Table of Contents
Introduction
Sperm or male reproductive cells formed in the seminiferous tubules of the testicles unite with an egg and form an embryo. Sperm of humans, non-human primates, and mammals are known to be antigenic. Sperm antigenicity has been known for centuries; different sperm-associated proteins that cause antigenicity have been recognized and characterized, and their role in various fertility disorders has been explained. Antisperm antibodies are naturally formed against these antigenic proteins following exposure to immune cells. Antisperm antibodies may be present in males and females to some extent; however, studies have shown that these were found in high concentrations (nine to 12 percent) among infertile individuals. The presence of antisperm antibodies can make it challenging for couples to conceive. However, progress has been made in the development of techniques to overcome antisperm antibody-induced fertility in people who wish to have children.
What Are Antisperm Antibodies?
Antisperm antibodies (ASA) are immunoglobulins (proteins) of IgA, IgG, or IgM produced by the immune system against sperms in response to bacterial or viral invasion or a foreign material in the body. ASAs can be present in the blood, semen, and in vaginal fluids of females. The presence of antisperm antibodies in infertile males was first reported by researchers Rumke and Wilson. The incidence of these antisperm antibodies varies between eight percent and 21 percent, accounting for approximately three percent of male factor infertility. Pregnancy can be difficult to achieve, especially when a high number of ASAs come into contact with sperm, making it difficult to fertilize an egg and thus resulting in a condition called immunologic infertility or immune infertility.
What Causes the Formation of Antisperm Antibodies?
Despite its potentially high relevance, the exact etiology of antisperm antibody formation has yet to be completely characterized. Antisperm antibodies can develop in both males and females; in males, they can be produced due to the following factors:
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Surgery: Following an injury or a surgical procedure, the blood-testis barrier can be breached, triggering an inflammatory response by the immune system when the sperm comes in contact with blood, thus resulting in the formation of antisperm antibodies. ASA may be detected in about 80 percent of men who have undergone a vasectomy (surgical birth-control method in males) and subsequently associated with infection, varicocele, vasovasostomy (reversal of vasectomy procedure), testicular biopsy (a small portion of the testicle is removed for microscopic examination), or testicular trauma. Studies have reported that significant levels of ASAs were detected in around 53 percent of patients with vasectomy reversal procedures.
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Infection: Infections or inflammations, such as chronic prostatitis (prostate inflammation), can trigger an inflammatory response and an imbalance of pro- and anti-oxidative factors in the semen, resulting in the development of antisperm antibodies.
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Genetic Factors: Some people may have a genetic predisposition that makes them prone to developing antisperm antibodies.
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Testicular Cancer: The presence of tumors or testicular cancer can trigger the immune response and disrupt the balance in the genetic environment, leading to the formation of antisperm antibodies.
How Are Antisperm Antibodies Detected?
In males, antisperm antibodies are found in the seminal plasma and blood serum, free and bound to the surface of the sperm. These are typically immunoglobulins IgA and IgG detected on the sperm surface and in biological fluids. However, the main immunoglobulin in the blood belongs predominantly to the IgG type. At the same time, those found in external secretions, such as cervical mucus and seminal plasma, are mostly IgA isotype. The IgA isotype is vital in defending against bacteria, viruses, and toxins.
The World Health Organization (WHO) has recommended antisperm antibody tests, such as direct and indirect tests for ASA detection. Direct test is performed by collecting the sperm through masturbation and adding a chemical agent that binds only to the affected sperm. The direct test includes the first line of choice tests, such as the mixed antiglobulin reaction (MAR) test and immunobead (IB) test, to detect ASA on the surface of the motile sperm cells. When direct tests are not possible to be conducted, or if necessary, indirect tests are preferred to detect ASA. It involves the collection of fluids such as blood serum, cervical mucus, or testicular fluid and testing for the presence of antisperm antibodies.
Enzyme-linked immunosorbent assay (ELISA) is a broadly accepted serological test that screens the blood serum to detect antisperm antibodies. It is highly effective as it bypasses the slowness and complexity of the indirect tests. A microarray-based technology has been recently validated, which employs the biochip approach, is highly sensitive, and uses minimal input from the sample to provide extremely specific results. It is recommended as an important tool for screening ASA in large groups of patients.
What Are the Risk Factors for the Development of Antisperm Antibodies?
Some of the risk factors for the development of antisperm antibodies include:
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Infections and inflammations of the genital tract.
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Injury to the testicles.
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Obstructions in the vas deferens.
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Varicocele (enlargement of veins in the scrotum).
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Vasectomy procedure.
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Tumors in the testicles.
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Autoimmune disorders.
How Do Antisperm Antibodies Affect Fertility?
Antisperm antibodies can attach to the sperm's surface and hamper their movement, making it difficult for the sperm to swim through the female genital tract to reach and fertilize the egg.
ASAs can cause agglutination of sperms (cluster formation or clumping of spermatozoa), affecting their movement towards the egg. The binding of ASAs can also impair the sperm's ability to change the structure required to penetrate the egg's outer layers. Antisperm antibodies can inhibit the sperm from penetrating the cervical mucus, which normally nourishes the sperm and transports it through the cervix to the fallopian tubes and uterus. ASAs present in the female reproductive tract can trigger an immune response that creates a hostile environment for the sperm, thus lowering the chances of fertilization.
What Is the Treatment for Antisperm Antibodies?
Studies have demonstrated that immunosuppressive therapy, including drugs such as corticosteroids and Cyclosporine, can be beneficial in treating antisperm antibodies. Laboratory techniques such as sperm washing, which involves placing the semen in a centrifuge and separating the sperm from seminal fluid and attached antibodies, can also be used to lower the impact of ASAs on fertility. Fertility therapies such as in vitro fertilization (IVF) (the egg is combined with the sperm outside the body) and intrauterine insemination (IUI) (the sperm is placed directly into the uterus during ovulation) can be beneficial. During these procedures, the collected sperm is first washed or treated with a buffer solution to eliminate ASAs before implantation. If IVF or IUI is not successful, intracytoplasmic sperm injection (ISCI) can be suggested to patients. In this technique, a single sperm is injected directly into an egg to develop a fertilized embryo.
Conclusion
Antisperm antibodies are proteins or immunoglobulins that mistakenly target the sperm and trigger the immune system. Males usually develop antisperm antibodies due to inflammatory conditions of the reproductive tract, injury to the testicles, vasectomy, autoimmune disorders, etc. If individuals are facing difficulties in conceiving, it is recommended to get tested early and consider an antisperm antibody test to evaluate sperm quality. There are various treatments to lower the ASAs and improve fertility. However, identifying the risk factors for ASA and understanding the health of the sperm can help in making informed decisions and prevent the chances of infertility in the future.
