MACS and Microfluidic Sperm Selection: What Are They and What Does the Evidence Say?

MACS sperm selection (magnetic-activated cell sorting) and microfluidic sperm selection are two separate add-on practices that aim to separate out, while sperm are being prepared in the laboratory, the sperm thought to be damaged. In a current assessment prepared for Europe, MACS is not recommended for routine clinical use; the microfluidic method is placed in the "may be considered" category, with limited evidence. In either case, a benefit in live birth has not been clearly shown. You can talk with your doctor about whether it will be considered in your own situation.

What are sperm preparation and selection?

Before insemination or IVF, the semen sample is processed in the laboratory and motile, normal-looking sperm are separated from the seminal fluid. In the current assessment on this subject, the form of this standard preparation that is generally used as the comparator is density gradient centrifugation. MACS and microfluidic practices are approaches added on top of this standard preparation that aim to make the selection by other criteria. Both target the sperm, not the embryo or the egg.

What is MACS meant to do?

In MACS the aim is for sperm thought to be damaged to be separated by a magnetic method and for the remaining sample to be used for ICSI. Whether this logic is reflected in the outcome is a separate question; however plausible the principle, showing a benefit depends on studies that measure clinical outcomes.

Does MACS improve the pregnancy and live birth outcome?

The current assessment on this subject reports that, compared with density gradient, MACS may provide sperm with more suitable motility and shape and less DNA damage. The effect on pregnancy and live birth, however, is uncertain, and there is not enough evidence to show superiority over conventional preparation. The same assessment also states that there are no data on the safety of MACS. The update of a review also reports that the effect of MACS on live birth, clinical pregnancy and miscarriage is not known and that the reliability of this evidence is very low. In the assessment of the regulator in the United Kingdom concerning sperm DNA damage, sperm selection by density gradient or MACS is shown in the uncertain category in infertility due to a male factor, because there is no medium- or high-quality evidence.

How is microfluidic sperm selection performed?

In the microfluidic method, sperm are separated on a chip made up of very fine channels according to their movement and their response to flow. In this method too, the aim is to leave behind the sperm thought to be damaged. Its difference from MACS is that the separation is based not on a magnetic but on a flow-based principle.

What does "may be considered" mean for the microfluidic method?

The current assessment on this subject places this method in the "may be considered" category. This expression does not mean "recommended"; it is a conditional and weak category. The basis is a single, small controlled study; in an observational study examining recipients of donor eggs, no benefit was seen. The same assessment reports that microfluidic chips may improve the number of motile sperm, shape and DNA integrity compared with conventional methods, but also writes that there are no data on their safety and that more research is needed. In the list of main add-on practices of the regulator in the United Kingdom, microfluidic selection does not appear as a separate line. Therefore it is not possible to draw a superiority in favour of microfluidic over the other method.

Are an improvement in the laboratory and live birth the same thing?

No. A method increasing motility in the sample or reducing the proportion of cells carrying DNA damage is a finding relating to laboratory measurements. The real aim of treatment, however, is the birth of a healthy baby. An improvement in measurements does not mean that this aim has been reached; to show the link between the two, studies of sufficient size that take live birth as the end point are needed. The uncertainty in assessments on this subject lies precisely at this point.

If there is sperm DNA damage, are these methods necessarily needed?

These practices can be brought up with reasons such as a finding of sperm DNA damage. But the current assessment on this subject does not recommend routine use of the sperm DNA damage test, and the predictive value of the test is uncertain. For this reason the inference "if there is DNA damage, these techniques are needed" is not supported by evidence. A sperm problem is part of the couple's shared treatment process; it does not require attributing blame to anyone.

Should these techniques be added to every ICSI cycle?

The current evidence does not support adding these techniques to every ICSI cycle. Since there are also no data to distinguish which group of patients would benefit, the recommendation of the practice is a clinical preference rather than a proven necessity.

What is known about safety for the man, the embryo and the baby?

The regulator in the United Kingdom states that sperm separation methods carry no risk to the man because they are applied to sperm in the ejaculate. As for the embryo and the baby, the current assessment on this subject says that there are no data on safety for either MACS or the microfluidic method. For this reason no assurance can be given; the right statement is that no known problem has been reported and that the data are limited. The risks of ICSI itself, for example the possibility of the egg being damaged during the procedure, also apply together with these selection steps.

Can an extra fee be requested for these methods?

Whether a separate fee is charged for a selection technique varies with the centre carrying out the treatment. Couples who fund their own treatment can also consider several standard cycles instead of a single cycle with an add-on whose evidence is insufficient. After a previous failure, the feeling "if I do not have this technique, my chance will fall" is understandable; knowing that the evidence is uncertain helps you weigh this worry more evenly.

Are MACS, microfluidic, PICSI and IMSI the same thing?

No. All four are additional approaches to which sperm is to be used during ICSI, but their principles are separate. MACS and the microfluidic method aim to separate sperm thought to be damaged; PICSI uses binding to hyaluronic acid, and IMSI uses the shape seen under high magnification. The evidence for each technique is assessed on its own, and the state of one cannot be transferred to another.

What questions can you ask your doctor?

• What is the finding in my sample that brings this method up?
• What change do you expect compared with standard preparation, and what do you base it on?
• Does the practice require an additional charge?
• Does my treatment plan change if it is not done?
• How is this selection step described in the consent document?