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Reproductive Immunology Practice in IVF

The concept of 'Reproductive Immunity' and its role in the field of IVF is one of the hotly debated and controversial elements of screening and therapy for IVF treatment. Some elements, such as coagulopathy are less controversial and investigated by many practitioners, other areas are reviewed with skepticism by some but investigated with conviction by others. As always in areas of medicine at the cutting edge of scientific validity there is huge variation in practice and no consensus to its value. It is hoped that this - the first survey of its kind - will obtain an understanding of the extent of its use in IVF centers internationally. If the response merits, a follow up survey will be compiled on the approach to treatment and therapies.

This survey, proposed by: Joanne Kwak-Kim , MD, Director, Reproductive Medicine Associate Prof. Dept. of Obstetrics and Gynecology, Associate Prof. Dept. of Microbiology and Immunology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, and Professor Simon Fishel, Managing Director - Professor of Human Reproduction CARE Fertility Group, UK.

Do you think understanding and use of principles of reproductive immunology is important for human reproduction?
  • Yes
  • No
  • I do not know

 

Where do you get reproductive immunology updates?
  • I do not think I need to know
  • I have no resources
  • Through academic press or professional journals
  • From professional colleagues
  • Through web site or on-line information site
  • Through patients

 

Do you think reproductive immunology updates are easy to obtain from the IVF society or network?
  • Yes
  • No
  • I do not know

 

Do you check the following information prior to IVF cycle?
  • A history of or active autoimmune disease
  • A history of or active coagulopathy
  • Family history of autoimmune disease
  • Family history of coagulopathy
  • I do not check any of above

 

What percentage of IVF patients in your practice has a history of recurrent pregnancy losses (2 or more pregnancy losses) (RPL) or chemical pregnancy losses?
  • 0
  • Less than 10%
  • 10% - 30%
  • 31% - 50%
  • >50%
  • I do not know

 

Which of the following do you do if you have IVF candidates with a history of RPL or chemical pregnancy losses? (More than one answer is allowed)
  • Treat patients with the usual protocol
  • Recommend parental genetic study
  • Recommend reproductive immunology evaluation
  • Recommend thrombophilia evaluation
  • Recommend sperm aneuploidy testing
  • Recommend sperm DNA fragmentation index (DFI) assessment
  • Recommend PGS (preimplantation genetic screening – also known as PGD)
  • Recommend egg donor cycle
  • Recommend surrogacy

 

Which of the following endocrine tests do you undertake for the evaluation of RPL: (More than one answer is allowed)
  • None
  • TSH
  • FT4
  • FT3
  • Prolactin
  • Fasting glucose
  • Fasting insulin level
  • Glucose tolerance testing

 

Which of the following reproductive immunology tests do you undertake for the evaluation of RPL: (More than one answer is allowed)
  • None
  • ANA
  • Thyroid peroxidase antibody
  • Thyroglobulin antibody
  • Cardiolipin antibodies (IgG, IgM)
  • Beta-2 glycoprotein 1 antibody
  • Lupus anticoagulant
  • Antiphospholipid antibodies such as Antiphosphatidyl ethanolamine antibody Antiphosphatidyl serine antibody Other autoantibodies to phospholipids
  • NK cell assay (blood)
  • Immunophenotype assay
  • TH1/TH2 cell ratio
  • HLA Class I and II antigens
  • HLA DQ alpha
  • Leukocyte antibody detection (crossmatch)

 

Which of the following thrombophilia tests do you undertake for the evaluation of RPL: (More than one answer is allowed)
  • None
  • APTT
  • Activated Protein C Resistance
  • Antithrombin III
  • Serum homocysteine
  • Protein C and Protein S
  • Serum PAI-1 level
  • Factor V Leiden
  • Prothrombin (Factor II) gene
  • MTHFR gene
  • PAI-1 gene

 

Do you know the percentage of patients with RPL who have abnormal reproductive immunology tests in your clinic?
  • I do not know
  • Less than 10%
  • 10% - 30%
  • 31% - 50%
  • >50%

 

Do you know the percentage of patients with RPL who have abnormal thrombophilia tests in your clinic?
  • I do not know
  • Less than 10%
  • 10% - 30%
  • 31% - 50%
  • >50%

 

Do you run karyotype assay on products of conception when patients miscarry after IVF treatment?
  • Yes, I run if the specimen is available
  • No, I don’t test
  • Follow patient’s decision

 

When a miscarriage after IVF is genetically normal, what do you recommend?
  • Try again with the same IVF protocol
  • Try a different IVF protocol
  • Recommend egg donor cycle
  • Recommend sperm donor
  • Recommend immunological evaluation
  • I do not check for genetic abnormality

 

After how many IVF cycles resulting in pregnancy losses do you undertake further investigations similar to RPL evaluation
  • 1
  • 2
  • 3
  • >3
  • I do not investigate at all

 

Do you consider recurrent implantation failure (3 or more failed ET) (RIF) in the same way as RPL including chemical losses?
  • Yes
  • No

 

If ‘No’, do you investigate for RIF with any reproductive immunology tests?
  • Yes
  • No

 

When do you think immunological assessment is needed for IVF population?
  • It is not necessary at all
  • I do not know
  • When starting infertility work up
  • Infertility of unknown etiology regardless of IVF treatment
  • When starting the first IVF cycle
  • After one failed IVF cycle
  • After two failed IVF cycles
  • After three failed IVF cycles

 

Which of the following endocrine tests do you undertake for the evaluation of RIF: (More than one answer is allowed)
  • None
  • TSH
  • FT4
  • FT3
  • Prolactin
  • Fasting glucose
  • Fasting insulin level
  • Glucose tolerance testing

 

Which of the following reproductive immunology tests do you undertake for the evaluation of RIF: (More than one answer is allowed)
  • None
  • ANA
  • Thyroid peroxidase antibody
  • Thyroglobulin antibody
  • Cardiolipin antibodies (IgG, IgM)
  • Beta-2 glycoprotein 1 antibody
  • Lupus anticoagulant
  • Antiphospholipid antibodies such as Antiphosphatidyl ethanolamine antibody Antiphosphatidyl serine antibody Other autoantibodies to phospholipids
  • NK cell assay (blood)
  • Immunophenotype assay
  • TH1/TH2 ratio (blood)
  • HLA Class I and II antigens
  • HLA DQ alpha
  • Leukocyte antibody detection (crossmatch)

 

Which of the following thrombophilia tests do you undertake for the evaluation of RIF? (More than one answer is allowed)
  • None
  • APTT
  • Activated Protein C Resistance
  • Antithrombin III
  • Serum homocysteine
  • Protein C and Protein S
  • Serum PAI-1 level
  • Factor V Leiden
  • Prothrombin (Factor II) gene
  • MTHFR gene
  • PAI-1 gene

 

Do you know the percentage of patients with RIF who have abnormal reproductive immunology tests in your clinic?
  • I do not know
  • Less than 10%
  • 10% - 30%
  • 31% - 50%
  • >50%

 

Do you know the percentage of patients with RIF who have abnormal thrombophilia tests in your clinic?
  • I do not know
  • Less than 10%
  • 10% - 30%
  • 31% - 50%
  • >50%