Intracytoplasmic sperm injection
Encyclopedia
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
.
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. 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 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.
as measured e.g. by Comet assay
, advanced maternal age
and semen quality
.
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...
is injected directly into an egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
.
Indications
This procedure is most commonly used to overcome male infertilityInfertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
problems, although it may also be used where eggs cannot easily be penetrated by sperm, and occasionally in addition to sperm donation
Sperm donation
Sperm donation is the provision by a man, , of his sperm, with the intention that it be used to impregnate a woman who is not usually the man's sexual partner, in order to produce a child....
.
It can be used in teratozoospermia, because once the egg is fertilized, abnormal sperm morphology does not appear to influence blastocyst
Blastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...
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. 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
Joseph D. Schulman
Joseph D. Schulman is a physician, medical researcher, and biomedical entrepreneur in the fields of genetics diseases and human reproduction....
and colleagues at Genetics and IVF Institute in 1995.
Procedure
ICSI is generally performed in addition an in vitro fertilisationIn vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...
procedure to extract often several oocytes from a woman.
The procedure is done under a microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
using multiple micromanipulation devices (micromanipulator
Micromanipulator
A micromanipulator is a device which is used to physically interact with a sample under a microscope, where a level of precision of movement is necessary that cannot be achieved by the unaided human hand...
, microinjectors
Microinjectors
A microinjector is a device which provides the pressure which is needed to deliver a sample solution from a micropipette into cells.It can be a mechanically or electronically regulated air pressure device or a simple glass syringe where the plunger is screw controlled for precise adjustments of the...
and micropipettes). A holding pipette (on the left of picture) stabilizes the mature oocyte
Oocyte
An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...
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
Polar body
A polar body is a cell structure found inside an ovum. Both animal and plant ova possess it. It is also known as a polar cell.Asymmetrical cell division leads to the production of polar bodies during oogenesis. To conserve nutrients, the majority of cytoplasm is segregated into the secondary...
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
Hyaluronan
Hyaluronan is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues...
, the main constituent of the gel layer (cumulus oophorus
Cumulus oophorus
The cumulus oophorus , also called discus proligerus, is a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation...
) 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
Aneuploidy
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
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 fragmentationDNA fragmentation
DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be intentional by laboratory personnel or the cells, or it can be spontaneous.-Intentional:Restriction digest is the intentional laboratory breaking of DNA strands....
as measured e.g. by Comet assay
Comet assay
The Single Cell Gel Electrophoresis assay is an uncomplicated and sensitive technique for the detection of DNA damage at the level of the individual eukaryotic cell. It was first described by Singh et al. in 1988...
, advanced maternal age
Advanced maternal age
Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....
and semen quality
Semen quality
Semen quality is a measure of the ability of semen to accomplish fertilization. Thus, it is a measure of fertility in a man. It is the sperm in the semen that are of importance, and therefore semen quality involves both sperm quantity and 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.See also
- The Human Fertilisation and Embryology Authority (HFEA)
- Reproductive technologyReproductive technologyReproductive technology encompasses all current and anticipated uses of technology in human and animal reproduction, including assisted reproductive technology, contraception and others.-Assisted reproductive technology:...
- The Epigenome Network of Excellence (NoE)