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Review
. 2023 Feb 14;14(2):486.
doi: 10.3390/genes14020486.

Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring

Aris Kaltsas  1 , Efthalia Moustakli  2 , Athanasios Zikopoulos  1 , Ioannis Georgiou  2 , Fotios Dimitriadis  3 , Evangelos N Symeonidis  3 , Eleftheria Markou  4 , Theologos M Michaelidis  5   6 , Dung Mai Ba Tien  7 , Ioannis Giannakis  1 , Eleni Maria Ioannidou  8 , Athanasios Papatsoris  9 , Panagiota Tsounapi  10 , Atsushi Takenaka  10 , Nikolaos Sofikitis  1 , Athanasios Zachariou  1
Affiliations
Review

Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring

Aris Kaltsas et al. Genes (Basel). .

Abstract

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father's age contributes to his offspring's higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father's advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father's advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring's diseases is crucial, so that they can be effectively guided through their reproductive years.

Keywords: assisted reproductive techniques; genetics; infertility; offspring; paternal age.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of increased paternal age on male fertility status, reproductive/fertility outcome and risk of offspring birth defects.
Figure 2
Figure 2
Effects of increased paternal age on sperm genetic and epigenetic changes.
See this image and copyright information in PMC

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