Epidemiology Research Center, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven 3000, Belgium.
L-Biostat, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven 3000, Belgium.
Hum Reprod. 2021 Jan 1;36(1):107-115. doi: 10.1093/humrep/deaa256.
Does male age affect embryo growth or quality in couples undergoing IVF treatment?
Advanced paternal age (APA) is negatively associated with the chance of an optimal eight-cell embryo on the third day of development.
Literature shows that APA is associated with decreased sperm quality and fecundity. However, the effect of male age on embryo growth in an IVF setting remains inconclusive. Literature concerning male influences on IVF success is scarce and approaches used to analyse embryo outcomes differ by study.
STUDY DESIGN, SIZE, DURATION: This study was part of the longitudinal Epigenetic Legacy of Paternal Obesity (ELPO) study for which fathers and mothers were followed from pre-pregnancy until the birth of their child. Couples were recruited from April 2015 to September 2017. A total of 1057 embryos from 87 couples were studied.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Dutch-speaking couples planning to undergo an IVF treatment were recruited at the Leuven University Fertility Center in Flanders, Belgium. Anthropometrics were documented and compared to the general Flemish population. Semen characteristics, pregnancy rates and the following embryo characteristics were recorded: number of blastomeres, symmetry and percentage fragmentation. Statistical modelling was applied taking into account correlation of within-cycle outcomes and use of multiple cycles per couple.
We observed a significant inverse association between APA and a key determinant for scoring of embryo quality: older men were less likely to produce an embryo of eight blastomeres at Day 3, compared to younger fathers; odds ratio for the effect of 1 year equals 0.960 (95% CI: 0.930-0.991; P = 0.011). Our finding remained significant after adjusting for female age and male and female BMI. Degree of fragmentation and symmetry were not significantly related to male age.
LIMITATIONS, REASONS FOR CAUTION: Because of the study's small sample size and its monocentric nature, a larger study is warranted to confirm our results. In addition, distribution of BMI and level of education were not representative of the general Flemish population. Although we corrected for BMI status, we do not exclude that obesity may be one of the determinants of infertility in our study population. Furthermore, it is known from other European countries that a higher education eases access to fertility treatment. Hence, caution should be taken when interpreting our findings from a fertility setting to the general population.
We suggest a heightened need for future research into male age and its potential effects on embryo growth, embryo quality and ART outcomes. Clinical decision-making and preventative public health programmes would benefit from a better understanding of the role of men, carried forward by the Paternal Origins of Health and Disease (POHaD) paradigm. We hope the current finding will encourage others to examine the role of the sperm epigenome in embryo development according to paternal age.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a research grant from KU Leuven University (OT/14/109). The authors declare no competing financial, professional or personal interests.
KU Leuven S57378 (ML11309), B322201523225.
男性年龄是否会影响接受体外受精治疗的夫妇的胚胎生长或质量？
高龄父亲（advanced paternal age，APA）与第三天发育的最佳八细胞胚胎的机会呈负相关。
文献表明，APA 与精子质量和生育能力下降有关。然而，男性年龄对体外受精环境中胚胎生长的影响仍不确定。关于男性对体外受精成功影响的文献很少，并且用于分析胚胎结果的方法因研究而异。
研究设计、大小和持续时间：本研究是纵向肥胖父亲的表观遗传后代（Epigenetic Legacy of Paternal Obesity，ELPO）研究的一部分，该研究对父母从孕前到孩子出生进行了跟踪。该研究于 2015 年 4 月至 2017 年 9 月在比利时佛兰德的鲁汶大学生育中心招募了荷兰语夫妇。记录了夫妇的人体测量学数据，并与一般佛兰德人口进行了比较。记录了精液特征、妊娠率以及以下胚胎特征：卵裂球数量、对称性和碎片百分比。在考虑到周期内结果的相关性和每对夫妇使用多个周期的情况下，应用了统计建模。
我们观察到 APA 与胚胎质量评分的一个关键决定因素呈显著负相关：与年轻父亲相比，年龄较大的男性在第三天产生八个卵裂球的胚胎的可能性较小；1 年的效应比值为 0.960（95%置信区间：0.930-0.991；P=0.011）。在调整了女性年龄以及男性和女性 BMI 后，我们的发现仍然具有统计学意义。碎片程度和对称性与男性年龄没有显著关系。
局限性、谨慎原因：由于研究样本量小且为单中心性质，因此需要更大的研究来证实我们的结果。此外，BMI 分布和教育水平并不代表一般佛兰德人口。尽管我们对 BMI 状况进行了校正，但我们不能排除肥胖可能是我们研究人群中不孕的一个决定因素。此外，其他欧洲国家的情况表明，较高的教育水平可以更容易获得生育治疗。因此，在将我们从生育角度的发现解释为一般人群时，应谨慎行事。
我们建议未来需要更多的研究来探讨男性年龄及其对胚胎生长、胚胎质量和辅助生殖技术结果的潜在影响。对男性角色的更好理解将使临床决策和预防性公共卫生计划受益，并推动健康与疾病的父系起源（Paternal Origins of Health and Disease，POHaD）范式的发展。我们希望目前的发现将鼓励其他人根据父亲年龄检查精子表观基因组在胚胎发育中的作用。
研究资金/利益冲突：这项工作得到了鲁汶大学研究基金的支持（OT/14/109）。作者没有财务、专业或个人利益冲突。
KU Leuven S57378（ML11309），B322201523225。
