Recommendations for Human Sperm Morphology Assessment in 2025: An Expert Review From the French BLEFCO Group

No genetic mutation has been identified in patients with <50% globozoospermia.

“No genetic mutation has been identified in patients with < 50% globozoospermia [29].”

• cites [29] T. Celse, C. Cazin, F. Mietton, et al., “ Genetic Analyses of a Large Cohort of Infertile Patients With Globozoospermia, DPY19L2 Still the Main Actor, GGN Confirmed as a Guest Player,” Human Genetics 140, no. 1 (2021): 43– 57, https://doi.org10.1007/s00439‐020‐02229‐0 33108537 sourcePartly supported

  The Diagnostic performances section reports no positive DPY19L2 diagnosis among the study’s patients with less than 50% globozoospermia. The claim omits those limits: the finding concerns DPY19L2 screening in this cohort, not an absence of any genetic mutation in all such patients. (LLM, conf=0.87)

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In this cohort, 86.8% of fertile men carry head abnormalities.

“In this cohort, we can also see the low predictivity of head abnormalities because 86.8% of these fertile men carry them [10, 22].”

• cites [10] L. Cheng, D. Miller, A. Wecht, D. Pelzman, and K. Hwang, “ The Questionable Clinical Utility of Sperm Morphology: Rate of Isolated Teratospermia in a Population of Fertile Men,” Journal of Sexual Medicine 21 (2024): qdae002.189, 10.1093/jsxmed/qdae002.189 PMC11228780 38983740 sourcePartly supported

  The Results (page unavailable) identify head-shape defects as the most common abnormality in this fertile cohort, but report 59 men (84.3%), not 86.8%. The claimed 86.8% can be calculated from 59 divided by the 68 men reported to have complete morphology assessments, so the source's counts support that figure even though its printed percentage differs. (LLM, conf=0.86)

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• cites [22] Corrigendum to ‘High Rate of Isolated Teratospermia in a Population of Fertile Men and the Questionable Clinical Utility of Sperm Morphology’ [F&S Reports 5 (2024) 140‐144]. F S Rep 2025; 6(1): 101. https://doi.org10.1016/j.xfre.2024.11.005 40201105 PMC11973682 sourceCould not verify

  The corrigendum’s Abstract and corrected Table 2 report normal morphology for 30 of 68 men (44.1%), but give no rate of head abnormalities. A search for “86.8%” and head abnormalities found no supporting passage in our copy; the corrigendum says the morphologic-abnormality-type section was removed from Table 2. (LLM, conf=0.75)

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Detailed abnormalities are of low clinical diagnostic value with the exception of monomorphic syndromes.

“In a previous literature review, focusing on the clinical relevance of detailed morphology assessment with a view to andrological diagnosis during fertility workup, we have demonstrated detailed abnormalities are of low clinical diagnostic value with the exception of the monomorphic syndromes.”

• cites [4] N. Gatimel, J. Moreau, J. Parinaud, and R. D. Leandri, “ Sperm Morphology: Assessment, Pathophysiology, Clinical Relevance, and State of the Art in 2017,” Andrology 5, no. 5 (2017): 845– 862, https://doi.org10.1111/andr.12389 28692759 sourceSupported

The method for sperm morphology assessment, the stains used, the thresholds that define teratozoospermia, and the morphological classifications employed suffer from extreme heterogeneity over time and between laboratories.

“The method for sperm morphology assessment, the stains used, the thresholds that define teratozoospermia, as well as the morphological classifications employed, suffer from extreme heterogeneity over time and between laboratories [4].”

• cites [4] N. Gatimel, J. Moreau, J. Parinaud, and R. D. Leandri, “ Sperm Morphology: Assessment, Pathophysiology, Clinical Relevance, and State of the Art in 2017,” Andrology 5, no. 5 (2017): 845– 862, https://doi.org10.1111/andr.12389 28692759 sourceSupported

In a prospective cohort of fertile controls undergoing contraceptive vasectomy, 55.9% had teratozoospermia <4%.

“A recent article again points to the poor clinical relevance of sperm morphology assessment, showing that in their prospective cohort of fertile controls undergoing contraceptive vasectomy, 55.9% had teratozoospermia < 4%.”

• cites [10] L. Cheng, D. Miller, A. Wecht, D. Pelzman, and K. Hwang, “ The Questionable Clinical Utility of Sperm Morphology: Rate of Isolated Teratospermia in a Population of Fertile Men,” Journal of Sexual Medicine 21 (2024): qdae002.189, 10.1093/jsxmed/qdae002.189 PMC11228780 38983740 sourceSupported
• cites [22] Corrigendum to ‘High Rate of Isolated Teratospermia in a Population of Fertile Men and the Questionable Clinical Utility of Sperm Morphology’ [F&S Reports 5 (2024) 140‐144]. F S Rep 2025; 6(1): 101. https://doi.org10.1016/j.xfre.2024.11.005 40201105 PMC11973682 sourcePartly supported

  The corrected Table 2 (Abstract; no page given) reports that 30 of 68 men (44.1%) had normal morphology >4%, leaving 38 (55.9%) at or below 4%. It does not establish that all 38 were strictly below 4%, and this corrigendum does not describe the cohort as prospective or say its participants were undergoing contraceptive vasectomy. (LLM, conf=0.82)

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Assessment of the percentage of some abnormalities, such as thin heads, amorphous heads, bent or asymmetrical necks, is of low clinical utility.

“Assessment of the percentage of some abnormalities, such as thin heads, amorphous heads, bent or asymmetrical necks, is of low clinical utility, and their pathophysiology is not well explained as they are mostly ‘physiological traits’ [4].”

• cites [4] N. Gatimel, J. Moreau, J. Parinaud, and R. D. Leandri, “ Sperm Morphology: Assessment, Pathophysiology, Clinical Relevance, and State of the Art in 2017,” Andrology 5, no. 5 (2017): 845– 862, https://doi.org10.1111/andr.12389 28692759 sourceSupported

Pathophysiological studies have shown sometimes controversial associations between sperm morphology and sperm competence (aptitude to undergo the acrosomal reaction, DNA integrity, chromatin condensation, etc.).

“Sperm morphology assessment has also been examined in numerous pathophysiological studies that have shown sometimes controversial associations between morphology and sperm competence (aptitude to undergo the acrosomal reaction, DNA integrity, chromatin condensation, etc.) [5, 6, 7, 8].”

• cites [5] D. Y. Liu, and H. W. Baker, “ Calcium Ionophore‐Induced Acrosome Reaction Correlates With Fertilization Rates In Vitro in Patients With Teratozoospermic Semen,” Human Reproduction 13, no. 4 (1998): 905– 910. 9619546 sourceNot checked — no full text of the source
• cites [6] A. Dubey, M. B. Dayal, D. Frankfurter, P. Balazy, D. Peak, and P. R. Gindoff, “ The Influence of Sperm Morphology on Preimplantation Genetic Diagnosis Cycles Outcome,” Fertility and Sterility 89, no. 6 (2008): 1665– 1669, https://doi.org10.1016/j.fertnstert.2007.06.052 17727848 sourcePartly supported

  The Discussion (page not provided) says studies of sperm morphology and chromosomal integrity have reached inconsistent conclusions, supporting the claim’s general point about controversial associations. It does not address the cited examples of acrosomal reaction or chromatin condensation, and its mention of DNA fragmentation does not establish an association with morphology. (LLM, conf=0.85)

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• cites [7] D. Abu Hassan Abu, D. R. Franken, B. Hoffman, and R. Henkel, “ Accurate Sperm Morphology Assessment Predicts Sperm Function,” Andrologia 44, no. S1 (2012): 571– 577, https://doi.org10.1111/j.1439‐0272.2011.01229.x 22040054 sourcePartly supported

  The Results and Discussion report associations between sperm morphology and acrosome reaction, DNA integrity, and chromatin condensation, and the Discussion cites previous studies of these relationships. Our copy does not characterize the associations across studies as controversial; it says only that the relationship between nuclear condensation and sperm-head morphology is not clearly understood. Page numbers were not available in the supplied passages. (LLM, conf=0.82)

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• cites [8] O. Ammar, M. Mehdi, and M. Muratori, “ Teratozoospermia: Its Association With Sperm DNA Defects, Apoptotic Alterations, and Oxidative Stress,” Andrology 8, no. 5 (2020): 1095– 1106, https://doi.org10.1111/andr.12778 32096605 sourcePartly supported

  The Discussion (page unavailable) reports an association between abnormal sperm morphology and DNA damage, while also noting studies that found no significant association. The Introduction links teratozoospermia with chromatin decondensation. Our copy does not establish an association between morphology and the ability to undergo the acrosomal reaction. (LLM, conf=0.84)

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Some sperm morphology criteria exhibit very high variability, such as head shape, midpiece contours, alignment of the axis of the midpiece and head, with poor agreement <60% between operators.

“A recent study, based on results from the Dutch External Quality Control Program, found some criteria exhibit very high variability such as head shape, midpieces contours, alignment of the axis of the midpiece and head with a poor agreement < 60% between operators [23].”

• cites [23] L. van den Hoven, N. J. van Vrouwerff, I. M. Dijkstra, et al., “ Evaluation of Structural Problems in the Application of Strict Criteria for Sperm Morphology Assessment,” Andrology 13, no. 3 (2025): 512– 518, https://doi.org10.1111/andr.13684 38924385 PMC11867914 sourceSupported

There was a statistically significant relationship between a decreased percentage of normal forms and lower chances of ongoing pregnancy after conventional IVF, with an area under the curve of only 54%.

“There was a statistically significant relationship between a decreased percentage of normal forms and lower chances of ongoing pregnancy after conventional IVF, with however an area under the curve of only 54%.”

• cites [98] L. van den Hoven, J. C. Hendriks, J. G. Verbeet, J. R. Westphal, and A. M. Wetzels, “ Status of Sperm Morphology Assessment: An Evaluation of Methodology and Clinical Value,” Fertility and Sterility 103, no. 1 (2015): 53– 58, https://doi.org10.1016/j.fertnstert.2014.09.036 25450299 sourceSupported

Exome sequencing approaches have identified pathogenic variants in more than 40 genes related to the MMAF phenotype.

“In this context, significant advances have been made, particularly exome sequencing approaches that have identified pathogenic variants in more than 40 genes related to the MMAF phenotype [68], see Supporting Information S1.”

• cites [68] B. Song, T. J. Yang, Q. S. Shen, et al., “ Novel Mutations in DNAH17 Cause Sperm Flagellum Defects and Their Influence on ICSI Outcome,” Journal of Assisted Reproduction and Genetics 40, no. 10 (2023): 2485– 2492, https://doi.org10.1007/s10815‐023‐02897‐7 37574497 PMC10504183 sourcePartly supported

  The Introduction (page not available in our copy) links whole-exome sequencing to the identification of numerous MMAF-associated pathogenic genes. It reports more than 30 genes, however, and does not substantiate the citing sentence’s threshold of more than 40. (LLM, conf=0.88)

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Live births after ICSI have been reported in acephalic/pinhead sperm syndrome, in particular when the few residual spermatozoa with a head and a tail were used.

“However, live births after ICSI have been reported, in particular when the few residual spermatozoa with a head and a tail were used, [50, 60, 61, 62, 63].”

• cites [50] J. Beurois, C. Cazin, Z. E. Kherraf, et al., “ Genetics of Teratozoospermia: Back to the Head,” Best Practice & Research. Clinical Endocrinology & Metabolism 34, no. 6 (2020): 101473, https://doi.org10.1016/j.beem.2020.101473 33183966 sourceSupported
• cites [60] H. Chen, Y. Zhu, Z. Zhu, et al., “ Detection of Heterozygous Mutation in Hook Microtubule‐Tethering Protein 1 in Three Patients With Decapitated and Decaudated Spermatozoa Syndrome,” Journal of Medical Genetics 55, no. 3 (2018): 150– 157, https://doi.org10.1136/jmedgenet‐2016‐104404 29330334 sourceNot checked — no full text of the source
• cites [61] F. Zhu, C. Liu, F. Wang, et al., “ Mutations in PMFBP1 Cause Acephalic Spermatozoa Syndrome,” American Journal of Human Genetics 103, no. 2 (2018): 188– 199, https://doi.org10.1016/j.ajhg.2018.06.010 30032984 PMC6080767 sourceSupported
• cites [62] J. Fang, J. Zhang, F. Zhu, X. Yang, Y. Cui, and J. Liu, “ Patients With Acephalic Spermatozoa Syndrome Linked to SUN5 Mutations Have a Favorable Pregnancy Outcome From ICSI,” Human Reproduction 33, no. 3 (2018): 372– 377, https://doi.org10.1093/humrep/dex382 29329387 sourceNot checked — no full text of the source
• cites [63] M. Mazaheri Moghaddam, M. Mazaheri Moghaddam, H. Hamzeiy, A. Baghbanzadeh, F. Pashazadeh, and E. Sakhinia, “ Genetic Basis of Acephalic Spermatozoa Syndrome, and Intracytoplasmic Sperm Injection Outcomes in Infertile Men: A Systematic Scoping Review,” Journal of Assisted Reproduction and Genetics 38, no. 3 (2021): 573– 586, https://doi.org10.1007/s10815‐020‐02008‐w 33452591 PMC7910383 sourceSupported

Luo et al. showed after multivariate analysis that sperm morphology had an impact on pregnancy rate with an odds ratio of 1.238 (p = 0.006) when sperm morphology was normal.

“The recent study by Luo et al. of more than 3000 cycles showed after multivariate analysis that sperm morphology had an impact on pregnancy rate with an odds ratio of 1.238 (p = 0.006) when sperm morphology was normal [84].”

• cites [84] Y. Luo, S. Wu, J. Yuan, et al., “ Evaluation of Prognostic Factors for Clinical Pregnancy Rate Following Artificial Insemination by Husband in the Chinese Population,” Frontiers in Medicine 8 (2021): 638560, https://doi.org10.3389/fmed.2021.638560 34041250 PMC8141639 sourceSupported

For patients who do not carry AURKC mutations and who have a lower percentage of macrocephalic spermatozoa, only rare spontaneous births or births after ICSI have been reported.

“For patients who do not carry AURKC mutations and who have a lower percentage of macrocephalic spermatozoa in the ejaculate, only rare spontaneous births or births after ICSI have been reported [36, 42, 43, 45, 46, 47, 48, 49] and ICSI may be debated [50].”

• cites [36] V. Achard, O. Paulmyer‐Lacroix, G. Mercier, et al., “ Reproductive Failure in Patients With Various Percentages of Macronuclear Spermatozoa: High Level of Aneuploid and Polyploid Spermatozoa,” Journal of Andrology 28, no. 4 (2007): 600– 606, https://doi.org10.2164/jandrol.106.001933 17412686 sourceNot checked — no full text of the source
• cites [42] V. Carmignac, J. M. Dupont, R. C. Fierro, et al., “ Diagnostic Genetic Screening for Assisted Reproductive Technologies Patients With Macrozoospermia,” Andrology 5, no. 2 (2017): 370– 380, https://doi.org10.1111/andr.12311 28187507 sourceSupported
• cites [43] B. Guthauser, M. Albert, F. Ferfouri, et al., “ Inverse Correlation Between Chromatin Condensation and Sperm Head Size in a Case of Enlarged Sperm Heads,” Reproductive Biomedicine Online 23, no. 6 (2011): 711– 716, https://doi.org10.1016/j.rbmo.2011.07.011 22033397 sourceSupported
• cites [45] H. Ghedir, M. Gribaa, O. Mamai, et al., “ Macrozoospermia: Screening for the Homozygous c.144delC Mutation in AURKC Gene in Infertile Men and Estimation of Its Heterozygosity Frequency in the Tunisian Population,” Journal of Assisted Reproduction and Genetics 32, no. 11 (2015): 1651– 1658, https://doi.org10.1007/s10815‐015‐0565‐4 26341096 PMC4651955 sourcePartly supported

  The Discussion (page unavailable) reports one healthy child after a spontaneous pregnancy in a patient with a milder phenotype and no identified AURKC mutation. It also reports a few successful deliveries after in vitro fertilization in milder cases, but does not specify that those births followed ICSI. (LLM, conf=0.85)

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• cites [46] M. R. Guichaoua, G. Mercier, C. Geoffroy‐Siraudin, et al., “ Macrocephalic Spermatozoa. What Would be the Impact on Reproduction?,” Gynecologie, Obstetrique & Fertilite 37, no. 9 (2009): 703– 711, https://doi.org10.1016/j.gyobfe.2009.05.011 19709918 sourceNot checked — no full text of the source
• cites [47] Y. Shimizu, F. Kiumura, S. Kaku, et al., “ Successful Delivery Following ICSI With Macrocephalic Sperm Head Syndrome: A Case Report,” Reproductive Biomedicine Online 24, no. 6 (2012): 603– 605, https://doi.org10.1016/j.rbmo.2012.02.022 22503269 sourcePartly supported

  The Case report describes one healthy birth after ICSI, and the Discussion calls it the first known such report for this syndrome. But the paper does not establish that this patient lacked an AURKC mutation or had a lower percentage of macrocephalic spermatozoa; the Case report says almost all were macrocephalic, with only 0.33% having almost normal morphology. Page numbers are not available in our copy. (LLM, conf=0.87)

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• cites [48] M. M. Kobesiy, B. M. Foda, O. S. M. Ali, I. Fahmy, and S. M. Ismail, “ Mutational Analysis of Aurora Kinase C Gene in Egyptian Patients With Macrozoospermia,” Andrologia 52, no. 7 (2020): e13619, https://doi.org10.1111/and.13619 32399982 sourcePartly supported

  The Results report one live birth after ICSI in a patient without a recorded AURKC mutation, but that patient had severe, not mild, macrozoospermia. The mild cases undergoing ICSI had no live birth, and the paper does not report spontaneous births in its cohort. The Introduction and Discussion cite successful ICSI in mild cases elsewhere, so the claim has some support, but its combined description of mutation status, lower macrocephalic-sperm percentage and rare births is not established by this paper. (LLM, conf=0.86)

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• cites [49] L. Ounis, A. Zoghmar, C. Coutton, et al., “ Mutations of the Aurora Kinase C Gene Causing Macrozoospermia Are the Most Frequent Genetic Cause of Male Infertility in Algerian Men,” Asian Journal of Andrology 17, no. 1 (2015): 68– 73, https://doi.org10.4103/1008‐682X.136441 25219909 PMC4291881 sourcePartly supported

  The Results report that the three men without AURKC mutations had milder sperm abnormalities (70%–75% abnormal spermatozoa) and that one ICSI procedure led to the birth of a healthy child. The same section reports a subsequent spontaneous pregnancy, but not a spontaneous birth; the paper also does not establish how rare such births are beyond its cohort. (LLM, conf=0.84)

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Analysis of ROC curves showed that sperm abnormality indexes had no predictive value for the outcome of IVF.

“Nevertheless, analysis of ROC curves showed that these indexes had no predictive value for the outcome of IVF [73].”

• cites [73] X. Chen, W. Zhang, Y. Luo, X. Long, and X. Sun, “ Predictive Value of Semen Parameters in In Vitro Fertilisation Pregnancy Outcome,” Andrologia 41, no. 2 (2009): 111– 117, https://doi.org10.1111/j.1439‐0272.2008.00898.x 19260848 sourcePartly supported

  The Results say ROC analysis found TZI and SDI were not good indicators of IVF pregnancy, with AUCs below 0.6. But the claim’s “no predictive value” is stronger than the paper’s conclusion of poor predictive value: the Abstract also reports significant differences in both indexes between pregnancy groups and says they may be more informative than other semen parameters. (LLM, conf=0.86)

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Mutations of the gene coding for SUN5 protein are the most frequent cause of acephalic sperm syndrome.

“Mutations of the gene coding for the SUN5 protein were the first to be recognised, with more than 10 biallelic variants identified. This is the most frequent cause of acephalic sperm syndrome [54, 55].”

• cites [54] C. Cazin, Y. Boumerdassi, G. Martinez, et al., “ Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating From North Africa,” International Journal of Molecular Sciences 22, no. 4 (2021): 2187, https://doi.org10.3390/ijms22042187 33671757 PMC7927044 sourceSupported
• cites [55] F. Zhu, F. Wang, X. Yang, et al., “ Biallelic SUN5 Mutations Cause Autosomal‐Recessive Acephalic Spermatozoa Syndrome,” American Journal of Human Genetics 99, no. 6 (2016): 1405, https://doi.org10.1016/j.ajhg.2016.11.002 PMC5142114 27912045 sourceCould not verify

  The indexed copy contains a correction notice (p. 1405) and publication-site material, but not the original article’s findings. Searches for SUN5 as the most frequent cause and for biallelic-variant frequency found no passage addressing how common SUN5 mutations are relative to other causes. (LLM, conf=0.72)

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According to Van den Hoven et al., the percentage of normal forms was correlated with ongoing pregnancy rate with an OR of 1.06 [1.02-1.16] after conventional IVF (n = 2323).

“According to Van den Hoven et al. [98], the percentage of normal forms was correlated with ongoing pregnancy rate with an OR of 1.06 [1.02–1.16] after conventional IVF (n = 2323).”

• cites [98] L. van den Hoven, J. C. Hendriks, J. G. Verbeet, J. R. Westphal, and A. M. Wetzels, “ Status of Sperm Morphology Assessment: An Evaluation of Methodology and Clinical Value,” Fertility and Sterility 103, no. 1 (2015): 53– 58, https://doi.org10.1016/j.fertnstert.2014.09.036 25450299 sourcePartly supported

  The “Sperm Morphology and Pregnancy” section reports 2,323 IVF treatments and a statistically significant association between the percentage of normal spermatozoa and ongoing pregnancy. It gives an OR of 1.09 (95% CI 1.02–1.16), not the claimed 1.06; Table 1 confirms the 1.09 figure. The supplied passages do not identify an exact page. (LLM, conf=0.94)

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The finding that sperm morphology had no impact on pregnancy rates after IUI was confirmed later on a larger cohort.

“This finding was confirmed later on a larger cohort [75].”

• cites [75] V. Immediata, P. Patrizio, M. R. Parisen Toldin, et al., “ Twenty‐One Year Experience With Intrauterine Inseminations After Controlled Ovarian Stimulation With Gonadotropins: Maternal Age Is the Only Prognostic Factor for Success,” Journal of Assisted Reproduction and Genetics 37, no. 5 (2020): 1195– 1201, https://doi.org10.1007/s10815‐020‐01752‐3 32215826 PMC7244676 sourcePartly supported

  The Discussion reports that semen parameters, including the morphology assessed in Methods, showed no impact on clinical outcomes in this large IUI cohort, provided post-treatment sperm counts met the study’s eligibility threshold. But the Results also report significantly better pretreatment normal morphology in the pregnant group. The unqualified claim therefore misses both the univariable finding and the study’s restriction. (LLM, conf=0.84)

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Nikolova et al. examined implantation rate after single embryo transfer in 86 couples and found that abnormalities of the head or the flagellum or high MAI appeared to be predictive of a lower success rate.

“Nikolova et al. [27] examined the implantation rate after single embryo transfer in 86 couples (42 successful vs. 44 unsuccessful implantations). Abnormalities of the head (vacuoles, wide acrosome) or the flagellum (coiled tail) or high MAI appeared to be predictive of a lower success rate.”

• cites [27] S. Nikolova, D. Parvanov, V. Georgieva, I. Ivanova, R. Ganeva, and G. Stamenov, “ Impact of Sperm Characteristics on Time‐Lapse Embryo Morphokinetic Parameters and Clinical Outcome of Conventional In Vitro Fertilization,” Andrology 8, no. 5 (2020): 1107– 1116, https://doi.org10.1111/andr.12781 32119189 sourceSupported

Most recent studies of smaller series confirmed that sperm morphology had no impact on pregnancy rates after IUI.

“Most recent studies, of smaller series, confirmed these results [76, 77, 78, 79, 80, 81, 82, 83]”

• cites [76] Y. Sun, B. Li, L. Q. Fan, et al., “ Does Sperm Morphology Affect the Outcome of Intrauterine Insemination in Patients With Normal Sperm Concentration and Motility?,” Andrologia 44, no. 5 (2012): 299– 304, https://doi.org10.1111/j.1439‐0272.2012.01280.x 22335521 sourcePartly supported

  The Discussion (page unavailable) reports no statistically significant difference in pregnancy rates across sperm-morphology groups, supporting the main point for couples with normal sperm concentration and motility. But the paper also reports no pregnancies among women over 35 when normal sperm forms were below 5%, so its findings do not support an unqualified claim that morphology had no impact. (LLM, conf=0.85)

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• cites [77] N. E. Deveneau, O. Sinno, M. Krause, et al., “ Impact of Sperm Morphology on the Likelihood of Pregnancy After Intrauterine Insemination,” Fertility and Sterility 102, no. 6 (2014): 1584– 1590, https://doi.org10.1016/j.fertnstert.2014.09.016 25439801 sourceNot checked — no full text of the source
• cites [78] G. M. Lockwood, N. E. Deveneau, A. N. Shridharani, E. Y. Strawn, and J. I. Sandlow, “ Isolated Abnormal Strict Morphology Is Not a Contraindication for Intrauterine Insemination,” Andrology 3, no. 6 (2015): 1088– 1093, https://doi.org10.1111/andr.12098 26384603 sourceSupported
• cites [79] F. Ghaffari, S. J. Sadatmahalleh, M. R. Akhoond, P. Eftekhari Yazdi, and Z. Zolfaghari, “ Evaluating the Effective Factors in Pregnancy After Intrauterine Insemination: A Retrospective Study,” International Journal of Fertility and Sterility 9, no. 3 (2015): 300– 308, https://doi.org10.22074/ijfs.2015.4544 26644852 PMC4671382 sourceSupported
• cites [80] A. Thijssen, A. Creemers, W. Van der Elst, et al., “ Predictive Value of Different Covariates Influencing Pregnancy Rate Following Intrauterine Insemination With Homologous Semen: A Prospective Cohort Study,” Reproductive Biomedicine Online 34, no. 5 (2017): 463– 472, https://doi.org10.1016/j.rbmo.2017.01.016 28285953 sourceNot checked — no full text of the source
• cites [81] M. Irani, S. Chow, D. Keating, S. Elder, Z. Rosenwaks, and G. Palermo, “ Optimizing the First‐Line Fertility Treatment,” Gynecological Endocrinology 34, no. 9 (2018): 742– 746, https://doi.org10.1080/09513590.2018.1441825 29463146 sourceNot checked — no full text of the source
• cites [82] P. Patel, R. Carrasquillo, V. Madhusoodanan, et al., “ Impact of Abnormal Sperm Morphology on Live Birth Rates Following Intrauterine Insemination,” Journal of Urology 202, no. 4 (2019): 801– 805, https://doi.org10.1097/JU.0000000000000288 31009287 sourceNot checked — no full text of the source
• cites [83] F. Mohammadi, Z. Mehdinia, S. Ghasemi, et al., “ Relationship Between Sperm Parameters and Clinical Outcomes of Intra Uterine Insemination (IUI),” Caspian Journal of Internal Medicine 12, no. 1 (2021): 70– 76, https://doi.org10.22088/cjim.12.1.70 33680401 PMC7919170 sourceSupported

When an AURKC mutation is identified, spermatozoa of normal appearance also carry an increased risk of aneuploidy.

“It is important to note that when a mutation of the gene coding for aurora kinase C (AURKC) has been identified, spermatozoa of normal appearance also carry an increased risk of aneuploidy [42], leading to a contraindication of ICSI in case of high percentage of macrocephalic spermatozoa.”

• cites [42] V. Carmignac, J. M. Dupont, R. C. Fierro, et al., “ Diagnostic Genetic Screening for Assisted Reproductive Technologies Patients With Macrozoospermia,” Andrology 5, no. 2 (2017): 370– 380, https://doi.org10.1111/andr.12311 28187507 sourceSupported

Other smaller studies observed that sperm morphology affected the outcome of IUI.

“Other studies of smaller series also observed that sperm morphology affected the outcome of IUI [86, 87, 88, 89, 90, 91, 92, 93].”

• cites [86] M. Erdem, A. Erdem, M. F. Mutlu, et al., “ The Impact of Sperm Morphology on the Outcome of Intrauterine Insemination Cycles With Gonadotropins in Unexplained and Male Subfertility,” European Journal of Obstetrics, Gynecology, and Reproductive Biology 197 (2016): 120– 124, https://doi.org10.1016/j.ejogrb.2015.12.014 26745391 sourceNot checked — no full text of the source
• cites [87] O. Grigoriou, K. Pantos, E. Makrakis, D. Hassiakos, S. Konidaris, and G. Creatsas, “ Impact of Isolated Teratozoospermia on the Outcome of Intrauterine Insemination,” Fertility and Sterility 83, no. 3 (2005): 773– 775, https://doi.org10.1016/j.fertnstert.2004.08.027 15749516 sourceSupported
• cites [88] R. Hauser, L. Yogev, A. Botchan, J. B. Lessing, and G. Paz, H. Yavetz, “ Intrauterine Insemination in Male Factor Subfertility: Significance of Sperm Motility and Morphology Assessed by Strict Criteria,” Andrologia 33, no. 1 (2001): 13– 17. 11167514 sourceNot checked — no full text of the source
• cites [89] R. K. Lee, J. W. Hou, H. Y. Ho, et al., “ Sperm Morphology Analysis Using Strict Criteria as a Prognostic Factor in Intrauterine Insemination,” International Journal of Andrology 25, no. 5 (2002): 277– 280. 12270024 sourceSupported
• cites [90] L. Mollaahmadi, A. Keramat, A. Ghiasi, and M. Hashemzadeh, “ The Relationship Between Semen Parameters in Processed and Unprocessed Semen With Intrauterine Insemination Success Rates,” Journal of the Turkish‐German Gynecological Association 20, no. 1 (2019): 1– 7, https://doi.org10.4274/jtgga.galenos.2018.2018.0089 30222125 PMC6501869 sourceSupported
• cites [91] H. Shibahara, H. Obara, Ayustawati, et al., “ Prediction of Pregnancy by Intrauterine Insemination Using CASA Estimates and Strict Criteria in Patients With Male Factor Infertility,” International Journal of Andrology 27, no. 2 (2004): 63– 68, https://doi.org10.1111/j.0105‐6263.2004.00437.x 15149462 sourcePartly supported

  The Results of IUI treatment report that normal sperm morphology predicted pregnancy after IUI, supporting the main point. The Discussion describes this study as a “large series of 682 consecutive IUI”; our copy does not establish that it was a smaller series relative to the citing study. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [92] C. Spiessens, D. Vanderschueren, C. Meuleman, and T. D'Hooghe, “ Isolated Teratozoospermia and Intrauterine Insemination,” Fertility and Sterility 80, no. 5 (2003): 1185– 1189. 14607572 sourceNot checked — no full text of the source
• cites [93] V. Viardot‐Foucault, B. C. Tai, E. B. Prasath, M. S. Lau, J. K. Chan, and S. F. Loh, “ Younger Women With Ovulation Disorders and Unexplained Infertility Predict a Higher Success Rate in Superovulation (SO) Intrauterine Insemination (IUI),” Annals of the Academy of Medicine Singapore 43, no. 4 (2014): 225– 231. 24833075 sourceSupported

In Zhu et al., there was a major bias related to the older age of women in the <2% group (36.11, 34.26 and 33.82 years, respectively, with no statistical analysis).

“Of note was a major bias related to the older age of the women in the < 2% group (36.11, 34.26 and 33.82 years, respectively, with no statistical analysis).”

• cites [99] Y. Zhu, F. Zhang, H. Cheng, X. X. Sun, and F. Jiang, “ Modified Strict Sperm Morphology Threshold Aids in the Clinical Selection of Conventional In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI),” Asian Journal of Andrology 24, no. 1 (2022): 62– 66, https://doi.org10.4103/aja.aja_45_21 34135171 PMC8788610 sourceSupported

For Zhu et al., teratozoospermia had an impact on pregnancy rate when divided into subgroups, with pregnancy rates of 37%, 56.5% and 53.4% for <2%, 2%-4% and ≥4% morphologically normal sperm, respectively.

“For Zhu et al. [99], teratozoospermia had an impact on pregnancy rate when divided into subgroups. These authors observed pregnancy rates of 37%, 56.5% and 53.4% for < 2%, 2%–4% and ≥ 4% morphologically normal sperm, respectively.”

• cites [99] Y. Zhu, F. Zhang, H. Cheng, X. X. Sun, and F. Jiang, “ Modified Strict Sperm Morphology Threshold Aids in the Clinical Selection of Conventional In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI),” Asian Journal of Andrology 24, no. 1 (2022): 62– 66, https://doi.org10.4103/aja.aja_45_21 34135171 PMC8788610 sourcePartly supported

  Table 2 (Results; page unavailable) reports clinical pregnancy rates of 37.0%, 56.5%, and 53.4% for the corresponding sperm-morphology groups, but these figures are for conventional IVF only. The Results section on implantation outcomes says pregnancy rates changed significantly across IVF groups, while the ICSI groups showed no significant differences. The citing sentence omits that treatment-specific qualification. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

The impact of teratozoospermia on fertilisation rate in Zhu et al. was confirmed by multivariate analysis (r = 0.057, p = 0.01).

“The impact on fertilisation rate was confirmed by multivariate analysis (r = 0.057, p = 0.01).”

• cites [97] Y. Zhu, Q. F. Wu, X. J. Zhou, C. L. Xin, G. Ling, and G. X. Lu, “ ICSI Improves Fertilization in Isolated Teratozoospermic Men: A Study With Strictly Controlled External Factors and WHO‐5 Standard,” Systems Biology in Reproductive Medicine 59, no. 1 (2013): 21– 26, https://doi.org10.3109/19396368.2012.727061 23043217 sourceSupported

FISH analysis of sperm aneuploidy in three patients with pinhead spermatozoa syndrome and carrying a SUN5 mutation revealed no increase in aneuploidy rate compared with five fertile controls.

“FISH analysis of sperm aneuploidy in three patients with pinhead spermatozoa syndrome and carrying a SUN5 mutation revealed no increase in aneuploidy rate compared with five fertile controls [54].”

• cites [54] C. Cazin, Y. Boumerdassi, G. Martinez, et al., “ Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating From North Africa,” International Journal of Molecular Sciences 22, no. 4 (2021): 2187, https://doi.org10.3390/ijms22042187 33671757 PMC7927044 sourceSupported

In a study by van den Hoven et al. of 1353 ICSI attempts, the percentage of normal forms was not correlated with the ongoing pregnancy rate.

“In a study by van den Hoven et al. [98] of 1353 ICSI attempts, the percentage of normal forms was not correlated with the ongoing pregnancy rate.”

• cites [98] L. van den Hoven, J. C. Hendriks, J. G. Verbeet, J. R. Westphal, and A. M. Wetzels, “ Status of Sperm Morphology Assessment: An Evaluation of Methodology and Clinical Value,” Fertility and Sterility 103, no. 1 (2015): 53– 58, https://doi.org10.1016/j.fertnstert.2014.09.036 25450299 sourceSupported

In the first study [103], the fertilisation failure rate was very high (33 of 120).

“Of note, in this study the fertilisation failure rate was very high (33 of 120) [103].”

• cites [103] A. Moubasher, T. Abdel‐Raheem, H. Ahmed, A. Salem, A. Doshi, and A. Abdel Raheem, “ An Open Prospective Study on Whether Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) Offers a Better Outcome Than Conventional Intracytoplasmic Sperm Injection (ICSI),” Cureus 13, no. 11 (2021): e19181, https://doi.org10.7759/cureus.19181 34737916 PMC8560014 sourceCould not verify

  The Results (page unavailable) report fertilization rates for 525 couples, including 446 in the ICSI group and 79 in the IMSI group, but do not report 33 fertilization failures among 120 cases. Searches for “33 of 120” and “fertilization failure” did not locate that figure in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

In the second study [102], sperm parameters other than morphology had a major impact.

“In the second one [102], sperm parameters other than morphology had a major impact.”

• cites [102] G. Cito, R. Picone, R. Fucci, et al., “ Sperm Morphology: What Implications on the Assisted Reproductive Outcomes?,” Andrology 8, no. 6 (2020): 1867– 1874, https://doi.org10.1111/andr.12883 32761795 sourcePartly supported

  The Results report that sperm concentration and total sperm count were positively correlated with fertilization rates. But viability was not associated with improved laboratory outcomes, and none of these parameters was associated with cleavage rate. The paper therefore supports an impact of some parameters other than morphology, not the broad claim that they had a major impact. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

In a secondary analysis of a large randomised controlled trial involving 1064 couples with normal total sperm count and motility, using ICSI over IVF in cases of teratozoospermia had no influence on the chances of clinical pregnancy or live birth.

“In addition, in a secondary analysis of a large randomised controlled trial (RCT), involving 1064 couples with normal total sperm count and motility, the authors shown that showed that using ICSI over IVF in cases of teratozoospermia had no influence on the chances of clinical pregnancy or live birth [110].”

• cites [110] T. D. Pham, V. Q. Dang, V. N. A. Ho, et al., “ Intracytoplasmic Sperm Injection Versus Conventional In Vitro Fertilization in Infertile Couples With Normal Total Sperm Count and Motility: Does Sperm Morphology Matter?,” Human Reproduction 40, no. 1 (2024): 23– 29, https://doi.org10.1093/humrep/deae252 PMC11700896 39547931 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Three studies reported significantly higher fertilisation rates after ICSI than after IVF.

“Lastly, three studies reported significantly higher fertilisation rates after ICSI than after IVF [97, 107, 108].”

• cites [97] Y. Zhu, Q. F. Wu, X. J. Zhou, C. L. Xin, G. Ling, and G. X. Lu, “ ICSI Improves Fertilization in Isolated Teratozoospermic Men: A Study With Strictly Controlled External Factors and WHO‐5 Standard,” Systems Biology in Reproductive Medicine 59, no. 1 (2013): 21– 26, https://doi.org10.3109/19396368.2012.727061 23043217 sourceSupported
• cites [107] J. H. Check, A. Bollendorf, C. Wilson, D. Summers‐Chase, D. Horwath, and W. Yuan, “ A Retrospective Comparison of Pregnancy Outcome Following Conventional Oocyte Insemination vs Intracytoplasmic Sperm Injection for Isolated Abnormalities in Sperm Morphology Using Strict Criteria,” Journal of Andrology 28, no. 4 (2007): 607– 612, https://doi.org10.2164/jandrol.106.001941 17409463 sourceNot checked — no full text of the source
• cites [108] M. Li, C. Ma, X. Xue, W. Zhao, S. Zhang, and J. Shi, “ Effect of Normal Sperm Morphology Rate (NSMR) on Clinical Outcomes and Fertilization Methods Selection in the Ultra‐Short‐Term GnRH‐a Protocol,” Gynecological Endocrinology 32, no. 2 (2016): 120– 123, https://doi.org10.3109/09513590.2015.1092514 26437674 sourceNot checked — no full text of the source

Detailed sperm morphology analysis has very limited reliability.

“Appropriate use of sperm morphology must take into account its analytical performance, given the very limited reliability of detailed sperm morphology analysis, as outlined in the Supporting Information associated with NQ#1.”

There is a lack of studies demonstrating the analytical performances, clinical usefulness, and medical service rendered by sperm morphology analysis.

“Unfortunately, there is a lack of studies demonstrating the analytical performances, clinical usefulness and thus the medical service rendered by sperm morphology analysis.”

In polymorphic syndromes, no article reports a diagnostic contribution of detailed abnormalities in the assessment of male infertility.

“In the case of polymorphic syndromes, we did not find any article reporting a diagnostic contribution of these detailed abnormalities in the assessment of male infertility.”

The small number of published studies did not report an impact of individual detailed abnormalities on ART outcomes in a polymorphic context.

“The small number of published studies did not report an impact of individual detailed abnormalities on ART outcomes, in a polymorphic context.”

Inter-rater and interlaboratory variability for the abnormalities identified is very unsatisfactory.

“Inter‐rater and interlaboratory variability for the abnormalities identified is very unsatisfactory (Supporting Information S1).”

Compared with manual analysis, some automated systems underestimate the percentage of abnormal forms.

“Compared with manual analysis, some systems underestimate the percentage of abnormal forms.”

Regarding macrozoospermia, an increased risk of genetic abnormality appears to have been observed above a macrocephalic spermatozoa cut-off varying from 30% to 70%.

“Regarding macrozoospermia, an increased risk of genetic abnormality appears to have been observed above a macrocephalic spermatozoa cut‐off varying from 30% to 70%.”

Current scientific data show superiority of automated systems over manual analysis for inter-rater reproducibility in assessment of the percentage of normal forms.

“Current scientific data show a superiority of automated systems over manual analysis for inter‐rater reproducibility in assessment of the percentage of normal forms.”

Of the studies that found that teratozoospermia had an impact on fertilisation rate, none found a significant effect on the second parameter.

“Of the studies that found that teratozoospermia had an impact on fertilisation rate, none found a significant effect on this second parameter.”

There is insufficient evidence to demonstrate the clinical value of indexes of multiple sperm defects (TZI, SDI, MAI) in investigation of infertility and before ART.

“There is insufficient evidence to demonstrate the clinical value of indexes of multiple sperm defects (TZI, SDI, MAI) in investigation of infertility and before ART.”

The only three studies that showed a significant impact of teratozoospermia on pregnancy rate had a low level of evidence (Grade 1).

“The only three studies that showed a significant impact of teratozoospermia on pregnancy rate had a low level of evidence (Grade 1).”

Most studies analysed (79%, but with a low level of evidence) showed that teratozoospermia did not decrease the chances of pregnancy after conventional IVF.

“Most studies analysed (79%, but with a low level of evidence) showed that teratozoospermia did not decrease the chances of pregnancy after conventional IVF.”

There is a lack of data in the literature on correlations for abnormal values in automated versus manual sperm morphology analysis.

“However, caution is needed in view of the lack of data on correlations for abnormal values in literature.”

No data were found on the predictive value of MAI for ICSI outcome.

“We found no data on the predictive value of MAI for ICSI outcome.”

There is a lack of evidence in the literature for systems using an algorithm to estimate the percentage of typical forms.

“because of a lack of evidence in the literature and as it is not a cytological analysis after staining”

For other criteria of analytical performance, superiority of automated systems over manual analysis has not been demonstrated.

“With regard to other criteria of analytical performances, the superiority of automated systems over manual analysis has not been demonstrated.”

Correlations between automated systems and manual analysis regarding the percentage of normal forms appear significant.

“Correlations between automated systems and manual analysis regarding the percentage of normal forms appear significant.”

Most publications analysed concerning the impact of teratozoospermia on ICSI outcome found that the percentage of morphologically normal sperm was not predictive either of fertilisation rate or of pregnancy rate.

“Most of publications analysed concerning the impact of teratozoospermia on ICSI outcome found that the percentage of morphologically normal sperm was not predictive either of fertilisation rate or of pregnancy rate.”

An important point from this literature analysis is that the overall level of evidence of the studies is low.

“An important point from this literature analysis is that the overall level of evidence of the studies is low.”

These pathophysiological studies are not methodologically constructed to validate a laboratory test in a well-defined clinical situation such as infertility workup or before ART.

“However, these studies are not methodologically constructed to validate a laboratory test in a well‐defined clinical situation as infertility workup or before ART.”

Sperm morphology is correlated with the chances of natural pregnancy in epidemiological studies comparing fertile men whose partners achieved natural pregnancy and infertile men.

“Epidemiological studies comparing fertile men whose partners achieved natural pregnancy and infertile men have demonstrated that sperm morphology was correlated with the chances of natural pregnancy [1, 2, 3].”

• cites [1] D. S. Guzick, J. W. Overstreet, P. Factor‐Litvak, et al., “ Sperm Morphology, Motility, and Concentration in Fertile and Infertile Men,” New England Journal of Medicine 345, no. 19 (2001): 1388– 1393, https://doi.org10.1056/NEJMoa003005 11794171 sourceNot checked — no full text of the source
• cites [2] J. P. Bonde, E. Ernst, T. K. Jensen, et al., “ Relation Between Semen Quality and Fertility: A Population‐Based Study of 430 First‐Pregnancy Planners,” Lancet 352, no. 9135 (1998): 1172– 1177, https://doi.org10.1016/S0140‐6736(97)10514‐1 9777833 sourceNot checked — no full text of the source
• cites [3] R. Slama, F. Eustache, B. Ducot, et al., “ Time to Pregnancy and Semen Parameters: A Cross‐Sectional Study Among Fertile Couples From Four European Cities,” Human Reproduction 17, no. 2 (2002): 503– 515, https://doi.org10.1093/humrep/17.2.503 11821304 sourceNot checked — no full text of the source

ICSI success rates in globozoospermia remain rather low, with many failures or lower fertilisation rates.

“Success rates of ICSI remain rather low, with many failures or with lower fertilisation rates [30, 31, 32, 33].”

• cites [30] J. Liu, Z. Nagy, H. Joris, H. Tournaye, P. Devroey, and A. Van Steirteghem, “ Successful Fertilization and Establishment of Pregnancies After Intracytoplasmic Sperm Injection in Patients With Globozoospermia,” Human Reproduction 10, no. 3 (1995): 626– 629. 7782443 sourceNot checked — no full text of the source
• cites [31] D. E. Battaglia, J. K. Koehler, N. A. Klein, and M. J. Tucker, “ Failure of Oocyte Activation After Intracytoplasmic Sperm Injection Using Round‐Headed Sperm,” Fertility and Sterility 68, no. 1 (1997): 118– 122. 9207595 sourceNot checked — no full text of the source
• cites [32] A. V. Rybouchkin, F. Van der Straeten, J. Quatacker, P. De Sutter, and M. Dhont, “ Fertilization and Pregnancy After Assisted Oocyte Activation and Intracytoplasmic Sperm Injection in a Case of Round‐Headed Sperm Associated With Deficient Oocyte Activation Capacity,” Fertility and Sterility 68, no. 6 (1997): 1144– 1147. 9418715 sourceNot checked — no full text of the source
• cites [33] L. Chansel‐Debordeaux, S. Dandieu, S. Bechoua, and C. Jimenez, “ Reproductive Outcome in Globozoospermic Men: Update and Prospects,” Andrology 3, no. 6 (2015): 1022– 1034, https://doi.org10.1111/andr.12081 26445006 sourceNot checked — no full text of the source

The predictive value of sperm parameters for detecting infertility is low.

“In these studies, although correlations were observed between morphology and natural fertility, the predictive value of sperm parameters for detecting infertility was low.”

• cites [1] D. S. Guzick, J. W. Overstreet, P. Factor‐Litvak, et al., “ Sperm Morphology, Motility, and Concentration in Fertile and Infertile Men,” New England Journal of Medicine 345, no. 19 (2001): 1388– 1393, https://doi.org10.1056/NEJMoa003005 11794171 sourceNot checked — no full text of the source
• cites [2] J. P. Bonde, E. Ernst, T. K. Jensen, et al., “ Relation Between Semen Quality and Fertility: A Population‐Based Study of 430 First‐Pregnancy Planners,” Lancet 352, no. 9135 (1998): 1172– 1177, https://doi.org10.1016/S0140‐6736(97)10514‐1 9777833 sourceNot checked — no full text of the source
• cites [3] R. Slama, F. Eustache, B. Ducot, et al., “ Time to Pregnancy and Semen Parameters: A Cross‐Sectional Study Among Fertile Couples From Four European Cities,” Human Reproduction 17, no. 2 (2002): 503– 515, https://doi.org10.1093/humrep/17.2.503 11821304 sourceNot checked — no full text of the source

Based on the studies, it is not possible to reach a conclusion on the impact of teratozoospermia alone on fertilisation rate because of confounding factors.

“Based on these studies, it is not possible to reach a conclusion on the impact of teratozoospermia alone on fertilisation rate because of confounding factors.”

Based on the literature, it is difficult to reach a conclusion on the possible impact of sperm morphology on IUI outcomes.

“Based on the literature, it seems difficult to reach a conclusion on the possible impact of sperm morphology on the IUI outcomes.”

Most studies on sperm morphology and IUI were not carried out on cases of isolated teratozoospermia, but often in association with other sperm abnormalities.

“Most studies were not carried out on cases of isolated teratozoospermia, but often in association with other sperm abnormalities.”

The diverse findings of the literature on sperm morphology and IUI may be explained by the difficulty of assessing sperm morphology and by differences in methodology from one laboratory to another.

“The diverse findings of the literature may be explained by the difficulty of assessing sperm morphology and by differences in methodology from one laboratory to another.”

Ozcan et al. found similar results after analysis of more than 500 IUI cycles.

“The findings of Ozcan et al. [85] were similar after analysis of more than 500 IUI cycles.”

• cites [85] P. Ozcan, and T. Takmaz, “ Identification of Predictive Factors for the Probability of Pregnancy Following Ovulation Stimulation‐Intra‐Uterine Insemination Cycles in Terms of Female and Male,” Journal of Obstetrics and Gynaecology Research 47, no. 3 (2021): 893– 899, https://doi.org10.1111/jog.14594 33403758 sourceNot checked — no full text of the source

The parameters of insemination by IVF (quantity of motile spermatozoa and contact time) were rarely detailed in PICO2 studies.

“The parameters of insemination by IVF (quantity of motile spermatozoa and contact time) were rarely detailed.”

In MMAF, sperm morphology assessment provides a diagnostic aid for infertility.

“In such cases, sperm morphology assessment provides a diagnostic aid for infertility.”

The review by [94] showed that sperm morphology had an impact on pregnancy rates in IUI only when the number of motile spermatozoa suitable for insemination was less than 1 million.

“The review by [94] showed that sperm morphology had an impact on pregnancy rates in IUI only when the number of motile spermatozoa suitable for insemination was less than 1 million”

• cites [94] W. Ombelet, K. Deblaere, E. Bosmans, et al., “ Semen Quality and Intrauterine Insemination,” Reproductive Biomedicine Online 7, no. 4 (2003): 485– 492. 14656412 sourceNot checked — no full text of the source

A low correlation between the SDI and the risk of complete failure of fertilisation by conventional IVF was found.

“A low correlation between the SDI and the risk of complete failure of fertilisation by conventional IVF was found [72].”

• cites [72] N. Aziz, I. Buchan, C. Taylor, C. R. Kingsland, and I. Lewis‐Jones, “ The Sperm Deformity Index: A Reliable Predictor of the Outcome of Oocyte Fertilization In Vitro,” Fertility and Sterility 66, no. 6 (1996): 1000– 1008. 8941069 sourceNot checked — no full text of the source

The two readers graded the studies for PICO1 with a moderate percentage of agreement (63.0%, kappa 0.43).

“The two readers graded the studies with a moderate percentage of agreement (63.0%, kappa 0.43), demonstrating the difficulty of evaluating these publications, in particular for determining bias.”

Statistical analysis in studies on sperm morphology and IUI did not always take female parameters into account.

“Also, statistical analysis did not always take female parameters into account.”

Inter-rater agreement was perfect for assessment of the impact of teratozoospermia in PICO1 (100%, kappa 1.0).

“Inter‐rater agreement was perfect for assessment of the impact of teratozoospermia (100%, kappa 1.0) (Table 2).”

There is insufficient evidence to demonstrate the clinical value of sperm abnormality indexes (TZI, SDI, MAI) in investigation of infertility and before ART.

“There is insufficient evidence to demonstrate the clinical value of abnormality indexes in investigation of infertility and before ART.”

The TZI cannot assess men's fertility potential because of significant overlap in values between fertile and sub-fertile populations.

“The TZI cannot assess men's fertility potential because of significant overlap in values between fertile and sub‐fertile populations, as demonstrated by [71] and published in the WHO recommendations, fifth edition.”

• cites [71] R. Menkveld, W. Y. Wong, C. J. Lombard, et al., “ Semen Parameters, Including WHO and Strict Criteria Morphology, in a Fertile and Subfertile Population: An Effort Towards Standardization of In‐Vivo Thresholds,” Human Reproduction 16, no. 6 (2001): 1165– 1171. 11387287 sourceNot checked — no full text of the source

The grade of all studies analysed for PICO2 is strongly affected by bias and limitations (13 of 20 studies).

“The grade of all the studies analysed is strongly affected by bias and limitations (13 of 20 studies).”

Failure of ICSI after injection of pinhead spermatozoa has been reported, related to non-fusion of the pro-nuclei (absence of syngamy) and absence of cleavage.

“Failure of ICSI after injection of pinhead spermatozoa have been reported, related to non‐fusion of the pro‐nuclei (absence of syngamy) and absence of cleavage [56, 57, 58, 59].”

• cites [56] H. E. Chemes, C. Carizza, F. Scarinci, S. Brugo, N. Neuspiller, and L. Schwarsztein, “ Lack of a Head in Human Spermatozoa From Sterile Patients: A Syndrome Associated With Impaired Fertilization,” Fertility and Sterility 47, no. 2 (1987): 310– 316. 3545911 sourceNot checked — no full text of the source
• cites [57] H. E. Chemes, E. T. Puigdomenech, C. Carizza, S. B. Olmedo, F. Zanchetti, and R. Hermes, “ Acephalic Spermatozoa and Abnormal Development of the Head‐Neck Attachment: A Human Syndrome of Genetic Origin,” Human Reproduction 14, no. 7 (1999): 1811– 1818. 10402395 sourceNot checked — no full text of the source
• cites [58] C. Rondanino, V. Duchesne, D. Escalier, et al., “ Evaluation of Sperm Nuclear Integrity in Patients With Different Percentages of Decapitated Sperm in Ejaculates,” Reproductive Biomedicine Online 31, no. 1 (2015): 89– 99, https://doi.org10.1016/j.rbmo.2015.04.002 26001636 sourceNot checked — no full text of the source
• cites [59] J. Saias‐Magnan, C. Metzler‐Guillemain, G. Mercier, F. Carles‐Marcorelles, J. M. Grillo, and M. R. Guichaoua, “ Failure of Pregnancy After Intracytoplasmic Sperm Injection With Decapitated Spermatozoa: Case Report,” Human Reproduction 14, no. 8 (1999): 1989– 1992, https://doi.org10.1093/humrep/14.8.1989 10438415 sourceNot checked — no full text of the source

In a multivariate analysis including more than 4200 cycles, sperm morphology had no impact on pregnancy rates after IUI.

“In a multivariate analysis including more than 4200 cycles, Lemmens et al. [74] highlight sperm morphology had no impact on pregnancy rates after IUI.”

• cites [74] L. Lemmens, S. Kos, C. Beijer, et al., “ Predictive Value of Sperm Morphology and Progressively Motile Sperm Count for Pregnancy Outcomes in Intrauterine Insemination,” Fertility and Sterility 105, no. 6 (2016): 1462– 1468, https://doi.org10.1016/j.fertnstert.2016.02.012 26930619 sourceNot checked — no full text of the source

In the latter study, no significant difference was observed between fertilisation rates after IVF and ICSI in the subgroup with 0% normal morphology.

“However, in the latter study, no significant difference was observed between fertilisation rates after IVF and ICSI in the subgroup with 0% normal morphology [108].”

• cites [108] M. Li, C. Ma, X. Xue, W. Zhao, S. Zhang, and J. Shi, “ Effect of Normal Sperm Morphology Rate (NSMR) on Clinical Outcomes and Fertilization Methods Selection in the Ultra‐Short‐Term GnRH‐a Protocol,” Gynecological Endocrinology 32, no. 2 (2016): 120– 123, https://doi.org10.3109/09513590.2015.1092514 26437674 sourceNot checked — no full text of the source

Because of the methodology of the randomised oocyte cohort studies, it was not possible to compare pregnancy rates according to the technique employed.

“Because of the methodology of these studies (randomisation of oocytes), it was not possible to compare pregnancy rates according to the technique employed.”

A retrospective study in 2007 carried out over 7 years reported higher pregnancy rates with IVF than with ICSI (51.4% vs 33.6%, p = 0.05).

“Conversely, a retrospective study in 2007 carried out over a long period of time (7 years) reported higher pregnancy rates with IVF than with ICSI (51.4% vs. 33.6%, p = 0.05) [107].”

• cites [107] J. H. Check, A. Bollendorf, C. Wilson, D. Summers‐Chase, D. Horwath, and W. Yuan, “ A Retrospective Comparison of Pregnancy Outcome Following Conventional Oocyte Insemination vs Intracytoplasmic Sperm Injection for Isolated Abnormalities in Sperm Morphology Using Strict Criteria,” Journal of Andrology 28, no. 4 (2007): 607– 612, https://doi.org10.2164/jandrol.106.001941 17409463 sourceNot checked — no full text of the source

Inter-rater agreement for PICO4 was good for assessment of the impact of teratozoospermia (91.7%, kappa 0.85).

“Inter‐rater agreement was good for assessment of the impact of teratozoospermia (91.7%, kappa 0.85) (Table 2).”

A major bias in all PICO3 studies was the absence of any adjustment for other sperm parameters (motility, sperm count).

“A major bias in all these studies was the absence of any adjustment for other sperm parameters (motility, sperm count).”

All the studies analysed for PICO3 were retrospective.

“Of note, all the studies analysed were retrospective.”

The clinical relevance of sperm morphology must be considered in light of its very high intra- and inter-laboratory variability, which has been well documented until recently.

“The clinical relevance of sperm morphology must be considered in light of its very high intra‐ and inter‐laboratory variability, which has been well documented until recently (Supporting Information S2) [81]”

• cites [81] M. Irani, S. Chow, D. Keating, S. Elder, Z. Rosenwaks, and G. Palermo, “ Optimizing the First‐Line Fertility Treatment,” Gynecological Endocrinology 34, no. 9 (2018): 742– 746, https://doi.org10.1080/09513590.2018.1441825 29463146 sourceNot checked — no full text of the source

Grades for PICO4 were markedly affected by bias.

“Grades were markedly affected by bias.”

Inter-rater agreement regarding bias for PICO3 was very good (94.4%, kappa 0.85).

“Inter‐rater agreement regarding bias was very good (94.4%, kappa 0.85) (Table 2).”

Sperm morphology assessment does not meet the requirements for a valid laboratory test.

“Sperm morphology assessment does not meet the requirements for a valid laboratory test.”

In the teratozoospermia groups of PICO3 studies, male factors pre-dominated with higher levels of oligoasthenozoospermia than in the groups without teratozoospermia.

“In the teratozoospermia groups, male factors pre‐dominated with higher levels of oligoasthenozoospermia than in the groups without teratozoospermia.”

By study of the four PICO questions, the authors have demonstrated that sperm morphology assessment no longer has a relevant role before ART.

“Lastly, by study of our four PICO questions, we have demonstrated that sperm morphology assessment no longer has a relevant role before ART.”