The first world pregnancies with IVF happened in the early 1980s. “Standard or conventional” IVF has been performed, and continues to be, when harvested eggs are co-incubated with prepared sperm in a petri dish under appropriate pH and temperature conditions. Typically, thousands of motile sperm must be incubated with one egg to achieve normal fertilization, which will then lead to embryo and blastocyst development.

By the late 1980s and early 1990s, there was big frustration with fertilization results in couples with moderate and severe male infertility. Men whose semen analysis showed low sperm counts, low progressive motility, and/or poor sperm morphology, typically would fail to fertilize or had very low rates of fertilization, thereby compromising the cycle outcome. In 1992 a group of investigators developed ICSI (intracytoplasmic sperm injection). This is a micro-fertilization technique, whereby a single sperm is directly microinjected into a mature oocyte.

It was immediately and worldwide noted that ICSI benefited all types of problems seen with sperm including low count, motility, shape or any other sperm dysfunctions, and ICSI is now the technique of choice to use in all couples with a diagnosis of male infertility. The application of this technique quickly expanded to other male indications such as use of cryopreserved (frozen) sperm, and to the discovery that sperm obtained from the testes or epididymis could successfully fertilize oocytes, a concept previously unheard of!! That is why today, men with complete absence of sperm from the semen (a condition called azoospermia), can be subjected to a testicular or epididymal biopsy for sperm recovery of low numbers of sperm, and through ICSI have normal babies.

Azoospermia can be obstructive (due to inflammatory-infectious scarring of the epididymis), iatrogenic such as vasectomy (contraceptive ligation of the vas deferens), or congenital (such as men presenting with congenital absence of the vas). Azoospermia can also be non-obstructive, and in these cases unlike the previous ones, there is a basic and fundamental problem with sperm production. These men need to be counseled as to the potential associations with chromosomal and other genetic issues, and that results may or not be optimal even if sperm are recovered at the time of biopsies.

Because of the excellent fertilization results, clinicians and embryologists have nowadays expanded on the indications for ICSI. It is mandatory to perform ICSI when egg freezing is performed. Today, more and more cases of egg freezing are done for fertility preservation, both in cases of cancer diseases, and for social reasons. Sperm injection into the vitrified-warmed eggs yields very high rates of fertilization, not seen without ICSI. ICSI is routinely used in cases of preimplantation genetic or chromosomal testing (PGD and PGS).

Other indications are more controversial and not totally implemented following evidence- based medicine. Nonetheless, ICSI is performed in over 60% of all IVF cycles in cases of non-male factor infertility including couples with unexplained infertility, maternal age 38 years or older, low oocyte yield, and having 2 or more prior assisted reproductive technology cycles and no prior live births.

Findings from some but not all studies suggest that ICSI is associated with an increased risk for chromosomal abnormalities, autism, intellectual disabilities, and birth defects compared with conventional IVF. But these increased risks may be because of subfertility (i.e., the genetic background) and not due to the technique.

According to The American Society of Reproductive Medicine ICSI is a safe and effective procedure for couples with male factor infertility, and also can improve the chance of fertilization for couples with poor fertilization in a previous IVF cycle. ICSI is here to stay and will continue to help thousands of couples conceive via ART.

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