Improving Sperm Selection with MACS: Definition & Indication

By (gynecologist), (gynecologist), (gynecologist), (embryologist), (gynecologist), (embryologist) and (invitra staff).
Last Update: 12/21/2023

MACS is a technique that allows the separation of healthy spermatozoa from spermatozoa that will soon die due to apoptosis. This technique is based on the application of magnetic fields, from which it gets its name (Magnetic Activated Cell Sorting), and on the use of annexin V.

This type of spermatozoa selection cannot be done with traditional methods, as apparently these spermatozoa that have started the apoptotic process do not differ from healthy spermatozoa. Therefore, the aim of the MACS technique is to perform a better sperm selection, discarding apoptotic spermatozoa that will probably not give rise to a viable embryo and pregnancy.

In this way, the MACS technique ultimately aims to increase the probability of obtaining a pregnancy and thus improve the results of assisted reproduction techniques.

Methods of sperm selection and fertility

Before using any semen sample during a fertility treatment, the semen quality is analyzed by means of a semen analysis, and a sperm selection is carried out to rule out spermatozoa possessing the worst quality.

The most common methods are density gradients and swim-up and both are based primarily on choosing the best motile sperm for treatment.

If you want more information about sperm selection techniques, have a look at this link: How is sperm selected?

However, the fact that a spermatozoon has good motility is not always an indication that it is capable of correctly fertilizing the egg. In some cases, there are genetic alterations that do not alter motility but can affect both fertilization and subsequent embryonic development.

Therefore, even if the result of the seminogram is good and the processed sample also shows adequate concentration and motility, some of the spermatozoa selected by traditional methods may not be of as good quality as expected.

For all these reasons, in recent years efforts are being made to find new methods of sperm selection that will allow sperm to be separated more precisely. In doing so, the aim is to improve the results of assisted reproduction techniques.

Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

What is the MACS technique?

The MACS sperm selection technique is used to separate spermatozoa that are entering apoptosis from healthy spermatozoa. Therefore, to understand this method, we must first be clear about apoptosis, which is programmed cell death.


Apoptosis is our body's mechanism for getting rid of damaged or defective cells. This ensures that these cells will not compromise the function of healthy cells in our body.

In order to carry out this process of apoptosis, the cells must undergo a series of changes, as it must be perfectly regulated. One of these changes is the externalisation of some molecules to the surface.

Phosphatidylserine is one such molecule, a phospholipid that healthy spermatozoa possess inside their membrane. This marker is externalised in the early stages of apoptosis, before sperm motility is affected. Therefore, by analysing this molecule, we can detect which sperm will die earlier than with conventional sperm selection methods. This will avoid fertilising the egg with a sperm that was already destined to die.

Annexin V columns

To detect phosphatidylserine, we have annexin V. This is a protein that specifically and with high affinity recognises the phosphatidylserine that has been externalised by these apoptotic spermatozoa. Thanks to this characteristic, by attaching annexin V to magnetic microspheres, we can separate spermatozoa that have entered apoptosis using a magnet.

The rationale for the magnetic selection of spermatozoa with annexin V consists of:

  • Add annexin V bound to magnetic beads to the semen sample. Annexin V will bind to phosphatidylserine from those apoptotic sperm that have externalised it.
  • Introduce the semen sample through a small column attached to a magnet. Apoptotic spermatozoa bound to annexin V will be retained in the magnetised column. This is because, as explained above, annexin V is in turn bound to the magnetic microspheres.

In this way, sperm that have not been trapped in the spine (and are therefore not apoptotic) will eventually be used for assisted reproductive techniques.

Advantages and disadvantages

The main benefit of this technique is that it allows for the discarding of apoptotic spermatozoa, which may not be detected by conventional sperm selection methods. Therefore, it is possible to separate the best quality spermatozoa at an early stage.

Several studies have confirmed that thanks to the MACS technique with annexin V, pregnancy rates improved.

However, it should be kept in mind that when annexin columns are used, the concentration of the sperm sample decreases considerably, since only healthy sperm will be present in the final sample. This means that the sample resulting from this procedure, in most cases, can only be used for ICSI, as the concentration is insufficient to perform artificial insemination or conventional in vitro fertilization (IVF).

Another disadvantage of this technique is that it is more expensive and laborious than traditional methods. Therefore, it is only recommended to use it in patients where it is indicated.

In which patients is MACS used?

The couples that can benefit most from this method of sperm selection are those in which the cause of sterility is the male factor or inexplained infertility. This technique is indicated in the following cases:

  • High percentage of sperm with fragmented DNA.
  • Recurrent failures in previous treatments, such as recurrent miscarriages with unknown cause.
  • Low fertilization rate.
  • Poor embryo quality.
  • Sterility of unknown origin.
  • Patients who underwent chemotherapy and/or radiotherapy.

In addition, the MACS technique could also be used for repeat miscarriages where the cause is unknown.

FAQs from users

By Sergio Rogel Cayetano M.D. (gynecologist).

MACS should be used whenever a higher than normal level of apoptosis is detected in a semen sample, in order to avoid cell-damaged sperm. Therefore, it is indicated in cases of: severe male factor, implantation failure (usually we talk about two transfers with high quality embryos, which have not generated pregnancy) and those previous IVF cycles in which fertilization or embryo development has not been as expected, despite the fact that the semen sample was normal or almost normal.
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What percentage of sperm selection using adnexin V columns increases the probability of successful treatment?

By Carmen Ochoa Marieta M.D., Ph.D., M.Sc. (gynecologist).

The selection of spermatozoa using adnexin columns substantially improves the chances of success in those cases where it is indicated.

The percentage of improvement will depend on the percentage of spermatozoa with fragmented DNA in the seminal sample, since this will allow us to select healthy spermatozoa, thus increasing the possibility of having good quality embryos.

Can MACS be performed with sperm obtained through testicular biopsy?

By Rebeca Reus BSc, MSc (embryologist).

No, because the sperm obtained by this technique are scarce. Therefore, when they are passed through the columns of adnexin V, it is very likely that there will not be enough to carry out the treatment.

Is a minimum semen volume required to make MACs?

By Paloma Sánchez Gómez M. D. (gynecologist).

The most important thing to perform a MACs technique is the sperm concentration, as well as the fluidity of the semen sample.
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By Luis Rodríguez Tabernero M.D., M.Sc., Ph.D. (gynecologist).

The MACS technique can be used in any situation, but is particularly recommended in the following cases:

  • DNA with a high fragmentation rate.
  • Previous IVF cycles characterised by low fertilisation rate or poor embryo quality, despite good egg quality.
  • Severe seminal infertility.
  • Patients undergoing radiotherapy or chemotherapy.
  • Repeated miscarriages with no other identified cause.
Imagen: MACS recommendations for use

Are Annex V columns an alternative to density gradients?

By Rebeca Reus BSc, MSc (embryologist).

No, the most advisable thing is to pass the sample through density gradients to eliminate spermatozoa with poor mobility and to make the sample cleaner. In this way, it is easier to make the subsequent magnetic selection more efficient.

Can sex be selected using this technique?

By Rebeca Reus BSc, MSc (embryologist).

No. This technique is based on a marker that is in the sperm cell membrane. To date, there is no known external marker that allows us to separate the sperm with the X sex chromosome (fetus will be XX, female) from those with the Y sex chromosome (fetus will be XY, male).

Suggested for you

As we have seen, patients with a DNA fragmentation index can benefit from the use of this new technique. You can find more information about this disorder in the following article: What is sperm DNA fragmentation?

In addition to the MACS technique, there are also other new sperm selection methods, such as IMSI and PICSI. IMSI (Intracytoplasmic Morphologically Selected Sperm Injection) consists of choosing the sperm to be used in ICSI using a more powerful microscope that allows a better visualization of the morphology. If you want to delve deeper into this topic, we recommend you to visit this article: What is IMSI?

On the other hand, PICSI (physiological ICSI) consists of selecting the spermatozoa that would be capable of fertilizing the egg under physiological conditions, i.e. in the mother's body. In the following article, you can read more about this technique: What is PICSI?

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Gil M, Sar-Shalom V, Melendez Sivira Y, Carreras R, Checa MA. Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet. 2013 Apr;30(4):479-85 (View)

Lee TH, Liu CH, Shih YT, Tsao HM, Huang CC, Chen HH, Lee MS. Magnetic-activated cell sorting for sperm preparation reduces spermatozoa with apoptotic markers and improves the acrosome reaction in couples with unexplained infertility. Hum Reprod. 2010 Apr;25(4):839-46 (View)

Lepine S, McDowell S, Searle LM, Kroon B, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction. Cochrane Database Syst Rev. 2019 Jul 30;7(7):CD010461 (View)

Makker K, Agarwal A, Sharma RK. Magnetic activated cell sorting (MACS): utility in assisted reproduction. Indian J Exp Biol. 2008 Jul;46(7):491-7.

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Pacheco A, Blanco A, Bronet F, Cruz M, García-Fernández J, García-Velasco JA. Magnetic-Activated Cell Sorting (MACS): A Useful Sperm-Selection Technique in Cases of High Levels of Sperm DNA Fragmentation. J Clin Med. 2020 Dec 8;9(12):3976 (View)

Pedrosa ML, Furtado MH, Ferreira MCF, Carneiro MM. Sperm selection in IVF: the long and winding road from bench to bedside. JBRA Assist Reprod. 2020 Jul 14;24(3):332-339 (View)

Romany L, Garrido N, Cobo A, Aparicio-Ruiz B, Serra V, Meseguer M. Obstetric and perinatal outcome of babies born from sperm selected by MACS from a randomized controlled trial. J Assist Reprod Genet. 2017 Feb;34(2):201-207 (View)

Sánchez-Martín P, Dorado-Silva M, Sánchez-Martín F, González Martínez M, Johnston SD, Gosálvez J. Magnetic cell sorting of semen containing spermatozoa with high DNA fragmentation in ICSI cycles decreases miscarriage rate. Reprod Biomed Online. 2017 May;34(5):506-512 (View)

Ziarati N, Tavalaee M, Bahadorani M, Nasr Esfahani MH. Clinical outcomes of magnetic activated sperm sorting in infertile men candidate for ICSI. Hum Fertil (Camb). 2019 Jun;22(2):118-125 (View)

FAQs from users: 'From how many failed cycles is it recommended to use the MACS technique?', 'What percentage of sperm selection using adnexin V columns increases the probability of successful treatment?', 'Can MACS be performed with sperm obtained through testicular biopsy?', 'Is a minimum semen volume required to make MACs?', 'When is MACS recommended?', 'Are Annex V columns an alternative to density gradients?' and 'Can sex be selected using this technique?'.

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Authors and contributors

 Carmen Ochoa Marieta
Carmen Ochoa Marieta
M.D., Ph.D., M.Sc.
Bachelor's Degree in Medicine from the Basque Country University. PhD in Medicine & Surgery from the University of Murcia. Currently, she is the director of the Assisted Reproduction Unit of Centro de Estudios para la Reproducción (CER SANTANDER) in Santander, Spain, as well as the director of the Diagnostic Unit of Human Assisted Reproduction in Bilbao. More information about Carmen Ochoa Marieta
License: 484805626
 Luis Rodríguez Tabernero
Luis Rodríguez Tabernero
M.D., M.Sc., Ph.D.
Degree in Medicine and Surgery from the University of Salamanca and Specialist in Obstetrics and Gynaecology via MIR. Dr. Rodríguez Tabernero is responsible for the Human Assisted Reproduction Unit of the Gyaecology and Obstetrics Department of the Hospital Clínico Universitario de Valladolid since 2013 and has also been working in the field of reproductive medicine since 2000. More information about Luis Rodríguez Tabernero
Licence number:474705276
 Paloma Sánchez Gómez
Paloma Sánchez Gómez
M. D.
Dr. Sánchez-Gómez has a degree in Medicine and Surgery from the Complutense University of Madrid. She also has a Master's degree in Assisted Reproduction from the Universidad Rey Juan Carlos de Madrid and a degree in Clinical Genetics in Assisted Reproduction from the Universidad Miguel Hernández de Elche. More information about Paloma Sánchez Gómez
Member number: 282863971
 Rebeca Reus
Rebeca Reus
BSc, MSc
Degree in Human Biology (Biochemistry) from the Pompeu Fabra University (UPF). Official Master's Degree in Clinical Analysis Laboratory from the UPF and Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). More information about Rebeca Reus
 Sergio Rogel Cayetano
Sergio Rogel Cayetano
Bachelor's Degree in Medicine from the Miguel Hernández University of Elche. Specialist in Obstetrics & Gynecology via M. I. R. at Hospital General de Alicante. He become an expert in Reproductive Medicine by working at different clinics of Alicante and Murcia, in Spain, until he joined the medical team of IVF Spain back in 2011. More information about Sergio Rogel Cayetano
License: 03-0309100
 Silvia Azaña Gutiérrez
Silvia Azaña Gutiérrez
B.Sc., M.Sc.
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
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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