Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Preamble:
The entity antisperm antibodies (ASA) is an enigma since it can be present in fertile males/couples. Controversy continues to exist regarding its actual purpose and clinical utility, especially in the current era of reproductive technology. While the presence of ASA may signal immunologic infertility, several factors such as types of ASA immunoglobulins, other semen parameters, and female factors can significantly alter egg fertilization rate. The GAF has taken the initiative to comprehensively review the current concept and clinical utility of ASA in the relatively sparse literature. Indeed, further research should be conducted to highlight the appropriate use of ASA testing
to optimize the management of infertile couples.

Capsule:
The article provides an overview of the causes of immunological male infertility, the clinical indications, and methods for antisperm antibody (ASA) testing, along with the results of a worldwide survey for the clinical application and management of antisperm antibody (ASA) testing in male infertility.

Spermatozoa are normally protected by the blood-testis barrier allowing them to remain undetectable to the male immune system, that would otherwise trigger a response against them. When the blood-testis barrier is breached or damaged due to injury or other pathologies, then antisperm antibodies (ASA) are formed that may affect sperm count, motility, vitality, capacitation, acrosome reaction and fertilizing potential of the spermatozoa. A varying prevalence of ASA has been reported in infertile men with percentages ranging from 2% to 15.6%, mainly due to variations in the applied thresholds to define the positive ASA test.

Referral for ASA testing often derives from certain indications from medical history or relevant findings during semen analysis, such as extensive agglutinations. According to the WHO guidelines, ASA testing can be either performed through direct testing for IgA/IgG by measuring the binding of immunobeads in the sperm surface, or through indirect testing by measuring sperm-specific immunoglobulins in sperm-free fluids such as seminal plasma. In the event of immunological infertility, management may include the prescription of corticosteroids to alleviate immunological response or the use of assisted reproductive technologies (ART) as sperm processing may remove
bounded antibodies.

The global online survey among experts revealed that there are reservations in ASA testing and its interpretation, but it remains widespread amongst clinicians for the diagnosis of immunological infertility, in the event of asthenozoospermia, agglutinations, or failed IUI/IVF and mostly performed by direct testing. Steroid administration to treat ASA positive cases is the most frequent approach, while many recommend Intrauterine insemination (IUI) and intracytoplasmic sperm injection (ICSI) as an alternate approach.

Recommendations:
ASA testing should be recommended in selected cases, based on suggestive clinical history and semen parameter outcomes, when the couple is trying for a natural pregnancy. However, if a couple is proceeding for IVF/ICSI, then there is no strong evidence to support ASA testing.

Postscript:
One interesting aspect of antisperm antibodies is their role in contraceptive vaccines for both males and females. However, developing contraceptive vaccines based on antisperm antibodies remains a complex and sensitive area of research. The main challenges include ensuring the safety and reversibility of the contraceptive effect, as well as addressing potential unintended immune reactions.

Acknowledgment: Pariskevi Vogiatzi, PhD (Greece), Eric Chung, MD (Australia) and Ashok Agarwal (Cleveland, USA) contributed to this summary piece.