Zhu Jin Liang, Basso Olga, Obel Carsten, Bille Camilla, Olsen Jørn
Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, University of Aarhus, DK 8000 Aarhus C, Denmark.
BMJ. 2006 Sep 30;333(7570):679. doi: 10.1136/bmj.38919.495718.AE. Epub 2006 Aug 7.
To examine whether infertile couples (with a time to pregnancy of > 12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations.
Longitudinal study.
Danish national birth cohort.
Three groups of liveborn children and their mothers: 50,897 singletons and 1366 twins born of fertile couples (time to pregnancy < or = 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy > 12 months), and 4588 singletons and 1690 twins born after infertility treatment.
Prevalence of congenital malformations determined from hospital discharge diagnoses.
Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations-hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins.
Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination.
研究不孕夫妇（受孕时间超过12个月）自然受孕或经治疗受孕后所生孩子的先天性畸形患病率是否增加。
纵向研究。
丹麦国家出生队列。
三组活产儿及其母亲：50897名单胎和1366对双胞胎，其母亲为生育能力正常的夫妇（受孕时间≤12个月）；5764名单胎和100对双胞胎，其母亲为自然受孕的不孕夫妇（受孕时间>12个月）；4588名单胎和1690对双胞胎，其母亲为不孕治疗后受孕的夫妇。
根据医院出院诊断确定的先天性畸形患病率。
与生育能力正常夫妇所生的单胎相比，自然受孕或经治疗受孕的不孕夫妇所生单胎的先天性畸形患病率更高，风险比分别为1.20（95%置信区间1.07至1.35）和1.39（1.23至1.57）。先天性畸形的总体患病率随受孕时间延长而增加。当分析仅限于不孕夫妇所生单胎时，与自然受孕的婴儿相比，治疗后出生的婴儿生殖器器官畸形患病率增加（风险比2.32，1.24至4.35）。双胞胎先天性畸形的总体患病率无显著差异。
不孕的激素治疗可能与生殖器器官畸形的发生有关，但我们的结果表明，辅助生殖技术后出生的单胎中报道的先天性畸形患病率增加部分归因于潜在的不孕或其决定因素。未经治疗的不孕与先天性畸形之间的关联值得进一步研究。
