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Correspondence to:
D BenEzra
Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel; benezra@md.huji.ac.il
Accepted for publication 20 August 2004
Keywords: retinoblastoma; in vitro fertilisation
I read with great interest the letter published in the BJO by Lee et al.1 It reports on the first child born after in vitro fertilisation (IVF) and harbouring a unilateral retinoblastoma in the United States.
However, it should be noted that this reported child is the eighth documented child (not the sixth as mentioned by the authors). The first child ever observed was reported by our group in 2001. He had a unilateral disease.2 In 2002, a second child with bilateral disease was documented in the Netherlands.3 In 2003, five additional cases were reported from the Netherlands (two with bilateral disease and three with unilateral disease). In this paper, an estimated relative risk of 4.9 to 7.2 for an IVF born child in the Netherlands to develop retinoblastoma was surmised.4
The issue of the possible association of assisted reproductive techniques (ART) with an increased risk of retinoblastoma has raised great concern worldwide. The interest of this association is highlighted by the fact that the expression of retinoblastoma in childhood is influenced by epigenetics—a regulatory mechanism not involving DNA sequence which could be affected by the various ART techniques.
In recent years, tens of thousands of children were born after ART. However, not one single case of retinoblastoma was observed until 2001. The possible reasons for this phenomenon were discussed.5 Awareness regarding the occurrence of retinoblastoma in ART born children sparked by our original observation of the first case in 2001 has probably been a trigger for the unveiling of additional cases. Therefore, more cases are to be expected in the near future.
Whether the increased number of observed cases indicates that ART born babies have a higher risk of developing retinoblastoma remains to be carefully investigated. None the less, a thorough prospective assessment of the possible association between ART and retinoblastoma is mandatory. Ongoing multicentre and multinational control studies will hopefully provide the needed answers to this "thorny" but most crucial aspect of ART. Till then, accurate accounting of previous observations is, of course, a key factor for a better insight into these issues.
References
Lee I, Finger PT, Grifo JA, et al. Retinoblastoma in a child conceived by in vitro fertilisation. Br J Ophthalmol 2004;88:1098–9.
Anteby I, Cohen E, Anteby E, et al. Ocular manifestations in children born after in-vitro fertilization. Arch Ophthalmol 2001;119:1525–9.
Cruysberg JR, Moll AC, Imhof SM. Bilateral sporadic retinoblastoma in a child born after in vitro fertilization. Arch Ophthalmol 2002;120:1773.
Moll AC, Imhof SM, Cruysberg JR, et al. Incidence of retinoblastoma in children born after in-vitro fertilization. Lancet 2003;361:309–10.
BenEzra D. In-vitro fertilization and retinoblastoma. Commentary. Lancet 2003;361:273–4.