June 23, 2025

Men’s Health Month: FACTS Focus on Male Fertility

The Role of Antisperm Antibodies in Human Infertility: A Review

By: David Sills, PA-C

Editor’s Note: Our 3-week series on male fertility concludes with an exploration of the role of antisperm antibodies (ASA) in human infertility and a brief review of the evolution of ASA testing. While on the FACTS elective, David Sills first shared background information from an article [1] by Naz and Menge published in 1994 in Fertility and Sterility. He then summarized Dr. JH Check’s article [3] published in Clinical and Experimental Obstetrics & Gynecology in 2010. Since these earlier publications, Silva et al published a 2021 update on this topic in Reproduction, calling for ASA testing in all routine seminal fluid analyses, in accordance with World Health Organization recommendations. Be sure to read through the end of this summary, where Sills shares “it was amazing to read a paper by a physician and, within a few days, see the impact of their work in a clinical setting,” thanks to the FACTS elective!

Introduction

Too many couples face the complex challenge of infertility, an important health concern that impacts both personal and societal health. Infertility has been shown to disrupt a couple’s mental and social health, and it is associated with an increase in marital conflict. [2]  While various underlying clinical factors may contribute to infertility in a couple, one that is less commonly discussed is an autoimmune state in which a man’s sperm will be covered with antisperm antibodies (ASA). Antisperm antibodies are present in approximately 1-2.5% of fertile males and up to 4% of fertile females. [3] The coating of sperm with antisperm antibodies leads to a low chance of fertilization, independent of the method used to conceive (natural conception, fertility awareness-based methods, in vitro fertilization, intrauterine insemination). [1]

The 2010 editorial article by Dr. JH Check [3] titled, “Antisperm Antibodies and Human Reproduction,” addressed the topic of infertility while focusing on strategies to diagnose and treat infertility caused by ASA. The author first outlined ways in which ASA may adversely affect fertility. Antisperm antibodies inhibit sperm’s ability to travel through cervical mucus and may also inhibit specific microbiological processes, including sperm-oocyte fusion, sperm capacitation, the acrosome reaction, and binding of sperm to the zona pellucida. According to Check, the two most common methods of ASA testing were the immunobead assay (IBD) and the mixed antiglobulin reaction (MAR) assay, and each test can reveal the percentage of sperm that are covered with antisperm antibodies. As of the time of publication, prior studies had mixed results as to which subtype of immunoglobulin to use for MAR testing; thus, the study reported by Check was measured with IgG and IgA only.[3]

“Antisperm antibodies inhibit sperm’s ability to travel through cervical mucus and may also inhibit specific microbiological processes, including sperm-oocyte fusion, sperm capacitation, the acrosome reaction, and binding of sperm to the zona pellucida.”

The Evolution of ASA Testing

The author discussed an approach to diagnostic evaluation and treatment of a patient with antisperm antibodies and made the case that ASA testing is an important part of the initial evaluation of male infertility. [3] The presence of sperm bound with antisperm antibodies is a likely contributing factor to infertility, either by preventing sperm from traveling through cervical mucus or by preventing direct fertilization of the oocyte by the sperm. Based on previous studies, Check concluded it is more important to test for antisperm antibodies on sperm than in cervical mucus. Earlier studies tried to bypass the impact of these antibodies by performing intrauterine insemination (IUI). However, this did not improve pregnancy rates, implicating that antisperm antibodies still play a role in preventing oocyte fertilization.

The author critiqued a 1990 meta-analysis that concluded testing for antisperm antibodies should be abandoned. Check advocated for ASA testing, given that antisperm antibodies may be an important contributor to male infertility in some couples. The author noted there was a “threefold increase” in the likelihood of achieving pregnancy with intracytoplasmic sperm injections (ICSI) compared to IUI.

Advocacy for ASA Testing

While Check’s article [3] covered a variety of concepts related to antisperm antibodies, its main purpose was to convey the importance of including ASA testing as part of a typical infertility diagnostic assessment.* Excluding ASA from routine evaluations of infertility may miss a significant factor contributing to a couple’s inability to conceive.

* “A review from 2021 by Silva et al confirms the need to assess antisperm antibodies in every semen analysis, and a 2024 review by Yuekun et al emphasized the need for standardized antisperm antibody detection methods.”

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Dr. Check’s advocacy transformed a couple’s experience!

As part of the elective course with FACTS, I had the gift of learning how fertility awareness-based methods (FABMs) can be utilized for diagnosis and treatment to support a couple navigating a diagnosis of infertility. I also learned that experiencing infertility may take a serious toll on a couple’s emotional health, causing some to feel like they are inherently “broken” because they cannot conceive a child. It was valuable to learn how antisperm antibodies can impact a couple’s fertility. It was especially meaningful to know there are physicians in practice like Dr. Check who believe it is important to test for ASA, since it is a possible cause of infertility, even when the mainstream consensus at the time was to abandon such testing.

“It was valuable to learn how antisperm antibodies can impact a couple’s fertility … (and) meaningful to know there are physicians in practice like Dr. Check who believe it is important to test for ASA, since it is a possible cause of infertility.”

I had the privilege of observing a few appointments during the FACTS elective to witness the impact of infertility in the clinical setting. During one of them, the patient’s husband had a history of antisperm antibodies coating his sperm. Moreover, this couple had undergone testing by Dr. JH Check, the author of this article! It was amazing to read a paper by a physician and, within a few days, see the impact of his work in a clinical setting. If this couple had not been tested for antisperm antibodies, they may never have been treated for an important contributing factor to their infertility.

The article by Check shows the importance of conducting a thorough evaluation in couples experiencing infertility, which should include testing for the presence of sperm coated with antisperm antibodies. Such a comprehensive evaluation may help identify the root cause of infertility, making it more likely for a couple to conceive and improve their individual health, while potentially impacting their community and societal health as well.

* Editor’s Note: A review from 2021 by Silva et al confirms the need to assess antisperm antibodies in every semen analysis, and a 2024 review by Yuekun et al emphasized the need for standardized antisperm antibody detection methods.

References

[1] Naz RK, Menge AC. Antisperm antibodies: origin, regulation, and sperm reactivity in human infertility. Fertility and sterility. 1994;61(6):1001-1013. doi:10.1016/s0015-0282(16)56747-8

[2] Tao P, Coates R, Maycock B. Investigating marital relationship in infertility: a systematic review of quantitative studies. Journal of reproduction & infertility. 2012;13(2):71-80.

[3] Check JH. Antisperm antibodies and human reproduction. Clinical and experimental obstetrics & gynecology. 2010;37(3):169-174.


ABOUT THE AUTHOR

David Sills, PA-C
David Sills is a physician assistant who earned his Master of Physician Assistant Practice from the University of Dayton in Dayton, OH. He completed his undergraduate education at Wright State University in Dayton, OH. He enrolled in the FACTS elective to gain a better understanding of fertility awareness-based methods and ways to share these methods with future patients so they can feel more empowered over their health and reproductive decisions.


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