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Reproductive Immunology

There are many reasons that recurrent miscarriage and IVF failure occur, and age is the biggest factor. Our clinic has a reputation for high levels of success in helping couples to conceive who have a previous history of IVF failures.  About half of our patients probably fall into this group. Our Medical Director, Dr George Ndukwe has specialised in this area for many years and is considered a world leader in the field.

One of the approaches we take with this patient group is based on the concept that repeated implantation failure, which some patients experience despite having good quality embryos, may be due to immunological issues.  It is thought that his may be the case in a small but significant minority – say 20% – of IVF patients.  This area of medicine is called reproductive immunology (RI), and there are specific specialised blood tests we can use to find out whether there may be immunological issues.
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A Couple’s Story following IVF at the Zita West Clinic

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How do we assess clients?

Many women with recurrent miscarriage do not need IVF.  However, we have observed that the following factors appear to be associated with an increased risk of immune problems and we would consider testing selected patients in these cases: –

  • Good quality embryos/blastocysts but 2 or more failed cycles
  • Women over the age of 35 who have had two or more miscarriages or two or more failed IVF/ICSI with good embryos
  • Unexplained infertility for 3 years or more
  • Previous immune problems or family history, such as:
    • Anti-nuclear antibody (ANA)
    • Anti-thyroid antibodies
    • Rheumatoid arthritis and/or lupus
    • Crohn’s disease
    • Psoriasis
    • Ulcerative colitis, etc
    • Previous pregnancies that have resulted in small babies (foetal growth retardation);
    • Endometriosis

“A successful pregnancy is a unique phenomenon because it is the only time a foreign protein (i.e. the foetus) stays in the human body and is not rejected” Dr Ndukwe

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Testing

We do two levels of tests. Level 1 tests are to rule out any treatable simple medical factors associated with recurrent IVF failure/miscarriage. Level 2 tests are more in-depth investigations into immunological factors that may be associated with recurrent embryo implantation failure and currently include Natural Killer (NK) assay and TH1/TH2 Intracellular Cytokine ratios. NK cells are one of several types of white blood cells in the immune system. They play a useful physiological role in the body but some research has suggested that raised NK levels or cytotoxicity (“killing capacity”) in the peripheral blood and raised NK infiltration in the endometrium (womb lining) may be associated with recurrent IVF failure and recurrent miscarriage. Cytokines are chemical messengers secreted by immune cells. Cytokines produced by the group of immune cells called TH2 are thought to be “baby-friendly” and support pregnancy whereas the cytokines produced by the group of immune cells called TH1 may inhibit pregnancy. For successful pregnancy it has been suggested that the TH2 (“baby-friendly”) cytokines should be dominant. If the TH1 cytokines are dominant this may impact adversely on pregnancy outcomes. We use the results of the blood tests done for NK assay and TH1/TH2 intracellular cytokine ratios to work out the most appropriate strategy to help us optimise the chances of a successful treatment and pregnancy.

If abnormalities are identified which we believe may impair the chances of a successful treatment and pregnancy, we will often suggest immunomodulation treatment for the female partner which may include the use of Prednisolone (steroids), Clexane and Intralipid infusions at appropriate stages in the IVF cycle. The extent of immunomodulation depends on the level of the immune abnormality the tests show. Intralipid is a sterile emulsion of egg proteins, soy oil, glycerine and water.

The status of the science behind Reproductive Immunology

The whole area of RI is controversial.   Most doctors and scientists in the field of reproductive medicine believe that the human immune response may be an adverse contributory factor to reproductive outcomes for some people, in some circumstances. However, where there is much disagreement is on what those circumstances may be, how the couples affected may be identified and the ways in which the immune response may work and, therefore, be treated. It’s an issue which has been in the public domain for many years and it has been debated regularly by clinicians and scientists at medical and scientific conferences. Most fertility specialists are not convinced by the existing science behind the approach. The Royal College of Gynaecologists and Obstetricians (RCOG) has published a very detailed scientific impact paper on the subject which concludes that the science behind RI remains uncertain. The Human Fertilisation & Embryo Authority (HFEA) goes further and describes the concept as “discredited.”  Nevertheless, a significant minority of clinicians, ourselves included, believe that it can be a very effective treatment approach, but only if it is used selectively.

The published research on the approach is, by itself, insufficient to form any firm conclusions about efficacy because no large scale randomised controlled trials (RCTs) have yet been carried out (though, there is a small RCT that shows intralipids improve live birth rates in women with recurrent IVF failure).  As we see it though, it is also critically important to take the results associated with its use in real life clinical practice into account as well – and here our clinical pregnancy rates speak for themselves. Our latest published results (July 15 – June 16) show, for example, a Clinical Pregnancy Rate of 68.8% per Fresh Embryo Transfer for women under 35 years of age, which is one of the very best in the UK. As we often say to the critics of the RI approach, if there is nothing to RI based treatment, how is it that we manage to deliver clinical pregnancy rates year after year which are substantially higher than those achieved by most other clinics, even though a large proportion of our patients have experienced previous failed cycles elsewhere and should, statistically, have a lower than average chance of success?

We do things differently

Many  women who have suffered recurrent miscarriage and IVF failure have not been given clear reasons why this has happened but are persuaded to keep repeating the same unsuccessful process.  With their fertile time often running out, it is important for them to consider other options.

At our clinic, we have always looked at what else can be done to help improve women’s chances and support them through a very stressful process.  We pride ourselves on doing things differently, not just seeing it as a numbers game and persisting with the same one-size-fits-all treatments.

When we argue the merits of the RI approach with our professional colleagues we often ask them: “What is their alternative for patients who have repeated implantation failure?”  We think this side of the debate needs to be opened up. We frequently see patients who have chosen the RI approach having had several failed cycles of IVF at other clinics, yet they often achieve their first pregnancy once they are given immune-based treatments following appropriate immunological investigation. This is a fact, and we have lots of patients who are happy to talk about it [see some of the videos on this page].  Many of our patients come to us because they want to talk to someone who is willing to “look outside the box” rather than persist with clinics whose practice hasn’t changed significantly in the last 10 years.

Complementary therapies to support Reproductive Immunology

Many factors affect our immune system and treatments may vary. For example, some patients with specific immune conditions such as thrombophilias and endocrine disorders may require additional treatment from a specialist in that field. For many women diet, processed foods, alcohol, cigarettes, stress, exercise, anxiety, will all have an impact too.

“Our work aims for positive changes in couples’ lives, and alongside your medical treatment plan we believe in an integrated approach, using other treatments that will support the immune system through diet, stress reduction, and mind / body factors.” Zita West 

Anyone diagnosed with a reproductive immunological issue may benefit from having a nutritional consultation

At a nutritional consultation, we will make an assessment of your current dietary intake and will formulate a nutrition plan specific to your individual needs which may include appropriate supplements.

Most women having reproductive immunology tests will have experienced the stress of unexplained infertility, IVF failure, or miscarriage. Stress, over-work, fatigue and even getting a cold can have a powerful impact on the immune system and we frequently recommend Acupuncture and Hypnotherapy which may help you physically and emotionally in achieving optimum mind-body balance to further support your medical treatment.

Check out this Daily Mail article on our success with Reproductive Immunology – Mayonnaise Miracle Babies

Next steps

                  • Phone for an appointment with Dr George Ndukwe or Dr Simone Rofena;
                  • At your consultation, we will discuss whether investigation is appropriate, and arrange any blood tests you might need;
                  • Return for a follow-up consultation to discuss any test results and plan any further treatment.

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We offer consultations at the clinic or via web conferencing
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Secrets of Successful IVF
by Zita West
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