When ICSI – intracytoplasmic sperm injection – was first introduced into clinical practice in the early 1990s, many doctors and scientists were concerned about the consequences for the health and development of individuals conceived this way. After all, the selection of sperm by an embryologist, and its subsequent injection into an unfertilised oocyte, was hardly under the influence of any kind of Darwinian evolution. Moreover, the poor sperm quality that required the use of ICSI in the first place almost certainly had some underlying genetic factor which was not yet understood.
Therefore, as time passed and ICSI was used more and more frequently around the world, reports began to emerge about the health and well-being of the ICSI children, who were being intensively studied and monitored as they grew up. The results of some of these studies have been reported in the pages of BioNews – the incidence of congenital abnormalities, neurological and mental development, the development of the male reproductive organs, IQ and motor skills, weight and finger length.
On the whole, these reports have been largely reassuring, with the overall health and development measures of ICSI-conceived children largely the same as those conceived naturally, when appropriate adjustments have been made for factors such as multiple births and the age of parents. However, there has, until now, been one of the pieces of the jigsaw missing: the fertility of those born using this technique when they reach adulthood, specifically the fertility of males. This has been of great interest because the reason for using the ICSI procedure to conceive these males in the first place was because of their father's poor sperm quality, which was almost certainly of genetic origin. Therefore, if those genes were inherited by any sons born through the ICSI procedure (and that seemed extremely likely given that ICSI just bypasses the problem rather than repairs it), then the logical conclusion is they would have a similar level of infertility as their father and therefore potentially require the use of ICSI themselves when they wanted to become a dad.
Therefore, the paper published this week in Human Reproduction by Belva et al has been long awaited and gives some intriguing insights about the semen quality – and therefore the future fertility prospects – of 54 males aged between 18 and 22 years old who were born between 1992 and 1996 following ICSI using fresh sperm and the transfer of fresh embryos (see BioNews 872). The authors of the paper then compared the semen quality of these males with a control group of 57 age matched, naturally conceived men) as well as with the sperm quality of their fathers at the time of ICSI.
Clearly, this is a study which has not been possible to perform until these males reached adulthood. The data shows that their sperm quality is noticeably lower than that seen in men who were conceived naturally. However, this result 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.
To me, what was more interesting about the paper was the fact that when the authors compared the semen quality of the ICSI-conceived males with that of their fathers, only a poor relationship was observed. The ICSI-conceived males were no more likely to have a sperm concentration below 15 million per ml even if their father had a sperm concentration of below 15 million per ml. This is not as expected, and it suggests that our assumptions about the inheritance of male infertility may be more complex than we have realised until now. Although the study only looked at a relatively small number of men – and it certainly needs to be repeated with a larger cohort – I see this result as being quite reassuring. Our worries over the past 25 years have been that ICSI-born males were destined for a poor reproductive future that may be equivalent to (or even worse than) that of their fathers, but this paper suggests this is not necessarily going to be the case.