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CAREunity: identifying a cause of miscarriage

A new test which identifies one of the causes of miscarriage (and other pregnancy complications).

  

Nearly 10 years ago, CARE became interested in the discovery of a new gene mutation that could cause miscarriage in early pregnancy. That gene mutation could also cause placenta-mediated pregnancy complications (also known as ‘PMPC’), such as ‘small for dates babies’, pregnancy-induced hypertension, venous thromboembolism or preeclampsia. The DNA coding for this particular gene, known as ‘Annexin A5’, has 58,000 DNA letters, but when only 4 of the letters are different to what they should be (a mutation, or ‘variant’) then this causes problems with blood clotting mechanisms. The gene is found on chromosome number 4; and this variant is known as the ‘M2’ variant, so we called our original work on this ‘C4M2’.

Annexin 5 is partly responsible for normal clotting in our body, but if the person carries the M2 variant it may result in blood clotting disorders (sticky blood). We know this variant is carried by about 15% of Caucasians (it differs in incidence in various ethnic groups) but up to 44% of IVF couples[1]. It is also equally present in men and women, so it can be passed on to the embryo equally from the man or the woman if either (or both) are carriers. If this variant passes into the embryo and its placenta after conception, then it increases the risk of early miscarriage (the risk being up to 12 weeks of pregnancy) as well as other potential pregnancy complications. There is a helpful treatment for this condition, which is the woman taking low molecular weight heparin (LMWH) to keep the blood from forming tiny micro-clots in the placenta. For couples with this condition, if the woman takes LMWH then it increases her chance of carrying the pregnancy to term from 16% (without treatment) to 42%[2].

In our early work, we had to take blood from the couples – it very important to test both the male (if he is providing the sperm) and female, so we were very keen to develop an easy test. Working with world-leading molecular geneticists in the US, CARE now has a simple saliva test to help us screen our patients: CAREunity.

 

How does the CAREunity test work?
This screening test can identify the presence of the Annexin A5 gene. If the gene is present in either the sperm of the egg provider then there is at least a 50% chance it will be present in the embryo.

Testing for it is simple, a swab is taken from the inside of the mouth of both partners and the results are available in about 3 weeks. If the Annexin A5 Variant is identified in either partner the woman having embryo transfer will be prescribed a blood thinning medication called Heparin, better known as Clexane. This is an under the skin injection that starts at the time of embryo transfer and continues until at least 12 weeks of pregnancy

 

 



Investigations and treatments for recurrent implantation failure and miscarriage

If you’ve previously had fertility treatment that hasn’t been successful, or if you have experienced recurrent miscarriage, we can investigate why this happened and hopefully help you to giver you a greater chance of success in the future.

  

In Summary

Up to 44% of couples (22% of women, 24% of men) attending for IVF may be carriers of the M2 variant.

 

Carriers have:

  • 4x risk of embryo loss up to 12 weeks of pregnancy
  • 2x risk of preeclampsia
  • 6x risk of the baby being small for its gestational age
  • 2x risk of venous thromboembolism
  • 2x risk of gestational hypertension

To find out more about CAREunity, PGT-A testing, or to ask any questions you may have, call our enquiry team on 0800 564 2270 or you can contact us.

 

 

1. Fishel, S. et al (2014). Multicentre study of the clinical relevance of screening IVF patients for carrier status of the annexin A5 M2 haplotype. Reprod. BioMed. Online 29, 80–87.

2. Fishel S, et al (2016). Precision Medicine in Assisted Conception: A Multicenter Observational Treatment Cohort Study of the Annexin A5 M2 Haplotype as a biomarker for Antithrombotic Treatment to Improve Pregnancy Outcome. EBioMedicine:10;298.

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