Last updated date: 18-Aug-2023

Originally Written in English

Physiological intracytoplasmic sperm injection (PICSI)


About 20 % of patients are diagnosed infertile without specific causes. Various techniques and procedures have rapidly emerged over 3 decades in assisted reproduction, but the success rate remains alike. In totting up, petite ratios of couples do not succeed in conceiving despite multiple in vitro fertilization (IVF) or ICSI Intracytoplasmic sperm injection procedures.


What is Physiological intracytoplasmic sperm injection (PICSI)?

Physiological intracytoplasmic sperm injection

Physiological intracytoplasmic sperm injection (PICSI) is a technique used to select sperm to use in Intracytoplasmic sperm injection (ICSI) treatment. It involves placing sperm with hyaluronic acid (HA), a natural compound found in the body. PICSI identifies sperm that can bind to HA and these sperm are selected for use in treatment.

Men with low sperm samples often have a greater degree of immature sperm. Immature sperm can still show normal motility and morphology, however, they may have higher levels of damaged DNA, which, if selected for insemination can result in poor embryo quality and pregnancy loss. PICSI is a method that helps us to select mature sperm for injection.

During ICSI, the spermatozoa are selected based on their morphology and motility. However, in this case, sperm selection is more subjective, as the embryologist selects the spermatozoon based on a visual assessment under low resolution, without having any indication on its dynamics and ability to fertilize the oocyte. On the other hand, PICSI, a physiological ICSI technique, provides sperm functionality testing, thus assisting the embryologist to select the best quality spermatozoon.


What’s the evidence for PICSI?

evidence for PICSI

There have been several studies comparing PICSI with standard ICSI, but there is very little evidence to suggest any benefit of using it. A large RCT was recently carried out which showed that using PICSI did not increase the chances of having a baby.

PICSI may be beneficial in relation to a potential reduction in miscarriage. It is important to keep in mind that this evidence was the secondary outcome, that is, it was not the aim of this research. This means that the study was not designed to investigate the effect of PICSI on the miscarriage rate, making these secondary results less reliable. For this reason, it is important to discuss your individual circumstances with your doctor. Also, PICSI might reduce the miscarriage rate but these results are less reliable. 


Mechanism of sperm binding

Mechanism of sperm binding

Hyaluronan is a naturally occurring biopolymer (polysaccharide) found in all human cells and is a foremost constituent of the cumulus oophorus layer that enfolds the human oocyte. The head of a mature sperm holds a hyaluronan-specific ligand receptor that facilitates mature sperm to unite to hyaluronan. Comparatively, immature sperm do not unite. Competent, mature, biochemically active sperm unite to the hyaluronan where they can be selected by the embryologist and used for ICSI procedure. This modus operandi mimics a focal step in the innate fertilization course of action, the binding of mature sperm to the oocyte complex. 

As a consequence, the opted spermatozoa are indispensable alike as one that would be successful and do well in the natural reproductive progression. Nevertheless, this advancement does not imitate the genomic integrity of the spermatozoa and its aptitude to deliver the best paternal contribution to the zygote.


Why PICSI is important?

Why PICSI is important?

This fertilization is intended to rule out incompetent sperm and select the best sperm with the ideal genetic composition for the oocyte and fertilizes it. The mature sperm cells are more competent to bind to the hyaluronic acid, implication that it is enhanced and ensemble to fertilizing the oocyte. PICSI toils on the root that the better sperm are in this reverence, the better they are in all high opinions, including motility and their ability to penetrate and insert into an oocyte.

A sperm’s ability to bind to HA draws a parallel to:

  1. Normal head morphology better-fertilizing potential
  2. Reduced amount of DNA fragmentation
  3. Reduced chromosomal Aneuploidy
  4. Amplified chromatin integrity
  5. Principle Cellular maturity


When may PICSI be required?

There is some evidence from the scientific literature that indicates that couples with recurrent pregnancy loss or those with slow or poorly developing embryos may also benefit from PICSI. However, the number of studies using PICSI is currently limited and there is no clear indication that this would be of benefit, with varying results from different studies to date. The Fertility Specialist will discuss this thoroughly with you if your sample demonstrates an increased percentage of immature sperm. You will then be able to decide if this is an additional treatment that you would like to include in your treatment with us. PICSI can also be performed at a patient’s request.

During PICSI, the embryologist is able to distinguish between mature sperm which have completed their full development and immature sperm which are more likely to have damaged DNA or the wrong number of chromosomes. The embryologist is not able to do this by just looking down the microscope, as in the routine ICSI procedure, as mature and immature sperm will have the same appearance.

In the PICSI procedure, the Embryologist will only use mature sperm to inject directly into mature eggs. Following the PICSI, the injected eggs are incubated overnight and assessed the following morning for evidence of fertilization. The average fertilization rate following PICSI is similar to ICSI and IVF, with 60-70% of injected eggs fertilizing normally following PICSI.

ICSI and PICSI are treatments that may be indicated for Male Factor infertility in the following cases:

  • Sperm defect is inferred, sperm immaturity, chromosomal anomaly, an elevated number of sperm with defected integrity of DNA.
  • Deprived embryo quality has been found on Day 2 to 5 (Blastocyst conversion rate).
  • Borderline sperm count with low fertilization with ICSI.
  • Repeated embryo transfers without implantation have occurred.
  • Repeated miscarriages and early pregnancy loss have occurred.
  • Reduced sperm morphology and motility.
  • The woman is over 38years old.
  • Low-quality cryopreserved sperm.
  • Sperm sample aspirated by testicular sperm aspiration (TESA).


What are the Advantages to PICSI?

Advantages to PICSI

Basically, PICSI is a more filtered way of selecting the best competent sperm for the fertilization process. Despite the fact that conventionally sperm are selected for ICSI based on their morphology and motility quotient, PICSI consents for this choice to be complete based on the sperm’s capability to fertilize and perform the role job. Additionally, the PICSI dishes are fairly easy to use. The technique of selecting sperm based on their facade and appearance is also flawed because chromosomal imperfections can still be found within healthy glance sperm.


What are the disadvantages to PICSI?

At present, there are no specific drawbacks to PICSI being fully instituted. Except in the TESA samples where sperms are immotile PICSI cannot be employed and patients with occasional spermia where sperm counts limited to ≤ 1 million/ml.


How is PICSI Performed?

PICSI Procedure

The PICSI dish is manufactured in the United States and comprises three micro-drops of hyaluronan attached to the interior bottom of a sterile polystyrene culture dish. Prepared sperm are then added to the micro-droplet and given a period of time to exhibit binding (this is usually between 15-30 mins). A sperm’s ability to bind to the hyaluronan hydrogel, therefore, assists the embryologist with selecting functionally competent mature sperm for injection.

Given that hyaluronan binding has been shown to be correlated with increased sperm maturity, improved sperm DNA integrity and a normal chromosomal complement, this, in turn, means better quality embryos for selection and pregnancy compared to conventional ICSI. Studies have also shown that early pregnancy loss can result from selecting compromised spermatozoa during ICSI.


In vitro fertilization (IVF)

In vitro fertilization (IVF)

IVF, or in vitro fertilization, is a technique used to help a woman get pregnant. It is when a human egg is fertilized with sperm in a laboratory. IVF is used to treat infertility and some genetic problems.


What happens during the IVF process?

During IVF, eggs are removed from the ovaries of a woman and fertilized in a laboratory with sperm provided by her partner or a donor.

One or two embryos — fertilized eggs — are implanted into the woman’s uterus (womb).

Here are the typical stages in an IVF cycle:

  • The woman’s natural menstrual cycle is switched off with daily injections or a nasal spray.
  • The woman has injections of fertility hormones to stimulate her ovaries so she produces several eggs, instead of just one.
  • When the eggs mature, they are collected using a fine needle, guided by ultrasound, under light sedation.
  • The eggs are fertilized in the laboratory with sperm provided by the woman’s partner or a donor.
  • Fertilized eggs (embryos) are grown in an incubator for a few days.
  • 1 or 2 healthy embryos are transferred into the woman’s uterus using a thin tube inserted into the vagina and cervix.
  • If an embryo successfully implants, the woman becomes pregnant. She will need to wait two weeks for a pregnancy test.
  • Any remaining healthy embryos can be frozen and stored for later use if needed.

There are many variations to the IVF procedure. For example, sperm or eggs may be collected from a donor. In some cases, a surrogate may carry the pregnancy.


Chances of success with IVF

On average, every time a woman has a cycle of IVF, she has about a 1 in 5 chance of becoming pregnant and having a baby. That chance is higher for women younger than 35 years old, and lower for older women, decreasing with age. By age 44, the chance of success is less than 1 in 10.

Some women need up to 5 cycles of treatment to be successful, while others never fall pregnant.


Intracytoplasmic sperm injection (ICSI)

Intracytoplasmic sperm injection (ICSI)

If the number of spermatozoa is small or their activity is reduced, the embryologist resorts to the ICSI procedure — sperm injection into the cytoplasm of the egg cell. The manipulation is carried out at a magnification of 400 times, with the help of holding and injection needles. For ICSI, the fastest morphologically normal spermatozoid is selected. It is immobilized and placed into a microneedle. Then while holding the egg on the micro-suction cup, an embryologist pierces the egg shell with a micro-needle and injects the spermatozoid into it.

Initially, the ICSI method was introduced to treat the most severe cases of male infertility, but it proved to be so effective that it is increasingly used as the main method of fertilization without additional indications.


Indications for ICSI:

  • A decreased number of spermatozoa;
  • Reduced sperm motility;
  • Numerous pathological forms of spermatozoa;
  • Combined sperm pathology;
  • Fertilization with spermatozoa thawed after freezing;
  • Fertilization with oocytes thawed after freezing;
  • Absence of spermatozoa in sperm (azoospermia), when spermatozoa are retrieved surgically from a testicle Testicular sperm extraction (TESE) or epididymis percutaneous epididymal sperm aspiration. (PESA)
  • Obtaining spermatozoa from urine in case of retrograde ejaculation;
  • Immunological infertility (positive MAR test);
  • Fertilization failure after conventional IVF.


Intracytoplasmic injection of morphologically selected spermatozoa (IMSI)


IMSI. With male infertility and a considerable decrease in the number of spermatozoa that have normal morphological characteristics, the search for a suitable spermatozoid for fertilization grows much more difficult. In this case IMSI technology (intracytoplasmic injection of morphologically selected spermatozoa) is used — a relatively new technique that allows choosing the best sperm cell at magnification by 6,600 times. This magnification allows specialists to determine the smallest changes in the morphology of spermatozoa.

The selection of spermatozoa at IMSI is a very long and laborious process. In particularly difficult cases, the search for a normal spermatozoid can last several hours. The use of IMSI reduces the risk of having a child with congenital malformations.


What happens during IMSI?

This technique consists of previously selecting the sperm through a microscope of approximately 6,000 times, 15 times more powerful than the microscope used in ICSI. Thanks to this microscope, sperm with abnormalities are discarded based on the morphology they present.

Sperm without abnormalities are implanted one by one in each embryo via intracytoplasmic injection. Finally, between one and three embryos are selected for transfer, which consists in introducing a thin catheter into the end of the uterus.


PICSI is a non-invasive test performed on a semen sample as an additional step in the ICSI process. The risks associated with the use of ICSI also apply to PICSI. However, PICSI does not carry any additional known risks for the person undergoing fertility treatment or the child born as a result of fertility treatment.