Immune risk factors in reproductive failures

Reproductive failure is the inability to achieve and maintain desired pregnancy. Results of recent research have suggested that adjustments in the woman’s immune system are important to a successful pregnancy. When these adjustments are not made or are made inappropriately, pregnancy is unsuccessful and the consequence manifests clinically as unexplained infertility or unexplained recurrent pregnancy loss. In recent years, several immune markers associated with reproductive failure have been identified. Identification of these markers has allowed the diagnosis and hence appropriate treatment of heretofore-unexplained reproductive failure.

Diagnosis of reproductive failure.

Establishing the correct diagnosis is the most important component in treating couples with reproductive failure.  Diagnostic tests useful in identifying causes of reproductive failure depend on the time during which the failure is occurring.  Reproductive failure can happen pre-implantation, peri-implantation or post-implantation.

The Center offers diagnostic panels with combination of tests detecting most prevalent abnormalities found to cause one or another reproductive failure.

1. Panel for ovarian reserve evaluation.
2. Diagnostic panel for premature ovarian failure.
3. Diagnostic panel for endometriosis.
4. Diagnostic panel for male factor.
5. Diagnostic panel in implantation failure.
6. Diagnostic panel in recurrent pregnancy loss.
7. Risk pregnancy-monitoring panel.
8. Coagulation panel.
9. Thrombophilia diagnostic panel.
10. Pre-IVF panel

Pre-implantation pregnancy loss occurs after fertilization and prior to implantation.  It can be the result of problems within the egg, sperm or environment in which the fertilized egg is exposed before implantation.

Problems within the egg can manifest clinically as

– Diminished ovarian reserve
– Premature ovarian failure
– Polycystic ovarian syndrome

Problems within the sperm not diagnosed by the standard parameters of semen analysis can be detected by

– Sperm DNA Integrity assay (SDIa)
– Y chromosome microdeletion assay

Problems within the environment in which the fertilized egg or pre-embryo is exposed present clinically as

– Luteal Phase Defect
– Endometriosis
– Implantation failure

Panels of tests that have been used to aid in the diagnosis of pre- implantation failure are a follows:

– Ovarian Reserve Panel:  Inhibin-B, LH, FSH & E2
– Premature Ovarian Failure Panel: antiphospholipd antibodies (APA), antinuclear antibodies (ANA), antithyroid antibodies (ATA),  antiovarian antibodies (AOA) &  Inhibin-B.
– Male Factor Panel: sperm analyses, SDIa, Y chromosome microdeletions
– Endometriosis Panel: APA, ANA, NKa, ETA.
– Pre-IVF Screen Panel: APA, ATA, reproductive immunophenotype (RIP) & NKa
– Implantation Panel: APA, ANA, ATA, Ig Panel, ETA, RIP & NKa

Peri-implantation pregnancy loss presents clinically as unexplained infertility and/or preclinical, occult or chemical pregnancy loss.  Laboratory tests that can aid in the diagnosis of peri-implantation failure include:
– Ovarian Reserve Panel: Inhibin-B, FSH & E2
– Sperm DNA Integrity assay
– Implantation failure panel: APA, ANA, ATA, RIP, NKa, ETA & Ig Panel

Post-implantation pregnancy loss presents clinically as embryonic (prior to 10 weeks gestation) or fetal (after 10 weeks gestation) pregnancy loss.  While most embryonic loss or miscarriages are due to chromosomal abnormalities, most fetal losses are not.  Therefore, patients with two or more recurrent miscarriages and 1 or more unexplained fatal losses are evaluated prior to pregnancy for the cause of post-implantation failure and during the pregnancy for prediction of recurrent failure.

– Evaluation of Recurrent Miscarriages.

Since recurrent miscarriage can result from either a problem with the embryo itself or a problem within the environment in which the embryo implants and grow, the following tests have been beneficial in the diagnosis:

– Ovarian Reserve Panel: Inhibin-B, FSH & E2
– Sperm DNA Integrity assay
– HLA-G Gene Testing
– Pregnancy Loss Panel: APA, ANA, ATA, LAC, APTT, PT, RIP, NKa, ETA & Ig Panel
– Thrombophilia Panel Mutations for Factor V von Leiden, Factor II prothrombin, Factor XIII, Fibrinogen, PAI 1, GPIIIa & MTHFR
– Coagulation Panel: LAC, APTT & PT

Evaluation for Fetal Loss.

Unexplained fetal loss can occur as a consequence of both thrombophilic and immunologic mechanisms.  Tests advantageous in diagnosing causes of fetal loss include:

– Thrombophilia Panel: Mutations for Factor V von Leiden,
– Factor II prothrombin, Factor XIII, Fibrinogen, PAI 1, GPIIIa & MTHFR
– Coagulation Panel: LAC, APTT & PT
– Pregnancy Loss Panel: APA, ANA, ATA, LAC, APTT, PT, RIP, NKa, ETA & Ig Panel

Prediction of Embryonic Loss

A number of biomarkers have been studies for their ability to predict viable vs non-viable pregnancies.  These markers have included hCG, progesterone, estradiol and inhibin-A.  If hormones are being supplemented to help maintain the pregnancy, then the only accurate way of monitoring early pregnancy is with

– Inhibin-A
– Antiphospholipid Antibodies (APA)
– Reproductive Immunophenotype (RIP)

Pregnancy Monitoring

Pregnancies at increased risk for subsequent failure are monitored with
– Antiphospholipid Antibodies
– Reproductive Immunophenotype

Those women being treated with heparin should also be monitored throughout their treatment with
– Activated Partial Thromboplastin Time
– Platelet Count