Male age interferes with embryo growth in IVF treatment
Authors: Van Opstal Jolien , Fieuws Steffen , Spiessens Carl , Soubry Adelheid 
Published: September 2020

Abstract

STUDY QUESTION
Does male age affect embryo growth or quality in couples undergoing IVF treatment?

SUMMARY ANSWER
Advanced paternal age (APA) is negatively associated with the chance of an optimal eight-cell embryo on the third day of development.

WHAT IS KNOWN ALREADY
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.

MAIN RESULTS AND THE ROLE OF CHANCE
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.

WIDER IMPLICATIONS OF THE FINDINGS
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.

TRIAL REGISTRATION NUMBER
KU Leuven S57378 (ML11309), B322201523225.