Add ons – do they add up?

I gave a talk at The Fertility Show on Saturday about add ons, and promised to put my notes on the blog, so these are some of the key points, and links to useful sources of information.

What are add-ons?

  • They are additional treatments which your clinic may offer on top of IVF/ICSI
  • They are new or emerging treatments and there may be limited evidence about how effective they are
  • Some may have shown some promising results in initial studies but may not be proven to improve pregnancy or birth rates
  • Some clinics offer lots of add ons and may give you what looks like a shopping list of additional treatments to choose from. Some don’t offer them. This isn’t an indication of how good or forward-thinking a clinic is – some fertility experts may not be convinced that some add ons are worthwhile or safe.
  • Some clinics charge for add ons, others may include particular add ons in the cost of treatment because they think they make a difference and believe they should be part of IVF.
  • Add ons can be expensive and may substantially increase what you pay for your IVF

The Human Fertilisation and Embryology Authority (HFEA) has a list of some of the more common add ons you may be offered on their website, and a grading system for them

They include:

  • Assisted hatching
  • Artificial egg activation
  • Elective freeze-all cycles
  • Embryo glue
  • Endometrial scratch
  • Intrauterine culture
  • Pre-implantation genetic screening (PGS)
  • Reproductive Immunology
  • Time-lapse imaging

It can be difficult to know what to think about these new treatments, and the HFEA carried out patient survey to try to find out what people thought. The views ranged from those who were very strongly in favour of add ons to those who felt patients should not be offered treatments that we don’t know work. The overwhelming feeling from patients was that they didn’t want to miss out on something which might make a difference, but that this had to be balanced by the need to protect their interests.

Assessing the evidence is key and you want to know is:

  • What evidence there is about how effective something is
  • What evidence there is about whether it is safe
  • Does it carry any risks
  • How much does it cost

How do you assess the evidence?

As lay people, when we hear about evidence we may give any research or scientific paper equal weight, but in fact evidence isn’t quite as black and white as we may think.

 

The best scientific evidence comes from randomised controlled trials. In these trials, people will be divided into those who have the new technique or treatment and those who don’t in a randomised way. It is important when assessing evidence to look at whether the study included all patients or just a specific group. Sometimes research may have a narrow age range, or may have only looked at people with one specific type of fertility problem.

You should also look at the number of people included in the study. The most meaningful research will have involved a large group but sometimes you may discover that studies have taken place in one specific clinic and may involve tiny numbers of people.

Finally, check the outcomes. You want to look at studies where a healthy live birth is the outcome but some studies may stop at a fertilised egg or positive pregnancy test and this may not translate into an increase in births.

How the HFEA can help

The HFEA got together a group of leading scientists and fertility experts to look at all the existing research on each of the add ons, to assess it and to develop a traffic light system for add ons.

There is a green symbol where there is more than one good quality study which shows that the procedure is effective and safe.

A yellow symbol where there is a some evidence or some promising results but where further research is still required.

And a red symbol where there is no evidence to show something works or that it is safe

The decisions made by the group were then re-assessed by an expert in evidence to ensure every traffic light had been correctly assigned.

Green lights

Not one of the add ons mentioned at the start was given a green light to say that there is “more than one good quality study which shows that the procedure is effective and safe”

Red lights

There are a few red lights which means there is currently no evidence for assisted hatching, intrauterine culture, PGS on day three and reproductive Immunology. There may also be risks here too so do read the evidence carefully on the HFEA’s information page.

Amber lights

A lot of the add ons fall into amber where more evidence is needed. This includes endometrial scratch, freeze all cycles, egg activation, embryo glue, PGS on day five or six and time lapse.

For two of the add ons in this category, freeze-all cycles and endometrial scratch, there are big multi-centre trials going on at present in clinics across the United Kingdom. If you want one of these add ons, ask your clinic if they are taking part in the trial as you could end up getting the add on itself free of charge (this doesn’t cover the cost of the IVF/ICSI and you may be randomised into the other part of the trial and not get the add on, but it may be a good way forward if can’t afford to pay for the add on)

The cost of add ons

Some clinics offer add ons such as embryo glue or time lapse as part of a treatment cycle to every patient they treat. Others charge, and prices can vary hugely. There is often no discernible reason for wide discrepancies in price, so do look into this by finding out what a number of different clinics are charging for any add on you are considering.

Key questions

If your clinic offers you an add on, make sure you ask some questions first:

  • Why are you offering me this treatment?
  • What evidence is there that it works?
  • What increase in success have you seen with patients similar to me?
  • What are you charging and how does it compare to other clinics?
  • If you are charging more, why is this?

There are also some questions to ask yourself:

  • Are you happy with the evidence your clinic has given you?
  • Have you read the information on the HFEA website?
  • Can you afford to pay for it?
  • If you pay for it, would it affect your chances of being able to pay for another cycle if it doesn’t work?

Whatever you decide,make sure you are as fully informed as you can be about your treatment, and make sure you have read through all the evidence on the HFEA website which is there to help you to make an informed decision about your treatment.

Your views needed!

If you are having fertility treatment, or have done recently, you may have been offered some additional extras on top of your IVF or ICSI. These additional treatments include things like time-lapse imaging, embryo glue, endometrial scratching or reproductive immunology. Not all clinics offer every type of additional treatment. Some may not suggest them at all, others include them in the price of IVF or you may be given the option to pay for add ons if you would like them.

Fertility Network UK, the patient charity, and the fertility regulator the Human Fertilisation and Embryology Authority, or HFEA, is interested in finding out more about what you think about these add ons, how they should be offered and what you need in order to make decisions about whether to pay for them. Most of these add ons are not fully proven to increase your chance of getting pregnant.

If you have had treatment recently or are going through treatment currently, do take a minute to answer the short questionnaire to help them find out more about what your views are on this subject. You can find the link by clicking here

 

Expert opinion on treatment add-ons

If you’ve been unsure who to believe about fertility proline_level_measurement_in_eurasian_national_universitytreatment add-ons, you may be interested in some impartial and expert advice in two new scientific opinion papers published by the Royal College of Obstetricians and Gynaecologists (RCOG). They call for more high quality research into the role of natural killer cells in fertility and the effect of endometrial scratching on pregnancy outcomes.

Scientific Impact Papers (SIP), are up-to-date reviews of emerging or controversial scientific issues. The first paper looks at the role of uterine natural killer (uNK) cells, how they are measured, the role of testing and the evidence behind any links to improving implantation rates and early placental development. The paper clarifies that uNK cells are completely different from peripheral blood natural killer cells (which you would be testing in the blood tests some fertility clinics currently offer).

The paper makes it clear that there is no evidence to offer routine tests for NK cells as part of fertility treatment or testing, and that there is uncertainty about how NK cells are measured and reported. The paper says that treatment for raised levels with intravenous immunoglobulin (IVIg)  is not supported by the current evidence and, since it may have serious adverse effects, should not be used..

The second opinion paper explores the effect of endometrial scratch on pregnancy outcomes in women who have experienced recurrent miscarriage and recurrent implantation failure.

Endometrial scratch is a procedure which is hypothesised to help embryos implant more successfully after IVF/ICSI and involves scratching the lining of the womb.

Several studies have examined the impact of endometrial scratch in the cycle preceding an IVF treatment cycle in women with recurrent implantation failure, which appear to provide convincing evidence of benefit of superficial endometrial scratch in improving the implantation rate in this group of women. However, the effect of this treatment on pregnancy outcomes in women who have experienced recurrent miscarriage or those undergoing their first IVF cycle is uncertain.

Professor Adam Balen, Chair of the British Fertility Society (BFS) and spokesperson for the RCOG, said: “These two papers look at the current available evidence which exists and give much-needed guidance to both healthcare professionals and the public on these two topics. It is important that patients receive full information about treatments, the current evidence for benefit and whether there are any side effects or risks associated with it.”

Mr Mostafa Metwally, Vice Chair of the RCOG’s Scientific Advisory Committee added: “There is currently no convincing evidence that uterine natural killer cells are the cause of reproductive failure. Despite this, a number of women are requesting and being offered analysis of either peripheral blood or uterine killer cells and the value of these measurements remains controversial. Current evidence suggests that endometrial scratch may benefit women with recurrent implantation failure and therefore defining the optimal number of previously failed embryo transfer cycles needs to be evaluated in large cohort randomised prospective clinical trials.We still do not understand the mechanism by which endometrial trauma may lead to improvements in IVF outcomes in women and further studies are needed looking specifically at its success among women undergoing their first IVF cycle.”

The papers are available here:

The Role of Natural Killer Cells in Human Fertility

Local Endometrial Trauma (Endometrial Scratch): A Treatment Strategy to Improve Implantation Rates

Left confused about intralipids?

lipidemulsionIf you watched Panorama yesterday and were left worried or confused about intralipids, there are sources of accurate and sensible information.

Looking at some of the comments from fertility patients after the programme, it seems that many people were actually surprisingly unconcerned by the lack of evidence for many of the treatments discussed because they felt if there was any chance at all of something making a difference, they would still be happy to try it.

What the programme didn’t make clear was that there are some potential health risks from using intralipids. These are clearly explained on the current HFEA website which has excellent information on reproductive immunology and covers intralipids. There is also a basic information sheet on add-ons from the British Fertility Society.

Should you pay for add-ons when having IVF?

proline_level_measurement_in_eurasian_national_universityWhether you are at the point of considering IVF or have already had some treatment, you will be aware of the wide range of additional treatments which some fertility clinics offer on top of the standard treatment cycle. The idea is that these will improve your chances of success, and as people inevitably want to do all they can to boost the likelihood of a positive outcome, it can be very tempting to pay for at least some of these.

It is clear that they will certainly add to the cost of your treatment, but whether they will add any benefits in terms of outcomes is still very much up for debate. Few of these add-ons have a reliable base of scientific evidence to prove that they are likely to work, yet patients are often paying for them believing that without them there is a lower chance of a successful cycle.

Yacoub Khalaf who is Director of the Assisted Conception Unit a Guy’s and St Thomas’ in London, spoke on the subject at The Fertility Show at the weekend. If you missed it, you may be interested in his article on the Huffington Post about this.

Treatment add-ons

ivf_science-300x168If you are currently having fertility treatment, you are likely to be aware of the many different additions that are offered on top of the standard IVF from immunology treatments to time-lapse imaging. Yesterday’s Independent contained three articles on the subject;  a news story, details of some of the treatments which may not be evidence-based and an editorial suggesting that clinics should not be offering unproven treatments. It is worth reading if you are thinking of having treatment.

It is to be welcomed that the Independent are exploring this issue – it is something which has been a concern to many of those supporting patients for some time as more and more additional treatments are offered in fertility clinics, just a few of which are listed in the paper. Patients are often worried that if they don’t pay for extras they will be reducing their chances of success, when there isn’t a strong evidence base to support this as the leading experts quoted in the articles explain.

I’m not entirely sure I agree with the editorial though, which seems to put some of the blame for this back at the door of fertility patients with the suggestion that  “We also live in an age in which people do not like to take no for an answer. Some couples may be reluctant to face the fact that there may be no simple answer to their fertility issues. If one treatment does not work, the temptation is to demand another.”.  Patients are not likely to demand different treatments if clinics don’t offer them, and it seems to me unfair to be blame patients for the fact that clinics are offering unproven treatments. In fact, the editorial does go on to say that “the onus lies on the clinics – not the patients – to be the voice of realism“. It also claims that only a quarter of women who have IVF conceive – this may be true of an individual cycle of treatment but cumulative outcomes are far higher – many of those who conceive after IVF treatment did not get pregnant in the first cycle.

If you are having fertility treatment and are being given the opportunity to pay for additional extras, it is really important to make sure that you are clear about the evidence. The best kind of evidence comes from a randomised controlled trial (an RCT) and it is always a good idea to ask whoever is treating you to point you in the direction of evidence in the form of an RCT to suggest that paying for an extra treatment is a good idea.

Reproductive immunology

Natural_killer_cellIf you look on fertility websites, you’ll often find people discussing reproductive immunology or their NK cell tests and results. What’s often not clear from the discussions is the fact that the reason many fertility specialists don’t offer this kind of treatment is because they don’t believe there is any scientific evidence to back up the theories.

This picture above is apparently an NK cell – I can’t imagine they are quite that purple in colour, but it gives them just the kind of slightly sinister look that the name conjures up. In fact, as Dr Norman Shreeve from Cambridge University explains in the latest edition of the BioNews online newsletter, the name is misleading as the cells play a key role in early pregnancy,

If you’re thinking of looking into having your NK cells tested, or taking some of the treatments currently offered in this field, you should first read the information on the HFEA website and a scientific impact paper on the subject from the Royal College of Obstetricians and Gynaecologists which is more complex but also concludes that there is little evidence to support the use of these treatments and that their use should be restricted to research trials.

What the experts have to say on reproductive immunology

If you are considering having immune tests or treatments along with your fertility treatment, it is important to have looked into this properly. You will find vast amounts of information about this online, some of it written by people who currently offer the treatment. More and more patients consider having NK cell testing along with other assessments, but not all are aware of the views of leading professionals in the field.

The things it is really worth reading about this are first, a Scientific Impact Paper from the Royal College of Obstetricians and Gynaecologists, which is the professional body for gynaecologists, including fertility specialists, in the UK. The other is the Human Fertilisation and Embryology Authority’s information for patients about reproductive immunology. These give an evidence-based view from professional experts and will give a good basis on which to make any decision about immune tests and treatments.