The science,
explained simply.

A human sperm cell is far more than a delivery vehicle for DNA — it's a highly organised sensory and mechanical system built from three specialised parts: the head, the midpiece, and the tail.

The head carries a tightly compacted nucleus, its DNA packed roughly six times denser than an ordinary cell's thanks to proteins called protamines. Capping it is the acrosome, a reservoir of enzymes the cell uses to penetrate the layers around an egg. The midpiece is wrapped in a sheath of mitochondria — the cell's power plant — while the tail (flagellum) is an engineering marvel: a 9+2 bundle of microtubules driven by dynein motor proteins that convert chemical energy into a rhythmic, whip-like beat.

Before it can fertilise an egg, a sperm cell must undergo capacitation — membrane and signalling changes triggered by bicarbonate and calcium that "arm" the cell and shift it into a powerful, hyperactivated beat.

Remarkably, sperm can sense their environment: thermosensitive channels let them detect temperature gradients of a fraction of a degree and steer toward warmth — one of several natural cues that guide them toward the egg. It's this behaviour, not centrifugal force, that EVA is built around.

Reaching the egg is a gauntlet. Of the millions of sperm that begin the journey through the cervix and uterus, only a few hundred ever approach the oocyte waiting in the oviduct. Getting there is not luck — it's navigation.

Sperm read a sequence of cues. Rheotaxis orients them to swim against the gentle current flowing out of the tract. Thermotaxis draws them up a subtle temperature gradient toward the warmer site of fertilisation. Chemotaxis steers them toward chemical signals released around the egg, and thigmotaxis keeps them following the tract's walls and contours.

Only cells with the motility, energy, and sensing to read these cues arrive — nature's own selection filter. EVA recreates the same cues on a chip so that, just as in the body, the most capable cells select themselves.

The single sperm that fertilises an egg hands over half the embryo's genome. If that DNA is damaged, everything downstream is affected — which is why sperm DNA integrity has become one of the most closely watched markers in reproductive medicine.

Sperm DNA is packaged under extraordinary tension: protamines replace the usual histones to compress it about six times tighter than a normal cell, and the mature cell has almost no capacity to repair damage on its own. That makes two threats significant. Oxidative stress — an excess of reactive oxygen species — can nick and fragment the DNA strands. And mechanical stress, including the g-forces of centrifugation, can compound that damage during preparation.

Elevated DNA fragmentation is associated with lower fertilisation rates, poorer embryo development, and higher miscarriage risk. Yet the most common preparation methods select largely on density and on surviving the spin — not on which cells actually carry intact DNA.

This makes the case for gentler, behaviour-based selection. When cells are chosen for their ability to swim and sense — as they are in the body — the fraction that arrives tends to be both highly motile and structurally sound. Protecting the cell during preparation isn't a nicety; it's part of choosing the right one.

Before sperm can be used in IUI, IVF, or ICSI, it has to be separated from seminal plasma, debris, and non-motile or abnormal cells. Two methods have long dominated the lab.

Swim-up is the oldest and simplest: motile sperm actively swim from the sample pellet up into a clean layer of medium above. It's inexpensive and gentle, but recovery can be low — often just 10–25% — in samples that already have low counts or motility.

Density gradient centrifugation (DGC) layers the raw sample over solutions of increasing density and centrifuges it, so morphologically normal, motile cells pass through to sediment in a pellet at the tube's tip, while immotile cells, debris and leukocytes remain in the layers above. DGC recovers more cells from poor-quality samples, but the centrifugal force itself can raise oxidative stress and, in some samples, DNA fragmentation.

Every method is a trade-off between how many cells you recover and how gently you treat them — and the field is steadily moving toward approaches that work with sperm biology rather than against it.

Beyond swim-up and DGC, a newer generation of methods aims to select on quality — not just density — by exploiting what individual cells do or how their surfaces behave.

Magnetic-activated cell sorting (MACS) tags dying (apoptotic) cells with magnetic beads and pulls them out, enriching the healthy fraction. Hyaluronic-acid binding selects mature sperm by their ability to bind HA, the same molecule they must bind around the egg. Electrophoretic and charge-based methods separate cells by surface properties.

Microfluidic selection is the most physiological of all: cells navigate microchannels by responding to flow, temperature, and chemical gradients — the same cues they read in the body — with no centrifugation at all. The WHO's 6th edition recognises these as a promising, active area of research pending broader validation. This is the family EVA belongs to.

The World Health Organization's Laboratory Manual for the Examination and Processing of Human Semen (now in its 6th edition) is the reference standard fertility labs worldwide use to prepare sperm for IUI, IVF, and ICSI. Importantly, the manual does not prescribe one single "best" method — instead, it sets out a framework of principles any validated method must satisfy.

At its core, the WHO framework requires that sperm preparation removes seminal plasma, leukocytes, and debris; enriches the sample for motile, morphologically normal sperm; and minimises iatrogenic damage — harm caused by the preparation process itself, such as oxidative stress or DNA fragmentation. Labs must use sterile, non-toxic media, maintain physiological pH, osmolarity, and temperature, and avoid contamination.

Rather than mandating a specific technique, WHO asks each laboratory to validate its own chosen method locally against defined performance criteria — recovery rate, motility, vitality, and DNA integrity — and to embed that method in a broader quality system: documented media batches, centrifugation parameters, staff training, and external quality-assessment participation.

The manual also distinguishes what's appropriate by procedure. IUI generally needs a reasonably high yield of motile sperm; IVF needs a clean, motile population for co-incubation with eggs; and ICSI needs only a handful of individually selected, high-quality cells. Newer approaches — including microfluidic devices that select sperm by motility or rheotaxis without centrifugation — are explicitly acknowledged by the WHO's 6th edition as an active area of research, though treated as optional or investigational pending further validation, rather than standard-of-care.

In short: WHO guidelines aren't a recipe — they're a safety and quality bar every method, from the decades-old swim-up to the newest microfluidic chip, has to clear before it belongs in a fertility lab.

Infertility affects roughly one in six people of reproductive age worldwide, according to the WHO. When couples need medical help to conceive, three procedures make up most of what's called Medically Assisted Reproduction (MAR): IUI, IVF, and ICSI. They aren't interchangeable — each intervenes at a different point in the fertilisation process.

IUI (intrauterine insemination) is the least invasive: prepared sperm are placed directly into the uterus around ovulation, and fertilisation still happens naturally, inside the body. It's typically used for mild sperm-quality issues, unexplained infertility, or donor-sperm cycles.

IVF (in vitro fertilisation) moves fertilisation into the lab: eggs are retrieved and combined with prepared sperm in a dish, where fertilisation happens by the sperm and egg meeting on their own. Resulting embryos are cultured, then transferred or frozen.

ICSI (intracytoplasmic sperm injection) is an IVF-based technique where a single sperm is injected directly into an egg with a microneedle — bypassing the steps sperm would otherwise need to complete on their own. According to European registry data cited by ESHRE, it now accounts for roughly two-thirds of ART fertilisations worldwide, even though pregnancy rates per embryo transfer are broadly similar between IVF and ICSI (29.4% vs. 27.7% in ESHRE's cited European dataset).

The right choice depends on female age, ovarian reserve, tubal status, and — critically — semen quality. That's precisely why sperm preparation matters so much: whichever procedure a couple pursues, the quality of the sperm fraction reaching the egg (or the needle) shapes the odds from the very first step.