First results from the world's oldest group of young men conceived by means of intracytoplasmic sperm injection (ICSI) fertility treatment because of their fathers' infertility have shown that they have lower sperm quantity and quality than men who were spontaneously conceived.
The study, which is published today (Thursday) in Human Reproduction , one of the world's leading reproductive medicine journals, has found that these men, who were aged between 18 to 22, had almost half the sperm concentration and a two-fold lower total sperm count  and total count of motile sperm (sperm that could swim well) than did naturally conceived men of a similar age.
In addition, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below 15 million per millilitre of semen, which is the World Health Organisation's definition of "normal", and four times more likely to have total sperm counts below 39 million.
ICSI was pioneered at the Centre for Reproductive Medicine at the Vrije Universiteit Brussel (VUB), Brussels, Belgium, which was headed by Professor André Van Steirteghem, one of the co-authors of this study. The first ICSI baby was born on 14 January 1992. The current study reports on 54 men, born in the early years of ICSI between 1992-1996, when ICSI was only used to treat male infertility.
ICSI is a procedure by which sperm from the father is injected directly into the mother's egg in the laboratory, and then the fertilised egg is placed in her womb. For men who have very few, viable sperm, this means that the fertility experts can choose the best quality sperm and ensure it fertilises the egg by injecting the sperm rather than leaving it to swim to the egg unaided.
Professor Van Steirteghem and his colleagues always knew that the problems that had caused the father's infertility, usually genetic factors, might be inherited by these men's offspring. However, until now, questions about the fertility of the ICSI offspring could not be answered because of their young age.
"These findings are not unexpected," said Professor Van Steirteghem, who is now emeritus professor at VUB and a consultant at the University Hospital (UZBrussel). "Before ICSI was carried out, prospective parents were informed that it may well be that their sons may have impaired sperm and semen like their fathers. For all the parents this information was not a reason to abstain from ICSI because, as they said: 'if this happens ICSI can then also be a solution for our sons'.
"These first results from the oldest group of ICSI-conceived adults worldwide indicate that a degree of 'sub-fertility' has, indeed, been passed on to sons of fathers who underwent ICSI because of impaired semen characteristics."
The study was carried out at UZBrussel between March 2013 and April 2016. It is part of a larger project that is following the health of young adults, male and female, born as a result of ICSI. The young men were approached via their parents in case the parents had not disclosed to their children the method of conception. Fifty-four out of a total of 215 young ICSI men on the UZBrussel database agreed to take part in the study and they were matched with a control group of men of a similar age who had been conceived naturally. They were asked to provide a semen sample for analysis; blood samples were also taken and other health checks performed. The participants were offered genetic testing in cases where sperm concentrations fell below 5 million/ml, and they were offered written feedback, appropriate counselling, investigation and follow-up.
ICSI had been carried out for the fathers of 50 out of 54 of the young men because of male-factor infertility (48 for male infertility only, two for combined male and female infertility), while the remaining four sets of parents suffered from infertility with unknown cause.
The researchers adjusted their results for factors that could affect semen quality, such as age, body mass index (BMI), genital malformations, time from ejaculation to analysis, and abstinence period.
Although sperm concentrations and counts were lower in the ICSI men than in their spontaneously conceived peers, the researchers found that a low sperm concentration and total motile sperm count in fathers did not correlate with corresponding values in their sons.
"The study shows that semen characteristics of ICSI fathers do not predict semen values in their sons. It is well established that genetic factors play a role in male infertility, but many other factors may also interfere. Furthermore, correlation is not the same thing as causation," said Prof Van Steirteghem.
"These results highlight the need to continue and expand other follow-up studies on children conceived by assisted reproduction techniques. For instance, paired analysis of samples from fathers and sons should be carried out, and we need to look at larger numbers of offspring. This remains a challenging project for the VUB. However, health authorities and funding agencies should provide the means to answer questions concerning the effects of genetics, mode of conception, foetal growth patterns and birth weights on the fertility of ICSI men," he said.
Since the early days of ICSI, the technique has been used increasingly to treat infertility, even when male infertility is not suspected. In some countries ICSI is used in nearly 100% of all in vitro fertilisation (IVF) procedures. Therefore, the authors warn that the findings from this study cannot be extrapolated to all offspring born after ICSI since nowadays ICSI is increasingly used even when there is no evidence that a couple's infertility is due to abnormal semen measurements in the man.
 "Semen quality of young adult ICSI offspring: the first results," by F. Belva et al. Human Reproduction journal. doi:10.1093/humrep/dew245.
 Total sperm count is semen volume x semen concentration.