{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:15:26Z","timestamp":1774271726047,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T00:00:00Z","timestamp":1596931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father\u2019s semen parameters?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers\u2019 sperm parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41\/1114; 3.7%; 95% CI 2.7\u20134.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3\u20134.4), either numerical (n\u2009=\u200925), sex (n\u2009=\u20096) or structural (n\u2009=\u20095), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96\u20131.15; P\u2009=\u20090.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm.<\/jats:p>\n                    <jats:p>Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6\u20131.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm.<\/jats:p>\n                    <jats:p>The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04\u20131.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration &amp;lt;15 million\/ml (adjusted OR (AOR) 2.10; 95% CI 1.14\u20133.78), sperm concentration &amp;lt;5 million\/ml (AOR 1.9; 95% CI 1.05\u20133.45) and total sperm count &amp;lt;10 million (AOR 1.97; 95% CI 1.04\u20133.74).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing.<\/jats:p>\n                    <jats:p>The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaa162","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T15:13:53Z","timestamp":1591974833000},"page":"2149-2162","source":"Crossref","is-referenced-by-count":29,"title":["Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center"],"prefix":"10.1093","volume":"35","author":[{"given":"F","family":"Belva","sequence":"first","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Bonduelle","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Buysse","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Van den Bogaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Hes","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Roelants","sequence":"additional","affiliation":[{"name":"Environment and Health\/Youth Health Care, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Tournaye","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Keymolen","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"2020101222244185400_deaa162-B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0015-0282(01)01927-6","article-title":"A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection","volume":"76","author":"Aboulghar","year":"2001","journal-title":"Fertil Steril"},{"key":"2020101222244185400_deaa162-B2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/oxfordjournals.humrep.a138791","article-title":"Prospective follow-up study of 55 children born after subzonal insemination and intracytoplasmic sperm injection","volume":"9","author":"Bonduelle","year":"1994","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B3","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/oxfordjournals.humrep.a019437","article-title":"Prospective follow-up study of 423 children born after intracytoplasmic sperm injection","volume":"11","author":"Bonduelle","year":"1996","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B4","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1093\/humrep\/17.10.2600","article-title":"Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters","volume":"17","author":"Bonduelle","year":"2002","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B5","first-page":"859","article-title":"Intracytoplasmic sperm injection in infertile patients with structural cytogenetic abnormalities","volume":"44","author":"Causio","year":"1999","journal-title":"J Reprod Med"},{"key":"2020101222244185400_deaa162-B6","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00404-018-4712-x","article-title":"Birth prevalence of congenital malformations in singleton pregnancies resulting from in vitro fertilization\/intracytoplasmic sperm injection worldwide: a systematic review and meta-analysis","volume":"297","author":"Chen","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"2020101222244185400_deaa162-B7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum Reprod Update"},{"key":"2020101222244185400_deaa162-B8","year":"2012"},{"key":"2020101222244185400_deaa162-B9","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/pd.1970040704","article-title":"Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative european study on 52 965 amniocenteses","volume":"4","author":"Ferguson-Smith","year":"1984","journal-title":"Prenat Diagn"},{"key":"2020101222244185400_deaa162-B10","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S1472-6483(10)60677-3","article-title":"Male infertility: role of genetic background","volume":"14","author":"Ferlin","year":"2007","journal-title":"Reprod Biomed Online"},{"key":"2020101222244185400_deaa162-B11","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1053\/beog.2000.0124","article-title":"Genetic aspects of miscarriage","volume":"14","author":"Goddijn","year":"2000","journal-title":"Baillieres Best Pract Res Clin Obstet Gynaecol"},{"key":"2020101222244185400_deaa162-B12","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0140-6736(95)91768-3","article-title":"Sex chromosome abnormalities after intracytoplasmic sperm injection","volume":"346","author":"Govaerts","year":"1995","journal-title":"Lancet"},{"key":"2020101222244185400_deaa162-B13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1469-1809.1987.tb00864.x","article-title":"Rates of mutant and inherited structural cytogenetic abnormalities detected at amniocentesis: results on about 63,000 fetuses","volume":"51","author":"Hook","year":"1987","journal-title":"Ann Hum Genet"},{"key":"2020101222244185400_deaa162-B14","first-page":"422","article-title":"Inherited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, parental-age associations, sex-ratio trends, and comparisons with rates of mutants","volume":"36","author":"Hook","year":"1984","journal-title":"Am J Hum Genet"},{"key":"2020101222244185400_deaa162-B15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/jmg.29.2.103","article-title":"Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding","volume":"29","author":"Jacobs","year":"1992","journal-title":"J Med Genet"},{"key":"2020101222244185400_deaa162-B16","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.fertnstert.2004.02.110","article-title":"Prenatal karyotypes of fetuses conceived by intracytoplasmic sperm injection","volume":"82","author":"Jozwiak","year":"2004","journal-title":"Fertil Steril"},{"key":"2020101222244185400_deaa162-B17","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/bdra.20107","article-title":"In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods","volume":"73","author":"K\u00e4ll\u00e9n","year":"2005","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"2020101222244185400_deaa162-B18","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/S0015-0282(01)02873-4","article-title":"Cytogenetic investigation of fetuses and infants conceived through intracytoplasmic sperm injection","volume":"76","author":"Lam","year":"2001","journal-title":"Fertil Steril"},{"key":"2020101222244185400_deaa162-B19","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1093\/humrep\/14.8.2143","article-title":"A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997","volume":"14","author":"Loft","year":"1999","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B20","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.fertnstert.2017.08.033","article-title":"Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles","volume":"108","author":"Mazzilli","year":"2017","journal-title":"Fertil Steril"},{"key":"2020101222244185400_deaa162-B21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF01213097","article-title":"Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark","volume":"87","author":"Nielsen","year":"1991","journal-title":"Hum Genet"},{"key":"2020101222244185400_deaa162-B22","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780199638406.001.0001","volume-title":"Human Cytogenetics: Constitutional Analysis. A Practical Approach","author":"Rooney","year":"2001","edition":"3rd edn."},{"key":"2020101222244185400_deaa162-B23","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/pd.706","article-title":"Fetal chromosomal analysis of pregnancies following intracytoplasmic sperm injection with amniotic tissue culture","volume":"23","author":"Samli","year":"2003","journal-title":"Prenat Diagn"},{"key":"2020101222244185400_deaa162-B24","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1093\/oxfordjournals.humrep.a019179","article-title":"Intracytoplasmic sperm injection in infertile patients with structural chromosome abnormalities","volume":"11","author":"Testart","year":"1996","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B25","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1093\/humrep\/12.4.682","article-title":"Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection","volume":"12","author":"Van Opstal","year":"1997","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B26","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.fertnstert.2012.02.053","article-title":"Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis","volume":"97","author":"Wen","year":"2012","journal-title":"Fertil Steril"},{"key":"2020101222244185400_deaa162-B27","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/humrep\/15.4.944","article-title":"Incidence of congenital malformations in children born after ICSI","volume":"15","author":"Wennerholm","year":"2000","journal-title":"Hum Reprod"},{"key":"2020101222244185400_deaa162-B28","volume-title":"WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction","year":"2010"},{"key":"2020101222244185400_deaa162-B29","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/14767058.2018.1488168","article-title":"Do the children born after assisted reproductive technology have an increased risk of birth defects? A systematic review and meta-analysis","volume":"33","author":"Zhao","year":"2020","journal-title":"J Matern Fetal Neonatal Med"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/9\/2149\/33867128\/deaa162.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/9\/2149\/33867128\/deaa162.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T10:39:01Z","timestamp":1723027141000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/35\/9\/2149\/5890120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,9]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,8,9]]},"published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deaa162","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.738472194.793579765","asserted-by":"object"}]},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,8,9]]}}}