| Study |
Test |
Method |
Tube Requirements |
Antiphospholipid Antibodies Panel
(18 antibodies) |
antibodies to cardiolipin,
phosphatidylserine,
phosphatidylethanolamine,
phosphatidic acid,
phosphatidylinositol,
phosphatidylglycerol
(IgM, IgG and IgA isotypes) |
ELISA |
10 cc SST |
| |
Indications:
Antiphospholipid antibodies should be tested in women with a history of recurrent pregnancy loss and/or failed in-vitro fertilization (IVF) cycles. |
| | Pathophysiology:
Antiphospholipid antibodies can interfere with implantation and placental formation. They also lead to a hypercoagulable state, resulting in arterial and venous blood clots.
|
Antinuclear Antibodies Panel
(6 antibodies) |
Antinuclear antibody,
double stranded DNA antibody,
anti-Sm antibody,
anti-RNP antibody,
anti-SS-A antibody,
anti-SS-B antibody |
ELISA |
10 cc SST |
| |
Indications:
Antinuclear antibodies should be tested in persons suspected of autoimmune or connective tissue diseases and women with a history of recurrent pregnancy loss and failed IVFs. |
| | Pathophysiology:
Antinuclear antibodies lead to intracellular destruction with resultant tissue inflammation. For example, placental villitis and vasculitis can contribute to a miscarriage.
|
Antithyroid Antibodies Panel
(2 antibodies) |
Anti-microsomal antibody,
anti-thyroglobulin antibody |
ELISA |
10 cc SST |
| |
Indications:
Antithyroid antibodies should be tested in women with a history of recurrent IVF failures. In addition, they are seen frequently in women with a history of recurrent pregnancy loss. |
| | Pathophysiology:
Antithyroid antibodies do not directly affect the placenta or fetus, but are a strong indication of polyclonal B-cell activation. The latter is implicated in reproductive failure.
|
Antisperm Antibodies Panel
(2 antibodies) |
Sperm antibodies on the sperm cell membrane
(IgA and IgG isotypes) |
Flow cytometric assay |
10 cc SST |
| |
Indications:
Antisperm antibodies should be tested in men and women with a history of infertility and recurrent IVF failure. |
| | Pathophysiology:
Antisperm antibodies interfere with fertilization. Antisperm antibodies measured by flow cytometry are an indirect measure of antiphospholipid antibodies.
|
Antipaternal Leukocyte Antibodies Panel
(2 antibodies) |
Non-complement fixing maternal antipaternal leukocyte antibodies (blocking antibodies or allo-antibodies) |
Flow cytometric assay |
female 10 cc SST
Male (2) 10 cc Na heparin |
| |
Indications:
Antipaternal leukocyte antibodies should be measured in women with a history of recurrent pregnancy loss. |
| | Pathophysiology:
Antipaternal leukocyte antibodies are normally produced in early pregnancy to block the maternal immune system from attacking the paternal antigens on the developing fetus. Lack of these antibodies leads to first and second trimester miscarriages.
|
Immunophenotype
(7 parameters) |
Extensive white blood cell differential, including
T-cells (CD3),
B-cells (CD19),
T helper cells (CD4),
T suppressor cells (CD8),
activated T cells (DR),
natural killer cells (CD56/CD16),
and cytotoxic B cells (CD5/CD19) |
Flow cytometric assay |
4 cc EDTA |
| |
Indications:
Natural killer cells and Cytotoxic B cells should be measured in women with a history of recurrent pregnancy loss and/or recurrent failed IVFs. |
| | Pathophysiology:
Natural killer cells detect small cancer cells and kill them before they can become tumors. In high numbers, these cells may misinterpret the fetus as a cancer and kill it.
|
| Natural Killer Cell Activation Assay |
The percentage of NK cells displaying the activation marker CD69 |
Flow cytometric assay |
(2) 10 cc Na heparin |
| |
Indications:
Natural killer cell activity should be measured in women with a history of recurrent pregnancy loss and/or recurrent failed IVFs. |
| | Pathophysiology:
Natural killer cells detect small cancer cells and kill them before they can become tumors. If these cells are highly active, they may misinterpret the fetus as a cancer and kill it.
|
Natural Killer Cell with IVIg Assay
(12 parameters) |
A functional assay that assesses killing power of NK cells and ability of IVIg to inhibit this activity in-vitro |
Flow cytometric assay |
(2) 10 cc Na heparin |
| |
Indications:
Natural killer cell activity should be measured in women with a history of recurrent pregnancy loss and/or recurrent failed IVFs. |
| | Pathophysiology:
Natural killer cells detect small cancer cells and kill them before they can become tumors. If these cells are highly active, they may misinterpret the fetus as a cancer and kill it.
|
Tumor Necrosis Factor Alpha
(TNF) Assay |
The NK cell intracellular concentration of the cytokine TNF |
Flow cytometric assay |
(2) 10 cc Na heparin |
| |
Indications:
Tumor necrosis factor alpha should be measured in women with a history of recurrent pregnancy loss and/or recurrent failed IVFs. |
| | Pathophysiology:
Natural killer cells detect small cancer cells and kill them before they can become tumors. One mechanism for this destruction is via the secretion of tumor necrosis factor alpha. High intracellular levels of TNF indicate that the natural killer cells are potentially efficient killers of trophoblastic tissue.
|
Human Leukocyte Antigens
(HLA) ABC |
Class I Major Hisotocompatability Antigens (tissue type) |
Class I HLA serotyping |
(2) 10 cc ACD |
| |
Indications:
HLA typing can be helpful in the diagnosis of patients with recurrent pregnancy loss. It is required if the patient will need a combination of paternal plus donor leukocyte immunization. HLA typing is also helpful in determining susceptibility of patients with specific diseases (e.g. Diabetes Mellitus I, rheumatoid arthritis, systemic lupus erythematosus) to certain complications. Classically, it is used to determine the appropriateness of tissue typing in transplantations. |
| | Pathophysiology:
When couples share HLA antigens there is a higher probability that the woman will not be able to synthesize protective allo-antibodies, resulting in an immune-mediated miscarriage.
|
Human Leukocyte Antigens
(HLA) DR/DQ |
Class II Major Hisotocompatability Antigens (tissue type) |
Class II HLA serotyping |
(2) 10 cc ACD |
| |
Indications:
HLA typing can be helpful in the diagnosis of patients with recurrent pregnancy loss. It is required if the patient will need a combination of paternal plus donor leukocyte immunization. HLA typing is also helpful in determining susceptibility of patients with specific diseases (e.g. Diabetes Mellitus I, rheumatoid arthritis, systemic lupus erythematosus) to certain complications. Classically, it is used to determine the appropriateness of tissue typing in transplantations. |
| | Pathophysiology:
When couples share HLA antigens there is a higher probability that the woman will not be able to synthesize protective allo-antibodies, resulting in an immune-mediated miscarriage.
|
DQα
(Genotyping) |
HLA DQα Alleles (Genotyping) |
PCR technology |
4 cc EDTA |
| |
Indications:
DQα and DQβ genotyping should be performed in patients suffering from recurrent pregnancy loss or multiple failed IVF cycles. |
| | Pathophysiology:
Autoimmune phenomena, such as antiphospholipid antibodies and natural killer cell activity, are exacerbated when the mother and fetus share the same DQα or DQβ genotypes.
|
DQβ
(Genotyping) |
HLA DQβ Alleles (Genotyping) |
PCR technology |
10 cc ACD |
| |
Indications:
DQα and DQβ genotyping should be performed in patients suffering from recurrent pregnancy loss or multiple failed IVF cycles. |
| | Pathophysiology:
Autoimmune phenomena, such as antiphospholipid antibodies and natural killer cell activity, are exacerbated when the mother and fetus share the same DQα or DQβ genotypes.
|
Factor II
(Prothrombin)
Gene Mutation
Factor V
Leiden
Gene Mutation |
Gene mutations implicated in acquired activated protein C resistance and clotting abnormalities |
Invader/Cleavase technology |
10 cc ACD |
Methylene Tetrahydrofolate Reductase Gene Mutation
(MTHFR) |
Indications:
The Inherited Thrombophilia gene mutations should be examined in patients with a history of recurrent pregnancy loss, or evidence of recurrent venous or arterial thrombosis, early MI or CVA. |
| | Pathophysiology:
The Inherited Thrombophilia gene mutations interfere with the normal coagulation pathway by predisposing the patient to activated protein C (APC) resistance. In the case of the MTHFR mutation excess levels of homocysteine are found leading to a hypercoagulable state.
|
