Reproductive immunology: NK cells, intralipids do they work?

Throughout our IVF journeys, I researched a substantial amount about IVF treatment and add-on’s, none caused me more concern than this one.

It has some very expensive tests and some of the medications for ‘treating’ these conditions can cause very bad side effects. Yet it is something which is still fairly commonplace in the UK.

Like me if you’re thinking then I must have a really good evidenced based benefit,

then you’d be wrong!

What is reproductive immunology?

Reproductive immunology is an incredible controversial area of reproductive science. It is the belief that the woman’s immune system impacts her chances of pregnancy.

One specific example of this is there is a belief that natural killer cells which we’ll call NK cells from this point which are involved in preventing cancers, can go into overdrive in the uterus and attack the foetus.

What does Reproductive immunology consist of?

It involves testing for items which can include:

  1. Natural Killer (NK) Cell Cytoxicity Assay and Immunophenotype – Levels of NK cells in the blood and white blood cell types
  2. TH1:TH2 Cytokine Ratio – A comparison of the cytokine ratio which is thought may be a factor in miscarriages
  3. Leukocyte Antibody Detection (LAD) – These are antibodies which attack leukocytes (white blood cells). These are a very important part of your immune system.
  4. And many other panels.

On finding of these results you will likely be prescribed a course of immunotherapies to try and change these levels in the blood these treatments can include

  • Intralipids – These are refined from egg whites and soya beans and are supposed to help with NK cells.
  • Intravenous immunoglobulin (IVIg) – Again immunotherapy designed to change the make up of your immune system.
  • Steroids e.g. prednisolone – Again to reduce natural killer cells by supressing your immune system
  • TNF (Tumour Necrosis Factor)-a blocking agent – These supress TNF activity

You will be given a schedule specific to your test results which will likely include a combination of the above medications for a specific number of times, before and after your IVF treatment. 

How much do reproductive immunology treatments cost

Let me state they are incredibly expensive. A list of prices from the most infamous reproductive immunology IVF clinic in the UK have these as their listed prices (Checked on 19/08/2019)

Tests

  • Antenatal Immune Support following first viability scan (excludes blood tests or treatments) £520
  • Natural killer cells panel screen £490
  • TH1/TH2 intracellular cytokine ratios £380
  • Natural killer cells panel TH1/TH2 intracellular cytokine ratios £785
  • Natural killer follow-up £420
  • Leukocyte antibody detection (or paternal leucocyte antibodies, blood sample from both partners) £230
  • Gene mutation test for factor II and V, MTHFR £260
  • DQα Genotype (for both partners) £230
  • Killer Cell Immunoglobulin-like Receptors (KIRs) £230
  • Endometrial Immune Profile Biopsy + NK cells £510
  • Thrombophilia (comprehensive including gene mutation for clotting factors) £560
  • Screening for Lymphocyte Immune Therapy (LIT) £290
  • FG1 (NK assay panel, TH1/TH2 Cytokin ration, LAD, DQAlpha) £1,250

Treatments (Per administration)

  • IVIG 25 Gms (IV drip) £1,700
  • IVIg 30 Gms (IV drip) £2,000
  • Lymphocyte Immune Therapy (LIT) – using partner £850
  • Lymphocyte Immune Therapy (LIT) – using pool of donors £900
  • Intralipid 20% 100 ml (IV drip) £275

Often patients are prescribed a combination of medications as well. But let’s take an easy case, a consultation, full blood work and then 2 x intralipid infusions before IVF and 2 x after.

This relatively simple reproductive immunology treatment would total £2,350 and this is one of the cheaper options and this before any IVF/ICSI treatment costs are added on.

A very famous professor said this of testing for NK cells in the blood.

“You don’t test how many black cabs there are in Trafalgar square by counting how many red minicabs there are on the M25”

She is of the firm belief that these blood tests don’t tell us anything of value in the field of IVF.

This, coupled with PGS/PGD (link to our article on these) are the most expensive IVF treatment add-ons you can get. So, you’d expect that they give a good return for your investment!

You may be surprised so let’s explore that.

What is the evidence for reproductive immunology?

You will see many sites, siting plenty of positive evidence about reproductive immunology and this often comes from clinic specific studies, or tiny studies with data that doesn’t have any statistical relevance.

You can find a detailed list of articles on the National Institute for Health and Care Excellence with 228 research pieces to peruse at your leisure here

There are few very small studies that I found which showed a beneficial impact of immunotherapies for IVF. They included a small study from the university of  Warwick in 2017, an Australian study looking at using the steroid Prednisone. Finally a small study which looked at IVG discussed below

  • A small non-randomised trial studied the effect of intravenous immunoglobulin G patients with recurrent miscarriage. In the trial 38 out of 44 women who received IVIG had successful pregnancy outcome (86.3%) whereas 21 out of 50 untreated women had a successful pregnancy outcome (42%)

It’s really important to note these were tiny studies and none of them were randomised control studies which are the gold standard.

I couldn’t go through all of the evidence against these costly and un-evidenced treatments as there are hundreds, however I’ll summarise some of the more recent studies

  • Li et al., 2017 – This study was a small one, it showed no statistical increase in live birth rates of those who had had up to 3 previous failed cycles and a small increase for those who have had 4 cycles or more. This was a small study, so the population size wasn’t great enough to be conclusive.
  • Moffett and Shreeve (2015) stated ‘it is surely no longer acceptable for licensed medical practitioners to continue to administer and profit from potentially unsafe and unproven treatments, based on belief and not scientific rationale’

Having read about 30 different research pieces there are two items that stand out

  1. There is currently no drug that has evidence of preventing miscarriage by inhibition of maternal immune responses
  2. We need to have a large-scale randomised control trial to finally bottom out the impacts of reproductive immunology. The issue is getting women to take the chance either way.

Having read about 30 different research pieces there are two items that stand out:

  1. There is currently no drug that has evidence of preventing miscarriage by inhibition of maternal immune responses
  2. We need to have a large-scale randomised control trial to finally bottom out the impacts of reproductive immunology. The issue is getting women to take the chance either way.

Are there substantial risks with reproductive immunology treatments and what are they?

The simple answer is yes. Taking these medications is not risk free. They come with some substantial risks that your doctor should make you completely aware of. If you are suggested certain medications, I would check each one’s patient information leaflet which are available online to help you understand the risks more thoroughly.

We will list the key risks for each main type of treatment which include:

  • Intralipids – These have side affects of headaches, hot flushes, dizziness, nausea and a small chance of infection and clotting (these are the safest of the bunch)
  • Steroids -The risks include diabetes, high blood pressure and premature birth
  • IVIG (Intravenous immunoglobulin) – The risks for this include muscle pain, chills, fevers, headaches, lower back pain. It can also have some rare serious side effects which include blood clots, kidney failure and anaphylaxis.
  • TNF blocking agents – Rare reactions can include infections, septicaemia, severe allergic reactions and chronic infections.

Should I get reproductive immunology testing or treatment as part of my IVF cycle?

As far as we’re concerned when you put the cost of testing and treatment, with the lack of concrete proof of effectiveness and finally include the risks of the medication we cannot recommend this treatment to 99.99% of cases.

There are some individuals who may have specific autoimmune diseases (which they would already know about) who would likely require these treatments. But this would be discussed during them trying to conceive naturally anyway.

We feel that if you don’t have these then there is absolutely no need to have these tests or treatments.

One of the problems we have is that they are common in the USA and so the web is inundated with success stories where these treatments meant they had a baby, but sadly because no randomly controlled trial has been performed, we cannot make a clear correlation between the treatment and the success.

The HFEA have rated this as red and state:

Not only will reproductive immunology treatments not improve your chances of getting pregnant, there are risks attached to these treatments, some of which are very serious.

Not a glowing endorsement!

I’m sure you’re wondering why the HFEA don’t do more to stop clinics offering these treatments, well the sad thing is that HFEA have no powers to stop them offering these treatments and control on the costs. As such there is no regulation.

I like to think of it like this, all medications have to go through large scale randomised controlled trials to ascertain the effectiveness in very specific treatments.

However, IVF treatments don’t require the same amount of rigour, which allows doctors and fertility specialist to suggest non-evidence-based treatments.

We trust our doctors and expect them to tell us everything, however in the IVF world this doesn’t always happen as it’s big business. As such the only way for you to be sure you can make completely informed consent is through your own research.

Let us know what you think of this IVF treatment add-on or any others you have had experience with.

0 Comments

Submit a Comment

Your email address will not be published.

YouTube
RSS