These patients have a poor prognosis, even with ICSI, and in cases in which fertilization has resulted, the pronuclei do not fuse, and zygotes fail to cleave and, thus, degenerate This sperm defect can be because of defective sperm aster formation, syngamy and cleavage.
Small-headed spermatozoa in men occur more frequently in couples complaining of infertility than currently diagnosed because of the unfortunate fact that this condition is not commonly recognized and reported as a severe sperm abnormality.
This abnormality is stable over time. These spermatozoa may also present with very small, abnormally formed acrosomes. These spermatozoa present with severely abnormal megalo heads and multiple tails, and are observed in the ejaculate and testicular biopsies Low fertilization and pregnancy rates are achieved with ICSI, which may be because of the high incidence of chromosomal aberrations in the ejaculated megalo-headed spermatozoa The second group, with unspecified or non-genetically determined sperm defects or patterns caused by environmental or other stress factors, including medication, differs from the group with genetically determined permanent sperm defects, which will not respond to treatment.
Sperm defects in the second group can return to normal or disappear when the source of the alternations or stress is removed or treated. Males with these types of sperm abnormalities still have a good chance for normal in vivo conception or, alternatively, a good prognosis for IVF without ICSI. To further enhance the diagnosis of men with a potentially good IVF chance, several additional morphology tools are available, such as the TZI, AI, the presence of cytoplasmic residues and sperm head measurements.
Megalo heads can also be caused by the use of medicine, such as sulfasalazine, for the treatment of ulcerative colitis 59 and Crohn's disease When sulfasalazine treatment is stopped, the semen parameters can return to normal values, and the megalo heads can disappear.
It is not clear whether this will result in fertilization and viable pregnancies. However, the substitution of sulfasalazine with mesalazine has resulted in improved semen quality and the reduction of the megalo heads, subsequently resulting in viable pregnancies Elongation is generally recognized as a stress-induced sperm morphology aberration, and is prevalent especially in MAGI and in the presence of a varicocele Pyriform heads are also included under elongation of spermatozoa.
Sperm elongation is accompanied by severe structural as well as DNA damage. The increased sperm head length results from an abnormally elongated nucleus, which also presents particular membranous layers between the outer and inner leaves of the nuclear envelope.
The sperm nuclear anomalies are also associated with anomalies of the neck region, persistence of cytoplasmic residual material and an increased frequency of chromosomal aneuploidies, together with impaired chromatin compaction, possibly because of meiotic non-disjunction during spermatogenesis Low ICSI fertilization rates have also been found in men with severely elongated spermatozoa compared with other sperm morphology abnormalities However, when the MAGI is treated with long-term antibiotics or the varicocele is treated with a varicocelectomy, semen characteristics, including sperm morphology, can improve and pregnancies can result In case of varicocelectomies, in which no substantial improvement in semen quality is observed, pregnancies do still occur because sperm DNA quality improves because of the reduction of ROS production following the varicocelectomy The presence, size and terminology of the cytoplasmic droplets or cytoplasmic residues are controversial.
Recently, Cooper et al. According to Cooper 68 , it is clear that retention of cytoplasmic material on spermatozoa, as seen in air dried and stained semen smears, can be associated with impaired sperm function. It is clear from this article and from our own experience 69 that no amount of cytoplasmic material should be present on a normal spermatozoon and, if observed, it should be regarded as an abnormality, regardless of the size or amount of cytoplasmic material present.
Cooper 68 also suggested that the correct term to be used for the presence of cytoplasmic material should be 'excess cytoplasmic residues' or cytoplasmic residues. The presence of cytoplasmic residues is associated with sperm immaturity and especially the production of ROS, with subsequent sperm DNA damage; although IVF pregnacies may occur, decreased pregnancy rates are reported Therefore, much more attention should be given to the presence of cytoplasmic residues with the routine evaluation of sperm morphology.
The earlier sections showed that sperm size, and therefore sperm measurement, is a very important aspect of the sperm morphology evaluation process. However, the measurements proposed by Eliasson 30 , and adopted in the WHO manuals 6 , 7 , 8 , 9 and other publications 12 are in need of re-evaluation, because the range allowed, especially the normal head length of 3.
Our own experience indicates that the head length for normal spermatozoa may vary between 4. Alternative measurements have been proposed by several authors, such as Katz et al.
The new WHO manual no longer refers to the 'old' sperm measurements, but states that head dimensions of 77 Papanicolaou-stained semen smears measured with a computerized system, have a median length of 4. Unfortunately, the manual also states that 'once a normally shaped spermatozoa is identified, an eye-piece micrometer may be useful for distinguishing between the normal and abnormal size — own word spermatozoa, but with this technique the form of the sperm head is much more important than its dimension unless grossly abnormal.
Sperm measurement is an area deserving much more attention in today's sperm morphology assessment methodology, and more research is needed to establish more accurate sperm measurements. Although not actually a sperm morphology parameter, determination of the presence of leukocytes, especially polymorphonuclear leukocytes, is an important aspect of the sperm morphology evaluation procedure Although sometimes reported as part of the morphology evaluation procedure, much more emphasis should be placed on the presence of polymorphonuclear leukocytes in semen and the importance of antibiotic treatment for leukocytospermia and the subsequent possible improvement in pregnancy outcome 65 , However, an abnormal spermatozoon may have only one specific abnormality or any combination of two to four abnormalities, as described above.
The TZI was introduced to reflect the mean number of abnormalities per abnormal spermatozoon. The usefulness of the TZI seems to be limited, and it is seldom used in the literature as a tool in decision-making with regard to possible treatment of patients because it does not indicate a specific dominant abnormality present in a specific semen sample.
Following a literature search and on the basis of an analysis of our own data, we concluded that the TZI has little predictive value for in vivo and IVF outcomes The AI is an indication of the percentage of spermatozoa with morphologically normal acrosomes present in a semen sample and can be regarded as a reflection of the functional ability of the spermatozoa, because the AI is based on the morphological appearance of the acrosomes with regard to size too small or too large , staining properties and form oval or amorphous shaped.
The results of sperm morphology evaluations can be further improved by better international standardization for the whole sperm morphology evaluation procedure, better international training and improvement, and standardization of international external quality control EQC schemes. Different staining procedures can lead to different sperm morphology evaluation results Therefore, before comparisons of the results of different laboratories can be made, large-scale standardization should be implemented in laboratories worldwide as far as preparation and staining techniques are concerned, focusing on well-prepared smears and staining according to the Papanicolaou method only.
The lack of standardization in the EQC schemes is illustrated in the article by Cooper et al. The users of different international EQC programs should start to work together by interchanging standardized QC material and then, after a trial period, come together to discuss the results and to try to standardize their interpretations for sperm morphology evaluations on the basis of strict evaluation principals.
On its own, the new proposed very low normal value may not provide a strong predictive value for a male's fertility potential, as originally reported for sperm morphology evaluated according to strict criteria In these cases, it becomes of utmost importance that clinicians receive more detailed data on abnormal sperm patterns and specific abnormalities so they may use the additional information to make a final decision regarding the treatment of the patient, because certain morphology patterns and sperm abnormalities are known to be of strong prognostic value.
The normal WHO value for sperm morphology is based on Papanicolaou-stained smears. Another set of normal cut-off values needs to be established for rapid staining methods because the literature indicates that higher normal values are obtained in Diff-Quik-stained semen samples compared with the same samples stained with the Papanicolaou method A high percentage of morphologically abnormal spermatozoa can be associated with the presence of poor sperm functionality.
On the other hand, morphologically normal-appearing spermatozoa should also be further investigated for normal sperm function and DNA content because morphological normality does not necessarily imply normal sperm function 80 , In addition, better international standardization of the technical methodology, consensus on the interpretation of sperm morphology evaluation criteria, and standardized international EQC schemes are of the utmost importance.
National Center for Biotechnology Information , U. Journal List Asian J Androl v. Asian J Androl. Published online Jan Author information Article notes Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Keywords: male fertility potential, normal cut-off values, semen analysis, sperm morphology evaluation, strict criteria, WHO manual.
Introduction Reaching a professional consensus always involves a difficult balance of divergent views, and no consensus has been more difficult to reach than that regarding the evaluation and reporting of sperm morphology. History of sperm morphology evaluation The interest in sperm morphology as a tool in the evaluation of a man's fertility potential started in the early s, when it became accepted that normal and pathological sperm forms could appear simultaneously in a semen sample 2.
Liberal approach Human males exhibit extreme heterogeneity, or pleomorphism, of sperm morphology among 13 and even within specific males Strict Tygerberg criteria The strict approach for sperm morphology evaluation was conceptualized in the late s and early s, as described by Menkveld in 11 and Menkveld et al.
Evolution of WHO criteria for sperm morphology evaluation There was no clear textual description for morphologically normal spermatozoa in the 1st WHO manual published in 6 , except in some legends for the color plates in which it is mentioned that 'the germinal cell classifications are based on those proposed by MacLeod,' thus following the liberal approach. Evolution of the WHO cut-off point for normal morphology Through the progression of the first four WHO manuals, some minor changes occurred in the cut-off values with respect to most semen variables, such as concentration, motility and viability.
Open in a separate window. Obtained from the lower fifth centile value. Comparison of the proposed WHO value with recently published normal sperm morphology values As early as and , Van Zyl et al. Table 2 Comparison of fifth World Health Organization WHO manual for normal morphology values with recently published literature values. Possible reasons for the decline in reference values The reason for the drastic decrease in normal sperm morphology cut-off values over the years, as illustrated in Figure 1 , are mainly three-fold, namely, i the implementation of strict evaluation criteria with the unfortunate result that sperm morphology evaluation became over-critical with regard to normality, ii the fact that over the years more criteria for sperm morphological abnormalities were identified and introduced into the evaluation system, and iii a true decline because of negative environmental factors.
Figure 1. Introduction of strict criteria The statement that, with strict evaluation, borderline spermatozoa should be regarded as abnormal, which is against the principle for the liberal approach that borderline spermatozoa should be regarded as normal, automatically placed a large number of spermatozoa, which would have been regarded as normal by the liberal approach, into the abnormal category when using the strict criteria approach, leading to an overall lower percentage of morphologically normal spermatozoa.
Introduction of additional criteria for sperm morphology evaluation The original description of sperm abnormalities, as described, for example, by MacLeod and Gold 16 , and Freund 44 , concerned head abnormalities only. Negative environmental factors Carlson et al. Genetically determined sperm defects Globozoospermia One of the best-known genetically determined sperm sterilizing defects or patterns is globozoospermia.
Short tail syndrome In some semen samples, the spermatozoa present with abnormalities of the spermatozoa tail and neck region. Small-headed spermatozoa Small-headed spermatozoa in men occur more frequently in couples complaining of infertility than currently diagnosed because of the unfortunate fact that this condition is not commonly recognized and reported as a severe sperm abnormality.
Large-headed spermatozoa These spermatozoa present with severely abnormal megalo heads and multiple tails, and are observed in the ejaculate and testicular biopsies Non-genetic sperm morphology aberrations The second group, with unspecified or non-genetically determined sperm defects or patterns caused by environmental or other stress factors, including medication, differs from the group with genetically determined permanent sperm defects, which will not respond to treatment.
Megalo heads Megalo heads can also be caused by the use of medicine, such as sulfasalazine, for the treatment of ulcerative colitis 59 and Crohn's disease Elongated spermatozoa Elongation is generally recognized as a stress-induced sperm morphology aberration, and is prevalent especially in MAGI and in the presence of a varicocele Sperm measurements The earlier sections showed that sperm size, and therefore sperm measurement, is a very important aspect of the sperm morphology evaluation process.
Detection of leukocytes Although not actually a sperm morphology parameter, determination of the presence of leukocytes, especially polymorphonuclear leukocytes, is an important aspect of the sperm morphology evaluation procedure Acrosome index AI The AI is an indication of the percentage of spermatozoa with morphologically normal acrosomes present in a semen sample and can be regarded as a reflection of the functional ability of the spermatozoa, because the AI is based on the morphological appearance of the acrosomes with regard to size too small or too large , staining properties and form oval or amorphous shaped.
Future aspects of sperm morphology evaluation The results of sperm morphology evaluations can be further improved by better international standardization for the whole sperm morphology evaluation procedure, better international training and improvement, and standardization of international external quality control EQC schemes.
Standardization of international external quality control schemes The lack of standardization in the EQC schemes is illustrated in the article by Cooper et al. International cooperation in standardization The users of different international EQC programs should start to work together by interchanging standardized QC material and then, after a trial period, come together to discuss the results and to try to standardize their interpretations for sperm morphology evaluations on the basis of strict evaluation principals.
References World Health Organisation. Human Spermatozoa in Assisted Reproduction. Carnforth: Parthenon Publishing; , p89— Cary HW. Examination of semen with reference to gynaecological aspects. Observations on the seminal micro-pathology of bulls. Cornell Vet. Sperm morphology in relation to fertility. Am J Obstet Gynecol. WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction, 1st edn.
WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction, 2nd edn. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 3rd edn. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th edn. Methodological aspects of sperm morphology evaluation: comparison between strict and liberal criteria. Fertil Steril. An investigation of environmental influences on spermatogenesis and semen parameters [PhD dissertation in Afrikaans ].
The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Human Reprod. Sperm morphology assessment—historical perspectives and current opinions. J Androl. Individualism in the seminal picture of infertile men. The male factor in fertility and infertility.
Sperm morphology in fertile and infertile marriage. The clinical interpretation of semen analyses among applicants for sterility studies. Sperm selection capacity of the human zona pellucida. Mol Reprod Dev. Morphology of spermatozoa bound to the zona pellucida of human oocytes that failed to fertilize in vitro.
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Oligozoospermia: a seven-year survey of the incidence, chromosomal aberrations, treatment and pregnancy rate. Int J Fertil. The importance of spermiograms that meet the requirements of international standards and the most important factors that influence semen parameters In: Proceedings of the 17th Congress of the International Urological Society. Balitimore: Williams and Wilkins; Menkveld R, Kruger TF. Basic semen analysis The Tygerberg experience.
Baltimore: Williams and Wilkins; Human Spermatozoa in Assisted Reproduction, 2nd edn. Carnforth: Parthenon Publishing; Menkveld R. The basic semen analysis Chapter 9. Male Infertility. Diagnosis and Treatment. Oxon: Informa Healthcare. Standards for investigation of human semen. Oligozoospermia: recent prognosis and outcome of 73 pregnancies in oligozoospermia couples.
Sperm morphological features as a prognostic factor in in vitro fertilization. Predictive value of abnormal sperm morphology in in vitro fertilization. Sperm morphology assessment using strict criteria and male fertility under in-vivo conditions of conception. Hum Reprod. Semen parameters in a fertile versus subfertile population: a need for a change in the interpretation of semen testing. Semen Quality and human fertility: a prospective study with health couples. Semen parameters including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardisation of in vivo thresholds.
A study of semen parameters with emphasis on sperm morphology in a fertile population: an attempt to develop clinical thresholds. Sperm morphology, motility and concentration in fertile and infertile men. N Engl J Med. Semen parameters in Norwegian fertile men. Int J Androl. Predictive ability of strict and WHO sperm morphology criteria for in vitro fertilization. Aust J Med Sci. Possible changes in male fertility over a year period. Arch Androl. Reassessment of sperm morphology of archival semen smears from the period — Standards for the rating of human sperm morphology.
Fertilization in mammals. Sci Am. Acrosomal morphology as a novel criterion for male fertility diagnosis: relation with acrosin activity, morphology strict criteria and fertilization in vitro.
Evidence for declining quality of semen during past 50 years. Br Med J. Clinical correlates of environmental endocrine disruptors. Trends Endocrinol Metab. The question of declining sperm density revisited: an analysis of studies published — Author information Article notes Copyright and License information Disclaimer. Marc Goldstein: ude. Copyright notice. Design Retrospective study.
Setting Tertiary hospital. Patient s Men without known azoospermia who had semen analysis SA collected over a year period of time. Result s A total of 4, SAs were identified during the study period. Key Words: I nfertility, semen analysis, sperm morphology. Sample Collection All individuals were provided instructions on sample collection, including collection after self-stimulation into a clean container.
Statistical Analysis Patient age was computed electronically using the date of the sample collection. Open in a separate window. Figure 1. Table 1 Summary of demographic data. Figure 2. Figure 3.
Discussion Semen analysis remains the gold standard in assessing male infertility and includes numerous parameters. Conclusion Given the limited predictive value of sperm morphology, the additional cost and effort of performing strict morphometric assessments using the Kruger strict criteria may not be warranted in comparison with the simpler WHO4 morphologic assessment.
Footnotes G. References 1. Kumar N. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. Thonneau P. Incidence and main causes of infertility in a resident population 1,, of three French regions Hum Reprod. Jarow J. American Urological Association Education and Research. Accessed June 20, ; World Health Organization. World Health Organzation; Switzerland: Laboratory manual for the examination and processing of human semen.
World Health Organisation. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Patel A. Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: a systematic review.
Arab J Urol. Chen X. Predictive value of semen parameters in in vitro fertilisation pregnancy outcome. Menkveld R. Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Asian J Androl. Horte A. Reassessment of sperm morphology of archival semen smears from the period Int J Androl. Kruger T. Predictive value of abnormal sperm morphology in in vitro fertilization.
Fertil Steril. Atlas of human sperm morphology evaluation. Gandini L. Study of apoptotic DNA fragmentation in human spermatozoa. Hum Reprod. Lee J. Analysis of chromosome constitution of human spermatozoa with normal and aberrant head morphologies after injection into mouse oocytes. Dadoune J. Correlation between defects in chromatin condensation of human spermatozoa stained by aniline blue and semen characteristics.
Martin R. A comparison of the frequency of sperm chromosome abnormalities in men with mild, moderate, and severe oligozoospermia. Biol Reprod. Hotaling J. The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis. Rybouchkin A. Analysis of the oocyte activating capacity and chromosomal complement of round-headed human spermatozoa by their injection into mouse oocytes.
Vicari E. Globozoospermia is associated with chromatin structure abnormalities: case report. Chemes H. Phenotypes of sperm pathology: genetic and acquired forms in infertile men.
J Androl. Kihaile P. Arch Androl. Chelli M. Can intracytoplasmic morphologically selected sperm injection be used to select normal-sized sperm heads in infertile patients with macrocephalic sperm head syndrome? Keegan B. Isolated teratozoospermia does not affect in vitro fertilization outcome and is not an indication for intracytoplasmic sperm injection. Lockwood G. Isolated abnormal strict morphology is not a contraindication for intrauterine insemination.
Kohn T. Effect of sperm morphology on pregnancy success via intrauterine insemination: a systematic review and meta-analysis. J Urol. Kovac J. Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction. The need of personalized medicine in coping with stress during infertility treatment. J Pers Med. Masoumi S. Comparison of quality of life, sexual satisfaction and marital satisfaction between fertile and infertile couples.
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