Hum. Reprod. Advance Access originally published online on January 5, 2006
Human Reproduction 2006 21(5):1105-1109; doi:10.1093/humrep/dei460
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DEBATE CONTINUED |
Is quality assurance in semen analysis still really necessary? A view from the andrology laboratory
Academic Unit of Reproductive and Developmental Medicine, The University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK
To whom correspondence should be addressed at: Academic Unit of Reproductive and Developmental Medicine, The University of Sheffield, Level 4, The Jessop Wing, Royal Hallamshire Hospital, Sheffield S10 2SF, UK. E-mail: a.pacey{at}sheffield.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
Quality assurance (QA) is a fundamental part of laboratory medicine, of which internal and external QA (proficiency testing) is an important part. In a recent debate article published in Human Reproduction, it was argued that it was no longer necessary for semen analysis to be subject to QA, primarily because it is now being performed robustly and there is little evidence that it has any real clinical value. In response to this argument, it is suggested here that although there may have been some improvements in the training of laboratory scientists, recent studies have shown that the techniques of semen analysis are still poorly implemented at many locations. Moreover, as the impact of the introduction of QA into the andrology laboratory begins to take effect, there are a growing number of studies showing that the results of semen analysis do correlate well with natural conception and some assisted reproductive technologies. However, since the processes of QA are central to the principles of total quality management, which in turn underpins the process of laboratory accreditation, QA needs to remain in the andrology (and embryology) laboratory so that they can achieve the same accredited status as medical laboratories in other disciplines.
Key words: male fertility/quality assurance/quality control/semen analysis
|
Introduction |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
Quality assurance (QA) is an essential part of any diagnostic testing in laboratory medicine and is a cornerstone of modern (ISO-based) accreditation systems (Burnett, 1996
). That it has only relatively recently (and I suspect somewhat reluctantly) been applied to semen analysis is of some concern, given the alarming variation in the results obtained between analysing laboratories shown by Matson (1995) and later confirmed by others. The view by Jequier (2005), that we have now made sufficient strides in improving the quality of semen analysis that QA is now ‘a waste of time and/or a waste of money’, is understandable, given the increasing pressures for cost efficiencies in health care. But, this view fails to acknowledge that QA ensures that the methods employed in the laboratory for measurement maintain an acceptable level of accuracy and precision that, as part of total quality management (TQM), is designed to give reassurances to patients, clinicians and the laboratory staff alike about the performance of a diagnostic pathway. Moreover, it allows the laboratory to have an idea of the errors of their results and detailed assessment of ‘measurement uncertainty’, and the reporting of this with the results would make it clear to all, even Dr Jequier, that QA is a crucial part of andrology. Unfortunately, QA of semen analysis is not as straightforward as with an automated analyser for blood constituents where standards and QA samples are included with every run. The counting of limited numbers of sperm (e.g. less than 200 in duplicate of a potential population of millions), lack of standards and the human element pose many unique problems that are covered in WHO (1999). |
Is semen analysis now being performed satisfactorily? |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
A central argument of Jequier (2005)
is that semen analysis is now being performed satisfactorily all over the world. But, what is the evidence for this? It has certainly been shown that attendance on training courses can have a significant improvement on the performance of individual scientists (Bjorndahl et al., 2002). But, this is far removed from whether or not these scientists continue to perform to the same levels of accuracy when they return to their laboratories. Moreover, in many countries, training programmes are not mandatory, and whether all laboratory staff engaged in performing semen analysis ever receive the appropriate training is unknown. Despite the efforts made by Dr. Jequier over 25 years ago to introduce training courses into the UK, it remains the case that there are still no mandatory training programmes for laboratory scientists undertaking semen analysis in the UK in the same way that there are for other techniques in other pathology-related disciplines. As such, the training course, initially set up by the British Andrology Society [and now running under the auspices of the Association of Biomedical Andrologists (ABA)], only fills a void that exists in the training routes for biomedical scientists in the UK. Only now is ABA in discussions with the relevant regulatory authorities within the UK to develop a system of training and registration of andrologists in line with other laboratory disciplines. To assess whether or not semen analysis is now being performed appropriately, we can examine evidence from two sources.
The first source is that there are recent surveys of laboratory practice which have been carried out in both the USA (Keel et al., 2002) and the UK (Riddell et al., 2005). Sadly, these have both shown relatively poor implementation of some aspects of semen analysis. For example, in the USA (Keel et al., 2002), 6 and 5% of laboratories fail to report data for sperm concentration and motility, respectively, as part of semen analysis. A further 15% fail to report sperm morphology.
In the assessment of sperm morphology, 83% of US (Keel et al., 2002) and 69% of UK (Riddell et al., 2005) laboratories that undertake sperm morphology assessment observe less than 100 sperm in order to report the percentage of morphologically normal sperm. Whilst this may appear like a small and trivial point, the impact of sample size on this kind of measurement is profound, given the relatively wide confidence interval obtained when counting so few cells (Kuster et al., 2004) particularly when the population range only goes from 0 to at most 20% normal. In theory, severe teratozoospermia (that could push the patient immediately towards ICSI treatment) could be diagnosed in an otherwise normal sample (where IVF or even intrauterine insemination might be more appropriate) through statistical chance alone when so few sperm are being counted. That laboratory staff appear unaware or unconcerned of this fact suggests that they still do not understand the statistical and theoretical basis of the measurements they are making. This is despite many excellent guidelines on the subject produced by the Clinical Laboratory Standards Institute (NCCLS, 1999, 2002, 2003).
The second source of evidence is an examination of laboratory performance in existing external QA (proficiency testing) schemes, such as the United Kingdom National External Quality Assurance Scheme (NEQAS) in andrology. In this scheme, participating laboratories are asked to examine on four occasions each year specimens of formalin-fixed aliquots of semen (for the examination of sperm concentration and morphology) and video recordings of samples (to evaluate sperm motility). QA material like this is not exchanged between participating laboratories as suggested in Jequier (2005), but it is sent out from a central (co-ordinating) laboratory in the expectation that the participants will return their assessment of the samples by a specified date. These data are then collated, and the participants sent details of their own results in comparison with the average and spread of results returned by others. The scheme has now been in operation for over 10 years, and what is clear is that there still remains considerable variation between participating laboratories in their results (although the situation is improving).
For example, Figure 1 shows the frequency distribution of the results returned to NEQAS by participating laboratories for four of the 16 QA samples for sperm concentration distributed between November 2004 and August 2005. In each example, (a) to (d), it can be seen that there is a considerable range of results returned. In the case of the samples shown in (a) and (c), although both samples are normozoospermic (from the mean result of all participants), in both cases a small number of laboratories reported that they were below 20 x 106/ml. Conversely, the sample shown in (b) is oligozoospermic (mean result 10.72 x 106 sperm/ml); yet again a small number of laboratories reported that this was normozoospermic with over 30 x 106 sperm/ml. Finally, whilst the mean result of all participants for sample (d) was at very close to the WHO (1999) threshold at 19.90 x 106 sperm/ml, some participants reported a sperm concentration of below 8 x 106 sperm/ml, with others reporting above 40 x 106 sperm/ml.
|
Therefore, the only conclusion that can be reached from the consideration of these two sources is that, although the situation may have improved in recent years in the eyes of Dr Jequier, semen analysis still remains poorly conducted in some laboratories around the world. There is little convincing evidence that it is being performed accurately and reproducibly at all locations, although individual laboratories may be doing an exemplary job. Moreover, it is probably true to say that clear examples of how semen analysis QA has resulted in the correction of a methodological problem are rare, but this may be because few laboratories are sufficiently dedicated to the principles.
|
Do the results of semen analysis predict fertility? |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
A second argument put forward by Jequier (2005)
is that QA in semen analysis is not essential because the results generated do not adequately predict fertility. Again, is this really true?
Over the past few years, there has been a considerable body of evidence showing that when semen analysis is performed robustly (i.e. with QA in place), impressive relationships between individual measures obtained at semen analysis (concentration, motility and morphology) and the probability of conception can be found in men from the general population. In the study by Bonde et al. (1998) for example, there is an increasing probability of conception within the follow-up period as the concentration of sperm rises to about 50 x 106/ml. This is echoed by the analysis by Larsen et al. (2000) who used computer-assisted sperm analysis to determine the concentration of motile spermatozoa (swimming at >25 microns/s). That these relationships exist despite the apparent day-to-day variation in ejaculate quality, the fact that semen analysis was not performed in the conception cycle and that variation in female physiology will introduce confounding factors that are difficult to control for, is impressive.
What is evident from these and other studies, however, is that there appears to be little relationship between their findings and the widely used 20 x 106/ml threshold in sperm concentration that is used by WHO (1999) to define an abnormal semen profile. This is further supported by the study of Guzick et al. (2001) who found that in order for a man to be considered fertile, his sperm concentration had to exceed 48 x 106/ml and he could only be considered subfertile if his sperm concentration fell below 13.5 x 106/ml. What this suggests is that there is an extensive ‘grey area’ over which it is difficult to use sperm concentration to make a robust prediction of fertility. However, what Guzick et al. (2001) found was that the percentage of morphologically normal sperm was a much greater discriminator between fertile and subfertile men, with only a 4% difference between them. This is particularly interesting, given the well-described relationship between sperm morphology and the probability of fertilization and pregnancy after IVF (Kruger et al., 1986; Grow et al., 1994); this has recently been given further support by the relationship between teratozoospermia and defective sperm–zona interaction (Liu and Baker, 2003). It is therefore somewhat ironic that sperm morphology assessment is so badly implemented in andrology laboratories around the world, as was discussed earlier.
Given the above discussion, I would argue that there is considerable amassing evidence that semen analysis can give an indication of fertility potential in males, over and above being able to identify at the outset overtly poor ejaculates where assisted conception is clearly indicated. However, I would concede that there is much work still to be done in this arena and now is not the time to be abandoning the principles of QA.
|
Can diagnostic methods be improved? |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
There can be no doubt that we have made significant advances in our approach to semen analysis since the pioneering work of MacLeod (1956)
. The successive editions of the World Health Organization Laboratory Manual (WHO, 1980, 1987, 1992, 1999) have provided increasingly stringent methodological approaches that should now be achieving global standardization of techniques. However, what each subsequent edition has done is primarily to restrict the range of techniques to be used in the laboratory and encourage a gradual move to those that have been shown to give the highest degrees of accuracy and precision. The manuals have not radically overhauled the science of male fertility assessment or introduced better or technologically more advanced methods of making measurements of male fertility. As such, we are still primarily making the same three measures of sperm concentration, motility and morphology that were first described by MacLeod nearly 50 years ago. Essentially what semen analysis is trying to achieve is to identify the population of sperm in an ejaculate (or a prepared sample) that has the potential to fertilize an oocyte. However, I accept that a weakness is that it is attempting to do this from characteristics of sperm that are ‘measurable’ by a human observer rather than by considering specific functions of sperm that may be important in the process of sperm transport and fertilization. Therefore, sperm concentration is an indication of the ability of the testes to produce spermatozoa, sperm motility gives a measure of the integrity of the sperm axoneme and tail structures as well as the metabolic machinery of the mitochondria and sperm morphology is a surrogate measure of the integrity of DNA packaging and the ‘quality’ of spermatogenesis.
In a recent book chapter (Pacey, 2005), I argued that the reason we only get broad correlations between semen analysis and outcome measures (see above) is because increasing numbers of sperm in an ejaculate (or prepared sample) increase the probability of having sufficient numbers of functionally competent sperm at the right place and the right time, rather than because semen analysis is able to identify and quantify ‘good sperm’. However, it is not fair to say that we do not understand the complexities of what happens to spermatozoa once they are inside the female reproductive tract as some of the fundamental processes are now well described (Suarez and Pacey, 2005), although there is undoubtedly more to learn. However, what we have so far been bad at doing is translating this knowledge into credible sperm function test(s) that can either be used as a replacement for the traditional semen analysis (WHO, 1999) or be complementary to it.
Perhaps the tests with most potential are those that examine the integrity of sperm DNA (Agarwal and Said, 2003). For example, Spano et al. (2000) used the sperm chromatin structure assay to investigate the DNA integrity of men entering a 2-year follow-up study with their partners and who were attempting to conceive for the first time. This study found that poor-quality chromatin structure was highly predictive of male subfertility regardless of the number, motility or morphology of spermatozoa. Moreover, no pregnancies were reported when more than 30–40% of spermatozoa were seen to contain damaged DNA. This has subsequently been confirmed by other studies. It is therefore perhaps not entirely surprising to find that men attending infertility clinics have higher levels of DNA damage in their sperm (Irvine et al., 2000). Indeed, several studies have shown that DNA integrity is directly related to IVF outcomes (Morris et al., 2002; Tomsu et al., 2002). Furthermore, a recent study (Seli et al., 2004) was able to show that blastocyst development was indirectly correlated to DNA damage as assessed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ DNA nick-end labelling (TUNEL) technique.
Therefore, it may be the case that the tests we currently rely upon to assess male fertility potential may ultimately become replaced or supplemented by tests of equal (or better) predictive power. However, again this is no justification for abandoning current QA measures in the andrology laboratory. Indeed, any new test would have to be subject to the same degree of rigour and TQM that is currently being implemented for the semen analysis as we know it.
|
The future of laboratory andrology |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
The final and perhaps most convincing argument to justify why QA will remain as an essential part of semen analysis surrounds the importance of QA in the fundamental principles of a TQM (Burnett, 1996
) which underpins the process of accreditation.
In general terms, health care organizations have lagged behind their manufacturing counterparts in recognizing the importance of implementing quality systems as an integral component of their operations. However, this is now changing, and the main driver for change has come from a greater regulatory and/or accreditation oversight of their activities. The main principles of a quality system have been laid down in the ISO 9000 Quality Standards (International Organisation for Standardization, 1996), but to date, most laboratory scientists have only emphasized the quality control level of this model as evidenced by Jequier’s arguments.
As pointed out by Burnett (1996), QA is not simply restricted to the analytical aspects of laboratory medicine but to all aspects of the analytical process: from referring the patient for testing and collecting the specimen (pre-analytical phase) to actually performing the laboratory tests (analytical phase) and then reporting the results and interpreting them (post-analytical phase). Interestingly, it has been shown that 84.5% of errors detected in a certified medical laboratory occurred in the pre-analytical phase (Wiwanitkit, 2001); yet the concerns emphasized by Jequier (2005) largely concern only the analytical and post-analytical phases of semen analysis. Sadly, we do not understand what effect such errors have on patients in an infertility setting, although it has been estimated that 12% of errors surrounding the diagnostic process actually impact on patient care (Goldschmidt and Lent, 1995). Therefore, I would argue that it is perhaps premature, and against the principles of TQM, to consider abandoning QA in semen analysis.
The implementation of ISO-based quality systems in, and therefore structures for laboratory accreditation of, semen analysis in countries such as the UK has been possible because of the obvious linkage between the andrology laboratory and other laboratory-based disciplines, such as pathology and microbiology where this is now mandatory (Burnett et al., 2002). Arguably, accreditation in semen analysis in this setting has led the way for this to be introduced into the assisted conception unit as a whole. Whilst the need for such a step has previously been identified (Alper et al., 2002) and has been implemented in a growing number of units across Europe (Wikland and Sjoblom, 2000), it will soon become mandatory in Europe, with the recent directive of the European Commission on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (Directive 2004/23/EC) being adopted into the legislation of member states. Therefore, rather than relax the QA of the andrology laboratory, it is set to become more commonplace in all aspects of diagnosis and treatment of infertile couples. And in my opinion, quite rightly so.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
The author thanks Dr Matthew Tomlinson (Queen’s Medical Centre, Nottingham, UK) and Dr Dave Morroll (Leeds Teaching Hospitals, UK) for commenting on this article. Thanks also to Mr Andrew Robins of the Wolfson Computer Laboratory, University Hospitals Birmingham NHS Trust for permission to reproduce the histograms shown in Figure 1 of the article.
|
References |
|---|
|
TopAbstractIntroductionIs semen analysis now...Do the results of...Can diagnostic methods be...The future of laboratory...AcknowledgementsReferences |
|---|
Agarwal A and Said TM (2003) Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update 9,331–345.
Alper MM, Brinsden PR, Fischer R and Wikland M (2002) Is your IVF programme good? Hum Reprod 17,8–10.
Bjorndahl L, Barratt CL, Fraser LR, Kvist U and Mortimer D (2002) ESHRE basic semen analysis courses 1995–1999: immediate beneficial of standardized training. Hum Reprod 17,1299–1305.
Bonde JP, Ernst E, Jensen TK, Hjollund NH, Kolstad H, Henriksen TB, Scheike T, Giwercman A, Olsen J and Skakkebaek NE (1998) Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352,1172–1177.[CrossRef][Web of Science][Medline]
Burnett D (1996) Understanding Accreditation in Laboratory Medicine. ACB Venture Publications, London.
Burnett D, Blair C, Haeney MR, Jeffcoate SL, Scott KWM and Williams DL (2002) Clinical pathology accreditation: standards for the medical laboratory. J Clin Pathol 55,729–733.
Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Official Journal of the European Union 47,L102,48–58.
Goldschmidt HM and Lent RW (1995) Gross errors and work flow analysis in the clinical laboratory. Klin Biochem Metab 3,131–140.
Grow DR, Oehninger S, Seltman HJ, Toner JP, Swanson RJ, Kruger TF and Muasher SJ (1994) 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 62,559–565.[Web of Science][Medline]
Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, Carson SA, Cisneros P, Steinkampf MP, Hill JA et al. (2001) Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 345,1388–1393.
International Organisation for Standardization (1996) ISO 9000 Compendium, 6th edn.
Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA and Aitken JR (2000) DNA integrity in human spermatozoa: relationship with semen quality. J Androl 21,33–44.[Abstract]
Jequier AM (2005) Is quality assurance in semen analysis still really necessary? A clinician’s viewpoint. Hum Reprod 20,2039–2042.
Keel BA, Sternbridge TW, Pineda G and Serafy NT (2002) Lack of standardisation in performance of the semen analysis among laboratories in the United States. Fertil Steril 78,603–608.[CrossRef][Web of Science][Medline]
Kruger TF, Menkweld R, Stander FSH and Lombard CJ (1986) Sperm morphological features as a prognostic factor in IVF. Fertil Steril 46,1118–1123.[Web of Science][Medline]
Kuster CE, Singer RS and Althouse GC (2004) Determining sample size for the morphological assessment of sperm. Theriogenology 61,691–703.[CrossRef][Web of Science][Medline]
Larsen L, Scheike T, Jensen TK, Bonde JP, Ernst E, Hjollund NH, Zhou Y, Skakkebaek NE and Giwercman A (2000) Computer-assisted semen analysis parameters as predictors for fertility of men from the general population. The Danish First Pregnancy Planner Study Team. Hum Reprod 15,1562–1567.
Liu DY and Baker HWG (2003) Frequency of defective sperm–zona interaction in severely teratozoospermic infertile men. Hum Reprod 18,802–807.
MacLeod J (1956) Human semen. Fertil Steril 7,368–386.[Web of Science][Medline]
Matson PL (1995) External quality assessment for semen analysis and sperm antibody detection: results of a pilot scheme. Hum Reprod 10,620–625.
Morris ID, Ilott S, Dixon L and Brison DR (2002) Spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilisation and embryo development. Hum Reprod 17,990–998.
NCCLS (1999) Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline, 2nd edn. NCCLS document C24-A2 (ISBN 1-56238-371-X). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.
NCCLS (2002) Method Comparison and Bias Estimation Using Patient Samples; Approved Guidelines, 2nd edn. NCCLS document EP9-A2 (ISBN 1-56238-472-4). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.
NCCLS (2003) Estimation of Total Analytical Error for Clinical Laboratory Methods; Approved Guideline. NCCLS document EP21-A (ISBN 1-56238-502-X). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.
Pacey AA (2005) What makes ‘good sperm’. In Critchley H, Cameron I and Smith S (eds) Implantation and Early Development. RCOG Press, London, pp. 119–128.
Riddell D, Pacey A and Whittington K (2005) Lack of compliance in UK andrology laboratories to World Health Organisation recommendations for sperm morphology assessment. Hum Reprod 20,3441–3445.
Seli E, Gardner DK, Schoolcraft WB, Moffatt O and Sakkas D (2004) Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilisation. Fertil Steril 82,378–383.[CrossRef][Web of Science][Medline]
Spano M, Bonde JP, Hjøllund HI, Kolstad HA, Cordelli E, Leter G and the Danish First Pregnancy Planner Study Team. (2000) Sperm chromatin damage impairs human fertility. Fertil Steril 73,43–50.[CrossRef][Web of Science][Medline]
Suarez SS and Pacey AA (2005) Sperm transport in the female reproductive tract. Human Reprod Update 12,23–37.
Tomsu M, Sharma V and Miller D (2002) Embryo quality and IVF treatment outcome may correlate with different sperm comet assay parameters. Hum Reprod 17,1856–1862.
Wikland M and Sjoblom C (2000) The application of quality systems in ART programs. Mol Cell Endocrinol 166,3–7.[CrossRef][Web of Science][Medline]
Wiwanitkit V (2001) Types and frequency of pre-analytical mistakes in the first ISO 9002: 1994 certified clinical laboratory, a 6-month monitoring. BMC Clin Pathol 1,5.[CrossRef][Medline]
World Health Organization (1980) WHO Laboratory Manual for the Examination of Human Semen and Sperm–Cervical Mucus Interaction, 1st edn. Cambridge University Press, Cambridge, UK.
World Health Organization (1987) WHO Laboratory Manual for the Examination of Human Semen and Sperm–Cervical Mucus Interaction, 2nd edn. Cambridge University Press, Cambridge, UK.
World Health Organization (1992) WHO Laboratory Manual for the Examination of Human Semen and Sperm–Cervical Mucus Interaction, 3rd edn. Cambridge University Press, Cambridge, UK.
World Health Organization (1999) WHO Laboratory Manual for the Examination of Human Semen and Sperm–Cervical Mucus Interaction, 4th edn. Cambridge University Press, Cambridge, UK.
Submitted on August 23, 2005; resubmitted on November 23, 2005; accepted on November 26, 2005.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. E M Lewis Is sperm evaluation useful in predicting human fertility? Reproduction, July 1, 2007; 134(1): 31 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lefievre, K. Bedu-Addo, S. J Conner, G. S M Machado-Oliveira, Y. Chen, J. C Kirkman-Brown, M. A Afnan, S. J Publicover, W C. L Ford, and C. L R Barratt Counting sperm does not add up any more: time for a new equation? Reproduction, April 1, 2007; 133(4): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||