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expert reaction to a study looking at semen quality of adult ICSI offspring

A group of researchers have examined the sperm quality of the world’s oldest group of young men conceived by of intracytoplasmic sperm injection (ICSI) fertility treatment and report their results in the journal Human Reproduction. The authors report that sperm quantity and quality of these man was lower than average.

All our previous output on this subject can be seen here.


Prof. Adam Balen, Chair of the British Fertility Society, said:

“ICSI, whereby sperm is injected into eggs as part of the IVF process, has revolutionised the treatment of male infertility, enabling millions of couples worldwide to have their own biological children, who otherwise would have remained childless.

“It is not surprising that some causes of infertility may be transmitted to children born by fertility treatments and whilst these young men may have lower sperm counts than the general population, they may still be able to father children without treatment and if they cannot they will have the opportunity to use the IVF/ICSI themselves. Over six million children have been conceived worldwide with IVF and in the UK approximately 40% of treatments involve ICSI.”


 Prof. Darren Griffin, Professor of Genetics, University of Kent, said:

“Move on, nothing to see here. We know infertility has a genetic component, these men were born from fathers who were severely infertile and many of them would not have been born at all if not for this pioneering treatment.  Nobody should really be surprised at this result. It would have in fact been more surprising had these men not had reduced fertility.

“That said, this was a study that needed to be performed and this was the team to do it.  This is the first opportunity that there has been where a sufficiently large number of men at reproductive age, originally born through ICSI could be studied. As such studies continue and we get the opportunity to examine larger cohorts, a more interesting question would be the nature and extent to which infertility is passed on in this way.”


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.”


Semen quality of young adult ICSI offspring: the first results’ by F. Belva et al. published in Human Reproduction on Thursday 6th October. 


Declared interests

Prof. Adam Balen: Has acted as a consultant for ad hoc advisory boards for Clear Blue, Ferring Pharmaceuticals, Astra Zeneca, Pharmasure, Merck Serono, Organon (now Merck Sharp & Dohme), Glaxo Smith Kline (GSK), Gideon Richter and Uteron Pharma. He has been paid for manuscript preparation by these companies and by various universities and societies. He provides expert reports in medical negligence cases for which the fee is paid by the instructing solicitors. Professor Balen’s research is largely funded by public bodies in the UK and European Union, although he has occasionally in the past participated in research projects where pharmaceutical companies have contributed a grant. He has received honoraria and had travel and accommodation expenses covered or reimbursed for speaking at meetings by the pharmaceutical companies listed above, various colleges, universities and societies, and public research funding bodies. His institution has received sponsorship for organising educational meetings and he receives royalties on his books from publishers.

Prof. Darren Griffin:

Treasurer of the Preimplantation Genetic Diagnosis International Society (PGDIS)

Faculty of COGEN (Controversies in Genetics)

President of the International Chromosome and Genome Society

Director of the Centre for Interdisciplinary Studies of Reproduction (CISoR)

Prof. Richard Sharpe: “I am deputy editor of Human Reproduction, but had nothing to do with the handling of this particular paper. No other conflicts of interest”

Prof. Sheena Lewis: Sheena is CEO of Lewis Fertility Testing Ltd, a university spin-out company marketing a test for male infertility:

Prof. Simon Fishel: “I am employed by and a shareholder in CARE Fertility.”

Prof. Allan Pacey: “Chairman of the advisory committee of the UK National External Quality Assurance Schemes in Andrology, Editor in Chief of Human Fertility and Trustee of the Progress Educational Trust (all unpaid). Also, recent work for the World Health Organisation, British Broadcasting Corporation, Purple Orchid Pharma (paid consultancy with all monies going to University of Sheffield). Co-applicant on a research grant from the Medical Research Council (ref: MR/M010473/1).”

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