Improving Sperm Selection with MACS: Definition & Indication

By (gynecologist), (embryologist), (gynecologist) and (invitra staff).
Last Update: 11/13/2020

In recent years, a new sperm selection technique has appeared: the annexin V columns. It allows the separation of the best quality spermatozoa by applying magnetic fields and is therefore also known as MACS(magnetic-activated cell sorting). In this article, we will explain what it is based on and what clinical applications it has.

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 are annexin V columns?

One of the new sperm selection techniques is based on the use of columns of annexin V.

To understand this method, it is first necessary to be clear what apoptosis, which is programmed cell death, consists of. It is our body's mechanism for getting rid of damaged or defective cells to ensure that they will not compromise the function of our body's healthy cells.

In order to carry out this process, the cells must undergo a series of changes, as it must be perfectly regulated. Some of these changes are, for example, the fragmentation of genetic material (DNA) or the externalization of some molecules to the outside so that they are recognized as apoptotic cells and are eliminated.

One of these molecules is phosphatidylserine, a phospholipid that apoptotic spermatozoa externalize in the cell membrane. This marker is present on the membrane before sperm motility is affected. Therefore, through their analysis, we can know which spermatozoa will die earlier than with conventional spermatozoa selection methods.

To detect these apoptotic spermatozoa, we have annexin V, a protein that specifically recognizes the phosphatidylserine of these spermatozoa with great affinity. By binding this protein to metal beads, we can select the apoptotic spermatozoa using a magnet.

Therefore, magnetic selection using columns of annexin V consists of adding this protein to the sample and retaining the apoptotic sperm in a column surrounded by a magnet. The ones that do not get stuck in the spine are the ones used in assisted reproduction treatment, as their quality is better.

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 ratesimproved.

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.

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.

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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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
 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
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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