Men over 45 have 31% more mutations in their sperm, according to a study presented at ESHRE

• The study reveals that mutations accumulate in sperm with age, highlighting the need for new approaches in male genetic analysis. It calls for the inclusion of specific genetic studies on sperm, not just blood, especially in men over 45.
• IVI’s presence at the ESHRE Congress was highlighted by another study that examined the differences between euploid and aneuploid embryos. This study identified indicators that allow us to determine, from very early stages, which embryos are more likely to develop properly, thereby helping to improve embryo selection.

LONDON, MONDAY, JULY 6, 2026

Paternal age, traditionally overshadowed by maternal age in fertility studies, is now taking center stage in the latest research on assisted reproduction. This is because men accumulate mutations in their sperm over time. Many of these mutations are undetectable in conventional genetic analyses, but they can still affect the embryo’s development.

This is revealed in the study “Increased sperm-specific somatic mutations in advanced paternal age: implications for preconception genetic screening,” led by the IVI Foundation and presented at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE).

“Until now, clinical practice has assumed that mutations found in the blood are representative of the entire body. However, we have found that this is not always the case. There are mutations that are found only in sperm and not in blood, meaning they can go unnoticed in these tests but can still be passed on to the future baby,” explains Dr. Patricia Díaz-Gimeno, IVI’s principal investigator and co-author of the study alongside Dr. Nicolás Garrido, director of the IVI Foundation.

This work arises from a key limitation in current diagnostic methods. The carrier genetic tests used in clinical practice do not analyze sperm-specific mutations. They are based on blood samples, which they assume are representative of mutations present throughout the body.

Until now, paternal age has not been considered a relevant risk factor for the health of offspring, but the results of this study call that into question.

“Specifically, the data reveals that men over 45 have 31% more mutations in their sperm than those under 30. There are relevant mutations in sperm that are not found in blood at any age, but the increase is clear in individuals of advanced paternal age,” emphasizes Dr. Díaz-Gimeno.

The analysis has identified genetic alterations found only in sperm, with varying degrees of impact—ranging from variants of uncertain significance to mutations in genes linked to serious conditions. “We have detected mutations linked to the nervous system, the autism spectrum, and intellectual disability, as well as ones associated with serious cardiovascular diseases, liver conditions, severe immunodeficiencies, and even processes related to cancer,” she explains.

Analysis of sperm mutations.

In Spain, the law sets a 50-year age limit for sperm donation. However, some centers have already adopted more restrictive criteria based on scientific evidence.

“At IVI, we’ve set the limit at 44 years, primarily to prevent potential negative effects on offspring linked to advanced paternal age. Our results suggest that such decisions are scientifically grounded, and that established limits could be reconsidered in the future,” explains Dr. Díaz-Gimeno.

Furthermore, the study highlights the need to move beyond current protocols and paves the way for a paradigm shift in assessing male fertility:

“It would be advisable to include mutation analysis in sperm, not just in blood, as is currently done, regardless of the man’s age in all cases, and especially in settings like donation programs. Moreover, given these results, it would be even more advisable for men over 45,” concludes the researcher.

New evidence on embryonic development

In parallel, the study “Different secretome profiles characterize euploid and aneuploid human embryos cultured up to 14 days in advanced 3D endometrial co-culture,” presented at the conference, delves into how genetic alterations can influence embryo development. The study examines the differences between euploid embryos—those with the correct number of chromosomes—and aneuploid embryos—one of the main causes of implantation failure and early miscarriage—by analyzing the molecules and proteins they release during their early stages of development.

The results show that embryos with chromosomal abnormalities exhibit different behaviors from very early stages, which allows for a better understanding of their ability to develop.

“We have growing evidence that the genetic quality of the embryo is crucial from the very start. This type of analysis helps us better understand which ones are most likely to develop properly,” says Dr. Francisco Domínguez, the study’s principal investigator.

This knowledge could be directly applied to clinical practice. The goal is to improve embryo selection and more accurately identify the embryos most likely to result in a developing pregnancy. Furthermore, the specialist emphasizes the shift toward more personalized medicine:

“We are moving toward treatments that are increasingly tailored to each patient’s biological profile, which will optimize results and reduce uncertainty in reproductive processes,” he explains.

About IVI RMA Global

IVI was founded in 1990 as the first medical institution in Spain fully dedicated to human reproduction. Since then, it has helped bring more than 250,000 children into the world through continuous innovation and the use of the latest assisted reproduction treatments.

It’s one of the European centers with the highest pregnancy rates; in fact, most couples who consult IVI for infertility issues achieve their goal. Furthermore, it boasts a team of over 2,500 professionals, including the world’s leading specialists in assisted reproduction.

IVI is part of the IVI RMA Global group, which operates in 15 countries. In addition to Spain, it has clinics in Portugal, Italy, the Czech Republic, the Nordic countries, the United Kingdom, the United States, Canada, Panama, Brazil, and Chile.