Environmental Health Department, Institut de Veille Sanitaire (InVS), F-94415 Saint Maurice, France.
Hum Reprod. 2013 Feb;28(2):462-70. doi: 10.1093/humrep/des415. Epub 2012 Dec 4.
Are temporal trends and values of semen quality parameters in France identifiable in partners of totally infertile women?
Among a sample of 26 609 partners of totally infertile women undergoing an assisted reproductive technology (ART) procedures in the whole of France over a 17-year period, there was a continuous decrease in semen concentration of about 1.9% per year and a significant decrease in the percentage with morphologically normal forms but no global trend for motility.
A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes.
STUDY DESIGN, SIZE, DURATION: This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989-2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18-70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model.
There was a significant and continuous decrease in sperm concentration of 32.2% [26.3-36.3] during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml [69.0-78.4] in 1989 to 49.9 million/ml [43.5-54.7] in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis.
LIMITATIONS, REASONS FOR CAUTION: Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality.
As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined.
在法国,完全不育女性的伴侣中是否可以识别精液质量参数的时间趋势和数值?
在法国,对 1989 年至 2005 年期间在整个法国的 126 个主要辅助生殖技术(ART)中心接受治疗的完全不育女性的伴侣进行了一项回顾性和描述性研究,在 17 年的时间里,精液浓度持续下降了约 1.9%,正常形态的精子比例显著下降,但总活力没有整体趋势。
虽然显示出了地域差异,并且对于研究人群规模小且存在偏差或统计方法不当等问题提出了许多批评,但人类精子质量整体下降的情况仍存在争议。然而,越来越多的生物学、毒理学、实验和人类暴露数据支持了内分泌干扰物假说,该假说假设胎儿暴露于内分泌干扰物可能会损害生殖结果。
研究设计、规模和持续时间:这是一项使用 1989 年至 2005 年期间 Fivnat(负责法国 ART 统计的专业协会)登记的数据进行的回顾性和描述性研究。数据由整个大都市地区的 126 个主要 ART 中心提供。该源人群包括 154712 名年龄在 18 至 70 岁之间的男性,他们是接受第一次 ART 周期治疗的夫妇的伴侣,并且他们的精液质量指标(浓度、总活力和正常形态的百分比)可用新鲜射出的精液进行测量。
参与者/材料、设置、方法:研究人群是 26609 名女性,她们的双侧输卵管缺失或堵塞。使用广义加性模型来模拟每个精液质量指标的时间趋势,该模型允许变量之间存在非线性关系,并根据季节和年龄进行调整。深入的敏感性分析包括对每个男性的另一个精子图数据的重复分析,以及对另一个被诊断为健康的男性样本的分析。还包括中心、技术(标准体外受精或胞浆内精子注射)以及技术和时间之间的相互作用因素等变量。
在研究期间,精子浓度显著且持续下降了 32.2%[26.3-36.3]。预测表明,35 岁男性的浓度从 1989 年的平均 7360 万/ml[69.0-78.4]下降到 2005 年的 4990 万/ml[43.5-54.7]。在 17 年的时间里,精子正常形态的比例也观察到了显著但不可量化的下降。没有整体趋势,但在 1994 年至 1998 年期间观察到总活力略有显著增加。在敏感性分析后,结果仍然稳健。
局限性、谨慎的原因:无法控制社会经济地位。尽管法国提供普遍的医疗服务,但预计接受 ART 的夫妇的教育水平普遍高于一般人群。因此,实际值可能略低于一般人群的水平,下降幅度可能更大,因为人群研究中不太可能吸烟或超重,这两个因素已知会影响精子质量。
由于男性是在没有精液质量特征先验知识的情况下被选择的,因此预期结果更接近法国一般人群的值。非常大的样本量和结果的稳健性赋予了结果强大的统计能力和可信度。据我们所知,这是第一项在整个国家范围内在相当长的时间内得出精液浓度和形态严重普遍下降的研究。这构成了一个严重的公共卫生警告。特别是需要确定与环境的联系。