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Science Alert: Experts Respond

Low sperm count following ICSI conception – Expert reaction

Posted in Science Alert: Experts Respond on October 6th, 2016.

A new study of men who were conceived in the 1990s using a now common fertility treatment has found they have lower-than-average fertility – suggesting the treatment passed the fathers’ fertility issues onto the sons.

medical illustrationThe 54 young men, now aged 18-22, were conceived using intracytoplasmic sperm injection (ICSI) – a method used for men who have a low sperm count or abnormal sperm. Though the study authors caution their findings are limited by the small available sample, it may indicate that the fathers’ fertility issues are hereditary.

The study was published today in Human Reproduction.

Our colleagues at the UK SMC collected expert reaction on the study’s findings.

Prof. Richard Sharpe, Group Leader of Male Reproductive Health Research Team, University of Edinburgh, said:

“Historically, when ICSI has been used as a means of assisted reproduction in couples, it has been because of ‘male-factor’ infertility, for example a very low sperm count and/or poorly functional sperm. If the cause of the male infertility was genetic, an obvious expectation would be that the infertility might be passed on (inherited) if the resulting baby was a male. However, as the cause of most cases of male infertility is unexplained, it was uncertain whether the fertility problem of the father would be ‘inherited’ in this way.

“The present study is the first to address this key question, by assessing sperm number and motility in ICSI-derived sons. In showing, as a group, that the ICSI sons have starkly abnormal semen quality (sperm count etc) compared with normal (non-ICSI derived sons), the results suggest strongly that male fertility problems severe enough to require ICSI may be inheritable. As the authors of this excellent, groundbreaking, study point out, the next step will be to undertake more detailed comparisons of sons and fathers to gain more clarity as to what  percentage of such cases are truly inheritable, as this might enable better tailoring of treatment. As also pointed out, this study may be difficult to add to because of the much wider use of ICSI nowadays.

“Importantly, the results are a reminder to us that ICSI is not a treatment for male infertility, but simply a way of bypassing a problem and leaving it for the next generation to deal with – something my generation seem horribly adept at doing.”

Prof. Sheena Lewis, Emeritus Professor of Reproductive Medicine, Queen’s University Belfast, said:

“This study is very small, including only 54 fathers and sons so no robust conclusions can be drawn. That said, the results are not surprising. Men undergo ICSI because their sperm quality is too poor to achieve a pregnancy naturally or with IVF. These fathers appear to have passed their infertility on to their sons.

“However, what is disappointing about the study is the lack of information about the genetic quality of the sons’ sperm. Sperm DNA quality has been omitted from the work and yet this is the most important factor in impacting on both the short and long term overall health of future generations.”

Prof. Simon Fishel, Managing Director of CARE Fertility, said:

“This small study is useful but not unexpected in that we have been counselling couples since first using sperm micro injection 25 years ago (I published a paper on births after sperm injection in the Lancet in 1990) that due to genetic reasons ‘ICSI may beget ICSI’.

“However, we may still find that these men are able to conceive naturally. Just having low semen parameters is not evidence for the requirement of ICSI or IVF technologies. We know many men with such are indeed able to conceive naturally. More follow up studies will be required to ascertain meaningful outcomes.”

Prof. Allan Pacey, Professor of Andrology, University of Sheffield, said:

“This is a very interesting and important study which examines the sperm quality of young adult men who were conceived using the ICSI procedure in the early 1990’s.

“When the ICSI procedure was first introduced into clinical practice there was much discussion and debate about what the future fertility prospects would be of any males that were conceived this way, when they reached adulthood. This was because the reason for using the ICSI procedure to conceive them in the first place was because of the father’s poor sperm quality, which was almost certainly of genetic origin. Therefore, if those genes were inherited by any son’s born through the ICSI procedure, it seemed likely that they would have the same level of infertility and potentially require the use of ICSI themselves when they wanted to become a father.

“What this current study shows is that the sperm quality of ICSI born adult males is noticeably lower than that seen in men who were conceived naturally (i.e. without the use of ICSI). However, this is completely expected, as the naturally conceived men are unlikely to have inherited a fertility-related genetic problem from their fathers and therefore should be able to produce more and better sperm all other things being equal (e.g. age and general health).

“However, what is interesting to me about the study, is that there appears to be a poor relationship between the sperm quality of ICSI-born males and their fathers. This means that it doesn’t automatically follow that ICSI-conceived males will always have the poor fertility seen by their fathers. Although the study only looked at a relatively small number of 54 men, I see this as quite reassuring as the worry has always been that ICSI-born males were destined for a poor reproductive future that may be equivalent to (or even worse than) their fathers, whereas this paper suggests this is not necessarily going to be the case.”

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