Original Articles

By Ms. Erin Embury , Mrs. Catherine Meunier , Ms. Trina Shah , Dr. Simon Turner , Dr. Phillip Matson
Corresponding Author Ms. Erin Embury
Hollywood Fertility Centre, Hollywood Private Hospital, Monash Avenue, Nedlands - Australia WA 6009
Submitting Author Dr. Phillip L Matson
Other Authors Mrs. Catherine Meunier
Hollywood Fertility Centre, Hollywood Private Hospital, Monash Avenue, Nedlands - Australia WA 6009

Ms. Trina Shah
Hollywood Fertility Centre, Hollywood Private Hospital, Monash Avenue, Nedlands - Australia WA 6009

Dr. Simon Turner
Hollywood Fertility Centre, Hollywood Private Hospital, Monash Avenue, Nedlands - Australia WA 6009

Dr. Phillip Matson
Hollywood Fertility Centre, Monash Avenue - Australia WA 6009


birth defects, boys, IVF, ICSI

Embury E, Meunier C, Shah T, Turner S, Matson P. The Prevalence Of Abnormalities At Birth In Boys Following Intracytoplasmic Sperm Injection Compared To Conventional In Vitro Fertilization. WebmedCentral NURSING 2010;1(12):WMC001249
doi: 10.9754/journal.wmc.2010.001249
Submitted on: 01 Dec 2010 12:56:56 AM GMT
Published on: 03 Dec 2010 05:36:25 PM GMT


Pregnancies achieved in one clinic by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and resulting in boys between 2000 and 2009 were reviewed. There were significant differences between the IVF and ICSI pregnancies, with the mothers of the ICSI boys being significantly younger at the time of embryo transfer (p<0.05) and the ICSI boys being significantly heavier than their IVF counterparts (p<0.01). There was a trend towards an increased incidence of abnormalities in boys after ICSI (18/326; 5.5%) compared with IVF (8/309; 2.6%) though this did not reach significance, a higher proportion of urogenital abnormalities after ICSI, and an increased number of abnormalities after ICSI in males compared to females. The data would support the need for further follow-up studies and continued vigilance. National regulatory authorities would seem ideally placed to gather such data, but they should differentiate between sex of the offspring when reporting on pregnancy outcomes following assisted reproduction.


Pregnancies achieved by in vitro fertilization (IVF) and allied techniques are often associated with increased preterm delivery, low birth weight and perinatal mortality when compared with naturally conceived pregnancies even when removing multiplicity as a confounding factor [11, 13]. Whilst the children often have an increased incidence of ill health [15] and are hospitalised more in early life [10], they appear to have normal cognitive [7] and psychomotor [15] development. However, a possible increased incidence of congenital abnormalities in children conceived following in vitro fertilisation (IVF) was first suggested back in 1987 during a review of the pregnancy outcomes reported voluntarily to the Fertility Society of Australia [17], and subsequent systematic reviews of the literature generally confirm this [9, 18, 21].

Unfortunately, there is still debate on the effect of the IVF technique in causing an increased incidence of birth defects despite a plethora of published data: some studies still show no increase at all [23], others find an increased incidence when re-analysing previously published data [16], and there is a possible confounding association with the presence of infertility per se [6, 19]. In addition, the widespread use of intracytoplasmic sperm injection (ICSI) in IVF laboratories has also enabled children to be fathered by men with poor semen parameters that would be unsuitable to achieve fertilization in vivo or with conventional IVF [8], and there appears to be strong evidence for the inheritance of male fertility disorders linked to the deletions on the Y-chromosome [14] or of undefined genetic cause [4, 19].

The aims and objectives of the present study were to (a) review all boys born during 2000-2009 following IVF or ICSI at the Hollywood Fertility Centre, (b) examine any differences between the IVF and ICSI births, (c) identify any particular pattern in abnormalities, and (d) determine the clinical relevance of the findings.


Treatment by IVF and ICSI was provided using standard protocols described previously [20]. All cycles in which fresh or frozen embryos were transferred were included.

All patient demographic data and treatment details were stored on a relational database developed in-house using Filemaker Pro (Filemaker Inc., Santa Clara, USA), and the data were entered by laboratory and nursing staff. All outcomes were identified at specific clinical milestones relative to Day 1 of the treatment cycle for (i) all cycles having an embryo transfer [4 weeks at the time of the pregnancy test], and (ii) cycles with a positive pregnancy test [ultrasound scan at 7 weeks, and 10 month follow up for birth details]. Data was exported to an Excel spreadsheet for analysis and mandatory reporting according to state [1] and federal [2] legislation.

Group statistics were expressed as the mean and standard deviation, and comparisons made using the Student’s t-test. Differences were considered significant if p<0.05.


There were differences in the characteristics of the pregnancies achieved by IVF or ICSI as shown in Table 1. The mothers of the ICSI boys were significantly younger at the time of transfer (p<0.05), and the ICSI boys were significantly heavier than their IVF counterparts (p<0.01).

The proportion of children born with a birth defect, and the range of anomalies reported, is shown in Table 2. There was a two-fold increase in the rate of abnormalities in the ICSI boys, but this failed to reach significance (χ2=2.77, df=1, p=0.062). There was also a greater range of conditions relating to the urogenital tract in the ICSI boys. A similar pattern of anomalies was not seen in girls, where there were 4.1% abnormalities in IVF cases compared to 0.9% in the IVF girls.


The current study has identified some significant differences between the IVF and ICSI pregnancies from which boys were born, ie mother’s age at transfer and the boys’ birth weight. This illustrates the problem of obtaining data in which all the confounding variables are controlled for, and differences in maternal characteristics have previously been noted to be important in influencing the rate of congenital malformations observed in IVF children [3].

The low numbers of affected children observed in the present study also shows how difficult it is to make conclusions based on one clinic’s data. Others have used the pooling of data from several units to form a multi-centre study, and were able to show an increase in the incidence of major congenital abnormalities in ICSI children [5]. The collection and reporting of data on congenital abnormalities, or simply defects noted at birth, in countries where data collection is mandatory would seem an ideal opportunity to monitor the children born following assisted reproduction. Currently in Australia, the National Perinatal Statistics Unit (NPSU) collects the information but does not include the findings in their annual report [22]. It is understood that a comparison with naturally conceived children would not be possible in such an audit but certainly a comparison between IVF and ICSI children could be made. The follow up of children delivered by obstetricians outside of the IVF clinic and even overseas can be challenging, and so the gathering of the data by the IVF clinics would need to be done methodically and accurately to prevent the generation of misinformation.  The difficulties of collecting information on births has already been noted elsewhere [12, 24]. One important point alluded to in the present study is the potential difference in the rate and nature of abnormalities in boys and girls. A common feature of many published studies is the comparison of children conceived in different ways, without consideration of the sex of the child. The reporting of any data on births following assisted reproduction should differentiate between boys and girls.

In conclusion, the current study has shown a trend towards an increase in the rate and range of birth defects in boys conceived by ICSI compared with IVF, although this did not achieve statistical significance. This illustrates the difficulty of using data from a single clinic where the numbers were low and there were confounding variables. Nevertheless, the evidence supports the need for further follow up studies and continued vigilance, with regulatory authorities needing to differentiate between sex when reporting on pregnancy outcomes following assisted reproduction.


The contribution of all the clinicians, nurses and scientists at the Hollywood Fertility Centre in providing the clinical service over the years is greatly appreciated.


1.Human Reproduction Technology Act 1991 (WA)
2.Prohibition of Human Cloning for Reproduction Act 2002 (Cth)
3.Anthony S, Buitendijk S, Dorrepaal C, Lindner K, Braat D, den Ouden A. Congenital malformations in 4224 children conceived after IVF. Hum Reprod 2002; 17: 2089-2095.
4.Asklund C, Jørgensen N, Skakkebæk N, Jensen T. Increased frequency of reproductive health problems among fathers of boys with hypospadias. Hum Reprod 2007; 22: 2639-2646.
5.Bonduelle M, Wennerholm U-B, Loft A, Tarlatzis B, Peters C, Henriet S, Mau C, Victorin-Cederquist A, Van Steirteghem A, Balaska A et al. A mutli-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 2005; 20: 413-419.
6.Buckett W, Tan S. Congenital abnormalities in children born after assisted reproductive techniques: how much is associated with the presence of infertility and how much with its treatment? Fertil Steril 2005; 84: 1318-1319.
7.Carson C, Kurinczuk J, Sacker A, Kelly Y, Klemetti R, Redshaw M, Quigley M. Cognitive development following ART: effect of choice of comparison group, confounding and mediating factors. Hum Reprod 2010; 25: 244-252.
8.Devroey P, Van Steirteghem A. A review of ten years experience of ICSI. Hum Reprod Update 2004; 10: 19-28.
9.Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk J. Assisted reproductive technologies and the risk of birth defects - a systematic review. Hum Reprod 2005; 20: 328-338.
10.Hansen M, Colvin L, Petterson B, Kurinczuk J, de Klerk N, Bower C. Admission to hospital of singleton children born following assisted reproductive technology (ART). Hum Reprod 2008; 23: 1297-1305.
11.Helmerhorst F, Perquin D, Donker D, Keirse M. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Br Med J 2004; 328: 261.
12.Hvidtjørn D, Grove J, Schendel D, Schieve L, Ernst E, Olsen J, Thorsen P. Validation of self-reported data on assisted conception in The Danish National Birth Cohort. Hum Reprod 2009; 24: 2332-2340.
13.Jackson R, Gibson K, Wu Y, Croughan M. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004; 103: 551-563.
14.Kai C, Juul A, McElreavey K, Ottesen A, Garn I, Main K, Loft A, Jørgensen N, Skakkebæk N, Andersen A et al. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number. Hum Reprod 2008; 23: 1669-1678.
15.Koivurova S, Hartikainen A, Sovio U, Gissler M, Hemminki E, Järvelin M. Growth, psychomotor development and morbidity up to3 years of age in children born after IVF. Hum Reprod 2003; 18: 2328-2336.
16.Kurinczuk J, Bower C. Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative interpretation. Br Med J 1997; 315: 1260.
17.Lancaster P. Congenital malformations after in-vitro fertilization. Lancet 1987; ii: 1392-1393.
18.McDonald S, Murphy K, Beyene J, Ohlsson A. Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. Journal of Obstetrics and Gynaecology Canada 2005; 27: 449-459.
19.Ramlau-Hansen C, Thulstrup A, Olsen J, Bonde J. Parental subfecundity and risk of decreased semen quality in the male offspring: a follow-up study. Am J Epidemiol 2008; 167: 1458-1464.
20.Rebollar Lazaro I, Matson P. The culture of human cleavage stage embryos alone or in groups: effect upon blastocyst utlization rates and implantation. Reproductive Biology 2010; 10: 227-234.
21.Rimm A, Katayama A, Diaz M, Katayama K. A meta-analysis of controlled studies comparing major malformations rates in IVF and ICSI infants with naturally conceived children. J Assist Reprod Genet 2004; 21: 437-443.
22.Wang Y, Chambers G, Sullivan E. Assisted reproduction technology in Australia and New Zealand 2008. Assisted reproduction technology series no. 14. Cat. no. PER 49. Canberra: AIHW. 2010.
23.Zádori J, Kozinszky Z, Orvos H, Katona M, Kaáli S, Pál A. The incidence of major birth defects following in vitro fertilization. J Assist Reprod Genet 2003; 20: 131-132.
24.Zhang Z, Macaluso M, Cohen B, Schieve L, Nannini A, Chen M, Wright V. Accuracy of assisted reproductive technology information on the Massachusetts birth certificate, 1997-2000. Fertil Steril 2010; 94: 1657-1661.

Source(s) of Funding

Funded by the Hollywood Fertility Centre.

Competing Interests



This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

0 reviews posted so far

0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.


Author Comments
0 comments posted so far


What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)