What is PICSI?

In 2006, the original discovery of PICSI was made by researchers at Yale University, and it was subsequently introduced to the market in 2008. The name "PICSI" incorporates the letter "P" from the term "petridish.” Today, it has evolved to also represent "physiological" ICSI. The invention of the PICSI dish was a significant advancement in the field of assisted reproductive technology (ART) and has been used to improve the selection of sperm for in vitro fertilization (IVF) procedures.

PICSI, is a method employed in the process of selecting sperm for Intracytoplasmic Sperm Injection (ICSI) treatment.PICSI entails combining sperm with hyaluronic acid (HA). Hyaluronic acid is a bioactive molecule and a primary constituent of the extracellular matrix enveloping the oocyte-cumulus complex.The mature sperm head contains a receptor for hyaluronic acid. The sperms that have undergone complete maturation (spermatogenesis) are only capable to adhere to HA found in the oocyte-cumulus complex1.

Through research it has been shown that the spermatozoa that has undergone complete maturation process of nuclear maturity, remodelling of plasma membrane and cytoplasmic extrusion is believed to have a whole DNA that leads to low frequency of aneuploids and miscarriages. Whereas, in contrast the immature spermatozoa, do not have the ability to bind to HA.

PICSI Procedure

PICSI dish incorporates hyaluronan samples that serve as a binding agent, attracting the most robust sperm. It involves the careful selection of the most viable sperm for fertilization prior to its introduction into the egg.

A systematic review revealed that a PICSI dish (manufactured by MidAtlantic Diagnostics Inc., Mt Laurel, NJ, USA), was devised by incorporating four designated regions of immobilized hyaluronic acid (HA) within a Falcon Petri dish. Following this, a single droplet of purified spermatozoa was carefully positioned at the periphery of the HA-coated area. Subsequently, the spermatozoa adhering to the HA surface are retrieved using an ICSI pipette after a 15-minute interval, and then utilized for the injection process (Image 1).2Although there is a chance that hyaluronic acid (HA) molecules might accompany the chosen sperm inside the ICSI pipette, it's worth noting that HA is a naturally occurring element found in cervical mucus, cumulus cells, and follicular fluid.2Up to now, there have been no documented negative effects on fertilization or embryo development linked to the application of HA-selected spermatozoa in clinical IVF environments.2 

PICSI

(Image 1) Sperm selection using PICSI dishes.
(A) A sperm drop is placed at the periphery of a HA drop, mature sperm binds to the HA-spot, while immature sperm moves freely.
(B) Bound sperm could be picked up with the ICSI pipette. (Jakab et al., 2005)

Advantages of using PICSI:

  1. Spermatozoa bound to hyaluronic acid (HA) have demonstrated lower levels of DNA fragmentation in comparison to spermatozoa prepared through density gradient centrifugation (DGC) and spermatozoa found in raw semen sample.
  2. The probability of enhancing a sperm population to the point where it encompasses >14% morphologically normal sperm was projected to increase 3 times after undergoing selection through HA binding.2
  3. Among semen samples collected from men undergoing fertility evaluations, spermatozoa bound by HA exhibited a notably reduced occurrence of autosomal disomy, diploidy, and sex chromosome disomy when compared to spermatozoa that were not subjected to HA binding selection.2

Disadvantages of using PICSI:

  1. It's crucial to emphasize that incorporating this additional step during the ICSI procedure will demand the embryologists to allocate extra time since the process of sperm binding alone may extend up to 30 minutes, which could present a challenge when dealing with a substantial quantity of oocytes during injection.
  2. The use of PICSI does not show superiority over standard ICSI in terms of enhancing the likelihood of achieving a live birth at full term, even though it does lead to a decrease in miscarriage rates.1

Who is PICSI recommended for?

  1. Males with high sperm DNA fragmentation.
  2. Patients with poor embryo quality.
  3. Patients with history of less or no fertilization rate.
  4. Patients with repeated implantation failure.
  5. Patients who have undergone recurrent miscarriages.

Difference between IVF, ICSI and PICSI:

PICSI

The widely employed technique in the field of ART is intracytoplasmic sperm injection (ICSI), either conventional or modified. However, in this process, the selection of sperm is based on subjective judgment by the embryologist, who chooses, based on their own criteria, the spermatozoa that appear best at low resolution. This effectively bypasses the natural selection process. Consequently, there is an increased risk of congenital abnormalities and miscarriages, as it is impossible to ascertain whether the selected spermatozoa have anomalies in their nucleus or if there is DNA fragmentation.

Hence, the physiological ICSI technique arose (PICSI - physiologically selected intracytoplasmic sperm injection).3

Research has demonstrated that by using PICSI technique, spermatozoa exhibiting binding to HA exhibit completed spermatogenic processes, including plasmatic membrane remodelling, cytoplasmic extrusion, and nuclear maturation. Consequently, they possess intact DNA with a reduced incidence of aneuploidies and miscarriages. This implies that the genomic contribution of these spermatozoa to the resulting zygotes can be likened to those selected by the cumulus oophorous during natural fertilization.

Conclusion:

The PICSI technique allows for the selection of spermatozoa based on their physiological binding capacity, enhancing the likelihood of successful fertilization and healthy embryo development. Studies have shown promising outcomes, with improved pregnancy rates and reduced risks of chromosomal abnormalities. However, it is important to note that implementing PICSI may require additional time and resources, particularly in cases involving many oocytes. Overall, the integration of PICSI into ART protocols holds great potential for further improving the success rates of fertility treatments, offering renewed hope to individuals and couples seeking to achieve their reproductive goals.

References:

1.Miller, David; Pavitt, Susan; Sharma, Vinay; Forbes, Gordon; Hooper, Richard; Bhattacharya, Siladitya; Kirkman-Brown, Jackson; Coomarasamy, Arri; Lewis, Sheena; Cutting, Rachel; Brison, Daniel; Pacey, Allan; West, Robert; Brian, Kate; Griffin, Darren; Khalaf, Yakoub (2019). Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial. The Lancet, 393(10170), 416–422. 

2.Said, T. M., & Land, J. A. (2011). Effects of advanced selection methods on sperm quality and ART outcome: a systematic review. Human Reproduction Update, 17(6), 719–733. 

3.Avalos-Durán, G., Ángel, A. M. E. C.-D., Rivero-Murillo, J., Zambrano-Guerrero, J. E., Carballo-Mondragón, E., & Checa-Vizcaíno, M. Á. (2018). Physiological ICSI (PICSI) vs. conventional ICSI in couples with male factor: A systematic review. JBRA Assisted Reproduction.