{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:47:46Z","timestamp":1766159266796,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"governmental grant Fonds voor Wetenschappelijk onderzoek (FWO), Research Foundation Flanders","doi-asserted-by":"publisher","award":["TBMT007016N"],"award-info":[{"award-number":["TBMT007016N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Intrauterine insemination with donor sperm (IUI-D) requires multiple in vitro manipulations such as sperm selection and cryopreservation during which spermatozoa may be exposed to oxidative stress (OS) and other insults that may produce potential damage including sperm DNA fragmentation (SDF). High levels of SDF, referring to damage or breaks in the genetic material of sperm cells, are linked to an increased risk of reproductive failure. This retrospective, observational study set out to evaluate whether SDF assessment could predict clinical outcome in an IUI-D program, where sperm donors are selected on strict conventional semen parameters. A total of 18 donors and 106 recipients were matched for IUI-D. Out of 429 cycles, 100 (23.3%) resulted in clinical pregnancy. We counted 78 live births (18.2% of cycles), while 20 pregnancies ended in miscarriage (4.7% of cycles), 1 in extra-uterine pregnancy and 1 in stillbirth. Female age significantly influenced clinical pregnancy and miscarriage rates. SDF increased after cryopreservation (26.3 \u00b1 14.5%; p &lt; 0.001) and more so after post-thaw density gradient (34.9 \u00b1 22.1%; p = 0.04) without affecting clinical pregnancy (OR [95% CI] 1.01 [0.99; 1.02]; p = 0.27), live birth (1.00 [0.99; 1.02]; p = 0.72) and miscarriage rates (1.02 [1.00; 1.05]; p = 0.08). The implications of our findings extend to a better selection of sperm donors and a better sperm preparation technique tailored to the donor semen\u2019s properties in order to maximize the chances of a favorable treatment outcome.<\/jats:p>","DOI":"10.3390\/jpm13121668","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T11:43:16Z","timestamp":1701171796000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sperm DNA Fragmentation after Cryopreservation and Sperm Selection Has No Implications for Clinical Pregnancies and Live Births after Intrauterine Insemination with Donor Sperm"],"prefix":"10.3390","volume":"13","author":[{"given":"Alessa","family":"Sugihara","sequence":"first","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp\u2014Campus Drie Eiken, 2610 Wilrijk, Belgium"},{"name":"Centre of Reproductive Medicine, Algemeen Ziekenhuis KLINA, 2930 Brasschaat, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-2511","authenticated-orcid":false,"given":"Usha","family":"Punjabi","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp\u2014Campus Drie Eiken, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Chimienti","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-8499","authenticated-orcid":false,"given":"Ilse","family":"Goovaerts","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp\u2014Campus Drie Eiken, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kris","family":"Peeters","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp\u2014Campus Drie Eiken, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-451X","authenticated-orcid":false,"given":"Jason","family":"Bouziotis","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, University Hospital of Antwerp, 2650 Edegem, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"De Neubourg","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine, University Hospital of Antwerp, 2650 Edegem, Belgium"},{"name":"Faculty of Medicine and Health Sciences, University of Antwerp\u2014Campus Drie Eiken, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/humupd\/dmx041","article-title":"IUI: Review and systematic assessment of the evidence that supports global recommendations","volume":"24","author":"Cohlen","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106314","DOI":"10.1016\/j.anireprosci.2020.106314","article-title":"Adverse effects of in vitro manipulation of spermatozoa","volume":"220","author":"Baldi","year":"2020","journal-title":"Anim. Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e3624","DOI":"10.1097\/MD.0000000000003624","article-title":"Variation of DNA fragmentation levels during density gradient sperm selection for assisted reproduction techniques: A possible new male predictive parameter of pregnancy?","volume":"95","author":"Muratori","year":"2016","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7492","DOI":"10.1038\/s41598-019-43981-2","article-title":"Sperm selection with density gradient centrifugation and swim up: Effect on DNA fragmentation in viable spermatozoa","volume":"9","author":"Muratori","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tamburrino, L., Traini, G., Marcellini, A., Vignozzi, L., Baldi, E., and Marchiani, S. (2023). Cryopreservation of Human Spermatozoa: Functional, Molecular and Clinical Aspects. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054656"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/humrep\/14.4.1039","article-title":"Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic","volume":"14","author":"Evenson","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.fertnstert.2015.11.037","article-title":"Sperm DNA fragmentation and mitochondrial membrane potential combined are better for predicting natural conception than standard sperm parameters","volume":"105","author":"Golob","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/humrep\/des261","article-title":"The effect of sperm DNA fragmentation on miscarriage rates: A systematic review and meta-analysis","volume":"27","author":"Robinson","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0015-0282(99)00462-8","article-title":"The Danish First Pregnancy Planner Study Team. Sperm chromatin damage impairs human fertility","volume":"73","author":"Bonde","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.clinbiochem.2018.05.011","article-title":"Sperm DNA fragmentation in the total and vital fractions before and after density gradient centrifugation: Significance in male fertility diagnosis","volume":"62","author":"Punjabi","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/S0015-0282(00)01796-9","article-title":"Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men","volume":"75","author":"Zini","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3109\/19396368.2010.515704","article-title":"Are sperm chromatin and DNA defects relevant in the clinic?","volume":"57","author":"Zini","year":"2011","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejogrb.2019.10.005","article-title":"The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: A systematic review and meta-analysis","volume":"244","author":"Sugihara","year":"2020","journal-title":"Eur. J. Obs. Gynecol. Reprod. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sugihara, A., Punjabi, U., Roelant, E., and De Neubourg, D. (2023). Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial. Life, 13.","DOI":"10.3390\/life13010011"},{"key":"ref_15","unstructured":"(2023, September 01). Law Concerning the Assisted Medical Reproduction and the Destination of Supernumerary Embryo\u2019s and Gametes. Available online: https:\/\/etaamb.openjustice.be\/nl\/wet-van-06-juli-2007_n2007023090.html."},{"key":"ref_16","unstructured":"World Health Organization (WHO) (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/oxfordjournals.humrep.a137046","article-title":"Comparison between different pre-treatment techniques for sperm recovery prior to intrauterine insemination, GIFT or IVF","volume":"5","author":"Punjabi","year":"1990","journal-title":"Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2605.2009.01042.x","article-title":"The TUNEL assay consistently underestimates DNA damage in human spermatozoa and is influenced by DNA compaction and cell vitality: Development of an improved methodology","volume":"34","author":"Mitchell","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s10815-019-01476-z","article-title":"DNA fragmentation in concert with the simultaneous assessment of cell viability in a subfertile population: Establishing thresholds of normality both before and after density gradient centrifugation","volume":"36","author":"Punjabi","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e12977","DOI":"10.1111\/and.12977","article-title":"Validating semen processing for an intrauterine program should take into consideration the inputs, actions and the outputs of the process","volume":"50","author":"Punjabi","year":"2018","journal-title":"Andrologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s10815-020-02020-0","article-title":"Time intervals between semen production, initiation of analysis, and IUI significantly influence clinical pregnancies and live births","volume":"38","author":"Punjabi","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.fertnstert.2017.06.005","article-title":"The International Glossary on Infertility and Fertility Care, 2017","volume":"108","author":"Adamson","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_23","unstructured":"HFEA (Human Fertilisation and Embryology Authority) (2023, September 01). Trends in Egg, Sperm and Embryo Donation 2020, Available online: https:\/\/www.hfea.gov.uk\/about-us\/publications\/research-and-data\/trends-in-egg-sperm-and-embryo-donation-2020\/."},{"key":"ref_24","first-page":"165","article-title":"Sperm DNA Fragmentation may Influence IUI Outcome but could be Treated by ICSI: Evidence from Human Sperm Bank","volume":"25","author":"Lu","year":"2014","journal-title":"J. Reprod. Contracept."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1439-0272.2009.01036.x","article-title":"Factors affecting fecundity among sperm donors: A multivariate analysis","volume":"43","author":"Hu","year":"2011","journal-title":"Andrologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.fertnstert.2019.03.003","article-title":"Sperm DNA fragmentation and recurrent pregnancy loss: A systematic review and meta-analysis","volume":"112","author":"McQueen","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1093\/humrep\/16.11.2298","article-title":"Results of 6139 artificial insemination cycles with donor spermatozoa","volume":"16","author":"Botchan","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1093\/humrep\/dez179","article-title":"Donor IUI is equally effective for heterosexual couples, single women and lesbians, but autologous IUI does worse","volume":"34","author":"Soares","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_29","unstructured":"(2023, September 01). BELRAP (Belgian Register for Assisted Reproduction). Available online: https:\/\/www.belrap.be."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1093\/humrep\/17.9.2320","article-title":"Intrauterine insemination with frozen donor sperm. Pregnancy outcome in relation to age and ovarian stimulation regime","volume":"17","author":"Ferrara","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/humrep\/dep085","article-title":"Cumulative delivery rates in different age groups after artificial insemination with donor sperm","volume":"24","author":"Haentjens","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/andr.12963","article-title":"Is there a temporal trend in semen quality in Belgian candidate sperm donors and in sperm donors\u2019 fertility potential from 1995 onwards?","volume":"9","author":"Sugihara","year":"2021","journal-title":"Andrology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/humrep\/dey242","article-title":"ART in Europe, 2014: Results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE)","volume":"33","author":"Kupka","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1093\/humrep\/deab198","article-title":"International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted reproductive technology, 2014","volume":"36","author":"Chambers","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.fertnstert.2010.05.055","article-title":"Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality","volume":"95","author":"Meseguer","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.rbmo.2017.03.012","article-title":"Predictive factors influencing pregnancy rates after intrauterine insemination with frozen donor semen: A prospective cohort study","volume":"34","author":"Thijssen","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1093\/humrep\/dev331","article-title":"Does age of the sperm donor influence live birth outcome in assisted reproduction?","volume":"31","author":"Ghuman","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Moustakli, E., Zikopoulos, A., Georgiou, I., Dimitriadis, F., Symeonidis, E.N., Markou, E., Michaelidis, T.M., Tien, D.M.B., and Giannakis, I. (2023). Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring. Genes, 14.","DOI":"10.3390\/genes14020486"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/humupd\/dmu063","article-title":"The effect of cryopreservation on the genome of gametes and embryos: Principles of cryobiology and critical appraisal of the evidence","volume":"21","author":"Kopeika","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S1472-6483(10)60073-9","article-title":"Influence of freeze-thawing on hyaluronic acid binding of human spermatozoa","volume":"19","author":"Nijs","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10815-008-9232-3","article-title":"Effects of cryopreservation on sperm parameters and ultrastructural morphology of human spermatozoa","volume":"25","author":"Ozkavukcu","year":"2008","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.rbmo.2010.05.011","article-title":"Implication of apoptosis in sperm cryoinjury","volume":"21","author":"Said","year":"2010","journal-title":"Reprod. Biomed. Online"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1095\/biolreprod.103.025627","article-title":"Cryopreservation and thawing is associated with varying extent of activation of apoptotic machinery in subsets of ejaculated human spermatozoa","volume":"71","author":"Paasch","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.fertnstert.2006.01.047","article-title":"Effect of cryopreservation on sperm apoptotic deoxyribonucleic acid fragmentation in patients with oligozoospermia","volume":"86","author":"Bertolla","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.fertnstert.2008.09.038","article-title":"Effects of cryopreservation on human sperm deoxyribonucleic acid integrity","volume":"93","author":"Zribi","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1177\/1933719119828096","article-title":"Evaluation of Sperm DNA Fragmentation via Halosperm Technique and TUNEL Assay Before and After Cryopreservation","volume":"26","author":"Cankut","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10561-020-09883-8","article-title":"Dynamic assessment of human sperm DNA damage III: The effect of sperm freezing techniques","volume":"22","author":"Arroyo","year":"2021","journal-title":"Cell Tissue Bank."},{"key":"ref_48","first-page":"991","article-title":"The total antioxidant power of semen and its correlation with the fertility potential of human male subjects","volume":"7","author":"Pahune","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/j.1939-4640.2001.tb02217.x","article-title":"Relationship between seminal white blood cell counts and oxidative stress in men treated at an infertility clinic","volume":"22","author":"Sharma","year":"2001","journal-title":"J. Androl."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Malvezzi, H., Sharma, R., Agarwal, A., Abuzenadah, A.M., and Abu-Elmagd, M. (2014). Sperm quality after density gradient centrifugation with three commercially available media: A controlled trial. Reprod. Biol. Endocrinol., 12.","DOI":"10.1186\/1477-7827-12-121"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39051","DOI":"10.1038\/srep39051","article-title":"Semen preparation methods and sperm telomere length: Density gradient centrifugation versus the swim up procedure","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Punjabi, U., Roelant, E., Peeters, K., Goovaerts, I., Van Mulders, H., and De Neubourg, D. (2022). Variability in Sperm DNA Fragmentation in Men with Mild\/Unexplained Subfertility in a Prospective Longitudinal Intrauterine Insemination Trial. Life, 12.","DOI":"10.3390\/life12111826"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/12\/1668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:32:52Z","timestamp":1760131972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/12\/1668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":52,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["jpm13121668"],"URL":"https:\/\/doi.org\/10.3390\/jpm13121668","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2023,11,28]]}}}