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The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis

2010; Elsevier BV; Volume: 95; Issue: 3 Linguagem: Inglês

10.1016/j.fertnstert.2010.09.029

1556-5653

James M. Hotaling, James F. Smith, Mitchell P. Rosen, Charles Müller, Thomas J. Walsh,

Assisted Reproductive Technology and Twin Pregnancy

We conducted a systematic review and meta-analysis of data from the literature from the years 1986 to 2009 using teratozoospermia and fertilization or IVF or in vitro fertilization as the keywords. A total of 31 studies were identified, and 4 met the inclusion criteria. Isolated teratozoospermia was not associated with a statistically significantly decreased probability of pregnancy with assisted reproduction. We conducted a systematic review and meta-analysis of data from the literature from the years 1986 to 2009 using teratozoospermia and fertilization or IVF or in vitro fertilization as the keywords. A total of 31 studies were identified, and 4 met the inclusion criteria. Isolated teratozoospermia was not associated with a statistically significantly decreased probability of pregnancy with assisted reproduction. Infertility is a common problem affecting 10% to 15% of couples. Of these, 20% have pure male factor infertility (1Spira A. Epidemiology of human reproduction.Hum Reprod. 1986; 1: 111-115PubMed Google Scholar, 2Velez de la Calle J.F. Rachou E. le Martelot M.T. Ducot B. Multigner L. Thonneau P.F. Male infertility risk factors in a French military population.Hum Reprod. 2001; 16: 481-486Crossref PubMed Scopus (29) Google Scholar). In 1986, Kruger et al. (3Kruger T.F. Menkveld R. Stander F.S. Lombard C.J. Van der Merwe J.P. van Zyl J.A. et al.Sperm morphologic features as a prognostic factor in in vitro fertilization.Fertil Steril. 1986; 46: 1118-1123Crossref PubMed Scopus (1067) Google Scholar) published a novel classification to analyze sperm morphology and correlate it with the likelihood of in vitro fertilization (IVF) success in terms of both increased rate of fertilization and clinical pregnancy. In that study, isolated severe teratozoospermia was defined as less than 5% normal morphologic forms with all other semen parameters being normal in the absence of other male or female factors. Subsequent studies have refined and modified this system, leading to the strict Tygerberg criteria, which has demonstrated markedly lower IVF success with severe (<5% normal forms) teratozoospermia (4Kruger T.F. Acosta A.A. Simmons K.F. Swanson R.J. Matta J.F. Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization.Fertil Steril. 1988; 49: 112-117Crossref PubMed Scopus (1033) Google Scholar, 5Menkveld R. Wong W.Y. Lombard C.J. Wetzels A.M. Thomas C.M. Merkus H.M. et al.Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in-vivo thresholds.Hum Reprod. 2001; 16: 1165-1171Crossref PubMed Scopus (195) Google Scholar, 6World Health Organisation Laboratory manual for examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, Cambridge, U.K.1999Google Scholar). Roughly 4% of infertile men have isolated teratozoospermia as defined by Tygerberg strict criteria (<5% normal forms) (4Kruger T.F. Acosta A.A. Simmons K.F. Swanson R.J. Matta J.F. Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization.Fertil Steril. 1988; 49: 112-117Crossref PubMed Scopus (1033) Google Scholar). Since the Kruger group's original description, there has been an increase in the prevalence of teratozoospermia, likely due to changes in the methods used to assess morphology whereby only "ideal" or perfectly formed sperm are counted as normal (5Menkveld R. Wong W.Y. Lombard C.J. Wetzels A.M. Thomas C.M. Merkus H.M. et al.Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in-vivo thresholds.Hum Reprod. 2001; 16: 1165-1171Crossref PubMed Scopus (195) Google Scholar). The impact of isolated teratozoospermia is inconclusive: studies have shown both improved (7Figueiredo H. Tavares A. Ferras L. Couceiro A. Chaves I. Isolated teratozoospermia and in vitro fertilization.J Assist Reprod Genet. 1996; 13: 64-68Crossref PubMed Scopus (11) Google Scholar) and worsened (8Grow D.R. Oehninger S. Seltman H.J. Toner J.P. Swanson R.J. Kruger T.F. et al.Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population.Fertil Steril. 1994; 62: 559-567Abstract Full Text PDF PubMed Scopus (169) Google Scholar, 9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 10Terriou P. Giorgetti C. Auquier P. Hans E. Spach J.L. Salzmann J. et al.Teratozoospermia influences fertilization rate in vitro but not embryo quality.Hum Reprod. 1997; 12: 1069-1072Crossref PubMed Scopus (24) Google Scholar, 11Ombelet W. Fourie F.L. Vandeput H. Bosmans E. Cox A. Janssen M. et al.Teratozoospermia and in-vitro fertilization: a randomized prospective study.Hum Reprod. 1994; 9: 1479-1484PubMed Google Scholar) assisted reproductive technology (ART) fertilization and/or pregnancy rates with IVF. Given the potential compromise on fertilization in vitro and possibly pregnancy, some investigators have suggested that all men with this finding undergo intracytoplasmic sperm injection (ICSI) (12McKenzie L.J. Kovanci E. Amato P. Cisneros P. Lamb D. Carson S.A. Pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection with profound teratospermia.Fertil Steril. 2004; 82: 847-849Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). Five studies have demonstrated improved outcomes by use of ICSI in men with teratozoospermia (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 13Kihaile P.E. Misumi J. Hirotsuru K. Kumasako Y. Kisanga R.E. Utsunomiya T. Comparison of sibling oocyte outcomes after intracytoplasmic sperm injection and in vitro fertilization in severe teratozoospermic patients in the first cycle.Int J Androl. 2003; 26: 57-62Crossref PubMed Scopus (34) Google Scholar, 14Pisarska M.D. Casson P.R. Cisneros P.L. Lamb D.J. Lipshultz L.I. Buster J.E. et al.Fertilization after standard in vitro fertilization versus intracytoplasmic sperm injection in subfertile males using sibling oocytes.Fertil Steril. 1999; 71: 627-632Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar, 16Obara H. Shibahara H. Tsunoda H. Taneichi A. Fujiwara H. Takamizawa S. et al.Prediction of unexpectedly poor fertilization and pregnancy outcome using the strict criteria for sperm morphology before and after sperm separation in IVF-ET.Int J Androl. 2001; 24: 102-108Crossref PubMed Scopus (31) Google Scholar); however, many of these studies included men with abnormal semen parameters in addition to the teratozoospermia. Three studies have demonstrated equivocal results with ICSI (12McKenzie L.J. Kovanci E. Amato P. Cisneros P. Lamb D. Carson S.A. Pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection with profound teratospermia.Fertil Steril. 2004; 82: 847-849Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 17Mansour R.T. Aboulghar M.A. Serour G.I. Amin Y.M. Ramzi A.M. The effect of sperm parameters on the outcome of intracytoplasmic sperm injection.Fertil Steril. 1995; 64: 982-986Abstract Full Text PDF PubMed Scopus (115) Google Scholar, 18Oehninger S. Kruger T.F. Simon T. Jones D. Mayer J. Lanzendorf S. et al.A comparative analysis of embryo implantation potential in patients with severe teratozoospermia undergoing in-vitro fertilization with a high insemination concentration or intracytoplasmic sperm injection.Hum Reprod. 1996; 11: 1086-1089Crossref PubMed Scopus (66) Google Scholar). As a result of these variable results, there is no consensus on whether ICSI should be recommended for men with isolated severe teratozoospermia. To consolidate the information on this topic, we performed a systematic review and meta-analysis of all available English-language literature pertaining to the impact of isolated severe teratozoospermia on ART outcomes. Our goal was to determine if isolated severe teratozoospermia was associated with clinical pregnancy after IVF with or without ICSI. A systematic review and meta-analysis were conducted based on the guidelines published by the Meta-Analysis of Observational Studies Epidemiology group (19Stroup D.F. Berlin J.A. Morton S.C. Olkin I. Williamson G.D. Rennie D. et al.Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012Crossref PubMed Scopus (15106) Google Scholar). All literature pertaining to teratozoospermia and IVF or ICSI was retrieved by searching MEDLINE (1966–2009), BIOSIS (1969–2006), EMBASE (1947–2009), and the Cochrane Library with sperm morphology and teratozoospermia as the key words in combination with ART, fertilization, in vitro fertilization, IVF, or ICSI. Literature searches were performed by two urologists trained in epidemiology (TJW and JMH) with the assistance of two certified medical librarians. Studies that did not provide risk estimates based on comparison with a control group were excluded. The studies included for meta-analysis were reviewed and mutually agreed upon by three authors (TJW, JMH, and JFS). The literature was then further reviewed by one investigator (CHM) for methodologic variation in the assessment of sperm morphology. For the data extraction and meta-analysis, we defined exposure as isolated severe teratozoospermia by Tygerberg criteria (<5% normal forms) without any other semen abnormalities (20Sigman M. Jarow J.P. Male infertility.in: Wein A.J. Kavoussi L.R. Novick A.C. Partin A.W. Peters C.A. Campbell-Walsh urology, vol. 1. Saunders Elsevier, Philadelphia2007: 609-653Google Scholar). All of the studies included in the meta-analysis used this criteria except for one: Kihaile et al. (13Kihaile P.E. Misumi J. Hirotsuru K. Kumasako Y. Kisanga R.E. Utsunomiya T. Comparison of sibling oocyte outcomes after intracytoplasmic sperm injection and in vitro fertilization in severe teratozoospermic patients in the first cycle.Int J Androl. 2003; 26: 57-62Crossref PubMed Scopus (34) Google Scholar) used <4% normal forms. Only studies that gave descriptive statistics of men with severe teratozoospermia compared with a control group were used for analysis. All of the studies chosen for final analysis provided descriptive statistics that showed no significant difference in the male and female demographics in the teratozoospermic group compared with the controls, and that controlled for female factors (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar, 21Dubey A. Dayal M.B. Frankfurter D. Balazy P. Peak D. Gindoff P.R. The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome.Fertil Steril. 2008; 89: 1665-1669Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 22Keegan B.R. Barton S. Sanchez X. Berkeley A.S. Krey L.C. Grifo J. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection.Fertil Steril. 2007; 88: 1583-1588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar). All the studies took steps to verify sperm morphology by averaging the results from two different technologists (22Keegan B.R. Barton S. Sanchez X. Berkeley A.S. Krey L.C. Grifo J. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection.Fertil Steril. 2007; 88: 1583-1588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar), providing a table or text listing the morphologic abnormalities seen (15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar, 21Dubey A. Dayal M.B. Frankfurter D. Balazy P. Peak D. Gindoff P.R. The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome.Fertil Steril. 2008; 89: 1665-1669Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar) or verifying the morphologic results from a Dr. Kruger–trained technician by control slides (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar). The outcome of interest was clinical pregnancy, defined by fetal heartbeat per number of cycles of IVF or ICSI. Relevant success rates were reverse calculated from existing data where necessary. Summary risk measures and 95% confidence intervals (CI) were calculated by use of a random effects model. Three separate analyses were performed: [1] combined IVF/ICSI: all IVF alone and IVF with ICSI cycles; [2] IVF: IVF cycles without ICSI; and [3] ICSI: IVF with ICSI. Statistical analysis was performed using STATA 10 (StataCorp LP, College Station, TX). We searched MEDLINE, BIOSIS, EMBASE, and the Cochrane Library using Medical SubHeading and keywords to identify all literature pertaining to teratozoospermia and outcomes with IVF/ICSI from 1986 to 2009 (3Kruger T.F. Menkveld R. Stander F.S. Lombard C.J. Van der Merwe J.P. van Zyl J.A. et al.Sperm morphologic features as a prognostic factor in in vitro fertilization.Fertil Steril. 1986; 46: 1118-1123Crossref PubMed Scopus (1067) Google Scholar). The initial search yielded 40 citations, of which 16 were not published in English and a translation of the title and/or abstract demonstrated that they were not relevant. A preliminary screen of the remaining 24 abstracts excluded another 12 that were either not related to IVF/ICSI outcomes of men with severe teratozoospermia or did not have an appropriate control group for analysis. The bibliographies of the remaining 12 articles did not yield any additional studies for review. Review of these 12 studies excluded 8 for lack of exposure and outcome measures that conformed to our criteria. The four remaining studies contained specific data comparing severe teratozoospermia outcomes with controls and measuring IVF/ICSI outcomes in terms of pregnancies achieved per number of cycles. These four studies were included for review and meta-analysis. Four retrospective cohort studies met our criteria. These studies included 2,853 IVF/ICSI cycles with 673 men with severe teratozoospermia and 2,183 men without severe teratozoospermia. All studies primarily analyzed the impact of severe teratozoospermia on IVF/ICSI outcomes with subanalyses based on the degree of teratozoospermia. One of the four studies used IVF only; three used IVF/ICSI and had subanalyses for both. Two studies concluded that there was no difference for IVF/ICSI outcomes for severely teratozoospermic men (15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar, 22Keegan B.R. Barton S. Sanchez X. Berkeley A.S. Krey L.C. Grifo J. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection.Fertil Steril. 2007; 88: 1583-1588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar). Osawa et al. (15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar) concluded that the clinical pregnancy rate was not altered by the presence of teratospermia when IVF/ICSI was used (odds ratio [OR] 1.01; 95% CI, 0.57–1.80). Likewise, Keegan et al. (22Keegan B.R. Barton S. Sanchez X. Berkeley A.S. Krey L.C. Grifo J. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection.Fertil Steril. 2007; 88: 1583-1588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar) concluded that teratospermia did not impact clinical pregnancy with IVF/ICSI (OR 1.01; 95% CI, 0.71–1.43). Two studies showed a statistically significantly worse outcome for these men (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 21Dubey A. Dayal M.B. Frankfurter D. Balazy P. Peak D. Gindoff P.R. The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome.Fertil Steril. 2008; 89: 1665-1669Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar). Dubey et al. (21Dubey A. Dayal M.B. Frankfurter D. Balazy P. Peak D. Gindoff P.R. The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome.Fertil Steril. 2008; 89: 1665-1669Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar) concluded that among couples undergoing IVF (without ICSI), men with normal sperm were much more likely to achieve a clinical pregnancy rate per cycle than those with teratozoospermia (OR 3.19; 95% CI, 1.1–9.0) (21Dubey A. Dayal M.B. Frankfurter D. Balazy P. Peak D. Gindoff P.R. The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome.Fertil Steril. 2008; 89: 1665-1669Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar). In a subanalysis of couples undergoing IVF-ICSI, Lundin et al. (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar) reported a more than threefold higher risk of poor outcome in cases of severe teratozoospermia compared with normal sperm (OR 3.36; 95% CI, 1.53–7.40). Data were extracted from all four studies based on our a priori definitions of exposure and outcome. Overall the meta-analysis revealed that teratozoospermia is not associated with clinical pregnancy success in cases of IVF with or without ICSI, in grouped or subset analyses, regardless of modality used (Fig. 1).Figure 1Forest plots of summary risk estimates. (A) IVF/ICSI combined: isolated teratozoospermia and all IVF/ICSI outcomes. Vertical line at 1 indicates the null hypothesis of no impact of teratozoospermia on IVF/ICSI clinical pregnancy. Size of the grey box around each odds ratio (OR) (black dot) reflects the magnitude of each study's individual contribution to the overall meta-analysis (represented by the diamond shape at the bottom). Black lines through the grey boxes show the limits of the 95% confidence intervals (95% CI) for each OR. (B) IVF: isolated teratozoospermia and IVF outcomes. (C) ICSI: isolated teratozoospermia and ICSI outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Summary risk estimates suggested that men with severe teratozoospermia were not less likely to cause a clinical pregnancy compared with nonteratozoospermic controls: IVF/ICSI had an OR 1.18 (95% CI, 0.83–1.67) of a successful pregnancy outcome per cycle; IVF had an OR 1.04 (95% CI, 0.90–1.21); and ICSI had an OR 0.95 (95% CI, 0.63–1.42). The IVF analysis group showed a more consistent trend toward no effect of severe teratozoospermia on outcomes: the highest-powered studies by Keegan et al. (22Keegan B.R. Barton S. Sanchez X. Berkeley A.S. Krey L.C. Grifo J. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection.Fertil Steril. 2007; 88: 1583-1588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar) and Cohen et al. (23Cohen J. Edwards R.G. Fehilly C.B. Fishel S.B. Hewitt J. Rowland G. et al.Treatment of male infertility by in vitro fertilization: factors affecting fertilization and pregnancy.Acta Eur Fertil. 1984; 15: 455-465PubMed Google Scholar) had a relative risk of approximately 1 (Fig. 1A–C). The ICSI analysis group demonstrated marked heterogeneity, with a relative risk from 0.40 to 3.36 (15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar). Our meta-analysis of the existing literature demonstrated that isolated teratozoospermia was not associated with decreased clinical pregnancy rates with IVF with or without ICSI. All of our summary risk estimates for outcomes of IVF/ICSI in the setting of teratozoospermia ranged from OR 0.95–1.03 and all 95% CIs crossed one. This conclusion challenges the previously held perception that sperm morphology is an important semen parameter for predicting fertilization success and clinical pregnancy in IVF (7Figueiredo H. Tavares A. Ferras L. Couceiro A. Chaves I. Isolated teratozoospermia and in vitro fertilization.J Assist Reprod Genet. 1996; 13: 64-68Crossref PubMed Scopus (11) Google Scholar). Despite the assertion that sperm morphology is an important predictor of pregnancy after IVF, previous studies have not definitively shown that teratozoospermia worsens the odds of pregnancy after IVF (10Terriou P. Giorgetti C. Auquier P. Hans E. Spach J.L. Salzmann J. et al.Teratozoospermia influences fertilization rate in vitro but not embryo quality.Hum Reprod. 1997; 12: 1069-1072Crossref PubMed Scopus (24) Google Scholar, 11Ombelet W. Fourie F.L. Vandeput H. Bosmans E. Cox A. Janssen M. et al.Teratozoospermia and in-vitro fertilization: a randomized prospective study.Hum Reprod. 1994; 9: 1479-1484PubMed Google Scholar). Variable results in the literature likely stem from interlaboratory and intralaboratory techniques in assessing sperm morphologies as well as disparity in how teratozoospermia is defined (Tygerberg <5% vs. WHO <15%) (2Velez de la Calle J.F. Rachou E. le Martelot M.T. Ducot B. Multigner L. Thonneau P.F. Male infertility risk factors in a French military population.Hum Reprod. 2001; 16: 481-486Crossref PubMed Scopus (29) Google Scholar, 6World Health Organisation Laboratory manual for examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, Cambridge, U.K.1999Google Scholar, 13Kihaile P.E. Misumi J. Hirotsuru K. Kumasako Y. Kisanga R.E. Utsunomiya T. Comparison of sibling oocyte outcomes after intracytoplasmic sperm injection and in vitro fertilization in severe teratozoospermic patients in the first cycle.Int J Androl. 2003; 26: 57-62Crossref PubMed Scopus (34) Google Scholar) and differences in how individual technologists classify sperm morphology, all of which have been shown to have an impact on morphology assessment (14Pisarska M.D. Casson P.R. Cisneros P.L. Lamb D.J. Lipshultz L.I. Buster J.E. et al.Fertilization after standard in vitro fertilization versus intracytoplasmic sperm injection in subfertile males using sibling oocytes.Fertil Steril. 1999; 71: 627-632Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar). For patients with previous IVF failure and in those with extremely impaired semen parameters, ICSI has resulted in successful fertilization (6World Health Organisation Laboratory manual for examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, Cambridge, U.K.1999Google Scholar). Previously, it had been thought that sperm morphology had a greater impact on ICSI clinical pregnancy outcomes than other parameters such as concentration and motility (9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar). There is no clear consensus in the literature as to whether ICSI improves outcomes in the setting of teratozoospermia (6World Health Organisation Laboratory manual for examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, Cambridge, U.K.1999Google Scholar, 7Figueiredo H. Tavares A. Ferras L. Couceiro A. Chaves I. Isolated teratozoospermia and in vitro fertilization.J Assist Reprod Genet. 1996; 13: 64-68Crossref PubMed Scopus (11) Google Scholar, 9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 10Terriou P. Giorgetti C. Auquier P. Hans E. Spach J.L. Salzmann J. et al.Teratozoospermia influences fertilization rate in vitro but not embryo quality.Hum Reprod. 1997; 12: 1069-1072Crossref PubMed Scopus (24) Google Scholar). Intracytoplasmic sperm injection is inherently difficult to study as even though a patient's overall population of sperm may be teratozoospermic, only the single sperm and oocyte selected by the technician defines the ICSI outcome, and many of the other abnormalities are likely bypassed. This introduces a large bias toward favorable outcomes with ICSI. Heterogeneity also exists with how a successful IVF/ICSI outcome is defined. Previous studies have defined pregnancy as a positive human chorionic gonadotropin level, a fetal heartbeat, or a delivery (6World Health Organisation Laboratory manual for examination of human semen and sperm-cervical mucus interaction.4th ed. Cambridge University Press, Cambridge, U.K.1999Google Scholar, 7Figueiredo H. Tavares A. Ferras L. Couceiro A. Chaves I. Isolated teratozoospermia and in vitro fertilization.J Assist Reprod Genet. 1996; 13: 64-68Crossref PubMed Scopus (11) Google Scholar, 9Lundin K. Soderlund B. Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.Hum Reprod. 1997; 12: 2676-2681Crossref PubMed Scopus (76) Google Scholar, 10Terriou P. Giorgetti C. Auquier P. Hans E. Spach J.L. Salzmann J. et al.Teratozoospermia influences fertilization rate in vitro but not embryo quality.Hum Reprod. 1997; 12: 1069-1072Crossref PubMed Scopus (24) Google Scholar). These outcomes have also been tabulated per embryo transfer and per cycle of IVF/ICSI, which has made comparison between studies very difficult. By using strict inclusion criteria and having rigidly defined outcomes such as clinical pregnancy defined by fetal heartbeat, we have attempted to remove some of the bias that has made analyzing previous work on this topic difficult. However, we cannot account for variations in the patient populations from these studies, variations in IVF or ICSI technique, and disparities in how sperm morphology was assessed. Further, we have analyzed only teratozoospermia and cannot comment on previous studies that have suggested that a combination of abnormal semen parameters along with teratozoospermia is prognostic in vitro and in vivo (15Osawa Y. Sueoka K. Iwata S. Shinohara M. Kobayashi N. Kuji N. et al.Assessment of the dominant abnormal form is useful for predicting the outcome of intracytoplasmic sperm injection in the case of severe teratozoospermia.J Assist Reprod Genet. 1999; 16: 436-442Crossref PubMed Scopus (32) Google Scholar, 24Guzick D.S. Overstreet J.W. Factor-Litvak P. Brazil C.K. Nakajima S.T. Coutifaris C. et al.Sperm morphology, motility, and concentration in fertile and infertile men.N Engl J Med. 2001; 345: 1388-1393Crossref PubMed Scopus (917) Google Scholar, 25van der Merwe F.H. Kruger T.F. Oehninger S.C. Lombard C.J. The use of semen parameters to identify the subfertile male in the general population.Gynecol Obstet Invest. 2005; 59: 86-91Crossref PubMed Scopus (69) Google Scholar). It is important that our study assesses the key outcome for couples undergoing IVF/ICSI: pregnancy. A key limitation is that our work does not assess the impact of sperm morphology on fertilization success but instead relies on the downstream clinical end point of the ART cycle. We cannot dismiss the idea that teratozoospermia may not impact fertilization success in the same way it impacts clinical pregnancy. Thus, this study is not inconsistent with prior studies that indicated decreased fertilization success in the setting of teratozoospermia. Our study has important implications for counseling teratozoospermic men, and further research is required to elucidate the predictors of ART success.