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Treatment · Reproductive Medicine

PICSI | Doctors, clinics & treatment information

Brief overview — the essentials first

The procedure builds on standard laboratory treatment: embryologists specifically select mature sperm cells. This is based on the sperm’s ability to bind hyaluronic acid, which is regarded as a sign of maturity and largely intact genetic material. There is no clear scientific evidence that the method increases the chances of having a baby. One possible benefit is a lower risk of miscarriage. Couples usually bear the costs themselves.

If your hopes of having a child remain unfulfilled despite regular attempts, this does not necessarily mean the end of hope. Sometimes stress or hormonal fluctuations play a part, but there are often physical causes. If physical problems are the cause, assisted reproduction through fertility treatment may be a sensible option.

Here you will find selected medical experts and specialists in clinics and practices for diagnosis, treatment and rehabilitation. 

Definition: What is Physiological Intracytoplasmic Sperm Injection (PICSI)?

The procedure is used to select sperm that have reached a specific stage of maturity. It is an extension of conventional ICSI: in the standard method, an embryologist injects a single sperm directly into the egg under a microscope. This extension adds an additional selection step to the process: only sperm with the appropriate degree of maturity are considered for treatment.

Physiological: What does this mean in terms of sperm selection?

The term ‘physiological’ describes the fact that the selection is based on a natural process. In natural fertilisation, only a small proportion of the sperm reach the egg. The egg is surrounded by a membrane, the zona pellucida, which contains hyaluronan as a key component. Only mature sperm have a receptor on the head with which they bind to the hyaluronic acid. This enables each sperm to penetrate the membrane and reach the egg. The procedure applies this principle in the laboratory.

The maturity of the sperm cannot be reliably determined by their appearance alone. Motility and morphology are just as important in the selection process as the state of maturity. A sperm must also be motile in order to find its way. The aim of laboratory diagnostics is to identify suitable sperm for fertilisation. For this reason, laboratories use dishes with a special coating to which mature sperm cells adhere.

Artificial insemination using PICSI: how does this method work?

If the desire to have a child remains unfulfilled, this may be due to the quality of the sperm. The shape and motility of the sperm are just as important in the selection process as their stage of maturity.

Physiological Intracytoplasmic Sperm Injection is an extension of Intracytoplasmic Sperm Injection (ICSI). In ICSI, doctors inject the sperm directly into the eggs.

The PICSI procedure differs from the standard treatment only in terms of sperm selection. First, the laboratory collects a semen sample and prepares it. Embryologists then place the prepared sperm onto a dish with hyaluronan-coated areas. Under the microscope, it can be observed that only the mature sperm bind to the surface. Binding to hyaluronan is considered a sign of maturity.

From the group of bound sperm, the embryologist can select the best ones. Any sperm that adheres firmly to the surface is suitable. The laboratory picks up a sperm and inserts it into the cytoplasm using micromanipulation. This is followed by injection into the egg. The next day, embryologists check whether the egg has been fertilised. If an embryo develops, they continue to culture it in the incubator. As a rule, the doctors then transfer one or two embryos into the womb. Success now depends on the embryo implanting.

How does in vitro fertilisation work in the laboratory?

There are essentially several methods used in reproductive medicine. They differ in how and where the sperm and eggs are brought together – in a test tube or inside the human body. In in vitro fertilisation (IVF), eggs and sperm meet in a dish and fusion takes place naturally. In insemination, doctors insert prepared sperm into the woman’s womb. Fusion then takes place in the fallopian tube.

ICSI
Artificial insemination under a microscope @ DAntes /AdobeStock

Cryopreservation: When it doesn’t work the first time

As pregnancy does not always occur on the first attempt at assisted reproduction, or if a couple would like to have another child, it is possible to have surplus fertilised eggs frozen.

This means you can avoid further stimulation and egg retrieval (follicular puncture). This method is known as cryopreservation.

It is suitable not only for couples trying for a baby, but also for young women who wish to store their eggs for later use. In this case, the term ‘social freezing’ is used.

Cryopreservation is also suitable for men who are due to undergo treatment that damages germ cells (chemotherapy). They can build up a ‘reserve’ as a precaution in case they decide to undergo sterilisation.

Hormone therapy

The hormone therapy used in artificial insemination enables several follicles to mature in a single cycle and allows for controlled ovulation. The medicines used include follicle-stimulating hormone (FSH) and human menopausal gonadotrophin (HMG). During follicular aspiration, doctors then retrieve the mature eggs. The treatment takes place at a fertility clinic. The stimulation can cause symptoms such as bloating or mood swings. In rare cases, ovarian hyperstimulation may occur, which requires medical supervision.

Couples should also not underestimate the emotional strain associated with fertility treatment.

Costs and cost coverage

For IVF and the ICSI method, statutory health insurance funds contribute at least half of the costs for married couples, subject to certain conditions. Couples pay a co-payment; they usually cover the cost of preliminary examinations themselves.

The costs of PICSI treatment are generally not covered by health insurance schemes, as it is considered an additional procedure.

You should therefore clarify the costs in advance with the clinic providing the treatment and ask for a written cost estimate.

PICSI, ICSI & IMSI: What is the difference?

In cases of reduced sperm quality and/or sperm concentration, doctors use the ICSI procedure. This involves injecting a single sperm directly into the egg using micromanipulation.

IMSI (intracytoplasmic morphologically selected sperm injection) is an extension of the standard ICSI treatment, in which experts examine the sperm beforehand. Using high magnification, they can select normally shaped spermatozoa without vacuoles (fluid-filled cavities) for treatment. In the hyaluronic acid-based variant, a spermatozoon is selected that is suitable based on its maturity.

The PICSI method (Physiological Intracytoplasmic Sperm Injection) is an extension of ICSI. Here, experts can specifically select mature sperm. The procedure assesses the maturity of a sperm rather than its appearance. Binding to hyaluronic acid is considered an indicator of less DNA damage. This reduces the risk of using sperm with an abnormal chromosome count, although it cannot be completely ruled out.

A potential advantage is that sperm with intact genetic material are used more frequently. Parmegiani et al. reported that selection via hyaluronic acid favours sperm without DNA fragmentation and may improve embryo quality. Higher fertilisation rates have also been reported in smaller studies. Analyses of several studies also suggest a lower rate of pregnancy loss.

These potential benefits are offset by a limited body of research. A large randomised study from the UK (HABSelect), involving couples from 16 centres for assisted reproduction, found no significantly higher rate of live births (27.4% compared with 25.2%). However, the rate of pregnancy loss was lower in the group undergoing hyaluronan-based selection (4.3% compared with 7.0% of treated couples). Nor has a higher pregnancy rate been conclusively demonstrated to date.

The UK regulatory body, the HFEA, assesses the benefit in terms of the chances of having a baby as unproven based on the current evidence. A randomised study from 2025 also concluded that hyaluronan-based selection does not increase the live birth rate. There is as yet no evidence of any additional harm caused by the procedure.

Furthermore, many earlier studies were small in scale and differed in their design and selection of participants. Couples should therefore assess the potential benefits realistically and not rely solely on individual positive results.

Who is PICSI suitable for?

The procedure is primarily suitable for couples who have undergone several rounds of treatment without achieving pregnancy, who have experienced recurrent pregnancy loss, or whose semen analysis shows abnormalities.

In some studies, couples whose sperm showed only weak binding to the coating benefited most. Couples should discuss with their treating doctors whether the procedure makes sense in their individual case. Honest information is crucial. The procedure is not standard practice and success cannot be guaranteed.

Specialists

Fertility treatment should be carried out by experienced specialists. On this page, you will find accredited doctors and clinics specialising in reproductive medicine. When choosing a clinic, look for a team with relevant experience, transparent information about benefits and costs, and a consultation that also outlines alternative options. During your initial consultation, discuss openly the benefits, limitations and costs of additional procedures. If you are unsure whether an additional procedure is suitable for you, a second medical opinion may help.

Frequently asked questions

What is the success rate for PICSI?

There are only limited reliable figures specifically for this procedure. In the UK’s HABSelect study, it did not significantly improve the live birth rate compared with standard treatment. Figures from individual centres cannot be readily generalised. A reputable consultation will therefore provide a range of possibilities rather than making promises.

Kryokonservierung
Cryopreservation allows women to store their eggs for later use @ sola_sola /AdobeStock

What factors influence the success rate of PICSI?

The woman’s age has the greatest impact, as the number and quality of eggs decline with age. The man’s age plays a lesser, but demonstrable, role.

Can the PICSI procedure reduce the risk of miscarriage?

Possibly. In the HABSelect study, the rate of pregnancy loss was significantly lower in the group using hyaluronan-based selection. However, this did not have a significant effect on the live birth rate. Anyone who has experienced a miscarriage should seek medical advice to determine the causes, regardless of this procedure.

Is there an increased risk of birth defects with the PICSI method?

Following ICSI, the risk of birth defects is slightly higher compared with natural conception. It is not yet conclusively clear whether hyaluronan-based selection changes this. Discuss individual risks with your doctor.

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Dr Melanie Henes

Medical Author · Tuebingen

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Here you will find selected medical experts and specialists in clinics and medical practices for the diagnosis, treatment, surgery and rehabilitation in the medical field PICSI. All listed physicians are specialists in their field and have been carefully selected for you according to strict guidelines.

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