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W4210367691 abstract "Intracytoplasmic sperm injection (ICSI) has undeniably been a breakthrough in assisted reproductive technology (ART). However, after its discovery, it has been followed by a period of hope, which led into a great paradox: believing that a new technique that helped overcome severe male factor infertility could be a panacea for all infertile patients (Fig. 1) (1Center for Diseases Control and Prevention. ART Success Rates and Reports. Available at: https://www.cdc.gov/art/artdata/index.html. Accessed September 15, 2021.Google Scholar). It is today more than clear that, although ICSI may improve surrogate outcomes, such as the fertilization rate and fertilization failure (FF), it does not improve the reproductive outcomes. Strong evidence from randomized controlled trials (RCTs) and large population-based studies has shown similar live birth rates (LBRs) and cumulative live birth rates (CLBRs) in patients with non-male factor infertility undergoing ICSI and conventional in vitro fertilization (IVF) (2Dang V.Q. Vuong L.N. Luu T.M. Pham T.D. Ho T.M. Ha A.N. et al.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.Lancet. 2021; 397: 1554-1563Google Scholar, 3Grimstad F.W. Nangia A.K. Luke B. Stern J.E. Mak W. Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.Hum Reprod. 2016; 31: 2750-2755Google Scholar, 4Supramaniam P.R. Granne I. Ohuma E.O. Lim L.N. McVeigh E. Venkatakrishnan R. et al.ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.Hum Reprod. 2020; 35: 583-594Google Scholar, 5Schwarze J.E. Jeria R. Crosby J. Villa S. Ortega C. Pommer R. Is there a reason to perform ICSI in the absence of male factor? Lessons from the Latin American Registry of ART.Hum Reprod Open. 2017; 2017hox013Google Scholar, 6Li Z. Wang A.Y. Bowman M. Hammarberg K. Farquhar C. Johnson L. et al.ICSI does not increase the cumulative live birth rate in non-male factor infertility.Hum Reprod. 2018; 33: 1322-1330Google Scholar). Still, several clinicians believe that this should be the way forward to improve fertilization rates or prevent a total FF (Table 1) (2Dang V.Q. Vuong L.N. Luu T.M. Pham T.D. Ho T.M. Ha A.N. et al.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.Lancet. 2021; 397: 1554-1563Google Scholar, 3Grimstad F.W. Nangia A.K. Luke B. Stern J.E. Mak W. Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.Hum Reprod. 2016; 31: 2750-2755Google Scholar, 4Supramaniam P.R. Granne I. Ohuma E.O. Lim L.N. McVeigh E. Venkatakrishnan R. et al.ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.Hum Reprod. 2020; 35: 583-594Google Scholar, 5Schwarze J.E. Jeria R. Crosby J. Villa S. Ortega C. Pommer R. Is there a reason to perform ICSI in the absence of male factor? Lessons from the Latin American Registry of ART.Hum Reprod Open. 2017; 2017hox013Google Scholar, 6Li Z. Wang A.Y. Bowman M. Hammarberg K. Farquhar C. Johnson L. et al.ICSI does not increase the cumulative live birth rate in non-male factor infertility.Hum Reprod. 2018; 33: 1322-1330Google Scholar, 7Ou Y.C. Lan K.C. Huang F.J. Kung F.T. Lan T.H. Chang S.Y. Comparison of in vitro fertilization versus intracytoplasmic sperm injection in extremely low oocyte retrieval cycles.Fertil Steril. 2010; 93: 96-100Google Scholar, 8Jaroudi K. Al-Hassan S. Al-Sufayan H. Al-Mayman H. Qeba M. Coskun S. Intracytoplasmic sperm injection and conventional in vitro fertilization are complementary techniques in management of unexplained infertility.J Assist Reprod Genet. 2003; 20: 377-381Google Scholar, 9Guo N. Hua X. Li Y.F. Jin L. Role of ICSI in non-male factor cycles as the number of oocytes retrieved decreases from four to one.Curr Med Sci. 2018; 38: 131-136Google Scholar, 10Artini P.G. Obino M.E. Carletti E. Pinelli S. Ruggiero M. Di Emidio G. et al.Conventional IVF as a laboratory strategy to rescue fertility potential in severe poor responder patients: the impact of reproductive aging.Gynecol Endocrinol. 2013; 29: 997-1001Google Scholar, 11Butts S. Owen C. Mainigi M. Senapati S. Seifer D.B. Dokras A. Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011.Fertil Steril. 2014; 102: 1041-1047.e1Google Scholar, 12Drakopoulos P. Garcia-Velasco J. Bosch E. Blockeel C. de Vos M. Santos-Ribeiro S. et al.ICSI does not offer any benefit over conventional IVF across different ovarian response categories in non-male factor infertility: a European multicenter analysis.J Assist Reprod Genet. 2019; 36: 2067-2076Google Scholar, 13Gozlan I. Dor A. Farber B. Meirow D. Feinstein S. Levron J. Comparing intracytoplasmic sperm injection and in vitro fertilization in patients with single oocyte retrieval.Fertil Steril. 2007; 87: 515-518Google Scholar, 14Luna M. Bigelow C. Duke M. Ruman J. Sandler B. Grunfeld L. et al.Should ICSI be recommended routinely in patients with four or fewer oocytes retrieved?.J Assist Reprod Genet. 2011; 28: 911-915Google Scholar, 15Moreno C. Ruiz A. Simón C. Pellicer A. Remohí J. Intracytoplasmic sperm injection as a routine indication in low responder patients.Hum Reprod. 1998; 13: 2126-2129Google Scholar, 16Sfontouris I. Kolibianakis E.M. Lainas G.T. Navaratnarajah R. Tarlatzis B.C. Lainas T.G. Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved.J Assist Reprod Genet. 2015; 32: 691-697Google Scholar, 17Liu H. Zhao H. Yu G. Li M. Ma S. Zhang H. et al.Conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI): which is preferred for advanced age patients with five or fewer oocytes retrieved?.Arch Gynecol Obstet. 2018; 297: 1301-1306Google Scholar, 18Farhi J. Cohen K. Mizrachi Y. Weissman A. Raziel A. Orvieto R. Should ICSI be implemented during IVF to all advanced-age patients with non-male factor subfertility?.Reprod Biol Endocrinol. 2019; 17: 30Google Scholar, 19Tannus S. Son W.Y. Gilman A. Younes G. Shavit T. Dahan M.H. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.Hum Reprod. 2017; 32: 119-124Google Scholar, 20Gennarelli G. Carosso A. Canosa S. Filippini C. Cesarano S. Scarafia C. et al.ICSI versus conventional IVF in women aged 40 years or more and unexplained infertility: a retrospective evaluation of 685 cycles with propensity score model.J Clin Med. 2019; 8: 1694Google Scholar, 21Haas J. Miller T.E. Nahum R. Aizer A. Kirshenbaum M. Zilberberg E. et al.The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.J Assist Reprod Genet. 2021; 38: 95-100Google Scholar, 22Check J.H. Chase D.S. Horwath D. Yuan W. Garberi-Levito M.C. Press M. Oocytes from women of advanced reproductive age do not appear to have an increased risk of zona pellucida hardening.Clin Exp Obstet Gynecol. 2012; 39: 440-441Google Scholar, 23McPherson N.O. Vincent A.D. Pacella-Ince L. Tremellen K. Comparison of in vitro fertilisation/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age.J Assist Reprod Genet. 2021; 38: 669-678Google Scholar, 24Khamsi F. Yavas Y. Roberge S. Wong J.C. Lacanna I.C. 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: 342-347Google Scholar, 25Bhattacharya S. Hamilton M.P. 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: 2075-2079Google Scholar, 26Boulet S.L. Mehta A. Kissin D.M. Lee W. Kawwass J.F. Jamieson D.J. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection.J Am Med Assoc. 2015; 313: 255-263Google Scholar, 27Biliangady R. Kinila P. Pandit R. Tudu N.K. Sundhararaj U.M. Gopal I.S.T. et al.Are we justified doing routine intracytoplasmic sperm injection in nonmale factor infertility? A retrospective study comparing reproductive outcomes between in vitro fertilization and intracytoplasmic sperm injection in nonmale factor infertility.J Hum Reprod Sci. 2019; 12: 210-215Google Scholar, 28Bukulmez O. Yarali H. Yucel A. Sari T. Gurgan T. Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial.Fertil Steril. 2000; 73: 38-42Google Scholar, 29Yang D. Shahata M.A. Al-Bader M. Al-Natsha S.D. Al-Flamerzia M. Al-Shawaf T. Intracytoplasmic sperm injection improving embryo quality: comparison of the sibling oocytes of non-male-factor couples.J Assist Reprod Genet. 1996; 13: 351-355Google Scholar, 30Staessen C. Camus M. Clasen K. De Vos A. Van Steirteghem A. Conventional in-vitro fertilization versus intracytoplasmic sperm injection in sibling oocytes from couples with tubal infertility and normozoospermic semen.Hum Reprod. 1999; 14: 2474-2479Google Scholar, 31Eftekhar M. Mohammadian F. Yousefnejad F. Molaei B. Aflatoonian A. Comparison of conventional IVF versus ICSI in non-male factor, normoresponder patients.Iran J Reprod Med. 2012; 10: 131-136Google Scholar, 32Sustar K. Rozen G. Agresta F. Polyakov A. Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates.Aust N Z J Obstet Gynaecol. 2019; 59: 706-711Google Scholar, 33Aboulghar M.A. Mansour R.T. Serour G.I. Amin Y.M. Kamal A. Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters.Fertil Steril. 1996; 66: 753-756Google Scholar, 34Kim H.H. Bundorf M.K. Behr B. McCallum S.W. Use and outcomes of intracytoplasmic sperm injection for non-male factor infertility.Fertil Steril. 2007; 88: 622-628Google Scholar, 35Johnson L.N. Sasson I.E. Sammel M.D. Dokras A. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis.Fertil Steril. 2013; 100: 704-711Google Scholar, 36Hershlag A. Paine T. Kvapil G. Feng H. Napolitano B. In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure.Fertil Steril. 2002; 77: 229-232Google Scholar, 37Omland A.K. Bjercke S. Ertzeid G. Fedorcsák P. Oldereid N.B. Storeng R. et al.Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF).J Assist Reprod Genet. 2006; 23: 351-357Google Scholar, 38Foong S.C. Fleetham J.A. O’Keane J.A. Scott S.G. Tough S.C. Greene C.A. A prospective randomized trial of conventional in vitro fertilization versus intracytoplasmic sperm injection in unexplained infertility.J Assist Reprod Genet. 2006; 23: 137-140Google Scholar, 39Song J. Liao T. Fu K. Xu J. ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in unexplained infertility.Front Med. 2021; 7614118Google Scholar, 40Vitek W.S. Galárraga O. Klatsky P.C. Robins J.C. Carson S.A. Blazar A.S. Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.Fertil Steril. 2013; 100: 1381-1388Google Scholar, 41Ruiz A. Remohí J. Minguez Y. Guanes P.P. Simón C. Pellicer A. The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.Fertil Steril. 1997; 68: 171-173Google Scholar, 42Azem F. Bernholtz O. Kapustiansky R. Wagman I. Lessing J.B. Amit A. A comparison between the outcome of conventional IVF and ICSI in sibling oocytes among couples with unexplained infertility.Fertil Steril. 2004; 82: S189Google Scholar, 43Larbuisson A. Raick D. Demelenne S. Delvigne A. ICSI diagnostic: a way to prevent total fertilization failure after 4 unsuccessful IUI.Basic Clin Androl. 2017; 27: 18Google Scholar, 44Bungum L. Bungum M. Humaidan P. Andersen C.Y. A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination.Reprod Biomed Online. 2004; 8: 584-589Google Scholar, 45van 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: 612-617Google Scholar, 4Supramaniam P.R. Granne I. Ohuma E.O. Lim L.N. McVeigh E. Venkatakrishnan R. et al.ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.Hum Reprod. 2020; 35: 583-594Google Scholar). Taking into account the impact that such an approach has in our everyday clinical practice, we need to demystify some concepts that have been taken for granted in the last few years.Table 1Scientific evidence regarding indications for ICSI.Indication for ICSIClinical rationale for ICSIIn favor of ICSINo difference/in favor of IVFPoor ovarian reserveLow oocyte yield(7Ou Y.C. Lan K.C. Huang F.J. Kung F.T. Lan T.H. Chang S.Y. Comparison of in vitro fertilization versus intracytoplasmic sperm injection in extremely low oocyte retrieval cycles.Fertil Steril. 2010; 93: 96-100Google Scholar, 8Jaroudi K. Al-Hassan S. Al-Sufayan H. Al-Mayman H. Qeba M. Coskun S. Intracytoplasmic sperm injection and conventional in vitro fertilization are complementary techniques in management of unexplained infertility.J Assist Reprod Genet. 2003; 20: 377-381Google Scholar)(4Supramaniam P.R. Granne I. Ohuma E.O. Lim L.N. McVeigh E. Venkatakrishnan R. et al.ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.Hum Reprod. 2020; 35: 583-594Google Scholar, 9Guo N. Hua X. Li Y.F. Jin L. Role of ICSI in non-male factor cycles as the number of oocytes retrieved decreases from four to one.Curr Med Sci. 2018; 38: 131-136Google Scholar, 10Artini P.G. Obino M.E. Carletti E. Pinelli S. Ruggiero M. Di Emidio G. et al.Conventional IVF as a laboratory strategy to rescue fertility potential in severe poor responder patients: the impact of reproductive aging.Gynecol Endocrinol. 2013; 29: 997-1001Google Scholar, 11Butts S. Owen C. Mainigi M. Senapati S. Seifer D.B. Dokras A. Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011.Fertil Steril. 2014; 102: 1041-1047.e1Google Scholar, 12Drakopoulos P. Garcia-Velasco J. Bosch E. Blockeel C. de Vos M. Santos-Ribeiro S. et al.ICSI does not offer any benefit over conventional IVF across different ovarian response categories in non-male factor infertility: a European multicenter analysis.J Assist Reprod Genet. 2019; 36: 2067-2076Google Scholar, 13Gozlan I. Dor A. Farber B. Meirow D. Feinstein S. Levron J. Comparing intracytoplasmic sperm injection and in vitro fertilization in patients with single oocyte retrieval.Fertil Steril. 2007; 87: 515-518Google Scholar, 14Luna M. Bigelow C. Duke M. Ruman J. Sandler B. Grunfeld L. et al.Should ICSI be recommended routinely in patients with four or fewer oocytes retrieved?.J Assist Reprod Genet. 2011; 28: 911-915Google Scholar, 15Moreno C. Ruiz A. Simón C. Pellicer A. Remohí J. Intracytoplasmic sperm injection as a routine indication in low responder patients.Hum Reprod. 1998; 13: 2126-2129Google Scholar, 16Sfontouris I. Kolibianakis E.M. Lainas G.T. Navaratnarajah R. Tarlatzis B.C. Lainas T.G. Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved.J Assist Reprod Genet. 2015; 32: 691-697Google Scholar, 17Liu H. Zhao H. Yu G. Li M. Ma S. Zhang H. et al.Conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI): which is preferred for advanced age patients with five or fewer oocytes retrieved?.Arch Gynecol Obstet. 2018; 297: 1301-1306Google Scholar)Advanced maternal ageAge-related decline in oocyte quality(18Farhi J. Cohen K. Mizrachi Y. Weissman A. Raziel A. Orvieto R. Should ICSI be implemented during IVF to all advanced-age patients with non-male factor subfertility?.Reprod Biol Endocrinol. 2019; 17: 30Google Scholar)(10Artini P.G. Obino M.E. Carletti E. Pinelli S. Ruggiero M. Di Emidio G. et al.Conventional IVF as a laboratory strategy to rescue fertility potential in severe poor responder patients: the impact of reproductive aging.Gynecol Endocrinol. 2013; 29: 997-1001Google Scholar, 16Sfontouris I. Kolibianakis E.M. Lainas G.T. Navaratnarajah R. Tarlatzis B.C. Lainas T.G. Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved.J Assist Reprod Genet. 2015; 32: 691-697Google Scholar, 17Liu H. Zhao H. Yu G. Li M. Ma S. Zhang H. et al.Conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI): which is preferred for advanced age patients with five or fewer oocytes retrieved?.Arch Gynecol Obstet. 2018; 297: 1301-1306Google Scholar, 19Tannus S. Son W.Y. Gilman A. Younes G. Shavit T. Dahan M.H. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.Hum Reprod. 2017; 32: 119-124Google Scholar, 20Gennarelli G. Carosso A. Canosa S. Filippini C. Cesarano S. Scarafia C. et al.ICSI versus conventional IVF in women aged 40 years or more and unexplained infertility: a retrospective evaluation of 685 cycles with propensity score model.J Clin Med. 2019; 8: 1694Google Scholar, 21Haas J. Miller T.E. Nahum R. Aizer A. Kirshenbaum M. Zilberberg E. et al.The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.J Assist Reprod Genet. 2021; 38: 95-100Google Scholar, 22Check J.H. Chase D.S. Horwath D. Yuan W. Garberi-Levito M.C. Press M. Oocytes from women of advanced reproductive age do not appear to have an increased risk of zona pellucida hardening.Clin Exp Obstet Gynecol. 2012; 39: 440-441Google Scholar, 23McPherson N.O. Vincent A.D. Pacella-Ince L. Tremellen K. Comparison of in vitro fertilisation/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age.J Assist Reprod Genet. 2021; 38: 669-678Google Scholar)General non-male factor infertilityUnknown fertilization factors or occult male factor(24Khamsi F. Yavas Y. Roberge S. Wong J.C. Lacanna I.C. 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: 342-347Google Scholar)(2Dang V.Q. Vuong L.N. Luu T.M. Pham T.D. Ho T.M. Ha A.N. et al.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.Lancet. 2021; 397: 1554-1563Google Scholar, 3Grimstad F.W. Nangia A.K. Luke B. Stern J.E. Mak W. Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.Hum Reprod. 2016; 31: 2750-2755Google Scholar, 4Supramaniam P.R. Granne I. Ohuma E.O. Lim L.N. McVeigh E. Venkatakrishnan R. et al.ICSI does not improve reproductive outcomes in autologous ovarian response cycles with non-male factor subfertility.Hum Reprod. 2020; 35: 583-594Google Scholar, 5Schwarze J.E. Jeria R. Crosby J. Villa S. Ortega C. Pommer R. Is there a reason to perform ICSI in the absence of male factor? Lessons from the Latin American Registry of ART.Hum Reprod Open. 2017; 2017hox013Google Scholar, 6Li Z. Wang A.Y. Bowman M. Hammarberg K. Farquhar C. Johnson L. et al.ICSI does not increase the cumulative live birth rate in non-male factor infertility.Hum Reprod. 2018; 33: 1322-1330Google Scholar, 12Drakopoulos P. Garcia-Velasco J. Bosch E. Blockeel C. de Vos M. Santos-Ribeiro S. et al.ICSI does not offer any benefit over conventional IVF across different ovarian response categories in non-male factor infertility: a European multicenter analysis.J Assist Reprod Genet. 2019; 36: 2067-2076Google Scholar, 25Bhattacharya S. Hamilton M.P. 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: 2075-2079Google Scholar, 26Boulet S.L. Mehta A. Kissin D.M. Lee W. Kawwass J.F. Jamieson D.J. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection.J Am Med Assoc. 2015; 313: 255-263Google Scholar, 27Biliangady R. Kinila P. Pandit R. Tudu N.K. Sundhararaj U.M. Gopal I.S.T. et al.Are we justified doing routine intracytoplasmic sperm injection in nonmale factor infertility? A retrospective study comparing reproductive outcomes between in vitro fertilization and intracytoplasmic sperm injection in nonmale factor infertility.J Hum Reprod Sci. 2019; 12: 210-215Google Scholar, 28Bukulmez O. Yarali H. Yucel A. Sari T. Gurgan T. Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial.Fertil Steril. 2000; 73: 38-42Google Scholar, 29Yang D. Shahata M.A. Al-Bader M. Al-Natsha S.D. Al-Flamerzia M. Al-Shawaf T. Intracytoplasmic sperm injection improving embryo quality: comparison of the sibling oocytes of non-male-factor couples.J Assist Reprod Genet. 1996; 13: 351-355Google Scholar, 30Staessen C. Camus M. Clasen K. De Vos A. Van Steirteghem A. Conventional in-vitro fertilization versus intracytoplasmic sperm injection in sibling oocytes from couples with tubal infertility and normozoospermic semen.Hum Reprod. 1999; 14: 2474-2479Google Scholar, 31Eftekhar M. Mohammadian F. Yousefnejad F. Molaei B. Aflatoonian A. Comparison of conventional IVF versus ICSI in non-male factor, normoresponder patients.Iran J Reprod Med. 2012; 10: 131-136Google Scholar, 32Sustar K. Rozen G. Agresta F. Polyakov A. Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates.Aust N Z J Obstet Gynaecol. 2019; 59: 706-711Google Scholar, 33Aboulghar M.A. Mansour R.T. Serour G.I. Amin Y.M. Kamal A. Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters.Fertil Steril. 1996; 66: 753-756Google Scholar, 34Kim H.H. Bundorf M.K. Behr B. McCallum S.W. Use and outcomes of intracytoplasmic sperm injection for non-male factor infertility.Fertil Steril. 2007; 88: 622-628Google Scholar)Unexplained infertilityUnknown fertilization factors or occult male factor(8Jaroudi K. Al-Hassan S. Al-Sufayan H. Al-Mayman H. Qeba M. Coskun S. Intracytoplasmic sperm injection and conventional in vitro fertilization are complementary techniques in management of unexplained infertility.J Assist Reprod Genet. 2003; 20: 377-381Google Scholar, 35Johnson L.N. Sasson I.E. Sammel M.D. Dokras A. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis.Fertil Steril. 2013; 100: 704-711Google Scholar, 36Hershlag A. Paine T. Kvapil G. Feng H. Napolitano B. In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure.Fertil Steril. 2002; 77: 229-232Google Scholar, 37Omland A.K. Bjercke S. Ertzeid G. Fedorcsák P. Oldereid N.B. Storeng R. et al.Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF).J Assist Reprod Genet. 2006; 23: 351-357Google Scholar)(6Li Z. Wang A.Y. Bowman M. Hammarberg K. Farquhar C. Johnson L. et al.ICSI does not increase the cumulative live birth rate in non-male factor infertility.Hum Reprod. 2018; 33: 1322-1330Google Scholar, 38Foong S.C. Fleetham J.A. O’Keane J.A. Scott S.G. Tough S.C. Greene C.A. A prospective randomized trial of conventional in vitro fertilization versus intracytoplasmic sperm injection in unexplained infertility.J Assist Reprod Genet. 2006; 23: 137-140Google Scholar, 39Song J. Liao T. Fu K. Xu J. ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in unexplained infertility.Front Med. 2021; 7614118Google Scholar, 40Vitek W.S. Galárraga O. Klatsky P.C. Robins J.C. Carson S.A. Blazar A.S. Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.Fertil Steril. 2013; 100: 1381-1388Google Scholar, 41Ruiz A. Remohí J. Minguez Y. Guanes P.P. Simón C. Pellicer A. The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.Fertil Steril. 1997; 68: 171-173Google Scholar, 42Azem F. Bernholtz O. Kapustiansky R. Wagman I. Lessing J.B. Amit A. A comparison between the outcome of conventional IVF and ICSI in sibling oocytes among couples with unexplained infertility.Fertil Steril. 2004; 82: S189Google Scholar)Failed previous attempts Failed IUIsUnknown fertilization factors or unknown male factor(43Larbuisson A. Raick D. Demelenne S. Delvigne A. ICSI diagnostic: a way to prevent total fertilization failure after 4 unsuccessful IUI.Basic Clin Androl. 2017; 27: 18Google Scholar, 44Bungum L. Bungum M. Humaidan P. Andersen C.Y. A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination.Reprod Biomed Online. 2004; 8: 584-589Google Scholar)(38Foong S.C. Fleetham J.A. O’Keane J.A. Scott S.G. Tough S.C. Greene C.A. A prospective randomized trial of conventional in vitro fertilization versus intracytoplasmic sperm injection in unexplained infertility.J Assist Reprod Genet. 2006; 23: 137-140Google Scholar, 41Ruiz A. Remohí J. Minguez Y. Guanes P.P. Simón C. Pellicer A. The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.Fertil Steril. 1997; 68: 171-173Google Scholar) Failed conventional IVFUnknown fertilization factors or unknown male factor(45van 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: 612-617Google Scholar, 37Omland A.K. Bjercke S. Ertzeid G. Fedorcsák P. Oldereid N.B. Storeng R. et al.Intracytoplasmic sperm injection (ICSI) in unexplained and stage I endometriosis-associated infertility after fertilization failure with in vitro fertilization (IVF).J Assist Reprod Genet. 2006; 23: 351-357Google Scholar)(36Hershlag A. Paine T. Kvapil G. Feng H. Napolitano B. 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W4210367691 title "Intracytoplasmic sperm injection for all or for a few?" @default.
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