Semen preparation techniques for intrauterine insemination

TLDR: 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.

Figures

Figure 2. Risk domains: review authors’ judgements about each potential risk of bias item for each included study.

Table 1. Characteristics of cross-over RCTs excluded from meta-analysis (Continued)

Table 2. Results from cross-over RCTs excluded from meta-analysis

Figure 1. Risk of bias: review authors’ judgements about each risk domain presented as percentages across all included studies.

Figure 5. Forest plot of comparison: 2 Swim-up versus wash and centrifugation; fresh semen, outcome: 2.1 Pregnancy rate per couple.

Figure 6. Forest plot of comparison: 3 Gradient technique versus wash and centrifugation; fresh semen, outcome: 3.1 Pregnancy rate per couple.

Full text

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
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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.

Frequently asked questions

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. 

Q2. What future works have the authors mentioned in the paper "Semen preparation techniques for intrauterine insemination (review)" ?

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. 

Q3. What is the importance of a high yield of sperm?

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. 

Q4. Who were the two main databases searched?

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

Q5. Who was the author of the study?

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). 

Q6. How many RCTs were included in the meta-analysis?

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

Q7. What is the definition of infertile couples?

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).