(311) THE INJECTION OF CONCEPTION: A BRIEF REVIEW ON THE HISTORY INTRACYTOPLASMIC SPERM INJECTION (ICSI)
Authors: O'connor L , Werner Z , Barnard J 
Published: December 2024

Abstract

Introduction
Intracytoplasmic sperm injection (ICSI) is one of the greatest breakthroughs in male infertility in recent history. This technique allows couples battling with infertility to conceive with just one single spermatozoon and one oocyte.

Objective
We sought to review the early history of ICSI.

Methods
Literature review for historical literature pertaining to ICSI was performed using Pubmed and Google Scholar.

Results
The first documented experiments with regards to fertility date back to the 1890s. In his original manuscript, Heape successfully transferred fertilized ova from one hare to another, resulting in viable offspring. In 1932, Pincus et al published a landmark in-vitro fertilization (IVF) study which proved that fertilized ova were able to mature and survive manipulation in vitro after a short period of incubation (20 hours). Chang et al expanded on this work in 1959 by demonstrating a more robust incubation and reimplantation protocol in hares. The first human IVF baby, Louise Brown, was born in 1978. It was not until 1962 when the first ICSI experiments were described. Hiramoto described experiments were fertilization of sea urchin occurred by injecting a single spermatozoon into single ooplasm. This same concept was later achieved with mice (1966) and hamsters (1977). As with any new technique, there were humble beginnings. The first studies using mammalian models demonstrated that only around 30% of oocytes survived the injection due to significant damage and lysis. In an effort to increase fertilization rates, several different techniques were trialed. In 1988, Kiessling et al published a technique were the zona pellucida (ZP) barrier was completely removed by treated the unfertilized ova with mild trypsin solution (digestive enzyme). While this did increase fertilization rates, polyspermy was an issue. As a result, another technique was born which focused on injecting sperm beyond ZP and into the perivitelline space. This technique was coined with the term sub-zonal insemination (SUZI) by Cohen et al in 1988. There was a significant decrease in polyspermy, however fertilization rates remained low. Efforts were then focused on not on abandoning, but refining techniques with better microsurgical precision. Dr. Gianpiero D. Palermo, one of the main pioneers of ICSI, helped with this refinement by ensuring that the lab was equipped with necessary equipment such an incubator and an anti-vibration table. Additionally, he helped developed small micro-needles (5 microns in diameter) and smoother micromanipulators to allow for steady pressure when injecting spermatozoa into ova. The first offspring using ICSI were achieved in rabbits (1988) and then bovine species (1990). Then, in 1992, when Palermo’s team was attempting SUZI, one single spermatozoon accidently pierced the oolemma and ooplasm of single oocyte. The next day, two pronuclei were noted, which confirmed the inception of ICSI. Four couples reported successful conception via ICSI that same year.

Conclusions
ICSI were made possible by the lessons learned from the development of IVF. This technique has since been refined and has provided infertile couples with the opportunity of conception for over 30 years.

Disclosure
No.