What Is Agglutination in Sperm? – Causes, Symptoms & Treatment

By (embryologist), (gynaecologist), (embryologist), (senior embryologist) and (invitra staff).
Last Update: 07/25/2023

In addition to basic semen characteristics such as concentration, motility, and morphology of spermatozoa, other factors that may influence male fertility such as sperm agglutination are studied in the semen analysis.

Agglutination in sperm may indicate infertility of immunological origin, which is why it is an important factor to consider when looking for an infertility diagnosis.

Having said that, there are different degrees of agglutination with more or less severe consequences for a man’s fertility and future pregnancy.

What is agglutination in sperm?

When a microscopic analysis of the semen is performed, it can be observed if there are motile spermatozoa adhered to each other, which is called sperm agglutination.

Depending on this semen parameter, the result of the semen analysis should indicate if the sample shows:

  • Positive agglutination: which means that motile spermatozoa have been observed sticking together forming clusters.
  • Negative agglutination: motile sperm are not attached in the ejaculate sample tested.

This union of motile spermatozoa can be head to head, tail to tail, or even mixed.

Sperm agglutination classification

There are different grades of sperm agglutination, depending on the number of sperm attached:

Grade 1
There are less than 10 sperm per agglutination and many free sperm.
Grade 2
Each agglutination consists of 10-50 spermatozoa, but there are free spermatozoa.
Grade 3
Agglutinations are formed by more than 50 spermatozoa and there are few free spermatozoa.
Grade 4
All spermatozoa are agglutinated and the agglutinations are interconnected.

A high percentage of sperm agglutination can be a cause of male infertility, since sperm adhesion hinders their progressive movement and, therefore, prevents fertilization from occurring. If the sperm cells do not move through the female reproductive tract, they will not be able to meet the egg and pregnancy will not occur.

Agglutination or aggregation?

Although it is true that sperm agglutination and sperm aggregation may seem to be the same thing, there are differences between the two concepts.

  • Agglutination. We speak of agglutination when motile sperm have joined together.
  • Aggregation. We speak of aggregation when immotile sperm cells are attached to each other, or motile sperm are attached to mucus, other cells or cellular debris.

Sperm aggregation is more non-specific in nature and is therefore of less clinical relevance than motile sperm agglutination.

Causes

Sperm agglutination may suggest the presence of anti-sperm antibodies in the ejaculate. These molecules recognize the membranes of the spermatozoa and bind to them, forming agglutinations. This can lead to the so-called immunological infertility.

In addition, there are other possible causes of sperm agglutination:

  • Very high concentration of sperm in the ejaculate.
  • Changes in the pH of the semen due to problems in the accessory glands (due to inflammatory or infectious processes).
  • Increased body temperature during febrile processes.
  • Certain types of bacteria can cause agglutination in semen.

Although the male may have some of these conditions, it does not automatically mean that agglutination is found in the semen analysis.

Treatment

In cases of agglutination due to febrile or infectious processes, this should disappear on its own after treating the infection and allowing a reasonable amount of time to pass.

The most common thing to do is to repeat the semen analysis after the treatment and analyze carefully if the sperm agglutination has been fixed.

Possible cure

Mild or moderate cases of sperm agglutination can be treated with various medications to see if it lessens or even goes away. Vitamin preparations are recommended, especially vitamin C, which activates the anti-agglutinin protein.

In severe cases, however, it is possible that the agglutination in sperm cannot be treated. In cases of severe sperm agglutination, it is best to resort to assisted reproduction treatments such as ICSI (intracytoplasmic sperm injection) to achieve pregnancy.

Considering seeing a fertility specialist? Don't forget that, in the field of Reproductive Medicine, as in any other medical area, it is crucial that patients rely on the doctors and staff that will help them through their treatment cycle. Logically, conditions vary from clinic to clinic. For this reason, we recommend that you generate your Fertility Report now. It will offer you a list of clinics that have passed our rigorous selection process successfully. Furthermore, the system will make a comparison between the fees and conditions of each clinic so that you can make a better-informed decision.

In the andrology laboratory, sperm capacitation is performed, where motile sperm that are able to move progressively are separated from the rest (agglutinated and immotile sperm). The specialist will select the best spermatozoon from among those obtained in the sperm capacitation to introduce it into the egg.

FAQs from users

What can sperm agglutination indicate?

By Claudia Flores M.D. (gynaecologist).

Sperm agglutination is defined as the union of motile spermatozoa with each other. This binding can occur head-to-head, tail-to-tail or head-to-tail.

This agglutination is observed in the semenogram. It is usually due to the presence of antibodies that are anti-spermatozoa. These antibodies bind to the surface of the spermatozoa, causing them to stick together.
Read more

What are the causes of sperm agglutination?

By Susana Cortés Gallego B.Sc., Ph.D. (senior embryologist).

Sperm agglutination may be a reflection of a possible immunological factor, observing the presence of spermatozoa joined together somewhere in their structure (head, intermediate segment or tail). The presence of this phenomenon is usually related to a decrease in fertility.

The male history of spermatozoa should be taken into account in the assessment, such as obstruction of the seminal tract, vasovasostomies or bacterial suspicion. The presence of antisperm antibodies in patients diagnosed with oligozoospermia may reflect the presence of unilateral obstruction of a seminal duct. The presence of such antibodies in infertile patients may be associated with chlamydial and mycoplasmal infections.
Read more

Is sperm agglutination always analyzed in a sperm test?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

Sperm agglutination is a parameter that is always taken into account when performing the microscopic examination of a semen analysis.

If agglutination is observed when a semen sample is analyzed under the microscope, the specialist should note it in the report. In addition, the degree of agglutination and the type of sperm union (e.g., grade 2, head-head unions) should be included.

Is sperm aggregation something serious?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

Sperm aggregation is nonspecific, as immotile sperm bind to each other or motile sperm to detritus or other cell types. This makes it of little clinical relevance, unlike agglutination.

Suggested for you

If you want to learn more about semen analysis, we recommend you to have a look at this post: What Is a Semen Analysis Report? - Purpose, Preparation & Cost

A possible solution for sperm agglutination is ICSI. If you want to have more in-depth information about this treatment, you can visit this article: What Is ICSI Technique? - Process, Success Rates & Cost

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References

Chereshnev VA, Pichugova SV, Beikin YB, Chereshneva MV, Iukhta AI, Stroev YI, Churilov LP. Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation. Pathophysiology. 2021 Oct 15;28(4):471-488. doi: 10.3390/pathophysiology28040030. PMID: 35366245; PMCID: PMC8830464. (View)

Gupta S, Sharma R, Agarwal A, Boitrelle F, Finelli R, Farkouh A, Saleh R, Abdel-Meguid TA, Gül M, Zilaitiene B, Ko E, Rambhatla A, Zini A, Leisegang K, Kuroda S, Henkel R, Cannarella R, Palani A, Cho CL, Ho CCK, Zylbersztejn DS, Pescatori E, Chung E, Dimitriadis F, Pinggera GM, Busetto GM, Balercia G, Salvio G, Colpi GM, Çeker G, Taniguchi H, Kandil H, Park HJ, Maldonado Rosas I, de la Rosette J, Cardoso JPG, Ramsay J, Alvarez J, Molina JMC, Khalafalla K, Bowa K, Tremellen K, Evgeni E, Rocco L, Rodriguez Peña MG, Sabbaghian M, Martinez M, Arafa M, Al-Marhoon MS, Tadros N, Garrido N, Rajmil O, Sengupta P, Vogiatzi P, Kavoussi P, Birowo P, Kosgi R, Bani-Hani S, Micic S, Parekattil S, Jindal S, Le TV, Mostafa T, Toprak T, Morimoto Y, Malhotra V, Aghamajidi A, Durairajanayagam D, Shah R. 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. World J Mens Health. 2022 Jul;40(3):380-398. doi: 10.5534/wjmh.210164. Epub 2022 Jan 1. PMID: 35021297; PMCID: PMC9253805. (View)

Leathersich S, Hart RJ. Immune infertility in men. Fertil Steril. 2022 Jun;117(6):1121-1131. doi: 10.1016/j.fertnstert.2022.02.010. Epub 2022 Mar 30. PMID: 35367058. (View)

Mahmoud A, Comhaire F. Antisperm antibodies: use of the mixed agglutination reaction (MAR) test using latex beads. Hum Reprod. 2000 Feb;15(2):231-3. doi: 10.1093/humrep/15.2.231. PMID: 10655287. (View)

Sociedad Española de Fertilidad (SEF) (2011). Manual de Andrología. Coordinador: Mario Brassesco. EdikaMed, S.L. ISBN: 978-84-7877 (View)

WHO laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization ; 2010. (View)

WHO laboratory manual for the examination and processing of human semen, sixth edition. Geneva: World Health Organization; 2021. (View)

FAQs from users: 'What can sperm agglutination indicate?', 'What are the causes of sperm agglutination?', 'Is sperm agglutination always analyzed in a sperm test?' and 'Is sperm aggregation something serious?'.

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Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
B.Sc., M.Sc.
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia. Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia along with the Valencian Infertility Institute (IVI). Postgraduate course in Medical Genetics. More information about Andrea Rodrigo
 Claudia Flores
Claudia Flores
M.D.
Gynaecologist
Claudia Flores is currently a specialist in Human Reproduction at the Ovoclinic Seville clinic. Dr. Flores studied medicine in Uruguay and obtained her degree in Spain. Subsequently, Dr. Flores completed a Master's degree in Human Reproduction at the Universidad Rey Juan Carlos in Madrid. More information about Claudia Flores
Licence: 411109126
 Silvia Azaña Gutiérrez
Silvia Azaña Gutiérrez
B.Sc., M.Sc.
Embryologist
Graduate in Health Biology from the University of Alcalá and specialized in Clinical Genetics from the same university. Master in Assisted Reproduction by the University of Valencia in collaboration with IVI clinics. More information about Silvia Azaña Gutiérrez
License: 3435-CV
 Susana Cortés Gallego
Susana Cortés Gallego
B.Sc., Ph.D.
Senior Embryologist
Bachelor's Degree in Biological Sciences from the Complutense University of Madrid, and PhD in Comparative Animal Physiology from the Faculty of Biological Sciences. Extensive experience in the scientific field, and currently working as the coordinator of the laboratories of Clínica Tambre in Madrid, Spain. More information about Susana Cortés Gallego
License: 17980-M
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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