Pooled Analysis of Cancer in Children after Assisted Reproductive Technologies

简介（申请人提供）：随着生育年龄的增长，不孕不育的发病率不断上升，辅助生殖技术（ART）在世界范围内非常普及。尽管有报道称抗逆转录病毒治疗后怀孕的儿童围产期死亡率、多胎妊娠、低出生体重和畸形的风险增加，但很少有研究分析与此类技术相关的长期癌症负担。儿童癌症发病率可能增加，这与实验室操纵配子引起的印迹障碍或表观遗传因素的发展有关，和/或接受抗逆转录病毒治疗的妇女大量使用不孕药物。然而，癌症在年轻人中的罕见性使得个体研究的力量非常有限。

DESCRIPTION (provided by applicant): The increasing frequency of infertility disorders along with the increasing age of parenthood makes Assisted Reproductive Technologies (ART) a very diffuse method all over the world. Although an increased risk in perinatal mortality, multiple pregnancies, low birth weight and malformations in children conceived after ART has been reported, few studies have analyzed the long-term cancer burden associated with such techniques. A possible increase in childhood cancer incidence has been suggested, and has been related to the development of imprinting disorders or epigenetic factors induced by the laboratory manipulation of gametes, and/or the large use of infertility drugs in women who undergo ART. However, the rarity of cancer at young ages makes the power of individual studies very limited. The aim of the proposed project is to evaluate the association between ART and childhood cancer by performing a pooled analysis of existing cohort studies, both published and unpublished. The endpoint of the project is development of cancer of all types in children born after ART. Investigators that have follow up data on children born after ART have been identified, and an initial contact has been made. Several investigators have already agreed to participate in data sharing and analysis. In order to compare cancer incidence in the exposed cohort with cancer incidence in children from the general population, expected cases will be calculated by applying national-, age- and sex-specific cancer rates to the exposed cohort; Standardized Incidence Ratios (SIR) will be calculated. Heterogeneity between studies and inclusion bias will be assessed statistically. The results provided by this study will add knowledge on the long term safety of ART; in fact, if no cancer increase will be documented by this large analysis, then the long-term safety of ART will be strongly supported. If a higher cancer risk will be found in children born after ART than in the general population, molecular studies on gene imprinting and epigenetic factors can be designed, as well as detailed studies on hormonal treatments administered to the mothers before ART, in order to understand the reasons for this increased risk. The results provided by this study will be very useful to assess the long term safety of Assisted Reproductive Technologies (ART) if no increased risk of cancer will be observed. If a higher cancer risk will be found in children born after ART than in the general population, actions will be necessary. Among the possible strategies to be undertaken, it will be necessary to deeply study the possible reasons for this increased risk, such as hormonal treatment for mothers, gene imprinting, gene methylation, in order to plan changes in the clinical approach to infertility. The present pooled analysis has created a network of investigators who will be a unique opportunity for any future molecular study in the population of children born after ART.