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11 June 1998

Dear Colleague

Risks Associated with ICSI Treatment

In July 1997 the HFEA circulated to centres revised guidelines for the licensing of ICSI. These guidelines re-iterated the HFEA's view that ICSI was a relatively new technique in assisted reproduction. They did not offer any guidance about what patient information on ICSI should be given nor on the counselling of ICSI patients.

Information on both the genetic consequences of the use of ICSI and on birth defects in infants conceived by ICSI is beginning to raise general concerns about the potential risks for the welfare of children born as a result of this treatment and the counselling needed to be offered to patients before they consent to such treatment. This letter addresses the issues of associated genetic and birth defects involved in the use of ICSI and provides guidance to centres on ICSI treatment.

Increased incidence of CF mutation status in azoospermic men

It appears that 5-10% of azoospermic men selected for ICSI have congenital bilateral absence of the vas deferens (CBAVD), a condition associated with certain cases of cystic fibrosis (CF). Men with this condition appear to be compound heterozygotes for rarer CF mutations. CF testing may therefore be indicated for azoospermic men with CBAVD, but need not be compulsory. It is also recommended that consideration be given to offering genetic testing to other azoospermic men.

Genetic counselling is strongly recommended for CBAVD azoospermic men and their partners. Those involved in counselling should understand the issues relating to CBAVD and its association with increased incidence of CF mutations.

The decision to proceed with ICSI in such cases rests with the clinician and the patients, but should the patients refuse testing, the HFEA feels that this should not be used as grounds on which to refuse treatment.  

Male fertility relating to Y chromosome deletions

Sub-fertile men with Y chromosome deletions may pass the same type of sub-fertility onto their sons. It is recommended that sub-fertile males and their partners contemplating ICSI treatment should be made aware of this situation via counselling.

Sex chromosomal anomalies

Where ICSI is used in the treatment of men with severe azoospermia or oligospermia there is a risk of an increased frequency of sex chromosome disorders. Sex chromosome abnormalities such as 47XXX; 47XXY and 47XYY occur at a relatively high frequency in the neonatal population - about 1 in 700 births for each of the aforementioned abnormalities. It is recommended that these issues are relayed to those seeking ICSI through counselling.

Birth defects

The group at the Brussels Free University responsible for the development of ICSI have conducted a follow up study on birth defects in children born at their centre as a result of ICSI treatment. This study indicated that the prevalence of major birth defects in liveborn infants was "within the expected range" when compared against published data. It has been recognised that the classification system used for a major defect in the ICSI group was not the same as that used in the comparison group and that the incidence of birth defects as a result of ICSI treatment could be understated in the Belgian study. Reclassification of the Brussels data and re-analysis indicates that children born as a result of ICSI are twice as likely to have a major birth defect and 50% more likely to have a minor birth defect. It is generally appreciated that further studies are needed in order to gain more insight into any possible effects.

To date ICSI has been considered to be a technique which offers considerable benefits to patients without increased risk of birth defects and patients may have been counselled on this basis. It is recommended by the HFEA that the implications of these, as yet unconfirmed results, be reflected whenever potential ICSI patients are counselled.

Developmental delays

Recent research papers concerning follow up of relatively small numbers of ICSI children give an indication of possible developmental delay in some children conceived using the ICSI technique. Potential ICSI patients should be counselled about the currently identified risks.

Other factors

Other sex abnormalities have been reported in babies born as a result of ICSI treatment. There are also reports that the miscarriage rate may increase in relation to the degree of spermatogenic impairment. These risk factors should be communicated to patients via counselling.

The guidance above has been directed towards the counselling of patients by centres once they have decided to consider ICSI treatment. Having said that, the first introduction patients have to IVF techniques including ICSI is via the written information supplied by centres. Much of this information, while stating that ICSI is a new technique, concentrates on the benefits of ICSI quoting relative fertilisation, pregnancy and live birth rates. Some patient information refers to the genetic consequences of ICSI. Considering what is said in this letter, it is strongly recommended by the HFEA that all patient information on ICSI should stress that it is still a new technique and provide a benefit/risk assessment which reflects the current state of knowledge.

Please contact the inspector co-ordinator for your clinic if you have any queries about this letter.

Yours faithfully

Ruth Deech

Chairman

Page last updated: 14 April 2009

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