Is there any data about the children created through the IVF method of
Intracytoplasmic Sperm Insertion (ICSI), which indicates that those
children present health problems (in body or mental) attributed to the
way they were conceived?

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Request for Question Clarification by librariankt-ga on 29 Aug 2003 11:32 PDT

Hi Anthe,

I have found about 31 article citations in PubMed MEDLINE that deal
with ICSI, IVF/adverse effects, and risk.  These appear to be studies
of genetic and teratogenic effects of this treatment (and of IVF in
general).  For instance, here's one:

Malformation rate in fetuses and children conceived after ICSI:
results of a prospective cohort study.
Reprod Biomed Online. 2002 Sep-Oct;5(2):171-8. 

I cannot give you the direct articles themselves, because of copyright
law, but can send you a number of abstracts (or links to abstracts)
that you could then track down if you were interested.   Thus, I am
posting this as a clarification.  How would you like for me to proceed
at this time?

Librariankt

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Clarification of Question by anthe-ga on 31 Aug 2003 11:07 PDT

hello Librariankt, thank you for providing me with this information
and sorry for not answering sooner. I am very interested in the
abstracts that you can provide from PubMed MEDLINE, provided that the
writters are making clear in those abstracts their positive or
negative point of view about ICSI. I have been doing a lot of research
on this topic myself and I have collected a lot of data from private
ART clinics. I am especially interested in "official" sites, like the
ones you proposed in your comments, and in forums - organizations (if
they exist) of people with children conceived through ICSI, and their
statistics.

Thank you very much
anthe

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Request for Question Clarification by librariankt-ga on 07 Sep 2003 10:07 PDT

Anthe - Thanks for the clarification.  I haven't forgotten you, I'm
working on this and will have an answer soon.  Sorry for the delay! -
librariankt

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Clarification of Question by anthe-ga on 08 Sep 2003 04:37 PDT

thank you, please take your time, I am not in a hurry.

Hi anthe –

Sorry to have taken so long to get back to you – this question is
really quite a doozy!

I have looked and looked and just have not had success finding groups
that specialize in supporting the parents of children conceived via
ICSI.  This is not really surprising – since the procedure has only
been available for 10 years, and since there are relatively few
children who’ve been created this way – thus even fewer with problems
– it could conceivably be hard to get a group going.  However, as I
note below (way below), there are a lot of groups and forums for IVF
and ICSI discussions, so you might try them.  Mostly they support
people going through the procedure, rather than people who’ve already
had it work.

I’ll also note that searching for statistics and studies on children
conceived by ICSI is somewhat challenging, since the vocabulary gets
in the way.  Most of the discussion out there is on the “success” rate
of ICSI in terms of whether or not it results in a viable offspring,
not in whether the resulting child can perform well in school. 
Whether this is because of the shortsightedness of medicine and the
infertility community (after all, if you’re desperate to have a baby,
you may not be thinking of what college it’ll get into in 18 years),
or simply from lack of data is unclear.

I’m including some specific studies that are cited a lot on websites. 
There are two that came out simultaneously in 1998, then two from this
year.  Of the four, two indicate that there are statistically no
differences between ICSI and non-IVF children; two indicate that there
may be, in some specific developmental areas.  You’ve certainly chosen
a very interesting research topic, and I wish you the best of luck
with it.

Do ICSI Children Risk Developmental Delays?
http://www.ivillagehealth.com/experts/fertility/qas/0,,166261_151130,00.html
Question asked on iVillage.com, and answered by Dr. Mark Perloe.  He
mentions two studies published in the British medical journal Lancet;
one (a small study) suggests that children conceived via ICSI suffer
developmentally, but the other (a much larger study) found no such
link.

If you do a search for “ICSI children” on Google you will likely find
a lot of pages that discuss the two studies referred to above.  I am
not giving you all of those pages, as that would just be overkill and
not be useful in terms of presenting new information.  The links to
the PubMed abstracts for these studies are:

Bonduelle M, et al. (1998 May 23). “Mental development of 201 ICSI
children at 2 years of age.” Lancet 351(9115): 1553.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10326540&dopt=Abstract
(no abstract available)

Bowen JR et al. (1998 May 23). “Medical and developmental outcome at 1
year for children conceived by intracytoplasmic sperm injection.”
Lancet 351(9115); 1529-34.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10326534&dopt=Abstract
BACKGROUND: Intracytoplasmic sperm injection (ICSI) was introduced as
a new form of in-vitro fertilisation (IVF) in 1993 and is now accepted
as the treatment of choice for severe male infertility in many centres
around the world. However, there is little information about the
long-term outcome of children conceived by ICSI. We aimed to find out
the medical and developmental outcome of children conceived by ICSI at
age 1 year. METHODS: In this prospective study, we compared the
medical and developmental outcome at 1 year of 89 children conceived
by ICSI with 84 children conceived by routine IVF, and with 80
children conceived naturally. Formal developmental assessment was done
with Bayley Scales of Infant Development (2nd edition) from which a
mental development index (MDI) was derived. FINDINGS: There was no
significant difference in the incidence of major congenital
malformations or major health problems in the first year of life.
However, the mean Bayley MDI was significantly lower for the children
conceived by ICSI than for the children conceived by routine IVF or
naturally (95.9 [SD 10.7], 101.8 [8.5], and 102.5 [7.6], respectively,
p < 0.0001). 15 (17%) of 89 children conceived by ICSI experienced
mildly or significantly delayed development (MDI < 85) at 1 year
compared with two (2%) of the 84 children conceived by IVF and one
(1%) of the 80 children conceived by natural conception (p < 0.0001).
INTERPRETATION: Although most children conceived by ICSI are healthy
and develop normally, there is an increased risk of mild delays in
development at 1 year when compared with children conceived by routine
IVF or conceived naturally. These findings support the need for
ongoing developmental follow-up of children conceived by ICSI to see
whether they are at increased risk of intellectual impairment or
learning difficulties at school age.

A more recent study found no difference between ICSI and non-ICSI
babies.  Here’s a news brief that explains the article:
IVF & ICSI Safe, Says Study
http://www.aphroditewomenshealth.com/news/20030610025446_health_news.shtml

And here’s the abstract from PubMed to the study itself:

Sutcliffe AG, et al. (2003 Mar). “A retrospective case-control study
of developmental and other outcomes in a cohort of Australian children
conceived by intracytoplasmic sperm injection compared with a similar
group in the United Kingdom.” Fertility & Sterility 79(3):512-6
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12620432&dopt=Abstract
OBJECTIVE: To investigate the possibility that children born after
ICSI were at increased risk for neurodevelopmental delay. DESIGN:
Retrospective case-control study. SETTING: IVF clinic. PATIENT(S):
Fifty-eight singleton children born after ICSI and 38 normally
conceived singleton children (controls), matched for relevant
sociodemographic characteristics, from Australia and 208 case-patients
and 221 controls from the United Kingdom. MAIN OUTCOME MEASURE(S):
Antenatal and perinatal, and sociodemographic characteristics;
physical health, including congenital abnormalities; and
neurodevelopment by using the Griffiths scales of mental development.
RESULT(S): Eighty-five percent of case-patients and 96% controls were
assessed at a mean age of 13 months. Neurodevelopmental scores were
similar in all children. Perinatal outcome was similar, apart from
more caesarean sections in the case-patients. Rates of congenital
anomalies were similar (5.6% among case-patients vs. 5.7% among
controls). Children from fathers with oligozoospermia showed no extra
problems. Children born after ICSI in the United Kingdom and Australia
were similar. CONCLUSION(S): Children conceived after ICSI did not
differ from their naturally conceived peers in physical health or
development at ages up to 15 months


This article from New Scientist, reporting that ICSI children do
suffer an increased risk of abnormalities – particularly boys – was
published this summer. The study was presented at the annual meeting
of the European Society of Human Reproduction and Embryology (ESHRE),
but does not appear to have been published in a medical journal yet. 
Here’s the news article, to give you some statistics:

ICSI kids have more malformations
http://www.newscientist.com/news/news.jsp?id=ns99993902
“The rate of malformations in ICSI children was 6.2 per cent, compared
with 4.1 per cent in IVF children, and 2.4 per cent in the control
group of naturally conceived children.  Only the difference in the
rates between ICSI children and the control group was statistically
significant.”
“There were no differences between the children in intelligence, birth
weight, height at five years or medical illnesses, although hospital
admissions were slightly higher for IVF and ICSI children.”

As you can see from the ESHRE programme for July 2, there was an
entire panel on ICSI and infertility, several speakers from which are
coauthors on the papers cited above:
http://www.eshre.com/ecm/main.asp?lan=63&typ=203

Okay, I think that’s probably enough of a survey of recent studies of
ICSI.  Here’s a link to a PubMed search for articles with statistics
and trends in ICSI:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term="Sperm+Injections,+Intracytoplasmic/statistics+and+numerical+data"[mh]
Note that these results (about 22 when I ran it today) don’t include
the studies above.  I’d suggest you try this search, then play around
with the database if you’re interested in seeing more.  A search you
could try putting into the search box is “Sperm Injections,
Intracytoplasmic/adverse effects"[MeSH]” which will get you articles
about the negative effects of ICSI (this is the one I ran and reported
in the clarification request earlier).


Here are some fertility centers and societies that have information
about ICSI and the risks to children:

UCSF Center for Reproductive Health
http://www.ucsfivf.org/icsi.html

American Society for Reproductive Medicine (quoted below)
http://www.asrm.org/Patients/FactSheets/invitro.html

The International Council on Infertility Information Dissemination,
Inc. (INCIID)
http://www.inciid.org/
There are a lot of great forums here, in addition to other information
and suggested reading (i.e., books) about IVF in general and ICSI in
specific.


This search of the Google group alt.infertility.* for posts relating
to ICSI gets a lot of hits:
http://groups.google.com/groups?hl=en&lr=&ie=ISO-8859-1&q=ICSI&btnG=Google+Search&meta=group%3Dalt.infertility.*
You might find it useful to narrow the results using such keywords as
“statistics” “development*”


Finally, I went to the DMOZ Open Directory Project to look through the
infertility section of the directory
(http://dmoz.org/Health/Reproductive_Health/Infertility/) for likely
candidates for your research.

First, some chat rooms and fora.  These may or may not have current
information about ICSI on them, but you can always start a thread if
you want to:

FertileThoughts.com (http://www3.fertilethoughts.com/forums/index.php)
Electronic Infertility Network (http://www.ein.org/support.htm)
HealthBoards.com: Infertility
(http://www.healthboards.com/infertility/)

You might also try the groups at
http://dmoz.org/Health/Reproductive_Health/Infertility/Support_Groups/
 and the various sources of information at
http://dmoz.org/Health/Reproductive_Health/Infertility/Male/.



For all of these searches, I used the following keywords, in a variety
of combinations (all on the search engine Google or the DMOZ
directory):
ICSI
Child* or children
Development* or develop*
Statistics
Parent*
“support group” or forum

Again, good luck, and please let me know if you need anything
clarified –

Librariankt

thank you very much. It may have taken you a while to answer but it
was indeed a difficult topic. I guess there is no a simple "yes" or
"no" in my question, but at least you found for me enough reliable
sources to research.

I'm posting the following abstract as a comment, since I think you'll
find it interesting regardless of what I or any other researcher posts
as an answer (found in PubMed MEDLINE):

Curr Urol Rep. 2001 Dec;2(6):423-31.  
Is intracytoplasmic sperm injection safe? Current status and future
concerns.
Nudell DM, Lipshultz LI.

In vitro fertilization with intracytoplasmic sperm injection (ICSI)
has revolutionized the treatment of patients with severe forms of male
infertility. However, because ICSI has been performed for only 10
years, long-term outcomes and risks to offspring remain largely
unknown. The fact that ICSI can potentially bypass natural selection
barriers to genetic disease transmission has brought a sobering but
important impetus to recent research on the risks and outcomes of
ICSI. Several studies were done recently to examine specific risks to
children born following ICSI. Because of rapid advances in the ICSI
procedure itself, studies evaluating the safety of using immature
sperm forms from the testis (spermatids, spermatocytes) also have been
undertaken. This review summarizes recent studies examining the risks
and long-term outcomes to date of in vitro fertilization with ICSI.


- librariankt

I also found the following (opposing view) quotation on a website of
the American Society for Reproductive Medicine
(http://www.asrm.org/Patients/FactSheets/invitro.html)

"Studies suggest that ICSI and in vitro fertilization are safe
technologies. A recent study covered nearly 1,000 children conceived
through these methods in five European countries and found that the
children, measured from birth to age 5, were as healthy as children
conceived naturally.  While other studies have found a slightly
increased risk of genetic defects and gene-imprinting disorders in
children conceived through ART, more research needs to be done to
determine the risks and the processes by which this might occur."