment of that condition, that currently exists in the father that might be passed on to the son, might exist in 20 or 25 years time when the son wants to reproduce - there may be a very simple resolution to that problem. And yet this is on the supposition that of course we are going to create those problems. We will in some situations but to refer to your question of having potentially a significant effect I'm not sure we will have and what is indeed a significant effect? It will be an individual effect and that's why couples will have to make an individual consideration of that for them and their offspring. But in terms of a population effect - a social effect - and therefore the doctors having a role in that I don't think at this stage that we can be the judge of whether it's right or wrong to help a couple have a family under those circumstances because the actual effect is only going to be, at the very worst, a future child - if there's no medical progress - requiring ICSI for them to conceive thereafter.
PORTER
Alison, Simon said there that an inherited fertility would be the worst thing that could affect a man born using ICSI but there has been concern, hasn't there, that all forms of IVF may have some, as yet, unrecognised effect. Is this just scaremongering or is there more to it?
MURDOCH
I think we've really got to put that preceding conversation very much in context and it is - of course it's responsible for those of us that are involved in providing these treatments to monitor what's going on, to discuss the potential - potential problems that might arise and to make sure they're reduced to the minimum but you have to remember what the risks are to normal conception. If you take a couple - if you try to conceive now with your chance of having a child that's got an abnormality it's about 4%. So we are well aware of the fact that in human beings problems will occur and we can never absolutely guarantee when we're offering fertility that the outcome for the baby will be absolute normality. Most people - most patients - when you actually discuss that with them they do understand that and the same as any other couple who are trying to conceive spontaneously.
PORTER
But is there any evidence yet that actually the processing involved in IVF - taking the egg out of its environment, injecting sperm, etc. etc. - does that actually have any untoward effect on the developing baby that we know of?
MURDOCH
I think it's incredible that it doesn't isn't it. The answer is no we don't know any evidence that it does and we're needing to look and we're need to watch and of course there's always the slight concern that the oldest child conceived from IVF is only 25, so we do have to keep watching but I mean I think it's quite incredible that we do have so many normal healthy babies from the procedures. The other issue, of course, that people ask about is whether there's any risk to the woman and - of going through all the drugs that they have to have and we get that as a question that's raised fairly frequently. Again there are theoretical reasons why there might be but all the evidence so far would suggest that there is not any increased risk and there's no need for these women to have any long term monitoring at all.
PORTER
Alison, what about the thorny issue of cost - up until now most couples have had to spend literally thousands and thousands of pounds on courses of IVF, the Government is in the process of changing the rules - what's the latest situation?
MURDOCH
Well NICE, which is the National Institute for Clinical Excellence, has put out a report at the beginning of this year which really has fundamentally changed where we came from. NICE has said that infertility is a justifiable call on NHS resources, it said that all couples who have more than a 10% chance of getting pregnant with IVF should be allowed to have three treatments on the NHS. That has yet to be implemented by the primary care trusts, so there's a lot of negotiating still to do. But for the first time infertility has finally been recognised as something that's deserving NHS input.
PORTER
Which is a major stride forward in itself Alison. I'm going to have stop you there. If you want any more details of the various areas we have touched on then do phone the Action Line, that's 0800 044 044, or for useful contacts and addresses try the website at bbc.co.uk/radio4.
Next week I'll be looking at how simple gene tests could one day predict how and when we are likely to die. Join me next week on Case Notes to find out.
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