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Incidence of retinoblastoma in Dutch children conceived by in vitro fertilization . An expanded study

Background In 2003, we reported an increased risk of retinoblastoma in children conceived by in vitro fertilization (IVF) between 1995 to 2002. However, population-based studies among children conceived by IVF did not find an elevated risk of retinoblastoma. Methods From nationwide estimates of numbers of live births conceived by IVF (n = 40,330), we estimated the expected numbers of retinoblastoma patients conceived by IVF in the period 1995-2007. The actual observed number of retinoblastoma diagnoses in children conceived by IVF was obtained by questionnaires sent to the parents of retinoblastoma patients diagnosed between 1995-2005. For non-responders and patients diagnosed after 2005, information was available through the medical files, in which information on fertility treatments of retinoblastoma patients is routinely recorded since 2000. The relative risk (RR) of retinoblastoma among children conceived by IVF was calculated for the total study period (1995-2007) and for the expanded study period (2002-2007). Results Of all eligible retinoblastoma patients (n = 162) diagnosed in the period 1995-2007, 7 retinoblastoma patients were conceived by IVF. In the total study period (1995-2007) the risk was statistically significantly elevated (RR = 2.54, 95% CI = 1.02-5.23). In the expanded study period (2002-2007), no significantly elevated risk (RR = 1.29, 95% CI = 0.16-4.66) was found. Conclusion We found a statistically significantly increased risk of retinoblastoma in children conceived by IVF in the period 1995-2007. However, the increased risk in the total study period was mostly based on the much stronger risk increase observed in our previous report for the period 1995 to 2002. Caution and awareness on the one hand and avoiding unnecessary worries on the other hand are important at this stage of our knowledge.