Immunotherapy

Natural killer cell testing and immune therapy

There are several factors that can cause embryo implantation to fail, including

  • Genetic causes
  • Anatomical causes
  • Endocrine causes
  • Haematologic causes
  • Immunologic causes
  • Miscellaneous causes.

 

In most cases, it is the result of a chromosomal abnormality (known as aneuploidy) within the embryo. In some cases, it can be a combination of the above causes. In the past decade, there has been considerable efforts and research trying to identify possible immunologic causes for poor fertility treatment outcome.

 

ImmunologyWhat happens around implantation?

The embryo is formed of two cell lines (the inner cell mass and the trophectoderm). The inner cell mass contains the cells that form the baby and the trophectoderm contains the cells that will form the fetal part of the placenta.  Implantation is a complex process that involves interaction between the trophectoderm and the womb lining (endometrium). During this process there is mutual exchange of substances and chemicals. This is sometimes referred to as ‘embryo-maternal cross talking’. Successful implantation is the first crucial step in achieving a pregnancy.

 

What do I need to know about Natural Killer cells (NK cells)?

NK cells are immune cells that belong to a subcategory of white blood cells called ‘Lymphocytes’. They provide the body with protection against virally infected cells and potential cancerous cells. NK cells are produced by the bone marrow and then they move to the blood circulation to play a role in the body natural defence mechanisms. Some of the NK cells will migrate to various organs including gastrointestinal tract, liver and the uterus where they undergo specific changes that render them as one of the immunological defence barriers in those tissues. In the uterine lining after ovulation and in early stages of pregnancy; NK cells account for more than 80% of the white blood cell population. NK cells produce and respond to a variety of chemical substances called ‘cytokines’.

 

Is there strong evidence to support that abnormal NK cells are associated with poor fertility or pregnancy outcome?

This matter is controversial within the medical field. NK cells are the most abundant immune cells in the womb lining (endometrium) at the time of implantation. There are different types of NK cells.  It has been speculated that an imbalance in the cytokines and the killing activity of the NK cells can have a negative impact on implantation or the progression of a healthy pregnancy.

 

Results published in the medical literature have been contradictory; however, it is thought that recurrent miscarriages and recurrent implantation failures that cannot be explained by routine investigations might have an immune based cause.

 

The HFEA, the Royal College of Obstetricians and Gynaecologists (RCOG), Science Advisory Committee and the American Society of Reproductive Medicine (ASRM) all agree that there is no strong evidence at the moment to justify immune testing and treatment in the context of fertility failure and recurrent miscarriages.

 

“There is no convincing evidence that a woman’s immune system will fail to accept an embryo due to differences in their genetic code. In fact, scientists now know that during pregnancy the mother’s immune system works with the embryo to support its development” HFEA.

 

These treatments are currently deemed as red in the HFEA’s traffic light system of addition treatment options. If the treatment is listed as red then there is currently no validated evidence to show that it is effective and safe

 

 

Are the natural killer tests offered routinely at CRGH?

NK tests are not routinely offered to all patients seeking fertility treatment as the majority of failed fertility treatments and miscarriages are secondary to a chromosomal abnormality in the embryo and not immune in origin. You will have the chance to discuss carrying out those tests with your doctor during the consultation if you have a history of recurrent miscarriages, recurrent implantation failures or if you have a personal history of autoimmune disorders (such as lupus, rheumatoid arthritis, ulcerative colitis, auto-immune thyroid issues, Crohn’s disease….).

 

What are the NK tests available at CRGH?

NK cells can be checked in the peripheral blood or in the womb lining (endometrium).  At CRGH we offer both tests. Endometrial NK cells are checked by doing minor procedure (lining scratch) that is done between days 15-25 of the period. The sample retrieved will be send to the laboratory for analysis. NK cell test is performed on specific days of the week, so please confirm with the clinic before booking the test. Natural killer cells in the blood are not a good reflection about the NK cells in the lining; however, there is evidence to suggest the association between NK cell activity in the blood and fertility issues. In most cases the blood test and the lining scratch are done on the same day.

 

What are the treatment options that are offered at the CRGH for elevated NK cells?

Several immunosuppressive treatments have been used in this context. Three treatment options are currently available at the CRGH.

 

  1. Oral steroid treatment (Prednisolone)
  2. Intralipid infusion
  3. IVIg (Intravenous immunoglobulin-g) infusion

 

No results from randomised clinical trials are available to show a clear benefit of patients receiving immunomodulatory treatment versus those who have not. However, several smaller studies suggest that there may be significant benefit of immunological treatments compared to no treatment at all. It is important to note that the Royal College of Obstetricians and Gynaecologists does not recommend testing or immunologic treatment except in the realm of experimental medicine.

 

The Royal College also mentions that:

“Women undergoing uterine NK cell testing should understand that there is, as yet, no proven effective treatment for those with what may be considered abnormal results, although preliminary data suggest a possible positive effect of prednisolone.”

 

 

Steroid (Prednisolone) Treatment

Steroid (Prednisolone) is a commonly used medication in the treatment of auto immune diseases. It acts by suppressing the immune system. The role of immune mediators in the process of embryo implantation has not been conclusively confirmed. However, there is some evidence that steroid treatment may be beneficial in improving the implantation of your embryo(s). As there is inconclusive evidence regarding the benefits of steroids, the clinic will only offer it when your consultant deems it appropriate for your treatment. In case you choose to take this medication, you will start receiving Prednisolone or when you commence progesterone’s.

 

 

Intralipid®

Intralipid® is a fatty mixture emulsion which has been shown to decrease natural killer cell activity in vitro. Intralipid® is usually used as a caloric and intravenous food supplement. Unlike other medications used to suppress natural killer cell activity, Intralipid® is not a human derived product. Intralipid® has been used for improving implantation in patients with high natural killer cell activity, but there is limited information available regarding its efficacy. The use of Intralipid® has not been recommended by the HFEA or the RCOG (Royal College of Obstetricians and Gynaecologists). Having Intralipid® infusion is not obligatory. Whilst there is inconclusive evidence regarding the benefits of Intralipid®, the clinic will only offer it when your consultant deems it appropriate for the treatment.

 

When is it performed?

Patients will receive a total of three doses for fresh IVF cycles as follows:

  • The first dose will be around day 6 – 8 of stimulation
  • The second dose will be given around embryo transfer day
  • The final dose is given around the first pregnancy scan (6-7 weeks)

 

For frozen cycles, the schedule is as follows:

  • The first dose will be around day 6-8 of progynova
  • The second dose will be given around embryo transfer day
  • The final dose is given around the first pregnancy scan (6-7 weeks)

 

How long does it take?

The infusion takes approximately 1 and a half hours in total.

 

What preparation do I need?

None. You may eat and drink as normal prior to, during and after the infusion.

 

 

If you would like to book an appointment with one of our doctors you can:

  • Speak to the booking team on +44 (0)20 7837 2905  (Mon – Fri 8.30am – 6pm)
  • Email us on info@crgh.co.uk 
  • Visit our Appointments page, fill out the contact form and a member of the team will be in touch

IVF Packages With Access Fertility

IVF Packages With Access Fertility
CRGH is partnering with Access Fertility to offer a series of IVF programmes and packages. For more information please click below.

NHS Funding for Fertility Care

CRGH is an NHS approved centre and funding may be available for some patients. You will need to meet certain criteria and be referred to us by your GP. Please call or email us for further information.
Call: +44 (0)20 7837 2905

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