Definition and pathogenesis of immunologic infertility
Immunologic infertility is a disease in which fertility is temporarily or permanently reduced due to an abnormal immune response of the body to reproduction-related antigens. According to global statistics, about 10%-30% of infertility is related to immune factors, of which anti-sperm antibodies (AsAb) is the most common causative factor, accounting for 60%-80% of immune infertility.
Core pathogenesis:
Antisperm antibody interference: when sperm antigens enter the bloodstream through sites of inflammation or injury in the reproductive tract, they trigger the immune system to produce antibodies. These antibodies can lead to sperm agglutination, decreased viability, and even destruction of the sperm structure, preventing it from penetrating the cervical mucus or completing fertilization.
Anti-endometrial antibodies: Attack the endometrial cells, reducing the success rate of embryo implantation, and are closely related to recurrent miscarriages.
Anti-ovarian antibodies: inhibit follicular development and ovulation, leading to an increased risk of premature ovarian failure.
Key triggers:
Inflammation of the reproductive tract (e.g., chronic cervicitis, pelvic inflammatory disease) disrupts the local immune barrier and increases the risk of sperm antigen exposure.
Surgery or trauma (e.g., vasectomy, endometriosis surgery) results in abnormal release of reproductive tissue antigens.
Genetic susceptibility: people with specific HLA genotypes are more likely to develop abnormal immune responses.
Diagnosis and screening: pinpointing immune abnormalities
Core Tests
Antibody Screening:
Anti-sperm antibodies (AsAb): detected by mixed antiglobulin test (MAR) or immunobead assay, with a positive rate of 70%-85% in patients with immune infertility.
Anti-endometrial antibodies (EMAb): detected by ELISA with a positivity rate of about 30%-40%.
Anti-Ovarian Antibodies (AoAb): closely related to ovarian hypoplasia, with a positivity rate of about 15%-25%.
Functional assessment:
Post-coital test (PCT): detects the number of viable spermatozoa in cervical mucus 2 hours after intercourse, if <5/high magnification field of view suggests antibody interference.
Sperm penetration test (SPA): assesses the ability of sperm to bind to the zona pellucida of the egg; a penetration rate of <10% suggests immunologic abnormality.
Systematic tests:
Ovarian reserve function: AMH test combined with sinus follicle count (AFC) to assess follicle number.
Endometrial tolerance: endometrial thickness and blood flow by endometrial biopsy or ultrasound.
Treatment Options: Stepped Management from Drugs to Assisted Reproduction
- Immunosuppressive therapy
Glucocorticoids: low-dose prednisone (5-10 mg/day) or dexamethasone reduces antibody titers and improves pregnancy rates to 35-45%. Note that prolonged use may cause osteoporosis or risk of infection.
Immunomodulators: Cyclosporin A (3-5 mg/kg/day) is indicated in refractory cases to restore immune balance by suppressing T-cell activity.
- Assisted Reproductive Technology (ART)
Intrauterine insemination (IUI): sperm is injected directly into the uterine cavity after washing to remove surface antibodies, success rate about 20%-25%.
In vitro fertilization (IVF): bypassing antibody interference by using intracytoplasmic monosperm injection (ICSI), with a clinical pregnancy rate of 50%-60%.
Pre-implantation Genetic Testing (PGT): Screening chromosomally normal embryos for patients with recurrent miscarriages, with live birth rate increased to over 65%.
Reproductive tract health maintenance:
Avoid menstrual sex to reduce inflammation and risk of antigen exposure.
Regular screening for chlamydia, gonococcal and other infections and timely treatment of chronic inflammation.
Metabolic and Nutritional Optimization:
Low-fat, high-fiber diet: reduce release of pro-inflammatory factors, Mediterranean dietary pattern recommended.
Antioxidant supplementation: coenzyme Q10 (200 mg/day) and vitamin E (400 IU/day) to improve egg mitochondrial function.
Psychological support:
Cognitive behavioral therapy (CBT) reduces anxiety scores by 30%-40% and improves treatment adherence.
Prevention Strategies and Cutting Edge Advances
Early screening:
Immunologic screening is recommended for infertile couples who have not conceived within 1 year of conception preparation, especially for those with a history of comorbid chronic inflammatory or autoimmune conditions.
Novel biologics:
Anti-CD20 monoclonal antibodies (e.g., rituximab) target B-cell clearance in refractory antisperm antibody-positive patients.
Gene editing techniques:
CRISPR-Cas9 technology is being explored to repair immune-related gene mutations (e.g., FOXP3), which may eradicate some immune infertility in the future.
Summarize.
Treatment of immune infertility requires an individualized, multidisciplinary model. Through precise diagnosis and targeting of the causative antibody type, combined with immunomodulation, assisted reproduction and lifestyle intervention, pregnancy can be achieved in about 70% of patients. For recurrent failure cases, emerging biologic therapies and genetic technologies will provide breakthrough solutions. Patients are advised to choose medical institutions with reproductive immunology specialties and develop a systematic treatment plan.
