A brief history of technical developments in intracytoplasmic sperm injection (ICSI). Dedicated to the memory of J.M. Cummins.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology for treatment of severe male infertility introduced into clinical practice in 1992. This review provides a brief history of the development of ICSI by acknowledging major developments in the field. The review addresses key developments in pre-clinical and early studies, how ICSI compares with in vitro fertilisation, long-term consequences, how the mechanistic approach to ICSI has changed in both manual and semi-automated approaches, and how sperm selection procedures are integrated into ICSI. From the beginnings using animal models in the 1960-1970s, the development of ICSI is a remarkable and transformative success story. Indeed, its broad use (70% of cycles globally) exceeds the need required for treating infertile males, and this remains a controversial issue. There remain questions around the long-term health impacts of ICSI. Furthermore, advances in automation of the ICSI procedure are occurring. An estimated 6million children have been born from the ICSI procedure. With further automation of sperm selection technologies, coupled with automation of the injection procedure, it is likely that the proportion of children born from ICSI will further increase.

Intracytoplasmic sperm injection 30 years on: too much of a good thing?

Intracytoplasmic sperm injection (ICSI) was introduced for male infertility but is now used in many other techniques in assisted reproduction. Indications for ICSI use need to be re-evaluated to ensure appropriate application in infertility management.

The pioneering of intracytoplasmic sperm injection: historical perspectives.

Intracytoplasmic sperm injection (ICSI) has often been heralded as a ground-breaking technique that has transformed the treatment of couples with infertility. By injecting a single spermatozoon into the cytoplasm of the oocyte, ICSI bypasses the zona pellucida and increases the chances of fertilization and subsequent embryo development, independent of semen parameters. Ever since the first live births using ICSI were reported in 1992, ICSI has become the mainstay of treating male factor infertility as well as overcoming fertilization failure associated with conventional in vitro insemination. Today, ICSI is utilized in nearly 66% of all assisted reproductive treatments worldwide and has resulted in the birth of millions of babies. The primary goal of this review is to provide historical perspectives about the pioneering of ICSI. We begin by highlighting the scientific work of early investigators who elucidated the mechanisms central to mammalian fertilization. Furthermore, we briefly discuss how these findings contributed to the development of IVF for the treatment of infertility. We then emphasize the shortcomings of IVF in treating severe forms of male factor infertility and enumerate the micromanipulation techniques that were developed to circumvent these shortcomings. Finally, we indicate how the inadequacies of these micromanipulation techniques lead to the inception, application and popularity of ICSI.

Development and current applications of assisted fertilization.

Since the very early establishment of in vitro insemination, it became clear that one of the limiting steps is the achievement of fertilization. Among the different assisted fertilization methods, intracytoplasmic sperm injection emerged as the ultimate technique to allow fertilization with ejaculated, epididymal, and testicular spermatozoa. This work describes the early steps that brought forth the development of intracytoplasmic sperm injection and its role in assisted reproductive techniques. The current methods to select the preferential male gamete will be elucidated and the concerns related to the offspring of severe male factor couples will be discussed.

ICSI: where we have been and where we are going.

Notwithstanding the broad success of in vitro fertilization (IVF), a failure to achieve fertilization still plagues a substantial group of patients, with sperm abnormalities the main culprit. In the 1980s, several micromanipulation procedures were adopted from animal husbandry to facilitate gamete interaction, and this resulted in the development of intracytoplasmic sperm injection (ICSI), a procedure through which an oocyte can be fertilized independently of the morphology and/or motility of the single spermatozoon injected. The procedure was first used in cases of fertilization failure after standard IVF or when an inadequate number of sperm cells were available. The consistency of fertilization independent of the functional quality of the spermatozoon has extended the application of ICSI to immature spermatozoa retrieved surgically from the epididymis and testis. Moreover, the need to denude the oocyte has allowed assessment of the nuclear maturity of the oocyte. ICSI is also preferred in conjunction with preimplantation genetic diagnosis and recently has been used to treat HIV discordant couples, where there is a pressing need to minimize the exposure of the oocyte to a large number of spermatozoa. For all ages and with all the different sperm types used, fertilization after ICSI is at approximately 70 to 80% and it ensures a clinical pregnancy rate of up to 45%. These results have made ICSI a procedure comparable in popularity with IVF and have minimized the need for couples suffering from all forms of male infertility to resort to adoption or the use of donor sperm.