Men conceived by IVF ‘may inherit sperm problems’
A new study has looked at a small sample of men born using the intracytoplasmic sperm injection (ICSI) technique. ICSI is a form of in vitro fertilisation (IVF) treatment introduced in the early 90s. It was designed to treat cases where infertility is caused by a problem with a man’s sperm. It involves “harvesting” a healthy sperm and then injecting it directly into an egg.
The study included 54 men conceived by ICSI and a similar number of men conceived naturally (the controls). When their sperm quality was compared, it was found that ICSI men had a lower average sperm concentration, total sperm count, and total motile sperm count (the amount of “active” sperm). There was no difference in sperm shape.
This finding supports concerns that a father’s infertility may be passed on to male offspring. However, this research has limitations that affect its reliability, including the small size of the study. And it remains to be seen how many of the men sampled will require fertility treatment themselves. Some men can still father a child naturally with suboptimal sperm quality. This study has too many limitations for us to be able to draw any firm conclusions. Simple measures you can take to improve your sperm include stopping smoking, avoiding excessive alcohol consumption, and avoiding tight underwear that can prevent the testicles maintaining a lower temperature than the body. Read more about protecting your fertility.
Where did the story come from?
The study was carried out by researchers from Universitair Ziekenhuis Brussel (UZ Brussel) and was funded by Methusalem grants and grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit of Brussels. It was published in the peer-reviewed journal, Human Reproduction. This study has been reported widely in the UK media, who failed to explain any of the important limitations of the study. In particular, this study cannot prove that fertility issues have been directly inherited from the father or are the result of ICSI.
What kind of research was this?
This small cross-sectional study aimed to compare the semen quality of young men who were conceived by ICSI with men conceived naturally. ICSI, where a single sperm is injected directly into an egg, differs from traditional in vitro fertilisation (IVF), where many sperm are mixed with eggs in a dish. It was originally performed if there was severe male infertility, but is now a commonly used procedure for any fertility issues. The young men in this study were conceived by ICSI because of the severe infertility of their fathers, and there have been concerns that this may be passed on to male offspring. This study is a good way of comparing the sperm quality of the young men with those conceived naturally. However, as it was a cross-sectional study, the sperm samples were only taken on one occasion. Many factors can affect the quality of the sample, such as the length of abstinence from ejaculation before the test and alcohol use. Though the researchers adjusted their results to take some of these factors into account, this study design cannot show that any fertility issue was inherited or caused by the ICSI procedure.
What did the research involve?
Young men conceived by ICSI were invited to participate in this study if they were:
- between 18 and 22 years old during the study period
The young men conceived by ICSI who took part in the study were asked to invite a friend who had been conceived naturally without the use of hormonal stimulation to be part of the control group. Both the men conceived by ICSI and the controls were asked to fill out questionnaires covering their family history, lifestyle and health history, including medication intake and surgical interventions. All participants were required to provide a semen sample at the hospital after abstaining from ejaculation for three days. The samples were measured for volume, concentration, total sperm count, motility and shape. Statistical analyses were performed to compare the two groups and were adjusted for the following possible confounding variables:
- body mass index
- genital malformations, such as the absence of one of the testicles
- time from ejaculation to analysis
- abstinence period
What were the basic results?
A total of 54 men conceived by ICSI and 57 naturally conceived men were included in the study. The men conceived by ICSI were found to have lower average sperm counts compared with the naturally conceived men:
- average sperm concentration (17.7 million/ml versus 37.0 million/ml)
- total sperm count (31.9 million versus 86.8 million)
- total motile sperm count (12.7 million versus 38.6 million)
After adjustment for potential confounders, the difference between the two groups remained. Men conceived naturally had:
- almost twice the sperm concentration compared with men conceived after ICSI (ratio 1.9, 95% confidence interval [CI] 1.1 to 3.2)
- more than twice the total sperm count (ratio 2.3, 95% CI 1.3 to 4.1)
- more than twice the total motile count (ratio 2.1, 95% CI 1.2 to 3.6)
- no difference in sperm shape (ratio 1.1, 95% CI 0.8 to 1.4)
When comparing offspring sperm counts with their fathers, fathers with a total sperm count of less than 39 million were more likely to have a son with a sperm count greater than 39 million. Low sperm concentration, according to World Health Organization (WHO) criteria of less than 15 million/ml, was present in 42.6% of men conceived by ICSI compared with 21.1% of men conceived naturally. Total sperm count is considered to be low if it is below 39 million. This occurred in 53.8% of men conceived by ICSI compared with 22.8% of men conceived naturally.
How did the researchers interpret the results?
The researchers conclude: “These first results in a small group of ICSI men indicate a lower semen quantity and quality in young adults born after ICSI for male infertility in their fathers.”
This small cross-sectional study aimed to assess the semen quality of young men who were conceived by ICSI. The study found that when compared with men conceived naturally, men conceived by ICSI had a lower average sperm concentration, total sperm count, and total motile sperm count. This effect remained after the team adjusted for potential confounders. This finding supports concerns that the infertility of a father could be passed on to male offspring, but does not prove it. The study does not rule in or out the possibility of the difference being a result of the ICSI procedure itself or an unrelated issue. This research has limitations that should be mentioned:
- These findings are based on a very small study population, and the same effect may not have been seen in a larger study.
- Of all the men conceived by ICSI invited to take part in the study, only 37.5% agreed. The researchers have provided a breakdown of those who declined, but it is possible that the 45 men and 21 families that declined did so because the young men do not have fertility issues and this would greatly alter the result.
- A number of confounders have been considered in the analysis. However, there is still a chance of residual confounding in the model or that important factors were not addressed.
- The samples were only provided on one occasion so may not be an accurate representation.
There are too many limitations to draw any firm conclusions from this research. Simple measures you can take to improve your sperm quality include stopping smoking, avoiding excessive alcohol consumption, and avoiding wearing tight underwear that can prevent the testicles maintaining a lower temperature than the body. Read more about protecting your fertility.