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Advanced Sperm Selection Techniques (PICSI, MACS, Zymot): Pros & Cons

Medically verified
Tomas Rieger, PhD
Head Embryologist, Gynem Fertility Clinic
From this event you will find out:
  • Why healthy-looking sperm can still have damaged DNA
  • What reported DNA damage reductions from 40% to 20% actually mean
  • How low sperm numbers affect your selection options
  • Why combining techniques still can’t guarantee healthy DNA
  • Which questions to ask before agreeing to advanced selection

Table of Contents - Quick Navigation

Advanced sperm selection can improve the pool of sperm available for IVF. Healthy DNA, however, remains beyond its guarantee. Laboratory techniques can identify sperm that swim well, appear more mature or have fewer visible abnormalities. For patients, the useful question is not simply which method sounds most advanced, but which one fits their sample and what benefit it can realistically offer.

Featuring: Tomáš Rieger, PhD, Head Embryologist at GYNEM Fertility Clinic.

Hosted by Carly Garrett, Reflexologist and Fertility Coach, UK.

Why a Good-Looking Sperm May Not Be Enough

Sperm quality is one factor to investigate after an unsuccessful IVF cycle. A semen assessment describes concentration, movement and morphology, meaning the sperm’s shape and structure. Those characteristics help laboratories decide how to prepare a sample, but they do not reveal everything about its genetic quality.

The gap between appearance and DNA is where sperm selection becomes more complicated. A sperm can look normal and swim well while still carrying DNA fragmentation, or damage to its DNA. No selection method can examine the DNA of an individual living sperm without destroying it, so the sperm chosen for fertilisation cannot also undergo that direct check.

Laboratories therefore select sperm by visible traits linked to better quality. Some methods favour strong, straight-line movement, while others assess maturity, visible structure or markers of cell deterioration. These are ways to improve the choice—not ways to certify that a particular sperm has normal DNA.

That distinction matters especially with ICSI, a fertilisation procedure in which the laboratory selects individual sperm for use with the eggs. Advanced selection supports that choice rather than replacing the fertilisation procedure itself. It narrows the field, but uncertainty remains even after careful selection.

Start With What the Sample Can Support

Before comparing techniques, the laboratory needs to know how many usable sperm are available. A sample with millions of moving sperm offers different possibilities from one containing only tens or hundreds. The concentration in the original ejaculate is therefore not the only number that matters: the number available after preparation also influences the next step.

One preparation technique, called swim-up, lets moving sperm swim upward from semen into a layer of sperm medium. The laboratory collects sperm from the upper layer for further selection. How many sperm reach that layer helps determine whether there are enough for a method that processes a large population.

A lower count does not automatically mean that advanced selection is impossible. Hyaluronic acid-based selection, for example, can work with tens or hundreds of sperm because they are evaluated individually. The practical discussion should begin with what the laboratory expects to recover from the sample, rather than with a preferred device or brand.

The intended treatment also changes what counts as a useful result. For ICSI, a device may yield tens or hundreds of sperm and still provide enough for the procedure. For IUI, in which sperm are placed into the uterus and must continue swimming through the fallopian tubes, the final preparation needs millions.

What the Main Selection Methods Actually Look For

The methods available in an IVF laboratory do not all test the same quality. Movement, maturity, cell condition and appearance each offer a different basis for selection. Understanding those differences makes it easier to see both the purpose of a recommendation and its limits.

Microfluidic sorting: choosing sperm by how they swim

Microfluidic sperm sorting uses a small device through which sperm must swim. Sperm moving straightforwardly can pass through, while those that veer off course become trapped.

The attraction is that movement can help identify a population with less DNA fragmentation. Reported reductions have been up to half, with a starting fragmentation level of 40% falling to 20% in the selected sample. That is a reduction in damage across the resulting population, not proof that every sperm passing through is genetically normal.

For someone concerned about DNA fragmentation, this is a crucial boundary. The device sorts by swimming behavior; it does not read the DNA or specifically identify a particular type of DNA break. It may improve the pool from which the embryologist chooses, while still leaving some damaged sperm in that pool.

Magnetic separation: removing sperm with a deterioration marker

Magnetic sperm separation takes a different approach by trying to remove sperm showing a marker of apoptosis, a process of cell deterioration. The sample is exposed to a reagent attached to magnetic particles that binds to this marker. As the sample passes through a magnetic column, marked sperm are retained, and unmarked sperm pass through.

This is selection by a biological signal rather than by swimming performance alone. Its limitation is that the marker does not identify every damaged sperm. Some sperm with damage can still pass through the column, so magnetic separation cannot guarantee an undamaged final sample.

Hyaluronic acid selection: looking for maturity

Selection using hyaluronic acid, often discussed as PICSI, draws on an interaction involved in natural conception. Mature sperm can bind to hyaluron, a component of the material surrounding the egg complex. In the laboratory, sperm are placed in drops containing hyaluronic acid, and those that attach can be considered for ICSI if they also appear to be of good quality.

Because sperm are assessed individually, this approach can remain an option when only tens or hundreds are available. It adds a sign of maturity to the embryologist’s decision rather than relying on appearance alone. Yet maturity is not the same as a guarantee of healthy DNA, and the reported improvement in live birth has been modest.

High-magnification selection: examining structure more closely

High-magnification selection concentrates on what the sperm looks like in greater detail. It can reveal irregularities in the head or neck, as well as features such as vacuoles and residual material around the neck. The aim is to choose sperm with better visible morphology before fertilization.

A closer view can refine a visual choice, but it cannot turn appearance into a genetic test. Even a sperm without obvious structural problems may have abnormal DNA. This method therefore addresses a different part of selection from a device that sorts primarily by movement.

A Better Sperm Sample Is Not the Same as a Better Birth Rate

The results most relevant to patients are pregnancy and live birth, not simply whether a selected sample looks better under the microscope. A reduction in DNA fragmentation describes a laboratory result. It does not, on its own, establish how much an individual couple’s chance of having a baby will change.

The modest improvement reported for hyaluronic acid-based selection helps explain why early enthusiasm for the technique was greater than the results later supported. The method remains an option, but it should not be presented as a large or certain improvement.

Different treatment outcomes also need to stay separate. Pregnancy results for IUI are not live birth results for ICSI, and they do not answer exactly the same question for someone planning IVF with ICSI.

The most useful conversation with a clinic is therefore about the outcome behind its recommendation. Is the expected benefit a lower proportion of fragmented DNA, a more favourable sperm appearance or an improvement in pregnancy or live birth? Keeping those distinctions clear helps prevent a promising laboratory result from sounding like a personal prediction.

Can Combining Methods Help?

Selection techniques can be combined because they examine different characteristics. A laboratory might first use microfluidic sorting to obtain well-moving sperm and then use high magnification to choose among them by appearance. This gives the embryologist more than one basis for making the final choice.

The reasoning is straightforward, but the limits remain. Small improvements at different stages may contribute to a better selection process, yet combining methods still does not reveal the DNA of the living sperm chosen for fertilisation. More stages should not be mistaken for certainty, and no combination guarantees success.

For patients, a useful explanation should connect each stage to a specific purpose. If one method selects by movement and another by structure, the laboratory should be able to describe why both are being considered for that sample. The decision is more meaningful when it is tied to the sperm available rather than to the number of techniques offered.

Keep Sperm Selection in the Wider Treatment Picture

Laboratory selection works with the sperm available on the day, but sperm quality is also associated with factors outside the laboratory. Smoking, alcohol, drug use, obesity, stress and lack of sleep can adversely affect sperm parameters. Stress also contributes to oxidative stress, which may be relevant when investigating sperm damage.

These factors deserve attention without turning an unsuccessful cycle into an exercise in blame. Oxidative stress can be evaluated, and antioxidants or reductants may be considered as part of its management. That discussion is separate from the choice of selection device, even though both concern the quality of sperm available for treatment.

Egg quality also remains part of the decision, particularly when age and low ovarian reserve are concerns. Healthy development depends on the genetic contribution from both sperm and egg. Improving the sperm population cannot by itself resolve difficulties arising from the eggs, which is why disappointing embryo development should not automatically be attributed to sperm selection alone.

Final Thoughts

Advanced sperm selection offers ways to make a more informed laboratory choice, not a way to eliminate every risk. The choice of method rests on sperm numbers and characteristics, as well as the treatment: ICSI needs only a small number, while IUI requires millions. Each method provides useful information, but none can confirm the DNA quality of the individual living sperm selected.

Before agreeing to a technique, ask what it selects for, whether your sample can support it and which outcome the evidence suggests it may improve. A clear answer should acknowledge both the potential benefit and the remaining uncertainty. The realistic goal is a better opportunity for fertilisation with the sperm available—not a promise that selection alone will determine the outcome.

Advanced Sperm Selection Techniques (PICSI, MACS, Zymot): Pros & Cons | FAQ

Does an MSS chip help with double-strand sperm DNA fragmentation?

An MSS chip can be used for all samples, but it does not provide a final assessment of DNA quality. It selects sperm based on motility rather than specifically targeting DNA fragmentation.

Studies have shown less fragmentation in selected sperm. Good, straightforward motility is associated with good DNA quality, but not with 100% certainty. The chip may therefore select sperm with less fragmentation without confirming their DNA quality.

What is the difference between MSS for ICSI and MSS for IUI?

The original device was developed for ICSI; a newer version was later developed for IUI. Other brands have since introduced similar devices.

The main difference is how many sperm are needed. IUI requires millions of sperm of the best possible quality because they are placed in the uterus and must swim through the fallopian tubes. For ICSI, tens or hundreds of selected sperm are enough because only a small number are needed.

Why is PICSI used less often, and when might it be chosen?

ICSI is the standard fertilisation procedure. PIXIE is a sperm-selection method using hyaluronic acid binding, either alone or in combination with MC.

PIXIE was considered new and promising about 10 to 15 years ago, but the results did not meet the initial expectations, and its popularity decreased. It remains an option. However, the best outcomes in the clinic’s own statistics were achieved with the combination of MSS and MC.

Would TESA help after sperm concentration fell from 12 million to 3 million, with high DNA fragmentation and 2% normal morphology?

The age difference between cycles and oocyte quality are important. A year and a half between ages 37 and 38.5 can make a difference because healthy oocyte quality declines after 35.

A concentration of 3 million per milliliter is not a bad number. TESA would not necessarily improve sperm quality when ejaculated sperm are already available at 10 to 12 million per milliliter, or even 3 million per milliliter.

Testicular retrieval may help when an obstruction prevents better-quality sperm in the testicles from getting out. Without an obstruction, TESA is not expected to improve quality. The recommendation is to use the IVF clinic’s available sperm preselection methods and hope for good oocyte DNA. Oxidative stress can also be evaluated and treated with antioxidants or reductants.

Can sperm selection increase the chance of a female embryo?

There is no known sperm-selection method for this purpose. Biologically, male and female sperm look the same and cannot be distinguished in the laboratory.

In the Czech Republic, selecting the sex of a child conceived through IVF is forbidden by law unless there is a genetic reason.

Is Zymote reasonable with 54% sperm DNA fragmentation when the woman is 43 with low ovarian reserve, or is sperm donation better?

DNA fragmentation of 54% is higher than normal, but not as extreme as 80% or 90%. MSS, including the MSS chip, can reduce the percentage of fragmentation in the final sample, so using Zymote is reasonable in this situation.

The more important issue is age 43 and low ovarian reserve. Even if stimulation produces several oocytes, none may be genetically normal. Both oocyte DNA and sperm DNA must be fine for a healthy child to result. If one side is not suitable, there is no point in trying to improve it further.

After 40, some genetically healthy oocytes remain, although fewer than 10%. Zymote may make a difference if such oocytes are present.

After 11 IVF rounds, one PGT-A normal blastocyst and sperm DNA fragmentation of 38, should magnetic selection or Zymot be chosen?

Age is essential to interpreting this history. With approximately 60 follicles retrieved and around 50 fertilised oocytes, one PGT-A normal blastocyst is a very small number. This pattern warrants looking beyond the choice of sperm-selection method.

Embryos can arrest on days 4 to 5, especially at higher ages, although some older patients still achieve success after culture. PGT testing is recommended in older patients. The chance is low but present, around 20% to 30%. Each year, the clinic sees one or two fortunate patients achieve a healthy child with their own cells despite unfavourable statistics.

This pattern is not normal: at 44 it would not be surprising, but at 35 other factors should be investigated. Karyotype testing should be considered for the woman and possibly her husband.

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