What Is PICSI or Physiological ICSI in IVF?

By (gynecologist), (embryologist), (senior clinical embryologist), (embryologist), (embryologist) and (invitra staff).
Last Update: 06/23/2020

PICSI is a variant of intracytoplasmic sperm injection, also known as ICSI. For this reason, PICSI is called physiological ICSI.

Sperm selection in traditional ICSI is done by the embryologist who looks at the semen sample and chooses a spermatozoon with good motility for microinjection.

However, through the PICSI technique, the aim is to make sperm selection less subjective and not dependent on laboratory staff. This is achieved by binding the mature spermatozoa to a substance similar to hyaluronic acid.

What is physiological ICSI?

The PICSI technique, also known as physiological ICSI, is a method of sperm selection based on the degree of maturation of the sperm. This technique allows the selection of spermatozoa according to their ability to bind to a synthetic molecule with properties similar to hyaluronic acid.

PICSI stands for Physiological Intracytoplasmic Sperm Injection.

In the head of the mature sperm, there is a specific receptor for hyaluronic acid (HA), which is an important component of the cluster where the oocytes are found. Those sperm that adhere to HA is because it has completed spermatogenesis and the processes of plasma membrane remodeling, cytoplasmic extrusion, and nuclear maturation.

PICSI procedure

The PICSI technique is a relatively simple process. The procedure is the same as ICSI, but changing the selection part of the male gamete.

Sperm collection is done as usual, i.e. by masturbation with a 3-5 day abstinence period. Later, the sperm capacitation in the laboratory takes place to separate the motile spermatozoa from the rest of the seminal components and from the immobile and/or dead spermatozoa.

The sperm are then placed on a special plate. This plate contains a few drops of a synthetic material very similar to hyaluronic acid that coats the oocytes naturally. Those spermatozoa of good quality and an adequate degree of maturity will remain attached to these drops and the embryologist will be able to easily identify them for the microinjection of the oocytes.


This method is very useful in cases of patients with sperm with good motility and a high degree of DNA fragmentation because they help to choose the mature spermatozoon with good quality.

The most frequent situations for sperm selection through PICSI are listed below:

  • Patients with altered spermatozoa FISH.
  • Sterility of unknown origin.
  • Patients with repeated miscarriages are suspected of male factor.
  • Previous IVF-ICSI cycle failures.

It should be noted that seminal samples with very low sperm motility are difficult to use for the PICSI technique.

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The combination of the PISCI technique with others offers help to many people who, due to different medical issues, have not been able to obtain a pregnancy naturally to fulfill their dream. Fortunately, assisted reproduction techniques are continuously advancing and new technologies and scientific knowledge allow for improvement on a daily basis.


The main advantage of the PICSI method is that it allows the selection of sperm in an objective way, that is, independently of the embryologist's opinion, contrary to what happens in ICSI. This means that the sperm are selected individually and have low fragmentation rates, reducing the possibility of genetic alterations. In addition, this sperm selection leads to increased pregnancy rates.

On the other hand, there are a large number of studies that indicate that, thanks to the PICSI technique, the abortion rate decreases. However, this reduction in the abortion rate is not related to the increase in the live birth rate, since it is a minimal decrease.

FAQs from users

What is PICSI?

By Rebeca Reus BSc, MSc (embryologist).

The PICSI technique refers to what is known as physiological ICSI. This is a form of sperm selection prior to introduction into the egg.

It is based on the ability of the sperm to bind to hyaluronic acid, a substance that coats eggs. To do this, a special plate is used in which there are a few drops of a substance similar to hyaluronic acid that covers the eggs. Thus, the sperm capable of adhering to the plate will be those of the highest quality and potential for fertilization.

What are the benefits of PICSI?

By Blanca Paraíso M.D., Ph.D., M.Sc. (gynecologist).

As possible advantages of the use of the PICSI we could talk about the following:

  • It is a complete, accurate and alternative sperm selection method. Complete because the sperm sample to be used for PICSI has already been improved with techniques such as Swim-up or Gradient; precise because the basis of the technique involves molecular components and alternative because it represents a different option to other means of sperm selection.
  • It seems to be associated with a reduction in the abortion rate: the different studies state that the use of PICSI does not increase the live birth rate compared to the use of ICSI but reveal that there is a lower abortion rate in the PICSI group. Why is it that if it reduces abortions it is not found in the studies that it increases the live birth rates? Because this decrease in the abortion rate is so low that in studies it has no influence on live birth rates.
  • It is an objective and simple method that does not require much experience to develop, unlike ICSI where there is a subjective component in the choice of sperm to microinject.

What is the difference between PICSI and ICSI?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

The technique of In Vitro Fertilization by Intracytoplasmic Sperm Injection (IVF-ICSI) consists of the fertilization of the egg by injecting a single sperm into the cytoplasm of each mature egg. The selection of the spermatozoon to be injected is carried out by the embryologist himself, taking into account morphological and mobility criteria.

In contrast, the PICSI technique, also called physiological ICSI, allows the selection of spermatozoa according to their attachment to a molecule similar to hyaluronic acid. Therefore, in this case, it is not the embryologist who performs the sperm selection. Only mature spermatozoa, and therefore those with the greatest capacity to fertilize the egg, will join these molecules.

Suggested for you

Once the spermatozoa capable of binding to hyaluronic acid have been selected, microinjection is carried out in the usual way. For more information about this, we recommend you visit the following article: Sperm Microinjection: What Is ICSI Technique?

On the other hand, one of the indications for performing the PICSI is repeated miscarriages. Read more about this topic here: What is Repeated Miscarriage? Causes, Diagnosis, and Treatment.

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Huszar G, Ozenci CC, Cayli S, Zavaczki Z, Hansch E, Vigue L. Hyaluronic acid binding by human sperm indicates cellular maturity, viability, and unreacted acrosomal status. Fertil Steril. 2003 Jun;79 Suppl 3:1616-24.

Huszar G, Jakab A, Sakkas D, Ozenci CC, Cayli S, Delpiano E, Ozkavukcu S. Fertility testing and ICSI sperm selection by hyaluronic acid binding: clinical and genetic aspects. Reprod Biomed Online. 2007 May;14(5):650-63. Review.

Parmegiani L. et al. “Physiologic ICSI”: Hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality. Fertility and Sterility. Vol 93. Nº2. January 15, 2010.

Parmegiani L. et al. Comparison of two ready-to-use systems designed for sperm-hyaluronic acid binding selection before intracytoplasmic sperm injection: PICSI vs. Sperm Slow: a prospective, randomized trial. Fertil Steril. 2012 Sep;98(3):632-7. doi: 10.1016/j.fertnstert.2012.05.043. Epub 2012 Jun 29.

Majumdar G. A prospective randomized study to evaluate the effect of hyaluronic acid sperm selection on the intracytoplasmic sperm injection outcome of patients with unexplained infertility having normal semen parameters. J Assist Reprod Genet. 2013 Nov;30(11):1471-5. doi: 10.1007/s10815-013-0108-9. Epub 2013 Oct 2.

Mokanszki A. et al. Is sperm hyaluronic acid binding ability predictive for clinical success of intracytoplasmic sperm injection: PICSI vs. ICSI? Syst Biol Reprod Med. 2014 Dec;60(6):348-54. doi: 10.3109/19396368.2014.948102. Epub 2014 Aug 14.

FAQs from users: 'What is PICSI?', 'What are the benefits of PICSI?' and 'What is the difference between PICSI and ICSI?'.

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Authors and contributors

 Blanca Paraíso
Blanca Paraíso
M.D., Ph.D., M.Sc.
Bachelor's Degree in Medicine and Ph.D from the Complutense University of Madrid (UCM). Postgraduate Course in Statistics of Health Sciences. Doctor specialized in Obstetrics & Gynecology, and Assisted Procreation. More information about Blanca Paraíso
License: 454505579
 Cristina Mestre Ferrer
Cristina Mestre Ferrer
B.Sc., M.Sc.
Bachelor's Degree in Biological Sciences, Genetics & Human Reproduction from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Embryologist at IVI Barcelona. More information about Cristina Mestre Ferrer
 José Muñoz Ramírez
José Muñoz Ramírez
B.Sc., M.Sc., Ph.D.
Senior Clinical Embryologist
Bachelor's Degree in Biology from the University of Malaga. Master's Degree in Genetics by the University of Alcalá, and Master's Degree in Assisted Reproduction from the University of Valencia. He works as a clinical embryologist at Clínica Tambre (Madrid, Spain), in addition to being an Associate Professor at the University of Murcia. More information about José Muñoz Ramírez
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
 Rebeca Reus
Rebeca Reus
BSc, MSc
Degree in Human Biology (Biochemistry) from the Pompeu Fabra University (UPF). Official Master's Degree in Clinical Analysis Laboratory from the UPF and Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). More information about Rebeca Reus
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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