What is Intracytoplasmic Sperm Injection?
Paul J. Turek, M.D.
Associate Professor of Urology, Ob-Gyn and Reproductive Services
Director of the Male Reproductive Laboratory
University of California, San Francisco
"What Nature does blindly, slowly, and ruthlessly,
man may do providently, quickly and kindly."
--Francis Galton, 1905.
Introduction
As a technique to help infertile couples conceive, in vitro fertilization
(IVF) is now over 20 years old. It involves controlled
ovarian stimulation and ultrasound-guided transvaginal
egg retrieval from the ovaries prior to ovulation.
Eggs are then fertilized in petri dishes (small
plastic dishes)with 500,000 to 5 million motile
sperm. In the late 1980's, many investigators attempted
to improve IVF success by further manipulating
the oocyte and its coverings (the zona pellucida)
to enhance fertilization success. Techniques such
as partial zona dissection and sub-zonal insemination
(SUZI) were reported to decrease even further the
number of sperm required to achieve a pregnancy
in vitro. With SUZI, good oocyte fertilization
rates were obtained with fewer than 20 motile sperm.
In 1992, a revolutionary advance in such manipulation
techniques was described by Jean-Pierro Palermo
and colleagues at the Dutch-speaking Brussels Free
University in Belgium. In this laboratory accident,
sperm were injected directly into the cytoplasm
of the egg in a technique now termed intracytoplasmic
sperm injection (ICSI). Since then, ICSI has replaced
all prior micromanipulation techniques and has
become a routine treatment for infertility throughout
the world.
Remarkably, the sperm requirement for egg fertilization dropped
from hundreds of thousands for IVF, to 1 viable
sperm for ICSI. This has led to the development
of aggressive new surgical techniques to provide
viable sperm for egg fertilization from men with
no sperm in the ejaculates, pushing urologists
beyond the ejaculate and into the male reproductive
tract to find sperm. Present sources of sperm in
azoospermic (no ejaculated sperm) patients include
the vas deferens, epididymis and testicle. In some
centers, fertilization rates using retrieved sperm
virtually approximate those obtained with normal,
ejaculated sperm.
Given that so few sperm are needed for success with ICSI,
many kinds of male factor infertility previously
deemed untreatable are, for the first time in history,
associated with biological paternity, including
conditions like Klinefelter and prune belly syndrome
as well as other forms of genetic infertility.
At present ICSI is indicated for: 1) failed fertilization
with IVF alone; 2) sperm retrieved from the reproductive
tract; 3) ejaculated sperm of very low density
or motility, and 4) ejaculated sperm with very
poor morphology (sperm shape).
ICSI Risks and Outcomes
Although a truly revolutionary technique, there are several
concerns about ICSI, mainly because its application
in humans was not preceded by work in animal models.
- We are not God or Darwin.
Because neither God nor Darwin chooses the sperm to be injected into the
oocyte, we must assume that many of the natural selection barriers that exist
during natural fertilization are bypassed. As such, genetic defects that
caused the infertility are expected to be passed on to offspring unabated.
This has already been demonstrated in certain cases of male genetic infertility.
Informed consent of patients on this issue is critical in cases of suspected
genetic causes of infertility. It is also the rationale behind the recent
increased use of genetic counselors in infertility programs all over the
world. At UCSF, we have instituted PROGENI (Program in the Genetics of Infertility),
a genetic counseling and testing program for infertile patients.
- Does ICSI Induce Birth Defects?
In the absence of relevant data from experimental
models, is very important that the safety of ICSI
be evaluated for the risk of congenital malformations.
Although it is an accepted fact that children born
to IVF are as healthy as those conceived normally,
any additional risk brought to bear on children's
health after conception with ICSI needs to be assessed.
Comparative data on perinatal and morphological
investigations of children born by IVF or IVF-ICSI
to age-matched parents at several centers have
revealed no increase in perinatal or neonatal complications
with ICSI. In addition, there are no clearly identifiable
birth defects associated with ICSI.
- Does ICSI Induce Chromosomal Abnormalities in Children?
There is sufficient evidence to suggest that ICSI is associated with a statistically
higher likelihood of producing offspring with chromosomal abnormalities when
compared to natural conception. The likelihood that a child conceived with
ICSI will have a sex chromosomal abnormality is 4 fold higher (0.83%) than
normal (0.2%). At present, we do not know why there is an increased risk
for children conceived with ICSI. Two possibilities are: 1) the sperm used
in the procedure is abnormal or 2) the procedure itself leads to an increased
risk of sex chromosome abnormalities. Some of the problems that may occur
with sex chromosome abnormalities include: increased risk of miscarriage
of affected embryos, heart problems for affected infants that may require
surgery, specific behavior or learning difficulties for affected children
and adults and infertility as adults for affected offspring. PROGENI now
recommends genetic counseling and consideration of a prenatal diagnosis procedure,
such as chorionic villus sampling or amniocentesis, for couples planning
ICSI.
- Does
ICSI Affect Childhood Development?
This issue is less clear and more controversial than the chromsosomal findings
in ICSI children. One study that suggests a higher rate of developmental
delay at 1 year of age for children conceived with ICSI compared to natural
and IVF conception. This difference was noted in the mental development index
but not the psychomotor index of the Bayley Scales of Infant Development.
However, these data have been disputed by the results from two other centers
that report no difference in mental development in 2 year old children conceived
with ICSI when compared to those naturally conceived. This issue is not resolved
by any means and suggests the importance of longterm followup of individuals
conceived with ICSI.
Summary
ICSI is
certainly a revolutionary advance in assisted reproductive
technology. Many couples with previously untreatable
forms of infertility can now conceive with the
use of this technique. However, its also has associated
risks that mandate informed consent from eligible
couples.
Paul J. Turek M.D.
Associate Professor of Urology, Ob-Gyn and Reproductive Sciences
Director, Male Reproductive Laboratory
University of California, San Francisco
2330 Post Street
6th Floor
San Francisco, CA 94115-1695
Tel: 415-353-7344 Fax: 415-353-7252
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