Ever Wondered Why IVF Fails? Read On

[3p]

Why does IVF fail repeatedly for no apparent reason?

It is an unfortunate fact that the UK is way behind in helping couples who have difficulty conceiving for no obvious reason. We trust our specialists and assume they are doing the best for us with regard to our emotional and physical health. But what if they were missing a major key to the puzzle due in part to ignorance and scepticism, but mostly because it would be much more effort to investigate and treat us all properly.

I’m sure many of you will identify with my experience.
I am a 36 year old living in South Wales, UK. DH is 46 (fit and healthy) and has a 19 year old son from a previous relationship. TTC 7 years. My relevant past medical history : allergies, Toxic Shock Syndrome age 15, mild endometriosis (patch up around liver causes pain during AF), laparoscopy in 2002 and recent hysteroscopy show normal anatomy / no tubal pathology.
Back in 2002 we were offered ovulation induction and when we exhausted all of our entitled tries we moved on to IUI (x3). When we failed here, privately funded IVF (x3) was the next option and when this too was unsuccessful we were offered ICSI and after further failure we were emotional heaps with no answers and no money!

I am a medic, blinded by the statistics that are rammed down our throats but my husband is not! Often he would ask “Why not this time, the embryos were perfect?” and eventually I went on a quest for information to find out.
My search lead me to the USA and more specifically to a reproductive immunologist based in California called Dr Beer. He has spent the last 30 years proving that treatable immunological issues are the reason that patients like us fail time and time again to get or to stay pregnant. His rates of success are not 20, 30 or 40% - they are up to 85%!
I have learnt that once there is an immunological issue any further attempts at fertility treatment will compound this issue and make a successful pregnancy increasingly unlikely. The ethos of “keep trying, it’ll happen one day” is simply untrue; our bodies are overreacting and misidentifying all intruders (including embryos) and even ourselves. At this point if we don’t get treated we will never give birth and in addition put ourselves at risk of all sorts of medical complications later in life.
If you have ever had any ‘flu type symptoms or severe cramping after embryo transfer these are typical of an immune reaction and are not normal.

Dr Beer has a website at :
www.repro-med.net
There is a massive amount of information available and the chance to consult with him remotely. First you need to fill in the online form, then he will send details of blood tests to get done and finally a telephone consultation is arranged to discuss the findings and suggest treatment. He will coordinate the protocol with any local doctor and when he is satisfied with your results he will clear you for a cycle of conception. Often it is possible to conceive naturally after his treatment.

This is my experience.
I had bloods taken here (UK) for haematological profile, biochemical profile, thyroid profile, FSH, Prolactin, Antinuclear Antibodies, Rheumatoid Factor, Anti-TPO (Peroxidase), MTHFR gene mutation, Prothrombin gene mutation, Leiden Factor V, HIV, Hepatitis B + C, HTLV-1, Infectious Mononucleosis, Immunoglobulins, Fasting Insulin, Serotonin and Thyroglobulin.
I sent blood to USA for DQ alpha testing (if your white cell markers are too closely matched to your DH’s you will reject the embryo), LAD (a low result means you don’t have antibodies to DH and implantation will fail), Antiphospholipid Antibodies (a positive result means you have antibodies to the glue molecules which allow the embryo to stick), Anti-DNA Antibodies (if they are positive you are making antibodies to the DNA in the embryo and pregnancy will fail), Natural Killer Cell (NK) Assay (tests whether your NK cells which are present in everybody at birth have become too aggressive and are killing the embryo) and TH1/TH2 Cytokine Ratio (measures the balance of good and bad cells).
I also had a Day 26 Hysteroscopy + Endometrial Biopsy with a tissue sample sent to USA for analysis.

The important results were that there are 5 categories of immune problems and I have category 1 (DQ alpha match), 2 (high positive for phosphoethanolamine antibodies and heterozygous for MTHFR gene which means I have an inherited thrombophilia or a clotting disorder and implantation will fail 58% of the time), 4 (antisperm antibodies) and 5 (increased NK activity and scattered NK's in the uterus).

I consulted with Dr Beer on the telephone on 13th April and he suggests that I am predisposed to immune problems because of my history of allergies since early childhood, Toxic Shock Syndrome when I was 15 and endometriosis. The DQ alpha match with DH is enough to tip the balance and cause an aggressive response from my immune system which escalates with any external "assault". This explains perfectly why my body has rejected every embryo, why I had a severe inflammatory response when I had a knee op for reconstruction of my anterior cruciate ligament and why I have developed recent contact allergies to nickel, plaster and rosin plus other immune symptoms such as 'flu symptoms and severe abdominal pain after each embryo transfer, transient weals, rashes, joint pains, muscle fatigue, restless legs, lethargy, and why I have always had dry eyes and dry skin. It also explains why the quality and quantity of embryos was deteriorating at each IVF cycle.

The protocol he suggests is as follows:

For life :
-Folgard RX 2.2 one daily (this is very high dose folic acid, Vit B6 and Vit B12 – 2.2mg/25mg/500mcg respectively and only prescribed in the USA so it has to be sent here. It is necessary for the inherited thrombophilia as this affects their metabolism).
-Aspirin 75mg one daily (for the thrombophilia).
-Calcium 500mg twice daily (to prevent osteoporosis which is linked to the thrombophilia).
-Fish Oil 1500mg daily (helps reduce NK activity by up to 48%).

Pre-conception :
-Lymphocyte Immunisation Therapy paternal, one dose (given in London, involves injecting DH’s white blood cells subcutaneously to force an antibody response and treat category 1 problems).
-Humira 40mg subcutaneously once every 2 weeks for one month (specifically to reduce NK activity and used a lot with endometriosis. Used in this country to treat rheumatoid arthritis)

I need to retest (LAD and NK assay) 1 month after the LIT and Humira and if all is OK I will be cleared for an IUI cycle (necessary as I have antisperm antibodies) using Clexane (an anticoagulant, for category 2 problems, initially daily, then twice daily) and progesterone in addition.
He would like to try 2 cycles of IUI first before considering reverting to IVF.
I have been having weekly acupuncture and Chinese herbs for the last six months and he suggests I continue with these right through pregnancy.

He gave me some really useful information regarding the future for myself and my relatives. As I have the MTHFR gene it is essential that my mother and brothers are tested for it because without treatment (Folgard, Aspirin and Calcium) they run the risk of clotting disorders, heart attacks, strokes, osteoporosis, panic attacks, ADHD and Alzheimer’s disease. He also thinks that I may fit into a category of patient who will require Humira long-term for one month out of four and whatever happens I will need to be re-tested yearly (NK assay, thyroid profile, free insulin and serotonin levels) for life.

The really good news is that he didn’t really have any bad news!!! 68% of ladies in my situation become pregnant the next cycle and I should expect an improvement not only in the typical immune symptoms but also in the endometriosis and allergies.

So that’s my story. I know I’m not pregnant yet but I feel confident that I will be soon and I’ll keep you posted.
Out of interest although testing costs a few hundred pounds I’m hoping that most of the medication will be prescribed on the NHS as the classification of the disorder is primarily an immune one and therefore I will end up saving money just for the fact that I will be having IUI costing £600 as opposed to ICSI costing £3000!
I am lucky; I have an extremely supportive GP and fertility consultant who have agreed to help me to carry out Dr Beer’s protocol. I would plead that you start asking your specialists questions about these issues. Knowledge is power. Maybe we can force change in the apathetic and random way the UK approaches infertility of unknown cause and in the future save the misery of multiple failed cycles.
If anybody has any questions or practical concerns please ask. At the time it seems too daunting to get everything arranged but I promise it’s worth every scrap of effort and it’s much easier asking advice from somebody who has been through it!

Clare x

[LittleP]

Hi Clare

I have read with interest your story and can relate to part of it. I have just been tested for the NK cells (blood samples sent to Chicago) and they showed that I have high levels.

Given my history this has been a relief that I now have a way forward.

It is important that everyone understands that this will not always be the answer, but it could prove a valuable starting point

Thanks Clare

Little P

[harri]

Hi Clare
Thanks for taking the time to post a really interesting piece. I have "unexplained infertility" and am adamant that not enough is being done to find a reason. I feel like unless you come into one of their obvious categories they all too quickly just put it down as "unexplained". Like you say they just send you for IVF and hope that it works. We too had failed IUI's and although i'm hopeful for IVF, I also know in the back of my mind that it doesn't work for so many people.
I am going to give it a go but am going to take what you've said into consideration also. Please please keep us up to date on whether it works for you as a success story is always great motiviation for something as complex as this.
I wish you all the success in the world and best of luck x

[Sand]

Hi Clare

I found your whole post extremely informing. Although with us it's male factor, it's good to be armed with all this additional knowledge. I'm pleased you feel you've found a +ve way forward, and we'll all be dying to hear your good news soon !!

Sandra x

[ogr1]

it is great that you took the time to share all of this..
thank you

[tracker]

Hi 3P,

Thanks for posting your experience here, it's fantastic to hear from someone who has been thru such extensive testing.

I've got a similar history - miscarriage (spontaneous pregnancy), and have just been thru 3 failed IVF/ICSI cycles - all cycles had nearly 100% fertilisation, and all transfers were 5-day.

When I had my review, my doctor asked what I wanted to do and of course I said - immune testing and thankfully he agreed - and I've been referred to a miscarriage management program. I'm having my cycle monitored, and finishing up with a biopsy. My husband is also having further testing sperm assay (sp), as well as further blood tests. We'll see if anything else shows up. All of this testing is being done here in Australia.

At the same time - same as you, I have been seeing a TCM and taking herbs (stacks), and having acupuncture. My dh is as well (since when I gave her his results she nearly exploded when she saw his morphology - something that had never been explained to us!) BTW she believes this is why we miscarried - because the sperm wasn't perfect - this affects the development of the foetus.

At the moment I'm confused about all of it, and in fact feel like the most positive thing we're doing is the acupuncture and herbs. Apparently chinese herbs can have an amazing impact on morphology.

Anyway, sorry to ramble, actually have just enjoyed the opportunity to write it all down.

The whole immunology thing is so controversial at the moment. I'm not sure if it's to do with the inconclusive evidence in the clinical trials. But I have read some doctors believe you should be wary of the treatment offered.

Anyway, I'd love to keep track of how things go for you, so please keep posting.

[AliasR]

Jess, i thought you might like to read what's in here... Maybe it can help you somehow

Rita

[Bronagh]

Hi,
I'm interested in your expereince and |I do think that there is something strange the way they check on issues to do with infertility. After unexplained infertility and 2 failed IVF's after TTC for 6years we got to the point of "what to do next" I have asked our consultant about Immune testing and what 2 different ones have said is this- they are very suspicious and wary of the immune tests and therapy offered as if there is any true inking of progress in infertility the university hospitals start researching it as they always have to stay ahead. They said they are suspicious that the only Dr offering the treatment is a private clinic .
I have no idea what to think but I'm going for IVF again.
I wish anyone going down this route luck but I wonder if the sucess rate is monitored by anyone independently.

B

[julie n]

Bronagh,

Following on from your comments re private clinics, I was recently tested at St Mary's hospital in London for APA (sticky blood) etc.. This is apparently the leading place in the UK for recurrent miscarriage and failed IVF research. I like most of you had grade 1 embryos but 3 failed fresh and 1 failed FET cycles. I am borderline APA and will now be treated with heparin for the next cycle.

I second what everyone else says I now feel that I have left no stone unturned!

Julie

[dancola]

I posted on this elsewhere, but my clinic will be testing me (tomorrow) for 3 different immune problems following just 2 cycles. The first was a +ve but I then lost the pg after a few days, and the 2nd in April was a –ve. Both times I had 5-day old good quality blastocysts transferred. They will be testing me for Natural Killer Cells, and two other conditions which relate to blood flow to the womb as mentioned above. NKC can be treated with steroids, and the latter two with a dose of Heparin and baby aspirin. I am pleased they are doing this now, rather than have me go through more cycles with the same result.

[tracker]

Hi everyone,

This is a really important thread and anyone going thru any of this testing, I encourage you to post your experience/findings/treatment.

It's understandable that while you're cycling the last thing you want to read about is the possibility of failure, let alone repeated failure, but if you do have this unfortunate experience the information and shared experience in a thread like this is invaluable.

I am nearing the end of my testing - I posted earlier, miscarriage, followed by 3 failed IVF/ICSI cycles (all 5-day embryos 'hours from hatching'). I am currently on a miscarriage management program in Sydney and have been monitored thru my full cycle, have had about 30 blood tests taken (including the APA, ATA, and Killer Cell - called T Cells as well(?). As I near the end of my cycle I will be having a biopsy.

Should anything be found, I'm hoping there will be treatment, if this testing shows up nothing then at least I can feel that when I go on, absolutely everything has been checked.

I feel the same concerns as everyone else that have posted earlier about the miracle treatment offered. It is very seducing to read stats like 85% success rate.

Also recommend, from my own experience, that if you can find a great traditional chinese practitioner specialising in fertility it's well worth it. In this instance there are clear results in clincial trials that confirm the benefits of acupuncture when going thru ivf. I also have felt great benefit to having someone else in my corner with me. My chinese doctor is working with both myself and dh to bolster our fertility with herbs - because she believes we can conceive naturally(!)

Anyway, everyone keep posting please.

[tracker]

Hi All,

I just thought I'd raise this thread once again as I have had my follow up appt. with my doctor and received my results.

In what is becoming an all too familiar story - I tested a low positive for anticardiolipin (ACA). The recommendation is that I take heparin on my next cycle.

Obviously this still doesn't guarantee any success, but in the absence of anything else to explain failure of what look to be perfect 5-day embryos, this something we now know that we didn't.

Our testing was as thorough and up to date as it can be in 2005 - and included all genetic - MTHFR.

I would absolutely encourage anyone that has experienced ivf failure (more than 2) and particularly anyone who has also been thru miscarriage as well to look into what testing you can get before proceeding straight into another cycle.

Look forward to hearing from anyone else who has recently undergone anything similar.

Cheers,

[dancola]

Thought I’d add my update here too. Friday I had my appointment with the head consultant at my clinic to discuss my test results (I was tested for NKC, anticardiolupins like tracker above, and anti-coagulants). The latter two are the ‘blood flow’ problems and I was hoping I’d come up +ve for one of those, as treatment with heparin/aspirin is preferable to steroids! Unfortunately I came up with higher than normal NKC. I’m told it’s perfectly normal to have slightly higher levels of NKC, and in a natural pregnancy would not cause any problems. However, with IVF the embryo is detected as being a foreign body hence the NKC will attack it. There are 3 types of NKC (C-numbers) and whilst I’m in the normal range for two of these tests, they are high for women undergoing IVF. The 3rd test I was higher than the normal range.

So, it’s steroids for me. Will start them after EC. Short-term they are not unsafe to take (only real side effect is unfortunately weight gain) but if I manage to get a +ve I’d have to take them until the 4th month of pg.

It’s interesting that my consultant referred to me as having suffered repeated miscarriages even though I’ve only had 2 cycles. Whilst the first was a short-lived +ve followed by an early m/c; the April cycle was a –ve. However, he seems to be treating my 2nd –ve as a m/c too. I’m sort of taking hope from the fact that he’s attributing them to my NKC. He did stress that NKC is a bit of a hot potato. Some clinics say it has nothing to do with m/c, whilst others think it has everything to do with it. Luckily for me, he works closely with a colleague at the Parkside hospital in Wimbledon who has done extensive research into the subject and makes a definite link between the two. Given that short-term of steroids will not cause harm, I am glad my clinic have tested me now for these conditions rather than wait for a few more –ve cycles.

My anti-coags came back –ve. Unfortunately I’d had to do the lupins as the lab made a mistake and didn’t do the tests!

[LittleP]

Just thought I would update here as well:

I've recently been diagnosed with higher levels of NK cells and will be having treatment for these during my IVF. After EC they will give me a drip and put me on steroids and heparin.

I'm keeping everything crossed that his will bring me and DH the solution we so desperately crave - a positive result that I can carry full term

Hope you are all ok

Little P

[eskavon]

I've just read this thread - WOW how interesting - I guess questions going through my mind now are why don't they test for these before doing ivf? It makes sense and if you're paying for it anyway what difference does a couple of hundred make. We had lots of tests for hiv, std's etc but none for something which could potentially make ivf fail.
I hope it all goes well for you ladies and it must be reassuring to have answers. But it also must be so frustrating the traumas that you've all been through.
I'm now going armed with a list of questions for my follow up appt.
Good luck to you all and I hope you get what you want - a +ve result