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28 February 2001

Dear Colleague,

The HFEA's Working Group on New Developments in Reproductive Technology has recently reviewed two issues:

• Evidence that use of donor gametes and embryos increases hypertensive problems in pregnancy; and
• Anecdotal evidence of an increase in imprinting disorders in children conceived by ICSI

The HFEA would like to bring the following information to the attention of centres.

Evidence that use of donor gametes and embryos increases hypertensive problems in pregnancy

The HFEA has recently reviewed evidence that pregnancies resulting from donated gametes and embryos have an increased incidence of complications in pregnancy, in particular hypertensive problems including pre-eclampsia.

The HFEA is aware that there have been several reports that in pregnancies resulting from oocyte donation, a significant increase in pregnancy-induced hypertension is apparent. In addition, a significantly higher rate of hospitalisation of oocyte recipients immediately before delivery and during the antenatal period has been reported, consistent with an increase in the incidence of pre-eclampsia. A significantly higher rate of Caesarean section and admission of the baby to the ICU during the first few days after birth have also been reported for oocyte recipients.

A higher incidence of pre-eclampsia in women conceiving by intrauterine insemination with donor sperm compared to women conceiving by intrauterine insemination with partner sperm has also been reported. The HFEA considers that although the reported differences are not significant when only singleton pregnancies are considered, the increased rate of hypertensive problems in both donor oocyte and donor sperm conceived pregnancies is still of concern.

Recently, higher rates of hypertension and pre-eclampsia have also been reported following embryo donation, although only a small number of pregnancies have been studied.

Due to pre-eclampsia being a common problem, especially in first pregnancies, the HFEA does not consider that the level of the problem is sufficient to affect the provision of treatment using donor gametes and embryos. The HFEA considers however that patients having treatment using donated gametes or embryos should be made aware of the increased risk of hypertensive problems including pre-eclampsia and that this information should be included in the relevant patient information. Pertinent references to which centres may wish to refer are listed in an annex to this letter.

Anecdotal evidence of an increase in imprinting disorders in children conceived by ICSI

It has come to the HFEA's attention that anecdotal reports that ICSI may increase the incidence of syndromes associated with aberrant genetic imprinting arose at the 2000 meeting of the American Society of Human Genetics. Such conditions include Beckwith-Weidemann, Prader-Willi and Angelman syndromes. Centres may wish to refer to the OMIM database and references therein for background on these conditions and their modes of inheritance. The OMIM number for Beckwith-Weidemann syndrome is 130650, for Prader-Willi syndrome it is 176270, and for Angelman syndrome it is 601491.

The incidence of these syndromes has been estimated at between 1 in 8,000 and 1 in 25,000 births. A recent paper by Manning et al. (2000) studied imprinting at the Prader-Willi/Angelman locus in children born after ICSI and found no defects. This study only involved 92 children however, and, unless the risk was greatly increased, could thus give no definitive answers regarding the risks.

The HFEA considers that, although not substantiated, the anecdotal evidence may be suggestive of an increase in the incidence of such disorders and wishes to bring this issue to the attention of centres. The HFEA would like to ask centres to keep a watching brief on the incidence of imprinting disorders and keep the HFEA appraised of any concerns.

The HFEA's ICSI leaflet has also been amended to address the importance of follow-up studies. A revised version is enclosed with this letter.

Yours sincerely,

Ruth Deech
Chairman

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Annex: Reference list

Evidence that use of donor gametes and embryos increases hypertensive problems in pregnancy

Abdalla, H. I., et al., 1998, British Journal of Obstetrics and Gynaecology, Vol.105, pp332-337

Pados, G., et al., 1994, Human Reproduction, Vol.9, pp538-542

Salha, O., et al., 1999, Human Reproduction, Vol.14, pp2268-2273

Soderstrom-Anttila, V., et aL, 1998, Human Reproduction, Vol.13, pp483-490

Soderstrom-Anttila, V., 2001, Human Reproduction Update, Vol.7, pp28-32

Smith, G. N., et al., 1997, American Journal of Obstetrics and Gynaecology, Vol.77, pp455-458

Anecdotal evidence of an increase in imprinting disorders in children conceived by ICSI

Manning, M., et al., 2000, Molecular Human Reproduction, Vol. 6, pp1049-1053

Page last updated: 14 April 2009

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