Impact of paternal age on assisted reproductive technology outcomes and offspring health: a systematic review

Abstract

Background The increase in paternal age and the percentage of births after assisted reproductive technologies (ART) may have consequences on offspring and society's position regarding access to ART must be questioned. Most countries recommend limiting ART to men under 60 years. What is the rationale for this threshold? Objective This systematic review assesses scientific arguments to establish links between paternal age, male fertility, and offspring health. Material and methods Using the PRISMA guidelines, this systematic review of the literature analyzed 111 articles selected after screening PubMed, ScienceDirect, and Web of Science for articles published between January 1, 1995 and December 31, 2021. Results A strong correlation was highlighted between advanced paternal age and a decrease of some sperm parameters (semen volume and sperm motility) and infant morbidity (exponentially increased incidence of achondroplasia and Apert syndrome, and more moderately increased incidence of autism and schizophrenia). The impact of paternal age on pregnancy and fetal aneuploidy rates is more controversial. No association was found with spontaneous abortion rates. Discussion and conclusion The scientific parameters should be explained to older parents undergoing ART. And for countries that discuss a limit on paternal age for access to ART, the debate requires consideration of social and ethical arguments.

Obstetrical and Perinatal Outcomes Are Not Associated with Advanced Paternal Age in IVF or ICSI Pregnancies with Autologous Oocytes

“…Remarkably, our findings support those from other studies concluding that an advanced paternal age was not a risk factor for perinatal outcomes [ 42 , 43 , 44 ]. Neurodevelopmental or genetic disorders in offspring were out of the scope of this study; however, their correlation with advanced paternal age has been well established by several authors [ 53 , 63 , 64 ] and merits further research, to fully understand these associations and the underlying physiopathological processes.…”

“…Interestingly, Wen et al, noticed that advanced paternal age was negatively associated with the lifespan of male offspring in the Ding genealogy after adjusting for maternal age [ 24 ]. Furthermore, advanced paternal age has been linked with an increased risk of some diseases developing in the offspring, including down syndrome, autism spectrum disorders [ 46 ], schizophrenia [ 47 ], bipolar disorders [ 17 , 48 ], several paediatric [ 49 , 50 ] and adult [ 51 ] cancers, orofacial clefts (cleft lip and palate) [ 17 , 29 , 51 ], achondroplasia [ 36 ], Apert syndrome [ 52 , 53 ], and congenital heart defects [ 51 , 54 , 55 ], as well as cardiovascular abnormalities, facial deformities, urogenital abnormalities, and chromosome disorders [ 56 ].…”

Unraveling the Impact of Sperm DNA Fragmentation on Reproductive Outcomes

“…100 Paternal age is associated with a wide range of pathologies, including dominant genetic diseases such as achondroplasia, as well as neurodevelopmental disorders such as autism and schizophrenia. 101 Similarly, high levels of SDF have been found in the sperm of male smokers 102 and paternal smoking before conception has been linked to an increased risk of some forms of childhood cancer, such as leukemia. 103 For many years, ICSI has been regarded as the prime solution to overcome the challenges of male infertility, offering couples the possibility of having a child even in cases of severely compromised sperm quality.…”

“…100 Paternal age is associated with a wide range of pathologies, including dominant genetic diseases such as achondroplasia, as well as neurodevelopmental disorders such as autism and schizophrenia. 101 Similarly, high levels of SDF have been found in the sperm of male smokers 102 and paternal smoking before conception has been linked to an increased risk of some forms of childhood cancer, such as leukemia. 103…”

Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes

“…In numerous nations, guidelines recommend restricting access to ART for men who are younger than 60 years due to the potential impacts on offspring health and ART outcomes. This threshold is based on the general observation of increasing risk with advancing age, although the rationale behind this specific age is not always clearly articulated [16]. However, in order to minimize the potential risks associated with couples using a sperm donation program, various countries have implemented age restrictions for sperm donors.…”