Intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI, pronounced "eeksee" or "icksy" ) is an in vitro fertilization procedure in which a single sperm is injected directly into an egg.

Indications
This procedure is most commonly used to overcome male infertility problems, although it may also be used where eggs cannot easily be penetrated by sperm, and occasionally in addition to sperm donation.

It can be used in teratozoospermia, because once the egg is fertilized, abnormal sperm morphology does not appear to influence blastocyst development or blastocyst morphology. Even with severe teratozoospermia, microscopy can still detect the few sperm cells that have a "normal" morphology, allowing for optimal success rate.<ref name=french/

History
The technique was developed by Gianpiero Palermo around 1991 at the Vrije Universiteit Brussel, in the Center for Reproductive Medicine headed by Paul Devroey and Andre Van Steirteghem. The first American baby was conceived with the technique At Reproductive Biology Associates (RBA) in Atlanta, Georgia in 1992 under the direction of Michael Tucker, PhD and Joe Massey, MD. ( ref. Case report, American Society for Reproductive Medicine, Abstract report at ASRM meeting, Montreal, Canada, 1993.) The first large experience with the technique in the United States was published by Joseph D. Schulman and colleagues at Genetics and IVF Institute in 1995.

Procedure
ICSI is generally performed in addition an in vitro fertilisation procedure to extract often several oocytes from a woman.

The procedure is done under a microscope using multiple micromanipulation devices (micromanipulator, microinjectors and micropipettes). A holding pipette (on the left of picture) stabilizes the mature oocyte with gentle suction applied by a microinjector. From the opposite side a thin, hollow glass micropipette is used to collect a single sperm, having immobilised it by cutting its tail with the point of the micropipette. The micropipette is pierced through the oolemma and into the inner part of the oocyte (cytoplasm). The sperm is then released into the oocyte. The pictured oocyte has an extruded polar body at about 12 o'clock indicating its maturity. After the procedure, the oocyte will be placed into cell culture and checked on the following day for signs of fertilization.

In contrast, in natural fertilization sperm compete and when the first sperm penetrates the oolemma, the oolemma hardens to block the entry of any other sperm. Concern has been raised that in ICSI this sperm selection process is bypassed and the sperm is selected by the embryologist without any specific testing. However, in mid 2006 the FDA cleared a device that allows embryologists to select mature sperm for ICSI based on sperm binding to hyaluronan, the main constituent of the gel layer (cumulus oophorus) surrounding the oocyte. The device provides microscopic droplets of hyaluronan hydrogel attached to the culture dish. The embryologist places the prepared sperm on the microdot, selects and captures sperm that bind to the dot. Basic research on the maturation of sperm shows that hyaluronan-binding sperm are more mature and show fewer DNA strand breaks and significantly lower levels of aneuploidy than the sperm population from which they were selected. A brand name for one such sperm selection device is PICSI.

'Washed' or 'unwashed' sperm may be used in the process.

Success or failure factors
Potential factors that may influence pregnancy rates (and live birth rates) in ICSI include level of DNA fragmentation as measured e.g. by Comet assay, advanced maternal age and semen quality.

Complications
There is some suggestion that birth defects are increased with the use of IVF in general, and ICSI specifically, though results of different studies differ. In a summary position paper, the Practice Committee of the American Society of Reproductive Medicine has said it considers ICSI safe and effective therapy for male factor infertility, but may carry an increased risk for the transmission of selected genetic abnormalities to offspring, either through the procedure itself or through the increased inherent risk of such abnormalities in parents undergoing the procedure.

Religious objections
The Roman Catholic Church, under the papacy of Benedict XVI, has condemned the practice of intracytoplasmic sperm injection, in the magisterial instruction Dignitas Personae because it causes a complete separation between the marital act and childbearing.