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Journal ArticleDOI

Semen preparation techniques for intrauterine insemination

TL;DR: There is insufficient evidence to recommend any specific preparation technique, and large high quality randomised controlled trials, comparing the effectiveness of a gradient and/or a swim-up and/ or wash and centrifugation technique on clinical outcome are lacking.
Abstract: Background Semen preparation techniques for assisted reproduction, including intrauterine insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa as possible might influence treatment choices and therefore outcomes. Objectives To compare the effectiveness of gradient, swim-up, or wash and centrifugation semen preparation techniques on clinical outcome in subfertile couples undergoing intrauterine insemination (IUI). Search strategy We searched the Menstrual Disorders and Subfertility Group Trials Register (3 January 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to January 2007), EMBASE (1980 to January 2007), Science Direct Database (1966 to January 2007), National Research Register (2000 to 2007), Biological Abstracts (2000 to January 2007), CINAHL (1982 to October 2006) and reference lists of relevant articles. We also contacted experts and authors in the field. Selection criteria Parallel randomized controlled trials (RCTs) comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI in terms of clinical outcome were included. Data collection and analysis Two reviewer authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Main results Five RCTs, including 262 couples in total, were included in the meta-analysis (Dodson 1998; Grigoriou 2005; Posada 2005; Soliman 2005; Xu 2000). Xu compared the three techniques; Soliman compared a gradient technique versus a wash technique; Dodson and Posada compared a gradient technique versus a swim-up technique; whereas Grigoriou compared swim-up versus a wash technique. No trials reported the primary outcome of live birth. There was no evidence of a difference between pregnancy rates (PR) for swim-up versus a gradient or wash and centrifugation technique (Peto OR 1.57, 95% CI 0.74 to 3.32; Peto OR 0.41, 95% CI 0.15 to 1.10, respectively); nor in the two studies comparing a gradient technique versus wash and centrifugation (Peto OR 1.76, 95% CI 0.57 to 5.44). There was no evidence of a difference in them is carriage rate (MR) in two studies comparing swim- up versus a gradient technique (Peto OR 0.13, 95% CI 0.01 to 1.33). Authors' conclusions There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/or a swim-up and/or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted.

Summary (1 min read)

Background

  • Semen preparation techniques for assisted reproduction, including intrauterine insemination (IUI), were developed to separate the motile morphologically normal spermatozoa.
  • Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg.
  • The yield of many motile, morphologically normal spermatozoa might influence treatment choices and therefore outcomes.

Data collection and analysis

  • Two review authors independently assessed trial quality and extracted data.
  • Study authors were contacted for additional information.

Main results

  • Soliman 2005 compared a gradient versus a wash technique.
  • No trials reported the primary outcome of live birth.
  • 1Semen preparation techniques for intrauterine insemination Copyright © 2011 The Cochrane Collaboration.

Authors’ conclusions

  • There is insufficient evidence to recommend any specific semen preparation technique.
  • The effectiveness of specific semen preparation techniques for increasing pregnancy rates in subfertile couples undergoing intrauterine insemination (IUI) is unknown.
  • With the emergence of in vitro fertilization (IVF) with uterine transfer of embryos (IVF-ET), semen preparation techniques were developed to separate motile sperm that are morphologically normal (normal appearance) from seminal plasma (the fluid portion of the semen in which the spermatozoa are suspended) and foreign material.
  • Types of participants Subfertility was defined as couples who have tried unsuccessfully to conceive for at least one year, despite regular and unprotected coital exposures (Evers 2002).
  • The following data were extracted from the included studies and presented in the table ’Characteristics of included studies’.

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University of Groningen
Semen preparation techniques for intrauterine insemination
Boomsma, Carolien M.; Heineman, M. J.; Cohlen, B. J.; Farquhar, C.
Published in:
Cochrane Database of Systematic Reviews
DOI:
10.1002/14651858.CD004507.pub3
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
2007
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Boomsma, C. M., Heineman, M. J., Cohlen, B. J., & Farquhar, C. (2007). Semen preparation techniques for
intrauterine insemination.
Cochrane Database of Systematic Reviews
, (4), [004507].
https://doi.org/10.1002/14651858.CD004507.pub3
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Cochrane Database of Systematic Reviews
Semen preparation techniques for intrauterine insemination
(Review)
Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C
Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C.
Semen preparation techniques for intrauterine insemination.
Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD004507.
DOI: 10.1002/14651858.CD004507.pub3.
www.cochranelibrary.com
Semen preparation techniques for intrauterine insemination (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .
5BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
15ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . .
19DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
23CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
32DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Swim-up versus gradient technique, fresh semen, Outcome 1 Pregnancy rate per couple. 33
Analysis 1.2. Comparison 1 Swim-up versus gradient technique, fresh semen, Outcome 2 Miscarriage rate per couple. 34
Analysis 1.3. Comparison 1 Swim-up versus gradient technique, fresh semen, Outcome 3 Multiple pregnancy rate per
couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Analysis 2.1. Comparison 2 Swim-up versus wash and centrifugation, fresh semen, Outcome 1 Pregnancy rate per couple. 35
Analysis 2.2. Comparison 2 Swim-up versus wash and centrifugation, fresh semen, Outcome 2 Miscarriage rate per
couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis 2.3. Comparison 2 Swim-up versus wash and centrifugation, fresh semen, Outcome 3 Multiple pregnancy rate per
couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis 3.1. Comparison 3 Gradient technique versus wash and centrifugation, fresh semen, Outcome 1 Pregnancy rate
per couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis 3.2. Comparison 3 Gradient technique versus wash and centrifugation, fresh semen, Outcome 2 Miscarriage rate
per couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis 3.3. Comparison 3 Gradient technique versus wash and centrifugation, fresh semen, Outcome 3 Multiple
pregnancy rate per couple. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
38ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
39APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
43NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iSemen preparation techniques for intrauterine insemination (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

[Intervention Review]
Semen preparation techniques for intrauterine insemination
Carolien M. Boomsma
1
, Maas Jan Heineman
2
, Ben J Cohlen
3
, Cindy Farquhar
4
1
Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, Netherlands.
2
Department of Obstetrics & Gynaecology
Academic Medical Ce ntre, University of Amsterdam, Amsterdam, Netherlands.
3
Department of Obstetrics & Gynaecology, Isala
Clinics, Location Sophia, Zwolle, Netherlands.
4
Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
Contact address: Carolien M. Boomsma, Obstetrics and Gynaecology, University Medical Center Utrecht, Jan van Scorelstraat 157,
Utrecht, 3583 CN, Netherlands.
c.m.boomsma@umcutrecht.nl.
Editorial group: Cochrane Gynaecology and Fertility Group.
Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 10, 2011.
Citation: Boomsma CM, Heineman MJ, Cohle n BJ, Farquhar C. Semen preparation techniques for intrauterine insemination.
Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD004507. DOI: 10.1002/14651858.CD004507.pub3.
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Semen preparation techniques for assisted reproduction, including intrauterine insemination (IUI), were developed to separate the
motile morphologically normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively
influence the ability to fertilize the egg. The yield of many motile, morphologically normal spermatozoa might influence treatment
choices and therefore outcomes.
Objectives
To compare the effectiveness of gradient, swim-up, or wash and centrifugation semen preparation techniques on clinical outcomes in
subfertile couples undergoing intrauterine insemination (IUI).
Search methods
We searched the Menstrual Disorders and Subfertility Group Trials Register (August 2011), MEDLINE (1966 to August 2011),
EMBASE (1980 to August 2011), Science Direct Database (1966 to August 2011), Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library 2011, Issue 7), National Research Register (2000 to 2011), Biological Abstracts (2000 to August
2011), CINAHL (1982 to August 2011) and reference lists of relevant articles. We also contacted experts and authors in the fiel d.
Selection criteria
Randomised controlled trials (RCTs) comparing the efficacy of semen preparation techniques used for subfertile couples undergoing
IUI in terms of clinical outcomes were included.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.
Main results
Five RCTs, including 262 couples in total, were included in the meta-analysis (Dodson 1998; Grigoriou 2005; Posada 2005; Soliman
2005; Xu 2000). Xu 2000 compared all three techniques. Soliman 2005 compared a gradient versus a wash technique. Dodson 1998
and Posada 2005 compared a gradient technique versus a swim-up technique, whereas Grigoriou 2005 compared swim-up versus a
wash technique. No trials reported the primary outcome of live birth.
1Semen preparation techniques for intrauterine insemination (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

There was no evidence of a difference between pregnancy rates (PR) for swim-up versus a gradient technique (PR 30.5% versus 21.5%
respectively; Peto odds ratio (OR) 1.57, 95% CI 0.74 to 3.32). A swim-up technique versus wash and centrifugation also showed no
significant difference in PR (PR 22.2% versus 38.1% respectively; Peto OR 0.41, 95% CI 0.15 to 1.10). Two studies compared a
gradient versus wash centrifugation technique (PR 23.5% versus 13.3%; Peto OR 1.76, 95% CI 0.57 to 5.44). There was no evidence
of a difference in the miscarriage rate (MR) in two studies comparing a swim-up versus gradient technique (MR 0% versus 6.7%; Peto
OR 0.13, 95% CI 0.01 to 1.33).
Authors conclusions
There is insufficient e vidence to recommend any specific semen preparation technique. Large, high quality randomised controlled trials
comparing the effectiveness of a gradient, swim-up and wash and centrifugation technique on clinical outcomes are lacking. Further
randomised trials are warranted.
P L A I N L A N G U A G E S U M M A R Y
Semen preparation techniques for intrauterine insemination
The effectiveness of specific semen preparation techniques for increasing pregnancy rates in subfertile couples undergoing intrauterine
insemination (IUI) is unknown.
Semen preparation tech niques are used in assisted reproduction to separate sperm which have a normal appearance and move sponta-
neously from the fluid portion of the semen in which the sperm are suspended. It is known that white blood cells, bacteria and dead
sperm in semen can impair fertilization of the egg. This review found that there is insufficient evidence to recommend any specific
semen preparation technique for subfertile couples undergoing intrauterine insemination (a procedure which places sperm directly into
the uterus) as there were no differences in pregnancy rates using the different techniques. More research is needed.
2Semen preparation techniques for intrauterine insemination (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Citations
More filters
Journal ArticleDOI
TL;DR: Robust evidence is lacking but based on the available results gonadotrophins might be the most effective drugs when IUI is combined with ovarian hyperstimulation, and low dose protocols are advised since pregnancy rates do not differ from pregnancy rates which result from high dose regimen, whereas the chances to encounter negative effects from ovarian stimulation such as multiples and OHSS are limited with low dose gonadotropic drugs.
Abstract: Background Intrauterine insemination (IUI) combined with ovarian hyperstimulation (OH) has been demonstrated to be an effective form of treatment for subfertile couples. Several ovarian stimulation protocols combined with IUI have been proposed, but it is still not clear which stimulation protocol and which dose is the most cost-effective. Objectives To evaluate ovarian stimulation protocols for intrauterine insemination for all indications. Search strategy We searched for all publications which described randomised controlled trials comparing different ovarian stimulation protocols followed by IUI. We searched the Menstrual Disorders and Subfertility Group's Central register of Controlled Trials (CENTRAL). We searched the electronic databases of MEDLINE (January 1966 to present) and EMBASE (1980 to present). Selection criteria Randomised controlled trials only were considered for inclusion in this review. Trials comparing different ovarian stimulation protocols combined with IUI were selected and reviewed in detail. Data collection and analysis Two independent review authors independently assess trial quality and extracted data. Main results Forty three trials involving 3957 women were included. There were 11 comparisons in this review. Pregnancy rates are reported here since results of live birth rates were lacking. Seven studies (n = 556) were pooled comparing gonadotrophins with anti-oestrogens showing significant higher pregnancy rates with gonadotrophins (OR 1.8, 95% CI 1.2 to 2.7). Five studies (n = 313) compared anti-oestrogens with aromatase inhibitors reporting no significant difference (OR 1.2 95% CI 0.64 to 2.1). The same could be concluded comparing different types of gonadotrophins (9 studies included, n = 576). Four studies (n = 391) reported the effect of adding a GnRH agonist which did not improve pregnancy rates (OR 0.98 95% CI 0.6 to 1.6), although it resulted in significant higher multiple pregnancy rates (OR 2.9 95% CI 1.0 to 8). Data of three studies (n = 299) showed no convincing evidence of adding a GnRH antagonist to gonadotrophins (OR 1.5 95% CI 0.83 to 2.8). The results of two studies (n = 297) reported no evidence of benefit in doubling the dose of gonadotrophins (OR 1.2 95% 0.67 to 1.9) although the multiple pregnancy rates and OHSS rates were increased. For the remaining five comparisons only one or none studies were included. Authors' conclusions Robust evidence is lacking but based on the available results gonadotrophins might be the most effective drugs when IUI is combined with ovarian hyperstimulation. When gonadotrophins are applied it might be done on a daily basis. When gonadotrophins are used for ovarian stimulation low dose protocols are advised since pregnancy rates do not differ from pregnancy rates which result from high dose regimen, whereas the chances to encounter negative effects from ovarian stimulation such as multiples and OHSS are limited with low dose gonadotrophins. Further research is needed for each comparison made.

154 citations

Journal Article
TL;DR: The authors deem that its recommendation to the analysis method and lower reference limit of sperm concentration may be a little arbitrary and lack of evidence-based support, and that the determination methods of anti-sperm antibody and seminal plasma biochemical markers are incompatible with the status of Chinese andrology laboratories.
Abstract: The 5th edition of WHO Laboratory Manual for the Examination and Processing of Human Semen (2010) represents a comprehensive revision. This article aims to explore the applicability of this manual to andrology laboratories in China mainland in view of sperm count analysis, sperm motility analysis, sperm morphology analysis, sperm function analysis, anti-sperm antibody and seminal plasma biochemical marker analysis, and quality assurance and quality control of semen analysis. The authors deem that its recommendation to the analysis method and lower reference limit of sperm concentration may be a little arbitrary and lack of evidence-based support, that the revised grading sperm motility, the strict criteria and the very low cut-off value of 4% morphologically normal spermatozoa for the evaluation of sperm morphology are not applicable to andrology laboratories in China mainland, that the sperm function markers need to be supplemented, and that the determination methods of anti-sperm antibody and seminal plasma biochemical markers are incompatible with the status of Chinese andrology laboratories. However, its recommended methods for quality assurance and quality control of semen analysis have a significant directive role in China mainland. It is worth to point out that the WHO manual ignored the data obtained from Chinese which accounts for approximate 20% of the world population. Thus, given the importance of the WHO manual, its general applicability should be evaluated in China.

130 citations

Journal ArticleDOI
TL;DR: An urgent need is identified for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate because of the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies.
Abstract: Many variables may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample. A literature search was performed to investigate the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved and/or the cut-off values reaching substantial discriminative performance in an IUI programme. A search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers. Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were analysed. Sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value ⩾5% normal morphology; (iii) total motile sperm count in the native sperm sample: cut-off value of 5-10 million; and (iv) total motility in the native sperm sample: threshold value of 30%. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. More prospective cohort trials and prospective randomized trials investigating the predictive value of semen parameters on IUI outcome are urgently needed. It is generally believed that intrauterine insemination (IUI) with homologous semen should be a first-choice treatment to more invasive and expensive techniques of assisted reproduction in cases of cervical, unexplained and moderate male factor subfertility. The rationale for the use of artificial insemination is to increase gamete density at the site of fertilization. Scientific validation of this strategy is difficult because literature is rather confusing and inconclusive. Many variables may influence success rates after IUI treatment procedures. It seems logical that sperm quality has to be one of the main determinants to predict IUI success. Clinical practice would benefit from the establishment of threshold levels for sperm parameters above which IUI pregnancy outcome is significantly improved and below which a successful outcome is unlikely. We performed a literature search to investigate if such threshold levels are known. Most striking were the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies. The four sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value >4% normal morphology; (iii) total motile sperm count in native sperm sample: cut-off value of 5-10 million; and (iv) total motility in native sperm sample: threshold value of 30%. This review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate.

129 citations

Journal ArticleDOI
TL;DR: Both sperm preparation methods allow obtaining a sperm population with a low percentage of apoptotic sperm, which seems to be rather low and depends on whether IVF/ICSI or intrauterine insemination is to be performed.

109 citations

References
More filters
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TL;DR: Methods do exist for including valuable information from two-period, two-treatment cross-over trials into quantitative reviews, however, poor reporting of cross- over trials will often impede attempts to perform a meta-analysis using the available methods.
Abstract: Background Meta-analysis of randomized controlled trials (RCTs) is usually based on trials where patients are randomized individually into two different, parallel, treatment groups. This paper concentrates on RCTs of a different design—two-period, twotreatment cross-over trials. Methods The characteristics of these trials are outlined, with detailed examples of methods for analysis for both continuous and binary data. These case studies are then extended into the context of a meta-analysis. The Cochrane Library was surveyed to assess current practice for synthesis. Results Methods are described for continuous and binary data for use both when the necessary paired data are given and also when they need to be calculated or imputed, and some suggestions are provided to help people wishing to synthesize data from cross-over trials into meta-analyses. The survey suggested that about 8% of the trials in the Cochrane library were cross-over trials and 18% of the reviews referred to such trials, although there was no consistent approach to their inclusion into the reviews. Conclusions Methods do exist for including valuable information from two-period, twotreatment cross-over trials into quantitative reviews. However, poor reporting of cross-over trials will often impede attempts to perform a meta-analysis using the available methods.

1,598 citations

Journal ArticleDOI
TL;DR: Human spermatozoa appear to use reactive oxygen species for a physiological purpose and have the difficult task of ensuring the balanced generation of these potentially harmful, but biologically important, modulators of cellular function.
Abstract: Although the generation of reactive oxygen species is an activity normally associated with phagocytic leucocytes, mammalian spermatozoa were, in fact, the first cell type in which this activity was described. In recent years it has become apparent that spermatozoa are not the only nonphagocytic cells to exhibit a capacity for reactive oxygen species production, because this activity has been detected in a wide variety of different cells including fibroblasts, mesangial cells, oocytes, Leydig cells, endothelial cells, thyroid cells, adipocytes, tumour cells and platelets. Since the capacity to generate reactive oxygen species is apparently so widespread, the risk-benefit equation for these potentially pernicious molecules becomes a matter of intense interest. In the case of human spermatozoa, the risk of manufacturing reactive oxygen metabolites is considerable because these cells are particularly vulnerable to lipid peroxidation. Indeed, there is now good evidence to indicate that oxygen radicals are involved in the initiation of peroxidative damage to the sperm plasma membrane, seen in many cases of male infertility. This risk is off-set by recent data suggesting that superoxide anions and hydrogen peroxide also participate in the induction of key biological events such as hyperactivated motility and the acrosome reaction. Thus, human spermatozoa appear to use reactive oxygen species for a physiological purpose and have the difficult task of ensuring the balanced generation of these potentially harmful, but biologically important, modulators of cellular function.

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TL;DR: Sperm separation methods that yield a higher number of motile spermatozoa are glass wool filtration or density gradient centrifugation with different media and caffeine, pentoxifylline and 2-deoxyadenosine are substances that were used to stimulate motility.
Abstract: The onset of clinical assisted reproduction, a quarter of a century ago, required the isolation of motile spermatozoa. As the indication of assisted reproduction shifted from mere gynaecological indications to andrological indications during the years, this urged andrological research to understand the physiology of male germ cell better and develop more sophisticated techniques to separate functional spermatozoa from those that are immotile, have poor morphology or are not capable to fertilize oocytes. Initially, starting from simple washing of spermatozoa, separation techniques, based on different principles like migration, filtration or density gradient centrifugation evolved. The most simple and cheapest is the conventional swim-up procedure. A more sophisticated and most gentle migration method is migration-sedimentation. However, its yield is relatively small and the technique is therefore normally only limited to ejaculates with a high number of motile spermatozoa. Recently, however, the method was also successfully used to isolate spermatozoa for intracytoplasmic sperm injection (ICSI). Sperm separation methods that yield a higher number of motile spermatozoa are glass wool filtration or density gradient centrifugation with different media. Since Percoll® as a density medium was removed from the market in 1996 for clinical use in the human because of its risk of contamination with endotoxins, other media like IxaPrep®, Nycodenz, SilSelect®, PureSperm® or Isolate® were developed in order to replace Percoll®. Today, an array of different methods is available and the selection depends on the quality of the ejaculates, which also includes production of reactive oxygen species (ROS) by spermatozoa and leukocytes. Ejaculates with ROS production should not be separated by means of conventional swim-up, as this can severely damage the spermatozoa. In order to protect the male germ cells from the influence of ROS and to stimulate their motility to increase the yield, a number of substances can be added to the ejaculate or the separation medium. Caffeine, pentoxifylline and 2-deoxyadenosine are substances that were used to stimulate motility. Recent approaches to stimulate spermatozoa include bicarbonate, metal chelators or platelet-activating factor (PAF). While the use of PAF already resulted in pregnancies in intrauterine insemination, the suitability of the other substances for the clinical use still needs to be tested. Finally, the isolation of functional spermatozoa from highly viscous ejaculates is a special challenge and can be performed enzymatically to liquefy the ejaculate. The older method, by which the ejaculate is forcefully aspirated through a narrow-gauge needle, should be abandoned as it can severely damage spermatozoa, thus resulting in immotile sperm.

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Journal ArticleDOI
TL;DR: Empiric studies have demonstrated that the induced bias is large and can have a serious impact on meta-analyses, in which data from several studies are aggregated, as well as on informal reviews.
Abstract: Publication bias is a widely recognized phenomenon that occurs because of the influence of study results on the chances of publication. Usually, studies with positive results are more likely to be published than studies with negative results, which leads to a preponderance of false-positive results in the literature. Empiric studies have demonstrated that the induced bias is large and can have a serious impact on meta-analyses, in which data from several studies are aggregated, as well as on informal reviews. The problem is deeply embedded in current research practice, which encourages demonstration of statistical significance to "prove" theories, and one of its causes is the pressure to publish extensively that is an integral part of the competition for academic promotion. Serious efforts to reduce this problem will involve restructuring the process by which study results are disseminated, changing editorial policies, and altering the style and methods of statistical analysis.

388 citations

Journal ArticleDOI
TL;DR: Results indicate that both the PureSperm((R)) and Percoll((R) techniques can enrich the sperm population by separating out those with nicked DNA and with poorly condensed chromatin.
Abstract: Human semen is heterogeneous in quality, not only between males but also within a single ejaculate. Differences in quality are evident, both when examining the classical parameters of sperm number, motility and morphology and in the integrity of the sperm nucleus. The aim of this study was to determine the efficiency of the PureSperm((R)), Percoll((R)) and swim-up preparation techniques to eliminate spermatozoa with nuclear anomalies. Semen samples were collected, washed and one part of the semen spread on a slide, the remainder was prepared using the swim-up, PureSperm((R)) or Percoll((R)) techniques. Spermatozoa from different fractions were fixed on slides and assessed. Sperm samples (n) from different men were stained using the chromomycin A(3) (CMA(3)) fluorochrome, which indirectly demonstrates a decreased presence of protamine (n = 31 for swim-up; n = 45 for PureSperm((R)); n = 39 for Percoll((R))). Spermatozoa prepared using PureSperm((R)) (n = 35) and Percoll((R)) (n = 37) were also examined for the presence of endogenous DNA nicks. Good quality spermatozoa should not possess DNA nicks and not stain (i.e. fluoresce) with CMA(3). When prepared using the swim-up technique the spermatozoa recovered showed no significant improvement with the CMA(3) staining. When spermatozoa were prepared using the PureSperm((R)) and Percoll((R)) techniques, a significant (P < 0.001) decrease in both CMA(3) positivity and DNA strand breakage was observed. These results indicate that both the PureSperm((R)) and Percoll((R)) techniques can enrich the sperm population by separating out those with nicked DNA and with poorly condensed chromatin.

239 citations

Frequently Asked Questions (7)
Q1. What contributions have the authors mentioned in the paper "Semen preparation techniques for intrauterine insemination (review)" ?

The effectiveness of specific semen preparation techniques for increasing pregnancy rates in subfertile couples undergoing intrauterine insemination ( IUI ) is unknown this paper. 

CI: Conf idence interval ; OR: Odds rat io ; GRADE Working Group grades of evidence High quality: Further research is very unlikely to change their conf idence in the est imate of ef fect. Moderate quality: Further research is likely to have an important impact on their conf idence in the est imate of ef fect and may change the est imate. Low quality: Further research is very likely to have an important impact on their conf idence in the est imate of ef fect and is likely to change the est imate. Some research has suggested an association between the probability of conception after IUI and the absolute number of motile sperm that are inseminated. 

In couples with subfertility, the yield of as many motile, morphologically normal spermatozoa as possible is important as it influences treatment choices and therefore outcomes. 

European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM) abstract books were also handsearched. 

A randomised controlled trial (RCT) of prepared sperm compared to unprepared first split ejaculates showed that semen preparation significantly increased the probability of conception after intrauterine insemination (IUI) in a group of couples with male subfertility (Goldenberg 1992). 

Five RCTs, including 262 couples in total, were included in the meta-analysis (Dodson 1998; Grigoriou 2005; Posada 2005; Soliman 2005; Xu 2000). 

Subfertile couples are defined as couples who have tried unsuccessfully to conceive for at least one year despite regular and unprotected coital exposures (sexual intercourse) (Evers 2002).