{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:38:01Z","timestamp":1792100281959,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Duc Hospital","award":["GNT2009767"],"award-info":[{"award-number":["GNT2009767"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit more from ICSI over c-IVF on live birth, ongoing pregnancy, clinical pregnancy or total fertilization failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Our recent RCT showed that ICSI did not result in higher live birth rates in couples with normal total sperm count and motility. It is unclear whether sperm morphology can be used as a biomarker to identify couples who benefit more from ICSI over c-IVF in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This was a secondary analysis of an open-label, multi-centre, RCT comparing ICSI versus c-IVF in 1064 couples with infertility and normal total sperm count and motility. In this secondary study, we evaluated the effectiveness of ICSI over c-IVF in relation to sperm morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Couples were eligible if they had \u22642 previous IVF\/ICSI attempts, and the male partner had normal total sperm count and motility according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Sperm morphology was measured from samples obtained during the first consultation and data for sperm morphology were available in partners of all participants in this trial. The outcomes of interest were live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure. We first conducted a logistic regression analysis with an interaction term (sperm morphology as a continuous variable by treatment (ICSI versus c-IVF)) on the four outcomes. We also used restricted cubic spline analysis to evaluate non-linear interaction and plotted the treatment effects of ICSI over c-IVF at different sperm morphology levels and the predicted probability of these outcomes in both ICSI and c-IVF groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>The median proportion of sperm with normal morphology in both groups was 3% (Interquartile range 1\u20136%). Live birth rates were (184\/532) 34.6% for ICSI versus (166\/532) 31.2% for c-IVF. No significant interaction was found between sperm morphology and treatment effect of ICSI versus c-IVF on the rates of live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure (P\u2009=\u20090.181, 0.153, 0.168, and 0.788 respectively). In the analyses using restricted cubic splines, no evidence of interaction between sperm morphology and the treatment effect was found. Interaction figures showed that the treatment effect of ICSI over c-IVF at different sperm morphology levels was fluctuating around no effect line, and the predicted outcomes for the two groups were mostly overlapping at different sperm morphology levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS AND REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>This secondary analysis may be underpowered to detect a difference in treatment effects at different sperm morphology levels due to relatively small number of events at some sperm morphology levels. Moreover, sperm morphology assessment was performed during the first consultation, rather than on the day of randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>In couples with infertility and normal total sperm count and motility, sperm morphology has a limited role as a biomarker to identify couples who benefit more from ICSI over c-IVF on fertility outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. RW was supported by an NHMRC EL Investigator Grant (GNT2009767). LNV has received speaker and conference fees from Merck, grant, speaker, conference fees from Merck Sharpe and Dohme, and speaker, conference, and scientific board fees from Ferring. TMH has received speaker fees from Merck, Merck Sharp Dohme, and Ferring. BWM reports consultancy, travel support and research funding from Merck and consultancy for Organon and Norgine. BWM holds stock from ObsEva.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>NCT03428919<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deae252","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:19:48Z","timestamp":1730161188000},"page":"23-29","source":"Crossref","is-referenced-by-count":13,"title":["Intracytoplasmic sperm injection versus conventional\n                    <i>in vitro<\/i>\n                    fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter?"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-2274","authenticated-orcid":false,"given":"Toan D","family":"Pham","sequence":"first","affiliation":[{"name":"IVFMD, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinh Q","family":"Dang","sequence":"additional","affiliation":[{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University , Melbourne, VIC,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-8393","authenticated-orcid":false,"given":"Vu N A","family":"Ho","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cam T","family":"Tran","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dung T P","family":"Nguyen","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-6912","authenticated-orcid":false,"given":"Lan N","family":"Vuong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Medicine and Pharmacy at Ho Chi Minh City , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-7358","authenticated-orcid":false,"given":"Tuong M","family":"Ho","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital , Ho Chi Minh City, Viet Nam"},{"name":"HOPE Research Center, My Duc Hospital , Ho Chi Minh City, Viet Nam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University , Melbourne, VIC,","place":["Australia"]},{"name":"Aberdeen Centre for Women\u2019s Health Research, University of Aberdeen , Aberdeen,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-8134","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University , Melbourne, VIC,","place":["Australia"]},{"name":"NHMRC Clinical Trials Centre, University of Sydney , Sydney, NSW,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"2025010605514774500_deae252-B1","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/S0140-6736(00)05179-5","article-title":"Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial","volume":"357","author":"Bhattacharya","year":"2001","journal-title":"Lancet"},{"key":"2025010605514774500_deae252-B2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1001\/jama.2014.17985","article-title":"Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection","volume":"313","author":"Boulet","year":"2015","journal-title":"JAMA"},{"key":"2025010605514774500_deae252-B3","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":"2025010605514774500_deae252-B4","doi-asserted-by":"crossref","first-page":"hoz006","DOI":"10.1093\/hropen\/hoz006","article-title":"The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial","volume":"2019","author":"Dang","year":"2019","journal-title":"Hum Reprod Open"},{"key":"2025010605514774500_deae252-B5","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1016\/S0140-6736(21)00535-3","article-title":"Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial","volume":"397","author":"Dang","year":"2021","journal-title":"Lancet"},{"key":"2025010605514774500_deae252-B6","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.fertnstert.2007.06.052","article-title":"The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome","volume":"89","author":"Dubey","year":"2008","journal-title":"Fertil Steril"},{"key":"2025010605514774500_deae252-B7","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0015-0282(03)00367-4","article-title":"Monitoring technologist reading skills in a sperm morphology quality control program","volume":"79","author":"Franken","year":"2003","journal-title":"Fertil Steril"},{"key":"2025010605514774500_deae252-B8","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/andr.12389","article-title":"Sperm morphology: assessment, pathophysiology, clinical relevance, and state of the art in 2017","volume":"5","author":"Gatimel","year":"2017","journal-title":"Andrology"},{"key":"2025010605514774500_deae252-B9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/humrep\/16.1.110","article-title":"A study of semen parameters with emphasis on sperm morphology in a fertile population: an attempt to develop clinical thresholds","volume":"16","author":"Gunalp","year":"2001","journal-title":"Hum Reprod"},{"key":"2025010605514774500_deae252-B10","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1056\/NEJMoa003005","article-title":"Sperm morphology, motility, and concentration in fertile and infertile men","volume":"345","author":"Guzick","year":"2001","journal-title":"N Engl J Med"},{"key":"2025010605514774500_deae252-B05991898","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-19425-7","volume-title":"Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis","author":"Harrell","year":"2015"},{"key":"2025010605514774500_deae252-B11","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.fertnstert.2007.01.057","article-title":"Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection","volume":"88","author":"Keegan","year":"2007","journal-title":"Fertil Steril"},{"key":"2025010605514774500_deae252-B12","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.juro.2017.11.045","article-title":"Effect of sperm morphology on pregnancy success via intrauterine insemination: a systematic review and meta-analysis","volume":"199","author":"Kohn","year":"2018","journal-title":"J Urol"},{"key":"2025010605514774500_deae252-B13","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0015-0282(16)49891-2","article-title":"Sperm morphologic features as a prognostic factor in in vitro fertilization","volume":"46","author":"Kruger","year":"1986","journal-title":"Fertil Steril"},{"key":"2025010605514774500_deae252-B14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0368-2315(07)78733-1","article-title":"L\u2019impact de l\u2019analyse de la morphologie du sperme sur le r\u00e9sultat de la FIV","volume":"36","author":"Lundin","year":"2007","journal-title":"J Gyn\u00e9col Obst\u00e9t Biol Reprod"},{"key":"2025010605514774500_deae252-B15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.rbmo.2021.11.005","article-title":"Human sperm morphology assessment since 2010: experience of an Australian external quality assurance programme","volume":"44","author":"Matson","year":"2022","journal-title":"Reprod Biomed Online"},{"key":"2025010605514774500_deae252-B16","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/humrep\/16.6.1165","article-title":"Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in-vivo thresholds","volume":"16","author":"Menkveld","year":"2001","journal-title":"Hum Reprod"},{"key":"2025010605514774500_deae252-B17","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1093\/humrep\/16.5.918","article-title":"The effect of intracytoplasmic sperm injection and semen parameters on blastocyst development in vitro","volume":"16","author":"Miller","year":"2001","journal-title":"Hum Reprod"},{"key":"2025010605514774500_deae252-B18","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.fertnstert.2011.08.036","article-title":"Sperm morphology: classification drift over time and clinical implications","volume":"96","author":"Morbeck","year":"2011","journal-title":"Fertil Steril"},{"key":"2025010605514774500_deae252-B19","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/j.1939-4640.2001.tb02171.x","article-title":"Sperm morphology assessment\u2014historical perspectives and current opinions","volume":"22","author":"Mortimer","year":"2001","journal-title":"J Androl"},{"key":"2025010605514774500_deae252-B20","doi-asserted-by":"crossref","first-page":"F51","DOI":"10.1530\/REP-18-0011","article-title":"Development of ICSI","volume":"156","author":"O\u2019Neill","year":"2018","journal-title":"Reproduction"},{"key":"2025010605514774500_deae252-B25352099","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0140-6736(92)92425-F","article-title":"Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte","volume":"340","author":"Palermo","year":"1992","journal-title":"The Lancet"},{"key":"2025010605514774500_deae252-B21","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/andr.13123","article-title":"Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles","volume":"10","author":"Villani","year":"2022","journal-title":"Andrology"},{"key":"2025010605514774500_deae252-B22","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0140-6736(23)02416-9","article-title":"Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial","volume":"403","author":"Wang","year":"2024","journal-title":"Lancet"},{"key":"2025010605514774500_deae252-B23","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"World Health Organization (WHO)","year":"2010"},{"key":"2025010605514774500_deae252-B24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/aogs.14698","article-title":"Efficacy of intracytoplasmic sperm injection in women with non-male factor infertility: a systematic review and meta-analysis","volume":"103","author":"Yang","year":"2024","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2025010605514774500_deae252-B25","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/AOG.0000000000002730","article-title":"Temporal differences in utilization of intracytoplasmic sperm injection among U.S. regions","volume":"132","author":"Zagadailov","year":"2018","journal-title":"Obstet Gynecol"},{"key":"2025010605514774500_deae252-B26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4103\/aja.aja_91_20","article-title":"Influence of sperm morphology on pregnancy outcome and offspring in in vitro fertilization and intracytoplasmic sperm injection: a matched case-control study","volume":"23","author":"Zhou","year":"2021","journal-title":"Asian J Androl"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/40\/1\/23\/60687634\/deae252.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/40\/1\/23\/60687634\/deae252.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:52:08Z","timestamp":1736124728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/40\/1\/23\/7901372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,15]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,11,15]]},"published-print":{"date-parts":[[2025,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deae252","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,11,15]]}}}