近日，丹麦癌症协会研究中心Susanne K. Kjær及其研究小组分析了生育治疗与儿童癌症风险之间的关系。这一研究成果于2019年12月10日发表在国际顶尖学术期刊《美国医学会杂志》上。

全世界越来越多的儿童通过生育治疗出生，目前尚不清楚这种治疗是否会增加儿童患癌的风险，以及使用特殊药物、特殊程序或潜在不孕症是否与儿童癌症相关。

研究组基于丹麦人口登记数据和丹麦不孕症队列进行了一项回顾性的队列研究。参与者包括1996年1月1日至2012年12月31日在丹麦出生的1085172名儿童，且父母信息详备。共有2217名儿童确诊癌症。

生育治疗包括使用生育药物（克罗米芬33835例，促性腺激素57136例，促性腺激素释放激素类似物38653例，人绒毛膜促性腺激素68181例，孕酮41628例，雌激素16948例）和辅助生殖技术（体外受精19448例，胞浆内精子注射13417例，冷冻胚胎移植3356例）。

平均随访11.3年后，有生育力女性（910291）所生儿童的患癌率为每10万人次17.5例，而冷冻胚胎移植为每10万人次44.4例。与正常生育的儿童相比，冷冻胚胎移植增加了儿童患癌的风险，主要原因是白血病和交感神经系统肿瘤的发病率增加。而其他类型的生育治疗与正常生育相比，差异无统计学意义。

结果表明，使用冷冻胚胎移植出生的儿童与正常生育的儿童相比，患癌风险显著增加。

附：英文原文

Title: Association Between Fertility Treatment and Cancer Risk in Children

Author: Marie Hargreave, Allan Jensen, Merete Kjr Hansen, Christian Dehlendorff, Jeanette Falck Winther, Kjeld Schmiegelow, Susanne K. Kjr

Issue&Volume: 2019/12/10

Abstract: 

Importance  An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility.

Objective  To examine the association between different types of fertility treatments and cancer risk in children.

Design, Setting, and Participants  A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1?085?172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015).

Exposures  Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33?835], gonadotropins [n = 57?136], gonadotropin-releasing hormone analogs [n = 38?653], human chorionic gonadotropin [n = 68?181], progesterone [n = 41?628], and estrogen [n = 16?948]) and assisted reproductive technology (in vitro fertilization [n = 19?448], intracytoplasmic sperm injection [n = 13?417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women.

Main Outcomes and Measures  Hazard ratios and incidence rate differences for childhood cancer.

Results  After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100?000 for children born to fertile women (n = 910?291) and 44.4 per 100?000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100?000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100?000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, −4.0 to 24.2] per 100?000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined.

Conclusions and Relevance  Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.

DOI: 10.1001/jama.2019.18037

Source: https://jamanetwork.com/journals/jama/article-abstract/2757228