{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:20:07Z","timestamp":1791872407807,"version":"4.3.4"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intracytoplasmic sperm injection (ICSI) is increasingly used among in vitro fertilization (IVF) cycles without male factor infertility. For couples with prolonged infertility duration, the preferred insemination method may vary across laboratories and clinics. We analyzed whether ICSI is effective for non-male factor infertility with long infertility duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventeen thousand four hundred seventy-seven\u00a0IVF\/ICSI cycles from women with non-male factor infertility were included, of these 4177 women with infertility duration\u2009\u2265\u20095\u00a0years were in the final analysis. Primary outcome was the live birth rate after first embryo transfer. Secondary outcomes were rates of clinical pregnancy and fertilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A nonlinear relationship was observed between infertility duration and IVF fertilization rate, which decreased with infertility years up to the turning point (4.8\u00a0years). 4177 women with infertility\u2009\u2265\u20095\u00a0years were categorized by IVF (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093806) or ICSI (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009371). Live birth rate after first embryo transfer was 43.02% in ICSI and 47.85% in IVF group (adjusted odds ratio (aOR), 0.91; 95% confidence interval (CI), 0.72\u20131.15). Fertilization rate per metaphaseII (aOR, 1.10; 95% CI, 0.86\u20131.40) and clinical pregnancy rate (aOR, 0.89; 95% CI, 0.71\u20131.13) were similar between the two groups. Sensitive analyses (women\u2009\u2265\u200935\u00a0years) did not show a benefit of ICSI over IVF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Women with infertility exceeding 4.8\u00a0years had decreased incidence of IVF fertilization. The use of ICSI showed no significant improvement in fertilization and live birth rates for non-male factor couples with\u2009\u2265\u20095\u00a0years of infertility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12905-022-02062-9","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T08:04:12Z","timestamp":1669622652000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Duration of infertility and assisted reproductive outcomes in non-male factor infertility: can use of ICSI turn the tide?"],"prefix":"10.1186","volume":"22","author":[{"given":"Liting","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanzi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"2062_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.ajog.2017.03.012","volume":"217","author":"B Luke","year":"2017","unstructured":"Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies. Am J Obstet Gynecol. 2017;217:270\u201381.","journal-title":"Am J Obstet Gynecol"},{"key":"2062_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S0140-6736(02)09417-5","volume":"360","author":"JLH Evers","year":"2002","unstructured":"Evers JLH. Female subfertility. Lancet. 2002;360:151\u20139.","journal-title":"Lancet"},{"key":"2062_CR3","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1093\/humrep\/deh870","volume":"20","author":"C Gnoth","year":"2005","unstructured":"Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod. 2005;20:1144\u20137.","journal-title":"Hum Reprod"},{"key":"2062_CR4","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1093\/humrep\/deh314","volume":"19","author":"I Brosens","year":"2004","unstructured":"Brosens I, Gordts S, Valkenburg M, Puttemans P, Campo R, Gordts S. Investigation of the infertile couple: When is the appropriate time to explore female infertility? Hum Reprod. 2004;19:1689\u201392.","journal-title":"Hum Reprod"},{"key":"2062_CR5","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1093\/humupd\/dmq015","volume":"16","author":"LL van Loendersloot","year":"2010","unstructured":"van Loendersloot LL, van Wely M, Limpens J, Bossuyt PMM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): A systematic review and meta-analysis. Hum Reprod Update. 2010;16:577\u201389.","journal-title":"Hum Reprod Update"},{"key":"2062_CR6","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1093\/humrep\/15.6.1278","volume":"15","author":"S Fishel","year":"2000","unstructured":"Fishel S, Aslam I, Lisi F, Rinaldi L, Timson J, Jacobson M, et al. Should ICSI be the treatment of choice for all cases of in-vitro conception? Hum Reprod. 2000;15:1278\u201383.","journal-title":"Hum Reprod"},{"key":"2062_CR7","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/S0015-0282(00)01674-5","volume":"75","author":"F Khamsi","year":"2001","unstructured":"Khamsi F, Yavas Y, Roberge S, Wong JC, Lacanna IC, Endman M. Intracytoplasmic sperm injection increased fertilization and good-quality embryo formation in patients with non-male factor indications for in vitro fertilization: A prospective randomized study. Fertil Steril. 2001;75:342\u20137.","journal-title":"Fertil Steril"},{"key":"2062_CR8","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.fertnstert.2004.08.029","volume":"83","author":"L Van Der Westerlaken","year":"2005","unstructured":"Van Der Westerlaken L, Helmerhorst F, Dieben S, Naaktgeboren N. Intracytoplasmic sperm injection as a treatment for unexplained total fertilization failure or low fertilization after conventional in vitro fertilization. Fertil Steril. 2005;83:612\u20137.","journal-title":"Fertil Steril"},{"key":"2062_CR9","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1007\/s10815-021-02210-4","volume":"38","author":"EK Dirican","year":"2021","unstructured":"Dirican EK, Olgan S. Comparison of in vitro fertilization\/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age: overlooked details. J Assist Reprod Genet. 2021;38:1891\u20132.","journal-title":"J Assist Reprod Genet"},{"key":"2062_CR10","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1093\/humrep\/dew082","volume":"31","author":"S Dyer","year":"2016","unstructured":"Dyer S, Chambers GM, De Mouzon J, Nygren KG, Zegers-Hochschild F, Mansour R, et al. International committee for monitoring assisted reproductive technologies world report: Assisted reproductive technology 2008, 2009 and 2010\u2020. Hum Reprod. 2016;31:1588\u2013609.","journal-title":"Hum Reprod"},{"key":"2062_CR11","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1093\/humrep\/dey242","volume":"33","author":"C De Geyter","year":"2018","unstructured":"De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: Results generated from European registries by ESHRE. Hum Reprod. 2018;33:1586\u2013601.","journal-title":"Hum Reprod"},{"key":"2062_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.fertnstert.2020.05.032","volume":"114","author":"Committees P, Society A, Technology R","year":"2020","unstructured":"Committees P, Society A, Technology R. Intracytoplasmic sperm injection (ICSI) for non\u2013male factor indications: a committee opinion. Fertil Steril. 2020;114:239\u201345.","journal-title":"Fertil Steril"},{"key":"2062_CR13","first-page":"119","volume":"32","author":"S Tannus","year":"2017","unstructured":"Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod. 2017;32:119\u201324.","journal-title":"Hum Reprod"},{"key":"2062_CR14","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.fertnstert.2012.08.026","volume":"98","author":"T Practice","year":"2012","unstructured":"Practice T, Medicine R, Reproductive A. Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: A committee opinion. Fertil Steril. 2012;98:1395\u20139.","journal-title":"Fertil Steril"},{"key":"2062_CR15","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"World Health Organisation","year":"2010","unstructured":"World Health Organisation. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva: World Health Organization; 2010.","edition":"5"},{"key":"2062_CR16","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1093\/humrep\/det094","volume":"28","author":"W Shi","year":"2013","unstructured":"Shi W, Zhang S, Zhao W, Xia X, Wang M, Wang H, et al. Factors related to clinical pregnancy after vitrified-warmed embryo transfer: a retrospective and multivariate logistic regression analysis of 2313 transfer cycles. Hum Reprod. 2013;28:1768\u201375.","journal-title":"Hum Reprod"},{"key":"2062_CR17","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1080\/09513590.2017.1302420","volume":"33","author":"M Li","year":"2017","unstructured":"Li M, Wang H, Ma C, Shi J. Transferring two grades I cleavage-stage embryo might not be a good protocol. Gynecol Endocrinol. 2017;33:557\u20139.","journal-title":"Gynecol Endocrinol"},{"key":"2062_CR18","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/S0015-0282(00)00518-5","volume":"73","author":"DK Gardner","year":"2000","unstructured":"Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertil Steril. 2000;73:1155\u20138.","journal-title":"Fertil Steril"},{"key":"2062_CR19","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.fertnstert.2019.12.036","volume":"113","author":"H Cai","year":"2020","unstructured":"Cai H, Mol BW, Li P, Liu X, Watrelot A, Shi J. Tubal factor infertility with prior ectopic pregnancy: a double whammy? A retrospective cohort study of 2,892 women. Fertil Steril. 2020;113:1032\u20138.","journal-title":"Fertil Steril"},{"key":"2062_CR20","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1093\/humrep\/dez046","volume":"34","author":"F Facchin","year":"2019","unstructured":"Facchin F, Somigliana E, Busnelli A, Catavorello A, Barbara G, Vercellini P. Infertility-related distress and female sexual function during assisted reproduction. Hum Reprod. 2019;34:1065\u201373.","journal-title":"Hum Reprod"},{"key":"2062_CR21","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1093\/humrep\/deh365","volume":"19","author":"CC Hunault","year":"2004","unstructured":"Hunault CC, Habbema JDF, Eijkemans MJC, Collins JA, Evers JLH, te Velde ER. Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couple, based on the synthesis of three previous models. Hum Reprod. 2004;19:2019\u201326.","journal-title":"Hum Reprod"},{"key":"2062_CR22","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1016\/S0140-6736(00)05179-5","volume":"357","author":"S Bhattacharya","year":"2001","unstructured":"Bhattacharya S, Hamilton MPR, Shaaban M, Khalaf Y, Seddler M, Ghobara T, et al. Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: A randomised controlled trial. Lancet. 2001;357:2075\u20139.","journal-title":"Lancet"},{"key":"2062_CR23","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1093\/humrep\/16.12.2485","volume":"16","author":"B Ola","year":"2001","unstructured":"Ola B, Afnan M, Sharif K, Papaioannou S, Hammadieh N, Barratt CLR. Should ICSI be the treatment of choice for all cases of in-vitro conception? Considerations of fertilization and embryo development, cost effectiveness and safety. Hum Reprod. 2001;16:2485\u201390.","journal-title":"Hum Reprod"},{"key":"2062_CR24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/00001703-200306000-00001","volume":"15","author":"NG Mahutte","year":"2003","unstructured":"Mahutte NG, Arici A. Failed fertilization: is it predictable? Curr Opin Obstet Gynecol. 2003;15:211\u20138.","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2062_CR25","first-page":"187","volume":"50","author":"N Esfandiari","year":"2005","unstructured":"Esfandiari N, Javed MH, Gotlieb L, Casper RF. Complete failed fertilization after intracytoplasmic sperm injection - Analysis of 10 years\u2019 data. Int J Fertil Womens Med. 2005;50:187\u201392.","journal-title":"Int J Fertil Womens Med"},{"key":"2062_CR26","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1093\/oxfordjournals.humrep.a135758","volume":"10","author":"L Jiaen","year":"1995","unstructured":"Jiaen L, Zsolt N, Hubert J, Herman T, Johan S, Michel C, et al. Analysis of 76 total fertilization failure cycles out of 2732 intracytoplasmic sperm injection cycles. Hum Reprod. 1995;10:2630\u20136.","journal-title":"Hum Reprod"},{"key":"2062_CR27","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1007\/s10815-014-0281-5","volume":"31","author":"I Kahyaoglu","year":"2014","unstructured":"Kahyaoglu I, Demir B, Turkkan\u0131 A, C\u0131nar O, Dilbaz S, Dilbaz B, et al. Total fertilization failure: is it the end of the story? J Assist Reprod Genet. 2014;31:1155\u201360.","journal-title":"J Assist Reprod Genet"},{"key":"2062_CR28","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ceca.2013.10.006","volume":"55","author":"QV Neri","year":"2014","unstructured":"Neri QV, Lee B, Rosenwaks Z, Machaca K, Palermo GD. Understanding fertilization through intracytoplasmic sperm injection (ICSI). Cell Calcium. 2014;55:24\u201337.","journal-title":"Cell Calcium"},{"key":"2062_CR29","doi-asserted-by":"publisher","first-page":"F39","DOI":"10.1530\/REP-21-0387","volume":"164","author":"A Cardona Barber\u00e1n","year":"2022","unstructured":"Cardona Barber\u00e1n A, Boel A, Vanden Meerschaut F, Stoop D, Heindryckx B. SPERM FACTORS AND EGG ACTIVATION: Fertilization failure after human ICSI and the clinical potential of PLCZ1. Reproduction. 2022;164:F39-51.","journal-title":"Reproduction"},{"key":"2062_CR30","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1001\/jama.2014.17985","volume":"313","author":"SL Boulet","year":"2015","unstructured":"Boulet SL, Mehta A, Kissin DM, Lee W, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA - J Am Med Assoc. 2015;313:255\u201363.","journal-title":"JAMA - J Am Med Assoc"},{"key":"2062_CR31","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1007\/s10815-020-01836-0","volume":"37","author":"E Bosch","year":"2020","unstructured":"Bosch E, Espin\u00f3s JJ, Fabregues F, Fontes J, Garc\u00eda-Velasco J, Ll\u00e1cer J, et al. ALWAYS ICSI? A SWOT analysis. J Assist Reprod Genet. 2020;37:2081\u201392.","journal-title":"J Assist Reprod Genet"},{"key":"2062_CR32","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1093\/humrep\/dez245","volume":"35","author":"F Bai","year":"2020","unstructured":"Bai F, Wang DY, Fan YJ, Qiu J, Wang L, Dai Y, et al. Assisted reproductive technology service availability, efficacy and safety in mainland China: 2016. Hum Reprod. 2020;35:446\u201352.","journal-title":"Hum Reprod"},{"key":"2062_CR33","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.fertnstert.2019.03.034","volume":"112","author":"JL Narvaez","year":"2019","unstructured":"Narvaez JL, Chang J, Boulet SL, Davies MJ, Kissin DM. Trends and correlates of the sex distribution among U.S. assisted reproductive technology births. Fertil Steril. 2019;112:305\u201314.","journal-title":"Fertil Steril"},{"key":"2062_CR34","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.fertnstert.2007.07.1338","volume":"90","author":"A Maheshwari","year":"2008","unstructured":"Maheshwari A, Porter M, Shetty A, Bhattacharya S. Women\u2019s awareness and perceptions of delay in childbearing. Fertil Steril. 2008;90:1036\u201342.","journal-title":"Fertil Steril"},{"key":"2062_CR35","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s11136-017-1781-4","volume":"27","author":"MC Zurlo","year":"2018","unstructured":"Zurlo MC, Cattaneo Della Volta MF, Vallone F. Predictors of quality of life and psychological health in infertile couples: the moderating role of duration of infertility. Qual Life Res. 2018;27:945\u201354.","journal-title":"Qual Life Res"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-022-02062-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-022-02062-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-022-02062-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T02:03:27Z","timestamp":1669687407000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcwomenshealth.biomedcentral.com\/articles\/10.1186\/s12905-022-02062-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2062"],"URL":"https:\/\/doi.org\/10.1186\/s12905-022-02062-9","relation":{},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"assertion":[{"value":"8 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional research ethics review board (No. 2021002). Written informed consent was obtained from all patients before treatment, and the patients consented to the use of their retrospective data in scientific publications. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"480"}}