Its a fascinating and slightly weird experience, walking into a clinic which holds such profoundly moving memories and acting in a totally different capacity.
There we were in this room where I had spent so many appointments. This room where I had sat, nervously waiting to hear how my follicles were getting on, where I had sat, listening intently to our treatment plan and trying to take everything in. This room where I had cried. This room where I first saw my daughter’s tiny, flickering heartbeat at our 6 week scan after a successful round of IVF.
And now, here I was, getting out my interview notes and voice recorder!
Dr. Shawaf treated my husband and I when we reached the end of our NHS road. He agreed to let me interview him and gave up 2 hours of his incredibly valuable time to talk to me.
So, I asked a lot of questions. From how to avoid being exploited by private clinics to whether you can do anything to give yourself the best chance of success (and the IVF process explained step by step).
A: What advice would you give to someone going for their first appointment with their doctor? What helps when somebody comes to see you for the first time?
T: I usually give some sort of questionnaire, but it is much more important that the couple have all the tests that they need done, so you don’t have to repeat them.
They need to read a few sites.
The Royal college of Gynaecologists https://www.rcog.org.uk
The British Fertility Society https://britishfertilitysociety.org.uk/
The Human Fertilisation and Embryology Authority https://www.hfea.gov.uk
Just spend a couple of hours on them– not long, because it can get overwhelming. You think, what am I going to do? Some of them are very gloomy! You can start feeling like, ‘why am I going through this?’
A: Yes, it’s very difficult – how do you manage that? You’re coming from a medical point of view. How do you manage patients’ expectations and emotions?
T: Well, I always tell anyone coming to see me, that you have to feel that you’re doing the best you can do. And if you feel there is anywhere better, then go for it! That link between me and whoever I see is very important. To give them the power to say, ‘well I’m doing the best I can’.
I sit down and let them talk about the issues that they have. There is that barrier – a doctor/patient relationship and you can’t open it, so I always talk about seeing somebody outside, a counsellor, not a psychiatrist just someone who can sit down with them and talk to them about what they can expect, and how they could deal with their emotions. That is helpful.
I do also think that some complimentary therapy can help, to help relax. Not sure that it’s very high element of importance in treatment because they are complimentary by nature and by name. You cannot be complimentary and be the centre of things. But anything that helps them feel relaxed.
A: How important is it to stay relaxed? You’re told to relax all the time and it’s so frustrating.
T: I think it’s mostly about expectation. I think the stress hormones are a small part of it, but it’s the expectations and the fear of failure. That is what makes it so hard. When a couple comes in, they finish their cycle and its negative, the general feeling is that “I want to go again immediately”. Sometimes I think it’s detrimental. It adds onto the emotional upheaval. I usually say, take 2 or 3 months. Not to do with the ovaries but the emotion. They can go back to normal, see friends, go out, not tied to injections, go on holiday for a bit to relax.
A: I think that’s very good advice. I remember wanting to just try again immediately when we had failed cycles.
T: Timewise – people say, “but I’m going to be 37 next month!” Well, OK, but it’s not like if you cross the line you’re out! One needs the perspective. You look at it much more as: ‘you as a person’ (holistic). Gradual, relax, take things easy. Think about something else, to clear the mind a bit. When people do that they start thinking in a different way. Approach the whole problem more positive rather than keep on the negative.
A: At what point should a couple go and seek medical advice?
T: If a couple feel there is a problem, a medical problem, they should try a few months and then go. But otherwise, if below 35: it’s a year. For investigation, not treatment. Over 35: 6 months. It doesn’t mean they should go for treatment, that’s a different issue. A couple could come in after a year and they could have all the tests and find nothing wrong, so you say, keep trying nothing wrong. But this is where NHS and private differ. NHS is bound by guidelines restrained by finance. Privately you can ask for treatment and it’s not that you won’t get the same objective, just that you get it quicker. That’s the only difference.
A: What are the treatment options available?
First, you make a decision about what the diagnosis is. You have a decision about that, then you go and target the diagnosis. If a woman has blocked tubes, you do surgery for the tubes, which is now not very much looked into – or you go for IVF. A man with very poor sperm count, you try and find out the reason and if you can’t, or there is nothing that you could do about it, then it’s IVF or ICSI. So, these are very much targeted.
Then you have things, for example, like a woman does not produce eggs regularly, so you give some medication. You do this for a few months and if that doesn’t work, you move to the next stage.
Then you have quite a large group which we call, ‘unexplained’ because we don’t know. Some are to do with some pathology, but that requires surgery like laparoscopy, to find out or you just don’t know.
The ‘unexplained’ category is getting bigger and bigger and particularly in the women who are over 37 and 35. People are delaying having a child and it is causing a lot of…work for us. People are making lots of money from it. It’s also causing a lot of difficulty, it gets difficult once you reach that age. Not impossible- but it gets a little bit difficult. It requires more money and more emotional stamina to persist, but mostly because we don’t know what it is.
We think it’s probably to do with the quality of the eggs. That’s what we believe now, at the present time (but in medicine…we always change our mind. And that is correct, because you always examine what you’ve done, and sometimes you find something wrong and that is quite common).
You try and treat the cause. If you can’t, then for young couples the advice is to wait. Don’t do anything. But if it doesn’t, then there’s two options. IUI or IVF. There’s a lot of controversy about IUI.
NICE has said it is not cost effective. They have stopped it from the NHS funded cycles. They thought it was better to direct the money to IVF. It has some sense…but has also some nonsense! Some do benefit from it. The question is time, it takes longer to achieve a pregnancy with IUI. And, of course, it’s the cost. 3 or 4 cycles of IUI would be the cost of IVF.
A: Do they still do ovarian drilling?
T: Yes, a possibility, but because of surgery and complications afterwards it’s a small group. You do it if a woman is having laparoscopy – because it is sometimes a combined problem – tubal disease, PCOS, a little bit of endometriosis. So, you do it as an adjunct to the main surgery. It’s not a decision that will be taken lightly because of the risk.
It is an easy procedure, but it is sometimes done by somebody who is inexperienced because of this, and people have noticed that some women who have been through it, you put them to the other end and they have very low egg reserve because they have burnt off so much in surgery. So, that is the difficulty. If it going to be done it needs to be by a highly specialised person. It has some bad press at the moment.
A: What are the IVF success rates for a live birth?
T: Totally dependent on age. It depends on the quality of the eggs mostly. Looking at Pre Genetic Screening (PGS), they can detect if the embryo is to do with a male or female issue. It needs further study. But it is 90% to do with the egg. 10% with the sperm. This is related to age.
If you see the graphs looking at few thousand embryos with PGS, you see as they get older, the percentage of abnormal embryos gets higher and higher, until you get to 97%, so only 3% of a normal one, so it’s pot luck.
It will come – yes! And this is why you can still get pregnant naturally. But it is lower rate. Of course, human beings are all different. But we’re looking at the whole population. Some people might be fine but in general, age is most important.
To choose a clinic, I would suggest to any couple that they must spend an hour going through the HFEA website and looking at the success rate of all the clinics, so they choose what is best.
If you have one that is repeatedly on the top and one repeatedly at the bottom, you need to stay away from them.
There are additional factors – nearby, comfortable with them – and that is why, and I always tell couples when they come to see me – you decide. But to me, a couple come for having a child. You need to think, I’m going to spend so much money – or if NHS- so much time with a clinic with such a lousy rate, why would I go there?
Ask your GP to send you somewhere else. Couples must have power in their hands to try and change these things. There are clinics – NHS and private – where their rate is so low, they should not be there. It’s not just one year, it is consistently low. Why should they be there? Everybody should be reaching more or less the same.
The HFEA publish rates according to the age of the woman. That’s because up until now, it is what we know is the best parameter.
People say you measure the AMH (egg reserve) but it is absolute rubbish! Many of the big guys in IVF said this will determine how we advise. But a publication in BMA (top journal in medicine), they had a group from university and followed women in 4 years- one with v low AMH (so everybody thinks: very low chance of pregnancy) and normal AMH. They followed them up and found natural conception was the same for both of them.
It makes no difference even with age. They had 200/300 in each. No difference.
A: That’s really interesting.
Low AMH only effects how many eggs we can collect from a woman; but it has no impact on live birth. It does have an impact on live IVF, as you have less chance of freezing embryos. We should be honest with couples, our only parameter that is important is age.
So, you go to the site, look for ‘find a clinic’, and then it will give you the region etc. Each one provides figures. Everyone starting stims has to be registered with the HFEA. Once registered, the HFEA will follow the progress of the woman being treated. If they don’t find them, they follow up with the clinic.
A: If you decide on private clinics there’s also an exploitation problem. How can couples avoid being exploited and get the best value?
T: It’s very difficult. The HFEA has not been able to tackle it. Patients are left to their own devices. The HFEA should take more responsibility in getting centres to be clearer, like put on their websites that the add-ons offered are not evidence based or accepted by main groups like Royal College of Gynaecologists.
They commissioned a centre in Oxford for stats and to look at add ons in IVF. From immunological tests, PGS, intravenous lipid (said to enhance implantation), endometrium scratching, assisted hatching; these are all the add-ons. They said maybe scratching will benefit – although recent evidence says it doesn’t…but there is no evidence to support them. It might work but there’s no evidence. Those people who provide it, must provide the evidence. It is not good. They just take one study that shows it works and not the others.
A: So, it is down to the patients to do research and make an informed decision on what they know, how they feel and what their budget is.
What are the best tips? How can I help myself succeed?
T: There are things. Lifestyle is very important. Just this week, something came up from Greece, a department from nutrition, for a couple going through IVF, those having a higher Mediterranean diet have significantly higher chance than those who do not. It is important to look at this. Eat healthily. Just a healthy diet. Fresh fruit, good veg, olive oil. Good exercise – not heavy. Heavy is not good because it has an effect on endocrine function with stressful exercise. Whatever is easy; don’t exert yourself. Something to enjoy and keep fit but not to do it to keep weight down and sweat…
Of course, the usual things smoking and drinking. Smoking you should stop completely. Alcohol, one glass or whatever or nothing…but this should be starting from women should start from when they are thinking about having a child. I read somewhere about Trimester Zero.
Take multi-vitamins and minerals. I’m not sure it’s that helpful for fertility, but for the baby.
There is more evidence from Israel–that taking the higher dose of folic acid may reduce the risk of autism. It first came from Australia a couple of years ago. So, you take 800mg instead of 400mg. I think it helps with having a healthy child – and healthy adult. The ideal for BMI is 20/25. Below 30 helps with a lot of things in fertility treatment.
You could be veggie or meat eater. Lifestyle, weight, smoking, alcohol excess. Once a couple decides they are going to try and have a child then you think: I will do that for the child. It’s for the woman and the baby.
A: Nice way to think about it. I’m doing it for the baby.
T: Yes, it is mostly to do with that. As to how much it helps with fertility it is debatable. Same with complimentary therapy. Not clear…
A: But it can compliment…
What advice would you give to someone deciding what treatment to have? I knew we wanted IVF even though you said we could have tried other things first for example.
T: I face it every day with every couple who comes to see me. I give percentages with what I know, and I will make a decision with them based on two things. One, the age of the woman and how long they have been trying. Age will influence how quickly we need to move to higher technology. Length of time, after 3 or 4 years, couples are desperate to get on with it. So, going for IUI or something else and if it fails first, second or third – you are emotionally drained after that. To take them to IVF, they already have their emotion strained and it causes strain between them as a couple, even if it is donor sperm for gay or transgender or whatever, these two elements are important.
I give them an informed opinion and the couple make an informed choice.
A: Why might it not work?
T: You have to do all the tests. Ensure uterus has no fibroids etc. impinging the cavity. Check any issue with how eggs are getting out, how the ovaries are – cysts etc. Uterus needs to be clear. Once that’s done we assess how to stimulate and I do use AMH and FSH tests on day 1 or 2, to decide how am I going to stimulate.
If they have high egg reserve it is easy and if low, we decide how to do it. I give them options. Full throttle, intermediate or low medication; and we decide. It is centred, individualised – I am very much into individualised advice. No rigid thing. I chose what I think is the best approach and take from there. End of the day, they decide what option they take.
A: What about abandoning? Can be very frustrating? OHSS (ovarian hyper stimulation syndrome)?
T: Haven’t had OHSS for donkey’s years! It is ‘Doctor made’. If you choose the right thing…it comes with experience. I do stop sometimes, but mostly because of poor response. I do ‘costing’, I’m pretty good at it – you stop the drugs for a couple of days, you manage it. You do a blood test every day and make quick decisions.
IVF PROCESS QUESTIONS
A: Can you tell us step by step what the IVF process is?
T: It is having more eggs, and more sperm together with very little distance between them. That’s what it is.
So, you stimulate more eggs to come out from the ovaries and we look and analyse and monitor with ultrasound and blood tests- hormone tests, what we call the follicle growth because we cannot see the eggs.
We usually give 2 types of injections. One is to stimulate the follicles and the second is to keep the eggs inside so you do not release before.
The stimulating drugs have many names. To me they’re all the same. They do the same thing. Some say my drug is better than yours but I say it’s Pepsi cola, Coca cola, what do you like, it’s a taste!
Mostly I think it’s important that you provide the drugs for the woman to use EASILY! That’s why I go for the easy option. Maybe a little more expensive, but it’s easier. You’re already under so much stress, then you have the stress also – oh 2 drops have stayed in the bottle, I couldn’t get it out, what do I do?, or there is so much air in this, is it going to go into my bloodstream, give it something simple. The stress is already too much.
So, to me that’s what the difference is. The administration for women so they can do this injection at home. But from an efficacy point of view, they’re all the same.
The other drug, the controlling ovulation drug, there are two types. You have to have a time limit on it, so you start it before a period starts, and I usually use a nasal spray for that rather than injection, to reduce number of injections. One: Gonadotropin-releasing hormone agonist (GnRH agonist) is used for luteal down regulation schedule of drugs.
Mid luteal phase, a week before ovulation, then you have the period. It stops the Luteinising hormone and the follicle stimulating hormone from the pituitary gland, so the body does not think that it is time for ovulation – the body doesn’t know that you’re going for IVF, just this idea that there is high oestrogen when we give the stimulation and with this the impulse comes in that you’re ready for ovulation. The surge comes up with the Luteinising Hormone coming in, and the eggs get released.
With this you need about 10 days to two weeks. So, you start a week before period, 2 days after that you come in for a scan and blood test, if these are alright, then you start the stimulating drug
With the antagonist, which is the other type of drugs, you start before the agonist because it does not need the time, it’s immediate.
A: Short protocol?
T: Yes, but I don’t like this term – short and long. But with the short protocol, you start stimulating with Follicle Stimulating Hormone (the same hormone all humans produce, in the man it stimulates the testicles, and in the woman ovaries) and it does what it says on the label. We give it much higher dose than physiological, as we’re aiming for more than one follicle.
In the antagonist group, once they reach a certain size or basically 6 days after starting stimulation, you add the antagonist. And it works immediately.
With both types of protocols (these are the most common but there are so many types of variation) you try and start at the beginning of the cycle and you give daily injections and you have monitoring with ultrasound. On average, you’d need about 4 scans in that period of time, in general you need about 12 days of injections. When you see that there are a good number of follicles at a good size – 18mm and above – then you have the trigger injection which is HCG, pregnancy hormone, (in the old days until now you collect it from women’s urine).
So, you give that because it’s exactly the same as the LH. Because we’ve suppressed the pituitary gland, we have to override that but it also gives us better control.
(When Edward and Steptoe started they used to give a blood test every 4 hours when they reach that stage, to find out when the LH would come. Then they go ahead and collect the egg. Mostly they would have only one egg.)
This is the advantage of using agonist and antagonist, it gives us better control for the timing of when to do the egg collection. So, we give the HCG and 36 hours (between 34/38 people still haven’t decided what’s best) but usually 36 hours later you do the egg collection.
So, for this, it’s usually done under intravenous sedation, but sometimes in Europe with local anaesthesia.
We use trans-vaginal ultrasound scanning and guided by the scan (which is the same we use for monitoring) while the woman is asleep/sedated we pass a needle into the follicle and apply some pressure, suction and suck fluid out and with it the egg also comes out.
It is transferred to the embryologist next door or side by side, sometimes next floor up, into the lift, and they look at the eggs and separate them. The process takes about 15/20 minutes. The woman wakes up and after that, she stays for a couple of hours, and goes home.
At the same time of course the male partner provides a sperm sample, or if you have a separate sperm donor you have it ready for the fertilisation. It is usually done on the same day.
They wait for a few hours. The person who does it takes time to prepare the sperm, and they think it is better to leave the eggs for a couple of hours in the incubator, and then they put them together.
If it is IVF, then you just add thousands of prepared sperm – they wash and take away the plasma, just the sperm cells, and they go through a column of culture medium so they select the most active and hyper-activate it, then they add it.
If it is ICSI, you strip away the cells surrounding the egg, the cumulus, and look at the egg. If it is mature, they take these and select the most normal sperm and inject one under a microscope.
Then they put in an incubator, they check overnight and the next day, you see what’s fertilised. After fertilisation, you can see the nuclei, you can see the sperm still surrounding it because only one enters then the zona pellucida (the membrane) ‘shuts the door’ and it’s just one. If more enters it becomes abnormal.
Day 2 you see 4 to 6 cells.
Day 3 there are 8 average and day 5, the blastocyst.
Usually we do a day 3 or day 5 transfer. Mostly day 5 so we can select the best and transfer only 1. Chances are more or less the same but with a higher multiple pregnancy chance because on day 3 you transfer 2 or 3 depending on age.
Putting the embryos back, you take a catheter, and gently thread the embryos into the uterus and you just leave them in there. They are kept with very small amount of fluid and you just inject there, and take the catheter out.
Remember the uterus is not a hollow thing. It’s a closed book you could say, really tight between the sheath but you have to remember it is three dimensional, so from all the sides it is held in.
A: Lots of women don’t want to get up because they feel it will fall out!
T: The evidence suggests it makes no difference if you get straight up. But it doesn’t matter if you want to lie down, that’s fine.
So there you have it ladies and gents. Have a nice lie down. Its fine. Personally I think that’s pretty good advice for life.
Dr. Talha Shawaf
Dr Shawaf is a Consultant in Gynaecology and Fertility management including IVF and similar therapies for more than 30 years. During this long span of time he was involved directly in assisting tens of thousands of patients. He worked with many of the early pioneers in the field as like Professor Ian Craft at the Wellington and Cozen’s House London Fertility Centre, and at Bourn Hall in the early days of IVF. He was a founder of the Assisted Reproductive and Gynaecology Centre (ARGC) in London and led the care in the Centre for the first year. From 1995 to 2013 Dr Shawaf was a senior consultant and led the fertility service for many years at the Barts and The London Centre for Reproductive Medicine, Barts Health NHS Trust. He is a leader and an expert in IVF and related fertility treatment, well known nationally and internationally with more than 100 research publications and many more presentations nationally and internationally.
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