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Author Topic: Semen quality of young adult ICSI offspring: the first results  (Read 2968 times)
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 Author Affiliations
1Centre for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium 
2Environment and Health/Youth Health Care, Department of Public Health and Primary Care, Kapucijnenvoer 35, 3000 Leuven, Belgium 
3Department of Urology, Universitair Ziekenhuis (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium 
4Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium 
↵*Correspondence address. E-mail: florence_belva@hotmail.com
Received July 15, 2016.
Revision received August 25, 2016.
Accepted August 31, 2016.


Abstract


STUDY QUESTION What is the semen quality of young adult men who were conceived 18–22 years ago by ICSI for male infertility?


SUMMARY ANSWER In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers.


WHAT IS KNOWN ALREADY The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated. Since these children were conceived by ICSI because of severe male-factor infertility, there is reasonable concern that male offspring have inherited the deficient spermatogenesis from their fathers. Previously normal pubertal development and adequate Sertoli and Leydig cell function have been described in pubertal ICSI boys; however, no information on their sperm quality is currently available.


STUDY DESIGN, SIZE, DURATION This study was conducted at UZ Brussel between March 2013 and April 2016 and is part of a large follow-up project focussing on reproductive and metabolic health of young adults, between 18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a physical examination and semen analysis were compared between young ICSI men being part of a longitudinally followed cohort and spontaneously conceived controls who were recruited cross-sectionally.


PARTICIPANTS/MATERIALS, SETTING, METHOD Results of a single semen sample in 54 young adult ICSI men and 57 spontaneously conceived men are reported. All young adults were individually assessed, and the results of their physical examination were completed by questionnaires. Data were analysed by multiple linear and logistic regression, adjusted for covariates. In addition, semen parameters of the ICSI fathers dating back from their ICSI treatment application were analysed for correlations.


MAIN RESULTS AND THE ROLE OF CHANCE Young ICSI adults had a lower median sperm concentration (17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count (12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million, respectively). The median percentage progressive and total motility, median percentage normal morphology and median semen volume were not significantly different between these groups. After adjustment for confounders (age, BMI, genital malformations, time from ejaculation to analysis, abstinence period), the statistically significant differences between ICSI men and spontaneously conceived peers remained: an almost doubled sperm concentration in spontaneously conceived peers in comparison to ICSI men (ratio 1.9, 95% CI 1.1–3.2) and a two-fold lower total sperm count (ratio 2.3, 95% CI 1.3–4.1) and total motile count (ratio 2.1, 95% CI 1.2–3.6) in ICSI men compared to controls were found. Furthermore, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below the WHO reference value of 15 million/ml (adjusted odds ratio (AOR) 2.7; 95% CI 1.1–6.7) and four times more likely to have total sperm counts below 39 million (AOR 4.3; 95% CI 1.7–11.3). In this small group of 54 father–son pairs, a weak negative correlation between total sperm count in fathers and their sons was found.


LIMITATIONS, REASONS FOR CAUTION The main limitation is the small study population. Also, the results of this study where ICSI was performed with ejaculated sperm and for male-factor infertility cannot be generalized to all ICSI offspring because the indications for ICSI have nowadays been extended and ICSI is also being performed with non-ejaculated sperm and reported differences may thus either decrease or increase.


WIDER IMPLICATIONS OF THE FINDINGS 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.


STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). All co-authors except M.B. and H.T. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough and Merck for establishing the database for follow-up research and organizing the data collection. The institution of H.T. has received research grants from the Research Fund of Flanders (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility.
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Semen quality of ICSI-born males - not as bad as we thought

10 October 2016

By Professor Allan Pacey
Appeared in BioNews 872


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, height, body mass index 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.
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