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Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction

  1. Danielle M Teixeira1,
  2. Mariana AP Barbosa1,
  3. Rui A Ferriani1,
  4. Paula A Navarro1,
  5. Nick Raine-Fenning2,
  6. Carolina O Nastri1,
  7. Wellington P Martins1,*

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 25 JUL 2013

Assessed as up-to-date: 8 MAY 2013

DOI: 10.1002/14651858.CD010167.pub2

How to Cite

Teixeira DM, Barbosa MAP, Ferriani RA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD010167. DOI: 10.1002/14651858.CD010167.pub2.

Author Information

  1. 1

    University of Sao Paulo, Department of Obstetrics and Gynecology, Medical School of Ribeirao Preto, Ribeirao Preto, Sao Paulo, Brazil

  2. 2

    University of Nottingham, Division of Obstetrics and Gynaecology, School of Clinical Sciences, Nottingham, UK

*Wellington P Martins, Department of Obstetrics and Gynecology, Medical School of Ribeirao Preto, University of Sao Paulo, Hospital das Clínicas da FMRP-USP, 8 andar, Campus Universitário, Campus Universitario da USP, Ribeirao Preto, Sao Paulo, 14048-900, Brazil. wpmartins@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 25 JUL 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

 
Summary of findings for the main comparison.

Regular (ICSI) compared with ultra-high magnification (IMSI) for assisted reproduction

Patient or population: couples undergoing assisted reproduction techniques

Intervention: sperm selection under ultra-high magnification (IMSI)

Comparison: sperm selection under regular magnification (ICSI)

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)

Assumed riskCorresponding risk

ICSIIMSINNTB

Live birth per allocated couple38 per 10044 per 100
(30 to 63)
-RR 1.14 (0.79 to 1.64)168
(1 study)
⊕⊕⊝⊝
low1

Clinical pregnancy per allocated couple33 per 10043 per 100
(36 to 52)
10

(5 to 33)
RR 1.29 (1.06 to 1.55)2014
(9 studies)
⊕⊝⊝⊝
very low2

Miscarriage per clinical pregnancy22 per 10018 per 100
(13 to 25)
-RR 0.82 (0.59 to 1.14)552
(6 studies)
⊕⊝⊝⊝
very low3

Congenital abnormalities per clinical pregnancyNo evidence.


The median control group risk across studies was used as the basis for the assumed risk. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ICSI: intracytoplasmic sperm injection; IMSI: intracytoplasmic morphologically selected sperm injection; NNTB: number needed to treat for an additional beneficial outcome; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1. The quality of the evidence was downgraded two levels due to very serious imprecision.
2. The quality of the evidence was downgraded one level due to the high risk of bias in the included studies; another level due to inconsistency across studies; and one further level because publication bias was strongly suspected.
3. The quality of the evidence was downgraded two levels due to very serious imprecision; and another level due to the high risk of bias in the included studies.

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Description of the condition

Subfertility is a condition found in up to 15% of couples of reproductive age and until the late 1970s, there were few options for treating these couples. Since the first successful in vitro fertilisation (IVF) was described, the efficacy of subfertility treatment has greatly improved. However, it was soon realised that the technique had great limitations in achieving pregnancy in couples with compromised semen parameters. During the 1980s, some other assisted reproductive technology techniques (ART) were developed focusing on gamete micromanipulation. However, for all these techniques, spermatozoa had to be progressively motile and needed to have the potential for an acrosome reaction, leaving infertility due to severe male factors inadequately treated. Then, in 1992, the first successful intracytoplasmic sperm injection (ICSI) was reported (Palermo 1992). For ICSI, after sperm preparation an optical magnification of 200x to 400x is used to examine the sample. The best 'normal looking' motile spermatozoa are selected based on their major morphology and then injected into oocytes retrieved after ovarian stimulation. With ICSI, even men with severe male factor infertility could possibly achieve pregnancy. However, despite 20 years of technological improvements, both clinical pregnancy and live birth rates remain relatively low at approximately 35% and 25% per started cycle, respectively (Jungheim 2010).

 

Description of the intervention

In the early 2000s, a new method of sperm selection named 'motile sperm organelle morphology examination' (MSOME) was described (Bartoov 2002). This technique requires the analysis of minor morphological criteria using ultra-high magnification (≥ 6000x) microscopy. The ART using MSOME to select the sperm was named intracytoplasmic morphologically selected sperm injection (IMSI) (Bartoov 2003). When using this technique, the motile sperm fraction is examined based on six subcellular organelles: acrosome, postacrosomal lamina, neck, mitochondria, tail, and nucleus.

 

How the intervention might work

By using MSOME, some organelle malformations that are not detectable using magnifications of 200x to 400x can be detected. Sperm selection based on these small details is thought to improve reproductive outcomes (Berkovitz 2006).

 

Why it is important to do this review

Initial reports have shown that IMSI is associated with higher pregnancy rates in couples with repeated implantation failures (Bartoov 2002; Bartoov 2003). However, both the effectiveness and safety of IMSI in clinical practice remain unclear. Since there are no large published studies, a systematic review of the best available evidence is needed to facilitate a more robust conclusion. Although a systematic review and meta-analysis on this issue has been published (Setti 2010), the authors of that review evaluated a single database (MEDLINE) and supplemented the evidence from a single randomised controlled trial (RCT) with non-randomised studies to improve precision, which is poorly justifiable, as this decision increases the risk of obtaining a biased estimate (Higgins 2011). The present review aims to perform a wider and updated search, considering only the evidence from RCTs .

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

To compare the effectiveness and safety of IMSI and ICSI in couples undergoing ART.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We considered only RCTs for inclusion; we excluded quasi- or pseudo-randomised trials. We included studies that allowed the inclusion of the same participant more than once (cross-over or 'per cycle' trials) only if we could obtain the data regarding the first inclusion of each participant.

 

Types of participants

Couples undergoing ART.

 

Types of interventions

Intracytoplasmic injection of sperm selected under high magnification (≥ 6000x = IMSI) compared to intracytoplasmic injection of sperm selected under regular magnification (200x to 400x = ICSI).

 

Types of outcome measures

 

Primary outcomes

Effectiveness: live birth per allocated couple.

 

Secondary outcomes

Effectiveness: clinical pregnancy per allocated couple.

Adverse events: miscarriage per clinical pregnancy; congenital abnormalities per live birth.

Although fertilisation and implantation rates were important outcomes for this review, we did not include them in the quantitative meta-analysis due to use of differing denominators (injected oocytes for fertilisation rate and transferred embryos for implantation rate). However, we included implantation and fertilisation rates in the review for completeness, and describe them in the Characteristics of included studies table.

 

Search methods for identification of studies

We developed the search strategy in consultation with the Menstrual Disorders and Subfertility Group (MDSG) Trials Search Co-ordinator. We did not limit searches by language or publication status.

 

Electronic searches

We performed the electronic searches on 31 August 2012 and updated them on 8 May 2013.

We searched for RCTs in the following electronic databases:

We searched for study protocols and ongoing trials in the following trials registers (Appendix 8):

We searched for conference abstracts in the Web of Knowledge (http://wokinfo.com; Appendix 9).

We searched for grey literature in Open Grey (www.opengrey.eu/) (Appendix 10).

We searched for similar reviews in the Database of Abstracts of Reviews of Effects (DARE) (Appendix 11).

 

Searching other resources

We handsearched the reference lists of included articles and related reviews.

 

Data collection and analysis

We conducted data collection and analyses in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

 

Selection of studies

Two review authors (DMT and MAPB) independently reviewed titles and abstracts, and checked for duplicates using the pre-established criteria for inclusion. We resolved disagreements by consulting a third review author (WPM). We retrieved the full-text manuscripts of trials considered potentially eligible for inclusion and two review authors (DMT and MAPB) independently evaluated eligibility of these trials. We resolved disagreements by consulting a third review author (WPM). We corresponded with study investigators as required to clarify study eligibility. We placed no limitations regarding language, publication date or publication status.

 

Data extraction and management

We extracted data from eligible studies using a data extraction form designed and pilot-tested by the review authors. Where studies had multiple publications, we used the main trial report as the reference and obtained additional details from secondary papers. We contacted study authors in order to resolve any data queries, as required. Two review authors (DMT and WPM) independently extracted the data and any disagreements between these review authors were resolved by consulting a third review author (CON).

 

Assessment of risk of bias in included studies

Two review authors (DMT and WPM) independently assessed the risk of selection bias (random sequence generation and allocation concealment); performance bias (blinding of participants and personnel); detection bias (blinding of outcome assessors); attrition bias (incomplete outcome data); reporting bias (selective outcome reporting); and other potential sources of bias (e.g. a difference in the number of embryos transferred, age of participants, co-interventions). We resolved any disagreements by consulting a third review author (CON). To judge the risk of bias, we used The Cochrane Collaboration's criteria for judging risk of bias (Higgins 2011): we classified the trials as being at 'low', 'high', or 'unclear' risk of bias.

 

Measures of treatment effect

For dichotomous data (e.g. live birth rates), we used the numbers of events in the control and intervention groups of each study to calculate the Mantel-Haenszel risk ratio (RR). We prefer to use RR because odds ratio (OR) is harder to understand and apply in practice. Misinterpretation of the OR as if it equated to the RR will tend to overestimate the intervention effect, especially when events are common, and there is concern that this occurs quite frequently in published reports of individual studies and systematic reviews (Higgins 2011). However, if we had observed a zero cell count or prevalence less than 1%, the Peto fixed-effect OR would have been used because this method is found to be the least biased and most powerful, providing the best confidence interval (CI) coverage in these situations (Higgins 2011); in additional the OR value in such situations is very similar to RR, avoiding misinterpretations. We calculated the 95% CI to determine the precision of the estimates. We considered the clinical relevance of any statistically significant findings; in these situations, we also determined the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH).

 

Unit of analysis issues

The primary analysis was per couple randomised. Exceptions were miscarriage, where we considered the number of clinical pregnancies in each group as the denominator, because miscarriage is a harm that can only occur in pregnant women; and congenital abnormalities, which would be analysed per live birth (but this outcome was not reported by any study). We did not find any studies that permitted the participant to be included more than once, as cross-over or 'per cycle' trials. We counted the delivery of a multiple pregnancy (e.g. twins or triplets) as one live birth event.

 

Dealing with missing data

We analysed the results on an intention-to-treat (ITT) basis, as far as possible, and we contacted most of the original investigators to obtain missing data. We planned that where these data were unobtainable, clinical pregnancy (and subsequent live birth or miscarriage) would be assumed not to have occurred in participants with unreported outcomes. This was not necessary, because all studies reported the occurrence of clinical pregnancy after embryo transfer for all participants.

 

Assessment of heterogeneity

We assessed heterogeneity using the I2 statistic and addressed substantial heterogeneity (I2 > 50%) by: checking again that the data were correct; performing the planned subgroup analysis; excluding studies with high risk of bias; and, if it could not be explained, we incorporated the heterogeneity by using a random-effects model.

 

Assessment of reporting biases

In view of the difficulty of detecting and correcting for publication bias and other reporting biases, we aimed to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert for duplication of data. Even though only nine studies were included, a funnel plot was used to explore the possibility of small studies effect (a tendency for estimates of the intervention effect to be more beneficial in smaller studies) for clinical pregnancy.

 

Data synthesis

We combined the data from primary studies to compare IMSI versus ICSI. An increased risk of a particular outcome associated with IMSI, which may be beneficial (e.g. live birth) or detrimental (e.g. miscarriage), was displayed graphically in the meta-analysis to the right of the centre line and a decreased risk to the left of the centre line.

 

Subgroup analysis and investigation of heterogeneity

We planned to perform the following subgroup analyses if substantial heterogeneity (I2 > 50%) was observed.

  • Sperm quality: studies including only couples where the male partner had poor sperm quality, or partners with good or unselected sperm quality.
  • Sperm source: ejaculate or surgical.
  • Previous unsuccessful embryo transfers: studies including only women with repeated previous unsuccessful embryo transfers, or any women.

However, we could only perform the first subgroup analysis as no studies evaluated only sperm obtained from surgical procedures or only women with repeated previous unsuccessful embryo transfers.

 

Sensitivity analysis

We performed sensitivity analyses to verify whether the conclusions about live birth and clinical pregnancy would differ if eligibility was restricted to studies without high risk of bias.

 

Overall quality of the body of evidence: 'Summary of findings' table

We generated a 'Summary of findings' table using GRADEpro software. This table evaluated the overall quality of the body of evidence for the main review outcomes, using the following GRADE criteria: study limitations (i.e. risk of bias), consistency of effect, imprecision, indirectness, and publication bias. Judgements about evidence quality (high, moderate, low, or very low) were justified, documented and incorporated into the reporting of results for each outcome.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Results of the search

The search retrieved 270 records after removing duplicates. We considered 28 to be potentially eligible and examined them for eligibility. Nine trials (from 12 records) met our inclusion criteria, and we excluded 11 studies (from 12 records). Three studies are awaiting classification. The study flow diagram is shown in Figure 1.

 FigureFigure 1. Study flow diagram.

 

Included studies

 

Study design and setting

We included nine RCTs in the review. All were single-centre studies conducted in academic centres from Italy (Antinori 2008), Turkey (Balaban 2011), Brazil (Figueira 2011; Setti 2011; Setti 2012a; Setti 2012b), Slovenia (Knez 2011; Knez 2012), and Tunisia (Mahmoud 2011).

 

Participants

The studies included 1002 women in the intervention groups (IMSI) and 1012 women in the control groups (ICSI). Five studies included only couples in which the male partner had poor sperm quality (Antinori 2008; Knez 2011; Knez 2012; Mahmoud 2011; Setti 2011); three included women with advanced maternal age (Figueira 2011; Setti 2012a; Setti 2012b); and one study included couples who underwent ART without specifying further details (Balaban 2011). One of the nine trials excluded couples with female factor infertility (Antinori 2008), and three excluded women with polycystic ovaries syndrome (PCOS) or endometriosis (Knez 2011; Knez 2012; Setti 2012b).

 

Interventions

All studies compared regular (ICSI) versus ultra-high magnification (IMSI).

 

Outcomes

  • One study reported live birth.
  • Nine studies reported clinical pregnancy.
  • Six studies reported miscarriage.
  • No studies reported congenital abnormalities.

 

Excluded studies

We excluded 11 studies from the review, for the following reasons:

  • eight were not RCTs (observational studies);
  • three randomly allocated the oocytes, not the couples.

 

Risk of bias in included studies

See table Characteristics of included studies; Figure 2; and Figure 3 for detailed information.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

Five of the nine studies were at low risk of selection bias related to sequence generation, as they used computer randomisation or a random numbers table. The other four studies did not describe the method used and were at unclear risk of this bias. Two studies were at low risk of selection bias related to allocation concealment, as they used sealed opaque envelopes prepared by research nurses (Antinori 2008; Knez 2011). The other seven studies did not describe the method for allocation concealment and we classified them to be at unclear risk of bias.

 

Blinding

We did not consider that blinding of participants, personnel, and outcome assessors was likely to influence findings for any of the outcomes evaluated by this review (live birth, pregnancy rates, miscarriage and congenital malformations). We judged all studies to be at low risk of bias in this domain.

 

Incomplete outcome data

We considered all nine studies to be at low risk of bias in this domain, as they stated that all allocated women were analysed.

 

Selective reporting

We considered all nine studies to be at low risk of selective reporting bias, because clinical pregnancy was reported by all included studies. Although eight studies did not report live birth and nine studies did not report congenital malformations, we believe these studies might not be designed to evaluate these outcomes, as they take longer to be assessed.

 

Other potential sources of bias

We deemed four studies to be at high risk of other bias, because there were substantial differences regarding the mean number of oocytes retrieved or embryos transferred between groups, or both (Figueira 2011; Setti 2011; Setti 2012a; Setti 2012b). We considered three studies to be at unclear risk of bias, because there was insufficient information to compare the number of oocytes retrieved or embryos transferred, or both, per participant (Knez 2011; Knez 2012; Mahmoud 2011). We judged two studies to be at low risk of other potential sources of bias (Antinori 2008; Balaban 2011).

 

Effects of interventions

See:  Summary of findings for the main comparison

 

1. Ultra-high magnification (IMSI) versus regular (ICSI) sperm selection for assisted reproduction

 

Primary outcomes

 
1. 1 Live birth (effectiveness)

No significant difference was observed between the IMSI and ICSI groups (RR 1.14, 95% CI 0.79 to 1.64, 1 RCT, 168 women, I2 = not applicable, low-quality evidence;  Analysis 1.1, Figure 4 ).

 FigureFigure 4. Forest plot of comparison: 1 Ultra high (IMSI) versus regular magnification (ICSI), outcome: 1.1 Live birth per allocated couple.

 

Secondary outcomes

 
1.2 Clinical pregnancy (effectiveness)

IMSI was associated with a significantly higher rate of clinical pregnancy than ICSI (RR 1.29, 95% CI 1.07 to 1.56, 9 RCTs, 2014 women, I2 = 57%, very-low-quality evidence, Figure 5). The resulting NNTB was 10 (95% CI 5 to 33).

 FigureFigure 5. Forest plot of comparison: 1 Ultra high (IMSI) versus regular magnification (ICSI), outcome: 1.2 Clinical pregnancy per allocated couple.

Subgroup analysis (separating the studies by those that included only couples with poor sperm quality and those that included couples with good or unselected sperm quality) did not reduce the observed heterogeneity ( Analysis 2.1). Sensitivity analysis restricting the eligibility to studies without high risk of bias did not change this estimate. We used a random-effects model to incorporate the observed heterogeneity. The funnel plot suggested a small studies effect (Figure 6), and therefore we strongly suspected publication bias.

 FigureFigure 6. Funnel plot of comparison: 1 Ultra high (IMSI) versus regular magnification (ICSI), outcome: 1.2 Clinical pregnancy per allocated couple.

 
1.3 Miscarriage (adverse events)

No significant difference between the groups was observed in miscarriage rates (RR 0.82, 95% CI 0.59 to 1.14, 6 RCTs, 552 women, I2 = 17%, very-low-quality evidence;  Analysis 1.3).

 
1.4 Congenital abnormalities (adverse events)

None of the included studies reported congenital abnormalities.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Summary of main results

There was no evidence of an effect on live birth (low-quality evidence) or miscarriage (very-low-quality evidence). The use of IMSI for sperm selection was associated with an improvement in the clinical pregnancy rate. However, we deemed this evidence to be of very low quality, and therefore we are very uncertain about this estimate. No included studies reported congenital abnormalities. See  Summary of findings for the main comparison for further details.

 

Overall completeness and applicability of evidence

The objectives of this review were addressed by the included studies. Five studies included only couples with poor sperm quality and four included couples with good or unselected sperm quality; however, such subgroup analysis ( Analysis 2.1) did not add to the global analysis. No study sorted the participants accordingly the sperm source - ejaculate or surgical - or by previous unsuccessful embryo transfers. However, the quality of the pooled evidence does not allow robust conclusions and we are uncertain about the true effect of IMSI on the studied reproductive outcomes. In this way, the review findings do not support the use of IMSI in clinical practice.

 

Quality of the evidence

We considered the pooled evidence to be very-low to low-quality (see  Summary of findings for the main comparison). Issues such as risk of bias in the included studies, imprecision and strong suspicion of publication bias contributed to the downgrading of the evidence quality.

The evidence of effect on live birth was deemed low-quality because only one study reported this outcome, with very serious imprecision in the estimate (Balaban 2011). There were only 69 events, and the 95% CI included appreciable harm, no effect, and appreciable benefit.

We considered the evidence of effect on clinical pregnancy to be of very-low-quality. We considered four out of the nine included studies to be at high risk of potential bias, regarding differences in the mean number of oocytes retrieved or embryos transferred between groups, or both (see Assessment of risk of bias in included studies; Figure 3). In addition, there was inconsistency across the included studies; and publication bias was strongly suspected, as funnel plot analysis (Figure 6) suggested a small studies effect.

Regarding miscarriage, we considered the evidence to be of very-low-quality. This occurred because the four out of six studies that reported this outcome were considered to be at high risk of bias related to differences in the mean number of oocytes retrieved or embryos transferred between groups, and there was also very serious imprecision in the estimate. There were only 107 miscarriages across both groups, and the 95% CI was compatible with both appreciable harm and no effect.

There was no evidence from RCTs on the effect of IMSI on congenital abnormalities.

 

Potential biases in the review process

We did not identify potential biases in the review process.

 

Agreements and disagreements with other studies or reviews

Another review evaluated the effect of IMSI (Setti 2010). It included studies recovered from a single database (MEDLINE) and supplemented evidence from a single RCT with non-RCT studies. In accordance to our review, they reported a significant improvement in clinical pregnancy rates. However, they observed a beneficial effect of IMSI decreasing the risk of miscarriage while we observed no evidence of such effect.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

 

Implications for practice

The current evidence from randomised controlled trials does not support the clinical use of intracytoplasmic sperm injection (intracytoplasmic morphologically selected sperm injection (IMSI)): there is no evidence of effect on live birth or miscarriage and the evidence that IMSI improves clinical pregnancy is of very low quality. There is no evidence regarding the effect of this intervention on the risk of congenital abnormalities. Further trials are necessary to improve the quality of the evidence before recommending IMSI in clinical practice.

 
Implications for research

More studies are needed to evaluate the effect of IMSI on live birth, clinical pregnancy, miscarriage, and congenital abnormalities.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

We acknowledge the important help provided by Helen Nagels, Managing Editor from the Cochrane Menstrual Disorders and Subfertility Group, and by Marian Showell, Trials Search Co-ordinator for the Cochrane Menstrual Disorders and Subfertility Group.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
Download statistical data

 
Comparison 1. Ultra high (IMSI) versus regular magnification (ICSI)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Live birth per allocated couple1168Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.79, 1.64]

 2 Clinical pregnancy per allocated couple92014Risk Ratio (M-H, Random, 95% CI)1.29 [1.07, 1.56]

 3 Miscarriage per clinical pregnancy6552Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.59, 1.14]

 
Comparison 2. IMSI versus ICSI: subgroup analysis by sperm quality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical pregnancy92014Risk Ratio (M-H, Random, 95% CI)1.29 [1.07, 1.56]

    1.1 Only poor sperm quality
51500Risk Ratio (M-H, Random, 95% CI)1.29 [0.98, 1.70]

    1.2 Good or unselected sperm quality
4514Risk Ratio (M-H, Random, 95% CI)1.33 [0.97, 1.82]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Appendix 1. Menstrual Disorders and Subfertility Group search strategy

Search results for Menstrual Disorders and Subfertility Group (MDSG) database, 8 May 2013:

Keywords CONTAINS "icsi"or "ICSI failure"or "ICSI injection site"or"intracytoplasmic sperm injection"or"intracytoplasmic sperm injection cycle"or "intracytoplasmic sperm injection techniques"or Title CONTAINS "icsi"or "ICSI failure"or "ICSI injection site"or"intracytoplasmic sperm injection"or"intracytoplasmic sperm injection cycle"or "intracytoplasmic sperm injection techniques"

AND

Keywords CONTAINS "IMSI" or "intracytoplasmic morphologically selected sperm injection" or Title CONTAINS "IMSI" or "intracytoplasmic morphologically selected sperm injection"

22 records

 

Appendix 2. CENTRAL search strategy

Database: EBM Reviews - Cochrane Central Register of Controlled Trials, 2013, Issue 2
Search strategy:
--------------------------------------------------------------------------------
1 icsi.tw. (684)
2 intracytoplasmic sperm injection$.tw. (417)
3 exp Sperm Injections, Intracytoplasmic/ (334)
4 conventional intracytoplasmic injection$.tw. (1)
5 regular magnification.tw. (0)
6 or/1-5 (886)
7 intracytoplasmic morphologically selected sperm injection$.tw. (11)
8 IMSI.tw. (11)
9 MSOME.tw. (0)
10 motile sperm organelle morphology examination$.tw. (0)
11 high magnification.tw. (18)
12 or/7-11 (27)
13 6 and 12 (10)

 

Appendix 3. MEDLINE search strategy

Search results for Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>, 8 May 2013:
1 icsi.tw. (5253)
2 intracytoplasmic sperm injection$.tw. (4724)
3 exp Sperm Injections, Intracytoplasmic/ (4426)
4 conventional intracytoplasmic injection$.tw. (1)
5 regular magnification.tw. (1)
6 or/1-5 (7703)
7 intracytoplasmic morphologically selected sperm injection$.tw. (36)
8 IMSI.tw. (40)
9 MSOME.tw. (29)
10 motile sperm organelle morphology examination$.tw. (22)
11 high magnification.tw. (1058)
12 or/7-11 (1101)
13 6 and 12 (62)
14 randomized controlled trial.pt. (348,486)
15 controlled clinical trial.pt. (85,883)
16 randomized.ab. (266,743)
17 placebo.tw. (147,938)
18 clinical trials as topic.sh. (164,266)
19 randomly.ab. (194,103)
20 trial.ti. (113,955)
21 (crossover or cross-over or cross over).tw. (56,715)
22 or/14-21 (857,284)
23 exp animals/ not humans.sh. (3,809,801)
24 22 not 23 (790,248)
25 13 and 24 (14)

 

Appendix 4. EMBASE search strategy

Database: EMBASE <1980 to 8 May 2013>
Search strategy:
--------------------------------------------------------------------------------
1 exp intracytoplasmic sperm injection/ (11,216)
2 icsi.tw. (8334)
3 intracytoplasmic sperm injection$.tw. (5798)
4 conventional intracytoplasmic injection$.tw. (1)
5 regular magnification.tw. (2)
6 or/1-5 (13,225)
7 intracytoplasmic morphologically selected sperm injection$.tw. (75)
8 IMSI.tw. (111)
9 MSOME.tw. (59)
10 motile sperm organelle morphology examination$.tw. (41)
11 high magnification.tw. (1291)
12 or/7-11 (1374)
13 6 and 12 (142)
14 Clinical Trial/ (877227)
15 Randomized Controlled Trial/ (341,619)
16 exp randomization/ (61290)
17 Single Blind Procedure/ (17,333)
18 Double Blind Procedure/ (114,409)
19 Crossover Procedure/ (36,788)
20 Placebo/ (217,264)
21 Randomi?ed controlled trial$.tw. (86,231)
22 Rct.tw. (11,331)
23 random allocation.tw. (1232)
24 randomly allocated.tw. (18,653)
25 allocated randomly.tw. (1878)
26 (allocated adj2 random).tw. (718)
27 Single blind$.tw. (13,248)
28 Double blind$.tw. (135,874)
29 ((treble or triple) adj blind$).tw. (312)
30 placebo$.tw. (187828)
31 prospective study/ (231,998)
32 or/14-31 (1,324,701)
33 case study/ (19,500)
34 case report.tw. (242,862)
35 abstract report/ or letter/ (866,817)
36 or/33-35 (1,124,107)
37 32 not 36 (1,288,419)
38 13 and 37 (34)

 

Appendix 5. CINAHL search strategy

Search results for Cumulative Index to Nursing and Allied Health Literature (CINAHL), 7 May 2013:

((intracytoplasmic sperm injection*) OR (icsi) OR (conventional intracytoplasmic injection*) OR (regular magnification)) AND ((intracytoplasmic morphologically selected sperm injection*) OR (IMSI) OR (MSOME) OR (motile sperm organelle morphology examination*) OR (high magnification))

0 records

 

Appendix 6. LILACS search strategy

Search results for Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), 7 May 2013:

((intracytoplasmic sperm injection$) OR (icsi) OR (conventional intracytoplasmic injection$) OR (regular magnification)) AND ((intracytoplasmic morphologically selected sperm injection$) OR (IMSI) OR (MSOME) OR (motile sperm organelle morphology examination$) OR (high magnification))

1 record

 

Appendix 7. PsycINFO search strategy

Search results for PsycINFO, 8 May 2013:
1 intracytoplasmic sperm injection$.tw. (33)
2 icsi.tw. (38)
3 conventional intracytoplasmic injection$.tw. (0)
4 regular magnification.tw. (0)
5 or/1-4 (50)
6 intracytoplasmic morphologically selected sperm injection$.tw. (0)
7 IMSI.tw. (1)
8 MSOME.tw. (0)
9 motile sperm organelle morphology examination$.tw. (0)
10 high magnification.tw. (20)
11 or/6-10 (21)
12 5 and 11 (0)

 

Appendix 8. Trials registers search strategy

Search results for ClinicalTrial.gov, 7 May 2013:

(imsi) OR (msome) OR (motile sperm organelle morphology examination) OR ((high magnification) AND (sperm))

6 records

Search results for Current Controlled Trials, 7 May 2013:

(imsi) OR (msome) OR (motile sperm organelle morphology examination) OR ((high magnification) AND (sperm))

0 records

Search results for World Health Organization International Clinical Trials Registry Platform, 7 May 2013:

IMSI OR MSOME

6 records

 

Appendix 9. Web of Knowledge search strategy

Search results for Web of Knowledge, 7 May 2013:

(((intracytoplasmic sperm injection*) OR (icsi) OR (conventional intracytoplasmic injection*) OR (regular magnification)) AND ((intracytoplasmic morphologically selected sperm injection*) OR (IMSI) OR (MSOME) OR (motile sperm organelle morphology examination*) OR (high magnification)))

240 records

 

Appendix 10. OpenGrey search strategy

Search results for OpenGrey, 7 May 2013:

((intracytoplasmic sperm injection*) OR (icsi) OR (conventional intracytoplasmic injection*) OR (regular magnification)) AND ((intracytoplasmic morphologically selected sperm injection*) OR (IMSI) OR (MSOME) OR (motile sperm organelle morphology examination*) OR (high magnification))

0 records

 

Appendix 11. DARE search strategy

Search results for Database of Abstracts of Reviews of Effects (DARE), 7 May 2013:

((intracytoplasmic sperm injection$) OR (icsi) OR (conventional intracytoplasmic injection$) OR (regular magnification)) AND ((intracytoplasmic morphologically selected sperm injection$) OR (IMSI) OR (MSOME) OR (motile sperm organelle morphology examination$) OR (high magnification))

5 records

 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

Drafting the protocol: Danielle M Teixeira, Mariana AP Barbosa, Rui A Ferriani, Paula A Navarro, Nick Raine-Fenning, Carolina O Nastri, Wellington P Martins.

Development of search strategy: Danielle M Teixeira, Wellington P Martins.

Search for trials: Danielle M Teixeira, Mariana AP Barbosa, Wellington P Martins.

Obtaining copies of trials: Danielle M Teixeira, Wellington P Martins.

Selection of which trials to include: Danielle M Teixeira, Mariana AP Barbosa, Wellington P Martins.

Extraction of data from trials: Danielle M Teixeira, Mariana AP Barbosa, Wellington P Martins.

Assessment of risk of bias in included studies: Danielle M Teixeira, Mariana AP Barbosa, Carolina O Nastri.

Entry of data into RevMan: Danielle M Teixeira, Carolina O Nastri, Wellington P Martins.

Drafting the review: Danielle M Teixeira, Mariana AP Barbosa, Rui A Ferriani, Paula A Navarro, Nick Raine-Fenning, Carolina O Nastri, Wellington P Martins.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

The authors declare no conflicts of interest.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms
 

Internal sources

  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.
    Scholarship
  • Hospital das Clínicas FMRP-USP, Brazil.
    Salary
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.
    Scholarship
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil.
    Scholarship

 

External sources

  • No sources of support supplied

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Index terms

None.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. References to studies awaiting assessment
  21. Additional references
Antinori 2008 {published data only}
  • Antinori M, Licata E, Dani G, Cerusico F, Versaci C, d'Angelo D, et al. Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. Reproductive BioMedicine Online 2008;16(6):835-41. [PUBMED: 18549694]
  • Antinori S, Licata E, Dani G, Cerusico F, Versaci C, Antinori M. A prospective randomized trial to verify the efficacy of IMSI procedure in daily IVF routine. Human Reproduction 2008;23 Suppl 1:i165.
Balaban 2011 {published data only}
  • Balaban B, Yakin K, Alatas C, Oktem O, Isiklar A, Urman B. Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study. Reproductive Biomedicine Online 2011;22(5):472-6. [PUBMED: 21324747]
Figueira 2011 {published data only}
  • Figueira RCS, Braga DPAF, Pasqualotto EB, Pasqualotto FF, Iaconelli A, Borges E. The role of morphological nuclear integrity of the sperm cells in preimplantation genetic aneuploidy screening cycles outcome. Journal fur Reproduktionsmedizin und Endokrinologie 2010;7:250-1.
  • Figueira RDC,  Braga DP,  Setti AS,  Iaconelli A Jr,  Borges E Jr. Morphological nuclear integrity of sperm cells is associated with preimplantation genetic aneuploidy screening cycle outcomes. Fertility and Sterility 2011;95(3):990-3. [PUBMED: 21130987]
Knez 2011 {published data only}
  • Knez K, Zorn B, Tomazevic T, Vrtacnik-Bokal E, Virant-Klun I. The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: a comparative prospective randomized study. Reproductive Biology and Endocrinology 2011;9:123. [PUBMED: 21875440]
Knez 2012 {published data only}
  • Knez K, Tomazevic T, Zorn B, Vrtacnik-Bokal E, Virant-Klun I. Intracytoplasmic morphologically selected sperm injection improves development and quality of preimplantation embryos in teratozoospermia patients. Reproductive Biomedicine Online 2012;25(2):168-79. [PUBMED: 22717245]
Mahmoud 2011 {published data only}
  • Mahmoud K, Triki-Hmam C, Terras K, Zhioua F, Hfaiedh T, Ben Aribia MH. How and in which indication the IMSI could improve outcomes?. Human Reproduction 2011;26 Suppl 1:i181.
Setti 2011 {published data only}
  • Setti AS, Figueira Rde C, Braga DP, Iaconelli A Jr, Borges E Jr. Intracytoplasmic morphologically selected sperm injection benefits for patients with oligoasthenozoospermia according to the 2010 World Health Organization reference values. Fertility and Sterility 2011;95(8):2711-4. [PUBMED: 21458802]
Setti 2012a {published data only}
  • Iaconelli JA, Figueira RCS, Setti AS, Braga DPAF, Pasqualotto EE, Borges E Jr. Gender incidence on intracytoplasmic morphologically selected sperm injection approach: a prospective randomized study. Human Reproduction 2011;26 Suppl 1:i71.
  • Setti AS, Figueira RC, Braga DP, Iaconelli A Jr, Borges E Jr. Gender incidence of intracytoplasmic morphologically selected sperm injection-derived embryos: a prospective randomized study. Reproductive BioMedicine Online 2012;24(4):420-3. [PUBMED: 22377154]
Setti 2012b {published data only}
  • Setti AS, Figueira, RDC, de Almeida Ferreira Braga DP, Iaconelli A, Borges E. IMSI is beneficial in cases of advanced maternal age: a prospective randomized study. Reproductive BioMedicine Online 2012;Withdrawn. [DOI: 10.1016/j.rbmo.2012.10.020]

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. References to studies awaiting assessment
  21. Additional references
Apryshko 2010 {published data only}
  • Apryshko VP, Yakovenko SA, Sivozhelezov VS, Yutkin EV, Rutman BK, Troshina MN, et al. IMSI based on Hoffman modulation contrast: 5 years experience. Reproductive BioMedicine Online 2010;20:S25.
Bartoov 2003 {published data only}
  • Bartoov B, Berkovitz A, Eltes F, Kogosovsky A, Yagoda A, Lederman H, et al. Pregnancy rates are higher with intracytoplasmic morphologically selected sperm injection than with conventional intracytoplasmic injection. Fertility and Sterility 2003;80(6):1413-9. [PUBMED: 14667877]
Berkovitz 2005 {published data only}
  • Berkovitz A, Eltes F, Yaari S, Katz N, Barr I, Fishman A, et al. The morphological normalcy of the sperm nucleus and pregnancy rate of intracytoplasmic injection with morphologically selected sperm. Human Reproduction 2005;20(1):185-90. [PUBMED: 15471930]
Berkovitz 2006 {published data only}
  • Berkovitz A, Eltes F, Lederman H, Peer S, Ellenbogen A, Feldberg B, et al. How to improve IVF-ICSI outcome by sperm selection. Reproductive Biomedicine Online 2006;12(5):634-8. [PUBMED: 16790113]
Braga 2011 {published data only}
  • Braga DPAF, Setti AS, Figueira RC, Nichi M, Martinhago CD, Iaconelli A Jr, et al. Sperm organelle morphologic abnormalities: contributing factors and effects on intracytoplasmic sperm injection cycles outcomes. Urology 2011;78(4):786-91. [PUBMED: 21820702]
Cassuto 2011 {published data only}
  • Cassuto NG, Hazout A, Benifla JL, Balet R, Larue L, Viot G. Decreasing birth defect in children by using high magnification selected spermatozoon injection. Fertility and Sterility 2011;1:S85.
De Vos 2013 {published data only}
  • De Vos A, Van de Velde H, Bocken G, Eylenbosch G, Franceus N, Meersdom G, et al. Does intracytoplasmic morphologically selected sperm injection improve embryo development? A randomized sibling-oocyte study. Human Reproduction 2013;28:617-26.
Hazout 2005 {published data only}
  • Hazout A, Dumont-Hassan M, Junca AM, Cohen Bacrie P, Tesarik J. High-magnification ICSI overcomes paternal effect resistant to conventional ICSI. Reproductive Biomedicine Online 2005;12(1):19-24. [PUBMED: 16454928]
Mauri 2011 {published data only}
  • Mauri AL, Petersen CG, Oliveira JB, Massaro FC, Baruffi RL, Franco JG Jr. Comparison of day 2 embryo quality after conventional ICSI versus intracytoplasmic morphologically selected sperm injection (IMSI) using sibling oocytes. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2011;150(1):42-6. [PUBMED: 20171776]
Oliveira 2011 {published data only}
  • Oliveira JBA, Cavagna M, Petersen CG, Mauri AL, Massaro FC, Silva LFI, et al. Pregnancy outcomes in women with repeated implantation failures after intracytoplasmic morphologically selected sperm injection (IMSI). Reproductive Biology and Endocrinology 2011;9:99. [PUBMED: 21781299]
  • Oliveira JBA, Petersen CG, Mauri AL, Massaro FC, Baruffi RLR, Franco JG Jr. Clinical outcomes of IMSI in previous ICSI failures. Fertility and Sterility 2010;1:S55.
Wilding 2011 {published data only}
  • Wilding M, Coppola G, di Matteo L, Palagiano A, Fusco E, Dale B. Intracytoplasmic injection of morphologically selected spermatozoa (IMSI) improves outcome after assisted reproduction by deselecting physiologically poor quality spermatozoa. Journal of Assisted Reproduction and Genetics 2011;28(3):253-62. [PUBMED: 21072684]

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. References to studies awaiting assessment
  21. Additional references
Check 2013 {published data only}
  • Check JH, Bollendorf A, Summers-Chase D, Yuan W, Horwath D. Isolating sperm by selecting those with normal nuclear morphology prior to intracytoplasmic sperm injection (ICSI) does not provide better pregnancy rates compared to conventional ICSI in women with repeated conception failure with in vitro fertilization. Clinical and Experimental Obstetrics & Gynecology 2013;40:15-7.
Parinaud 2013 {unpublished data only}

 

Setti 2012c {published data only}
  • Setti AS, Braga DPAF, Figueira RCS, Colturato SS, Iaconelli A, Borges E. Intracytoplasmic morphologically selected sperm injection (IMSI) benefits in the presence of unexplained infertility: a prospective randomized study. Fertility and Sterility 2012; Vol. 98 Suppl 1, issue 3:S80.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. References to studies awaiting assessment
  21. Additional references
Bartoov 2002
  • Bartoov B, Berkovitz A, Eltes F, Kogosowski A, Menezo Y, Barak Y. Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. Journal of Andrology 2002;23(1):1-8. [PUBMED: 11780915]
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Jungheim 2010
  • Jungheim ES, Ryan GL, Levens ED, Cunningham AF, Macones GA, Carson KR, et al. Embryo transfer practices in the United States: a survey of clinics registered with the Society for Assisted Reproductive Technology. Fertility and Sterility 2010;94(4):1432-6. [PUBMED: 19748089]
Palermo 1992
Setti 2010
  • Setti AS, Ferreira RC, Braga DPAF, Figueira RCS, Iaconelli A Jr, Borges E Jr. Intracytoplasmic sperm injection outcome versus intracytoplasmic morphologically selected sperm injection outcome: a meta-analysis. Reproductive Biomedicine Online 2010;21(4):450-5. [PUBMED: 20800549]