Eijkemans Marinus J C, van Poppel Frans, Habbema Dik F, Smith Ken R, Leridon Henri, te Velde Egbert R
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
Hum Reprod. 2014 Jun;29(6):1304-12. doi: 10.1093/humrep/deu056. Epub 2014 Mar 27.
Is it possible to construct an age curve denoting the ages above which women are biologically too old to reproduce?
We constructed a curve based on the distribution of female age at last birth in natural fertility populations reflecting the ages above which women have become biologically too old to have children.
The median age at last birth (ALB) for females is ∼40-41 years of age across a range of natural fertility populations. This suggests that there is a fairly universal pattern of age-related fertility decline. However, little is known about the distribution of female ALB and in the present era of modern birth control, it is impossible to assess the age-specific distribution of ALB. Reliable information is lacking that could benefit couples who envisage delaying childbearing.
STUDY DESIGN, SIZE, DURATION: This study is a review of high-quality historical data sets of natural fertility populations in which the distributions of female age at last birth were analysed. The studies selected used a retrospective cohort design where women were followed as they age through their reproductive years.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Using a common set of eligibility criteria, large data files of natural fertility populations were prepared such that the analysis could be performed in parallel across all populations. Data on the ALB and confounding variables are presented as box and whisker plots denoting the 5th, 25th, 50th, 75th and 95th percentile distribution of the age at last birth for each population. The analysis includes the estimation of Kaplan-Meier curves for age at last birth of each population. The hazard curve for ALB was obtained by plotting the smoothed hazard curve of each population and taking the lowest hazard within a time period of at least 5 years. This lowest hazard curve was then transformed into a cumulative distribution function representing the composite curve of the end of biological fertility. This curve was based on the data from three of the six populations, having the lowest hazards of end of fertility.
We selected six natural fertility populations comprising 58 051 eligible women. While these populations represent different historical time periods, the distribution of the ages at last birth is remarkably similar. The curve denoting the end of fertility indicates that <3% of women had their last birth at age 20 years meaning that almost 98% were able to have at least one child thereafter. The cumulative curve for the end of fertility slowly increases from 4.5% at age 25 years, 7% at age 30 years, 12% at age 35 years and 20% at age 38 years. Thereafter, it rises rapidly to about 50% at age 41, almost 90% at age 45 years and approaching 100% at age 50 years.
LIMITATIONS, REASONS FOR CAUTION: It may be argued that these historical fertility data do not apply to the present time; however, the age-dependent decline in fertility is similar to current populations and is consistent with the pattern seen in women treated by donor insemination. Furthermore, for reproductive ageing, we note that it is unlikely that such a conserved biological process with a high degree of heritability would have changed significantly within a century or two.
We argue that the age-specific ALB curve can be used to counsel couples who envisage having children in the future. Our findings challenge the unsubstantiated pessimism regarding the possibility of natural conception after age 35 years.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.
是否有可能构建一条年龄曲线,用以表示女性在生物学上已过生育年龄的岁数?
我们根据自然生育人群中最后一次生育时的女性年龄分布构建了一条曲线,该曲线反映了女性在生物学上已过生育年龄的岁数。
在一系列自然生育人群中,女性最后一次生育的年龄中位数(ALB)约为40 - 41岁。这表明存在一种相当普遍的与年龄相关的生育能力下降模式。然而,对于女性ALB的分布了解甚少,并且在现代节育时代,无法评估ALB的年龄特异性分布。缺乏可靠信息,而这些信息本可以使那些打算推迟生育的夫妇受益。
研究设计、规模、持续时间:本研究是对自然生育人群高质量历史数据集的回顾,分析了其中女性最后一次生育的年龄分布。所选用的研究采用回顾性队列设计,对女性从生育年龄开始随年龄增长进行跟踪。
参与者/材料、环境、方法:使用一组通用的纳入标准,准备了自然生育人群的大数据文件,以便能够对所有人群进行并行分析。关于ALB和混杂变量的数据以箱线图形式呈现,分别表示各人群最后一次生育年龄的第5、25、50、75和95百分位数分布。分析包括对各人群最后一次生育年龄的Kaplan - Meier曲线估计。通过绘制各人群的平滑风险曲线,并取至少5年时间段内的最低风险,得到ALB的风险曲线。然后将这条最低风险曲线转换为累积分布函数,代表生物生育结束的综合曲线。这条曲线基于六个群体中三个群体的数据,这些群体的生育结束风险最低。
我们选取了六个自然生育人群,包括58051名符合条件的女性。虽然这些人群代表不同的历史时期,但最后一次生育年龄的分布非常相似。表示生育结束的曲线表明,不到3%的女性在20岁时最后一次生育,这意味着此后几乎98%的女性能够至少生育一个孩子。生育结束的累积曲线从25岁时的4.5%、30岁时的7%、35岁时的12%和38岁时的20%缓慢上升。此后,在41岁时迅速上升至约50%,45岁时接近90%,50岁时接近100%。
局限性、谨慎理由:可能有人认为这些历史生育数据不适用于当前;然而,生育能力随年龄下降的情况与当前人群相似,并且与接受供精人工授精治疗的女性所呈现的模式一致。此外,对于生殖衰老,我们注意到这样一个具有高度遗传性的保守生物过程在一两个世纪内不太可能发生显著变化。
我们认为特定年龄的ALB曲线可用于为那些打算未来生育的夫妇提供咨询。我们的研究结果挑战了关于35岁以后自然受孕可能性的毫无根据悲观态度。
研究资金/利益冲突:本研究未寻求或获得外部资金。不存在需要申报的利益冲突。