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How sperm are selected for IVF: ICSI, PICSI and ZyMot

When people think about IVF, much of the attention naturally falls on the egg and the developing embryo. But sperm contributes half of the genetic material required to create an embryo, so the quality of the sperm we work with matters too.

In the IVF laboratory, there are now several techniques available to help embryologists prepare and select sperm for fertilisation. You may have heard terms such as ICSI, HA-ICSI (also known as PICSI) or ZyMot, particularly if male factor infertility has been identified or you’ve previously undergone an unsuccessful IVF cycle. We explored male factor infertility more broadly, including when and how it should be assessed, in our recent blog post, Half the Picture.

These technologies can be valuable in the right circumstances. But one of the most important things for patients to understand is that a more advanced technique does not automatically mean a better result.

Our role in the laboratory is not to somehow transform poor-quality sperm into healthy sperm. Rather, we use our experience, laboratory techniques and available technology to select the most suitable sperm from the sample we have.

Why Does Sperm Selection Matter in IVF?

Sperm is half of the equation when creating an embryo; it contributes half of the embryo’s DNA, and although a great deal of discussion around embryo quality focuses on the egg, abnormalities can arise from either the egg or the sperm.

This makes sperm assessment and selection an important part of IVF laboratory treatment, particularly where there is an identified male fertility factor. The challenge is that there are limits to what an embryologist can see.

Under the microscope, we can assess how sperm are moving and examine their morphology — their size, shape and physical appearance. We look for sperm that are moving progressively forward and have an appropriately shaped head, midpiece and tail. We can also assess features of the sperm head, including the acrosome, which contains enzymes that would normally help a sperm penetrate the outer layer of an egg.

We avoid sperm with obvious abnormalities such as unusually large or small heads, abnormal head shapes, multiple heads or tails, significant midpiece or tail abnormalities, or prominent vacuoles.

What we cannot determine simply by looking at a sperm under a standard microscope is whether its DNA is healthy or whether it carries a chromosomal abnormality. That distinction is important when considering the various sperm-selection technologies available.

What Is ICSI?

ICSI, or intracytoplasmic sperm injection, is a fertilisation technique commonly used in IVF treatment.

With conventional IVF, thousands of sperm are placed together with an egg in a laboratory dish and fertilisation is allowed to occur without the embryologist selecting the individual sperm that enters the egg.

ICSI is different, as the embryologist selects a single sperm and injects it directly into the egg.

This means ICSI can overcome some of the barriers to fertilisation that occur when sperm concentration, motility or other sperm parameters are significantly reduced.

ICSI is particularly useful where infertility involves a significant male factor.

When Is ICSI Recommended?

ICSI is particularly useful where infertility involves a significant male factor.

For example, if a semen sample contains a very low concentration of sperm or the sperm have poor motility, there may not be enough suitably moving sperm available to achieve fertilisation through conventional IVF. In circumstances like these, directly injecting an individual sperm into the egg can increase the likelihood of fertilisation.

However, ICSI is not automatically required for every patient undergoing IVF.

Where the reason for treatment is unrelated to sperm (for example, certain ovulatory problems) and the male partner has normal sperm parameters, conventional IVF may be appropriate. As with many aspects of fertility treatment, the right approach depends on the individual circumstances rather than simply choosing the most technically advanced option available.

What Is HA-ICSI or PICSI?

HA-ICSI stands for Hyaluronic Acid-Intracytoplasmic Sperm Injection and is also commonly referred to as PICSI, or physiological ICSI. It adds another selection step before ICSI is performed.

Hyaluronic acid is a substance naturally found around the human egg. Mature sperm develop receptors that allow them to bind to hyaluronic acid.

With HA-ICSI, sperm are exposed to hyaluronic acid, and the embryologist can identify sperm that successfully bind to it. These sperm can then be considered alongside the usual characteristics we assess, such as morphology and motility, when choosing a sperm for injection. The idea is that hyaluronic acid binding may provide another way of identifying mature sperm within the sample.

HA-ICSI may be considered in certain situations, including some patients with elevated sperm DNA fragmentation or a history of recurrent miscarriage. However, this does not mean that every patient undergoing ICSI will benefit from HA-ICSI.

What Is ZyMot?

ZyMot is a microfluidic sperm-selection device designed to provide an alternative method of preparing a sperm sample for treatment. The device’s supplier, CooperSurgical, provides a detailed description of how it works.

A freshly produced semen sample contains sperm alongside seminal fluid and a mixture of sperm of varying quality. Before the sample is used for IVF or ICSI, the laboratory needs to process it so that suitable sperm can be separated and prepared for fertilisation. Traditional sperm-preparation methods can involve centrifugation, where a sample is spun at high speed as part of the separation process.

ZyMot uses a different approach. The sperm sample is placed into a chamber, and sperm are allowed to swim through a microporous membrane into another area of the device.

You can think of it as a small obstacle course. Sperm must be sufficiently motile to move through the device, allowing the embryologist to recover a population of progressively moving sperm without relying on the same centrifugation process.

The technique is designed to mimic some aspects of the natural selection process sperm encounter within the female reproductive tract.

Does a More Advanced Sperm-Selection Technique Mean Better Sperm?

This is one of the most important misconceptions to address.

More advanced sperm selection does not necessarily mean better sperm or a better IVF outcome, because none of these technologies can repair sperm or improve the underlying quality of the sperm produced by the body.

What we can do is try to identify suitable sperm from the sample available to us.

New laboratory technologies can provide us with additional ways of doing that, and some may be useful for particular groups of patients. But simply adding more technology to an IVF cycle does not guarantee an improved chance of pregnancy or live birth. 

This is why we don’t believe every available IVF add-on should automatically become part of routine treatment.

What is IVF

What Does the Evidence Tell Us About HA-ICSI and ZyMot?

There are supportive studies investigating both HA-ICSI and microfluidic sperm-selection techniques such as ZyMot, but there are also areas where the evidence remains uncertain.

For example, research into HA-ICSI has suggested that it may reduce miscarriage in some people undergoing ICSI. However, it has not clearly been shown to increase the chance of becoming pregnant, and whether it improves live birth rates remains uncertain.

There are also practical differences between how individual studies are conducted and how technologies may be used in different IVF laboratories and patient populations. That doesn’t mean these techniques have no value; it simply means we need to be careful about making broad claims from evidence that may only apply to certain groups of patients.

In reproductive medicine, this distinction is particularly important. Patients deserve to understand not only what a technology might offer, but also what has and hasn’t yet been proven.

For an independent, plain-language summary of the HA-ICSI evidence, the University of Melbourne’s Evidence-based IVF resource, produced with Cochrane, is a useful reference for anyone weighing up IVF add-ons more broadly.

Who Might Benefit From Advanced Sperm Selection?

There is no single answer that applies to every patient.

Techniques such as HA-ICSI or ZyMot may be considered where there is a specific clinical or laboratory reason to believe an alternative sperm-selection method could be helpful.

This may include circumstances involving male factor infertility, elevated sperm DNA fragmentation, recurrent miscarriage or previous IVF outcomes that warrant closer review. However, they are not necessarily beneficial for someone simply because they are undergoing IVF or ICSI.

At Thrive Fertility, we do not recommend HA-ICSI or ZyMot as standard treatment for every patient.

If an IVF cycle has not resulted in the outcome we hoped for, our embryology team and fertility specialists review the cycle together. We look at the entire picture, including the sperm sample, fertilisation, embryo development and the patient’s clinical circumstances before deciding whether a different laboratory approach should be considered in a subsequent cycle.

Having the laboratory and clinical team working closely together is important because these decisions shouldn’t be made in isolation.

What Are the Downsides?

Techniques such as HA-ICSI and ZyMot are designed to provide alternative methods of sperm selection rather than introduce major additional procedures for the patient. But the more relevant question is often whether an additional technique is necessary and supported by evidence in your particular circumstances.

Any IVF add-on can also involve additional cost, decision-making and emotional pressure. When you’re undergoing fertility treatment, it can be easy to feel that saying yes to every available option must give you the greatest chance of success. Unfortunately, fertility treatment isn’t that simple, and more treatment doesn’t always mean better treatment.

How Should Patients Think About IVF Add-Ons?

Patients should feel comfortable asking questions whenever an optional treatment or laboratory technique is recommended.

Useful questions include:

  • Why are you recommending this treatment for me?
  • What evidence is there that it improves pregnancy or live birth rates for patients in my situation?
  • What happens if I don’t use it?
  • Could it reduce my chance of success or introduce any additional risks?
  • Are there simpler alternatives?
  • What will it cost?

The financial cost matters, but it isn’t the only cost involved.

Fertility treatment carries an emotional and practical burden as well. Patients deserve enough information to decide whether an additional treatment is genuinely worthwhile for them.

Understanding why a treatment is being recommended is an important part of making informed decisions about your fertility care.

Sometimes the Most Important Work Happens Before the Laboratory

With all the technology available in modern IVF laboratories, it can be tempting to focus entirely on what can be done to sperm once a sample reaches us.

But sperm health begins well before that.

The process of producing sperm (spermatogenesis) takes approximately 75 days, and closer to three months by the time sperm finish maturing. This means that factors affecting your health over the preceding months can influence the sperm present in a sample today: temperature, hormones, general health and lifestyle factors can all play a role. This is why I encourage patients to think about optimising both partners’ health before beginning IVF wherever possible.

Advanced laboratory technology is incredibly valuable, and as embryologists we are continually looking at how science can help us improve treatment. But technology is only one part of the picture. For me, the goal isn’t to use the greatest number of laboratory techniques. It’s to use the right techniques for the right patient, based on their individual circumstances and the best evidence available.

If you have questions about ICSI, sperm selection or whether a particular IVF laboratory technique may be appropriate for you, speak with your fertility specialist and embryology team. Understanding why a treatment is being recommended is an important part of making informed decisions about your fertility care.