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Brief co-incubation of sperm and oocytes for in vitro fertilization techniques

  1. Zhongying Huang1,*,
  2. Jun Li2,
  3. Li Wang3,
  4. Jing Yan4,
  5. Yijiang Shi5,
  6. Shangwei Li6

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 30 APR 2013

Assessed as up-to-date: 26 MAR 2013

DOI: 10.1002/14651858.CD009391.pub2

How to Cite

Huang Z, Li J, Wang L, Yan J, Shi Y, Li S. Brief co-incubation of sperm and oocytes for in vitro fertilization techniques. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD009391. DOI: 10.1002/14651858.CD009391.pub2.

Author Information

  1. 1

    West China 2nd Hospital, Sichuan University, Reproductive Medical Centre, Department of Obstetrics and Gynecology, Chengdu, China

  2. 2

    West China Hospital, Sichuan University, Department of Geriatrics, Chengdu, Sichuan, China

  3. 3

    West China Hospital, Sichuan University, Chinese Cochrane Centre, Chengdu, Sichuan, China

  4. 4

    Sichuan University, Institute of Preliminary and Forensic Medicine, Chengdu, China

  5. 5

    San Joaquin Community Hospital, Bakersfield, California, USA

  6. 6

    West China 2nd Hospital, Sichuan University, Reproductive Medicine Centre, Department of Obstetrics and Gynaecology, Chengdu, Sichuan, China

*Zhongying Huang, Reproductive Medical Centre, Department of Obstetrics and Gynecology, West China 2nd Hospital, Sichuan University, Chengdu, 610041, China. huangzyhxyd@scu.edu.cn.

Publication History

  1. Publication Status: New
  2. Published Online: 30 APR 2013

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Characteristics of included studies [ordered by study ID]
Boone 2001

MethodsRandomized controlled trial


ParticipantsCountry: USA
Female infertility
Mean age: 32.8 years ( age range 23-40 years)
n=20 recruited
Inclusion criteria:

Infertile women with known indications for conventional IVF, under the age of 41 years. Patients provided at least 9 oocytes retrieved on the day of oocyte recovery during in vitro fertilization treatment were included.


InterventionsShort exposure (3h)

versus 

control standard IVF procedure (19h)


OutcomesFertilization rate, polyploid rate, embryo cell stages and quality scores


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskOocytes randomized into two treatment groups; randomization method not mentioned

Allocation concealment (selection bias)Unclear riskNo details

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPer woman data not reported

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot stated, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Coskun 1998

MethodsRandomized controlled trial


ParticipantsCountry: Saudi Arabia
Infertile women
mean age 32.1 (32.1 ± 4.9 years)
n=36 recruited

Inclusion criteria: Infertile women with known indications for conventional IVF. Patients with six or more oocytes retrieved on the day of oocyte recovery during in vitro fertilization treatment were included.


InterventionsReduced insemination (1h )
versus
regular insemination (18h)


OutcomesFertilization rate, embryo cell stages and embryo quality grading


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskOocytes from each patient were randomly allocated to two treatment groups; randomization method not mentioned

Allocation concealment (selection bias)Unclear riskNo details

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPer woman data not reported

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot stated, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Dirnfeld 1999

MethodsRandomized controlled trial


ParticipantsCountry: Israel

Female infertility

Mean age: 32.8 ± 3.8 years for short exposure group, 33.2 ± 4.2 years for standard exposure group (range 23-34 years)

n= 158 recruited

Inclusion criteria: infertile women with known indications for conventional IVF, with normo-ovulatory, 23-41 years, with normal uterine morphology and endometrial line (assessed by hysteron-salpingography and ultrasound)

Exclusion criteria: very poor responders, patients with polycystic ovary syndrome and men with severe oligozoospermia


InterventionsShort exposure (1h)

versus   

control standard IVF procedure (16-20h)


OutcomesClinical pregnancy rate, fertilization rate, cleavage rate, embryo quality grading and implantation rate


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomized into two study groups using standard random number tables

Allocation concealment (selection bias)Unclear riskNo details

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot stated, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Dirnfeld 2003

MethodsRandomized controlled trial


ParticipantsCountry: Israel

Female infertility

Mean age: 30±4.5 years for short exposure group, 30±6.1 years for standard exposure group

n=23 recruited

Inclusion criteria: infertile women with known indications for conventional IVF, with normal cycles and a normal endometrial lining (demonstrated by a previous hysterosalpingography)

Exclusion criteria: very poor responders, patients with unexplained infertility and patients who were regularly taking any drugs other than those for infertility


InterventionsShort exposure (2h)

versus  

control standard exposure (16-20h)


OutcomesFertilization rate, cleavage rate and embryo quality grading


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomized into two treatment groups using standard random number tables

Allocation concealment (selection bias)Unclear riskNot mentioned

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot stated, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Gianaroli 1996b

MethodsRandomized controlled trial


ParticipantsCountry: Italy
Female infertility
n=167 recruited
Inclusion criteria: infertile women with known indications for conventional IVF, with normo-ovulatory, aged ≤38years, normal uterine morphology and endometrial biopsies.
Duration of study: 18 months


InterventionsShort exposure (1h)

versus  

control standard exposure (16h)


OutcomesOngoing pregnancy rate, clinical pregnancy rate, miscarriage rate, fertilization rate, polypronuclear rate, implantation rate


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk No details of how randomization was carried out

Allocation concealment (selection bias)Unclear riskNot mentioned

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot mentioned, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Kattera 2003

MethodsRandomized controlled trial


ParticipantsCountry: Singapore

Female infertility

(range: 25–44 years) Mean age: 35.4 ± 4.1 years for short exposure group, 35.1 ± 3.9 years for standard exposure group

n=259 recruited

Inclusion criteria: infertile women with known indications for conventional IVF

Exclusion criteria: very poor responders (those who produced fewer than three follicles) and men with severe oligoasthenoteratozoospermia

Duration of study: 18 months


InterventionsShort co-incubation (2h)

versus  

long co-incubation (20h)


OutcomesOngoing pregnancy rate, fertilization rate, abnormal fertilization rate, embryo grading and implantation rate


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomized into two groups using standard random number tables

Allocation concealment (selection bias)Unclear riskNot stated

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot mentioned, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Lin 2000

MethodsRandomized controlled trial


ParticipantsCountry: Taiwan, China

Female infertility

n=23 recruited

Inclusion criteria: subfertile women with known indications for conventional IVF

Exclusion criteria: women with male infertility factors


InterventionsShort time co-incubation (1h or 3h)

versus  

standard overnight gamete co-incubation (16-18h)


OutcomesFertilization rate, abnormal fertilzation rate, cleavage rate and embryo quality grading  


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe patients were randomly allocated to two groups. No details of how randomization was performed

Allocation concealment (selection bias)Unclear riskNot stated

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPer woman data not reported

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot mentioned, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot stated, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Waldenström 1998

MethodsRandomized controlled trial


ParticipantsCountry: Sweden

Female infertility

Mean age: 32 years (range 25–40 years)

n=47 recruited

Inclusion criteria: infertile women with known indications for standard  IVF

Exclusion criteria: infertility with male factors, poor responders


InterventionsShort time sperm exposure (1.5-2h)

versus  

long time sperm exposure (16-18h)


OutcomesClinical pregnancy rate, fertilization rate, polyspermy rate


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskPatients were randomized to two treatment groups. How randomization performed was not mentioned

Allocation concealment (selection bias)Unclear riskNot mentioned

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskDid not report live birth, the primary outcome of the review

Other biasUnclear riskCan not definitively assess other bias

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot stated, but the review authors considered that blinding was not likely to influence the risk of performance bias for the primary review outcome and secondary outcomes

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNot mentioned, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Barraud 2003Quasi-randomized controlled trial.

Barraud 2008Quasi-randomized controlled trial.

Bungum 2005Not a randomized controlled trial. Interventions did not meet the requirements.

Bungum 2006Not a randomized controlled trial. Interventions did not meet the requirements.

Gianoroli 1996aThere were some overlap of participation between the two studies (Gianoroli 1996a and 1996b), the former one with smaller sample size was excluded after contacting authors for detailed information.

Granham 1999Lacked appropriate inclusion criteria for population.

Hammit 1999Not a randomized controlled trial.

Lundqvist 2001Not a randomized controlled trial.

Navarro 2004Quasi-randomized controlled trial.

Quinn 1998Quasi-randomized controlled trial.

Swenson 2000Quasi-randomized controlled trial.

Swenson 1998Not a randomized controlled trial.

Swenson 1999Superseded by full paper of the trial - Swenson 2000.

Xiong 2011Not a randomized controlled trial.

Zhang 2009Not a randomized controlled trial.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Jamieson 1999

MethodsTo be added when confirmed.

Participants

Interventions

Outcomes

Notes

Pattanayak 2001

MethodsTo be added when confirmed.

Participants

Interventions

Outcomes

Notes

 
Comparison 1. Brief co-incubation versus standard insemination

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

 1 Ongoing pregnancy per randomized woman2426Odds Ratio (M-H, Fixed, 95% CI)2.42 [1.55, 3.77]

 2 Clinical pregnancy rate per randomized woman3372Odds Ratio (M-H, Fixed, 95% CI)2.36 [1.45, 3.85]

 3 Miscarriage rate per randomized woman1167Odds Ratio (M-H, Fixed, 95% CI)1.98 [0.35, 11.09]

 
Summary of findings for the main comparison. Brief co-incubation compared to standard insemination for in vitro fertilization techniques

Brief co-incubation compared to standard insemination for in vitro fertilization techniques

Patient or population: patients with in vitro fertilization techniques
Settings:
Intervention: Brief co-incubation
Comparison: standard insemination

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

Assumed riskCorresponding risk

Standard inseminationBrief co-incubation

Ongoing pregnancy per randomized woman213 per 1000396 per 1000
(296 to 505)
OR 2.42
(1.55 to 3.77)
426
(2 studies)
⊕⊕⊝⊝
low1

Clinical pregnancy rate per randomized woman177 per 1000337 per 1000
(238 to 453)
OR 2.36
(1.45 to 3.85)
372
(3 studies)
⊕⊕⊝⊝
low2

Miscarriage rate per randomized woman24 per 100047 per 1000
(9 to 217)
OR 1.98
(0.35 to 11.09)
167
(1 study)
⊕⊕⊝⊝
low3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. 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; OR: Odds 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 One trial lacked adequate explanation for methods of randomization. Allocation concealment not mentioned in any trial.
2 Two trials lacked adequate explanation for randomization methods. Allocation concealment not mentioned in any trial.
3 One trial only and no method of randomization or allocation concealment stated.
 
Table 1. Fertilization rate

Study IDBrief co-incubationStandard inseminationP value

Boone 2001  Co-incubation time:3h

Fertilization rate: 70.9% (117/165)
Co-incubation time: 19h

Fertilization rate:

80.4% (135/168)
P = 0.001

Coskun 1998Co-incubation time:1h

Fertilization rate: 59.0% (135/229)
Co-incubation time: 18h

Fertilization rate: 63.8% (150/235)
NS

Dirnfeld 1999Co-incubation time:1h

Fertilization rate: 56.1% (411/732))
Co-incubation time: 16-20h

Fertilization rate: 61% (501/822)
NS

Dirnfeld 2003Co-incubation time:2h

Fertilization rate: 66.8% (20/30)
Co-incubation time: 16-20h

Fertilization rate: 65.4% (52/79)
NS

Gianaroli 1996bCo-incubation time:1h

Fertilization rate: 74.0% (440/595)
Co-incubation time: 16h

Fertilization rate: 67.7% (376/555)
P < 0.025

Kattera 2003Co-incubation time:2h

Fertilization rate: 75.8% (838/1105)
Co-incubation time:20h

Fertilization rate: 77.0% (924/1200)
NS

Lin 2000Co-incubation time:1,3h

Fertilization rate: 79.5% (93/117)
Co-incubation time:16-18h

Fertilization rate: 85.7% (191/223)
NS

Waldenström 1998Co-incubation time:2h

Fertilization rate: 69.4% (177/255)
Co-incubation time: 16-18h

Fertilization rate: 64.9% (196/302)
Not stated

 P < 0.05 was defined as statistically significant
NS = not significant
 
Table 2. Polyspermy rate

Study IDBrief co-incubationStandard inseminationP value

Boone 2001Co-incubation time: 3h

Polyspermy rate:

2.4% (4/165)
Co-incubation time: 19h

Polyspermy rate: 6.5% (11/168)
P = 0.110

Gianaroli 1996bCo-incubation time: 1h

Polyspermy rate: 0.9% (5/555)
Co-incubation time: 16h

Polyspermy rate: 2.3% (13/555)
Not stated

Lin 2000Co-incubation time: 1, 3h

Polyspermy rate: 6.8% (8/117)
Co-incubation time: 16-18h

Polyspermy rate: 4.0% (9/223)
Not stated

Waldenström 1998Co-incubation time:2h

Polyspermy rate: 1.6% (4/255)
Co-incubation time: 16-18h

Polyspermy rate: 3.3% (10/302)
Not stated

 
Table 3. Implantation rate

Study IDBrief co-incubationStandard inseminationP value

Dirnfeld 1999Co-incubation time: 1h

Implantation rate: 16.2% (31/191)
Co-incubation time: 16-20h

Implantation rate: 9.8% (23/234)
P < 0.05

Gianaroli 1996bCo-incubation time: 1h

Implantation rate: 11.9% (31/261)
Co-incubation time: 16h

Implantation rate: 5.6% (14/249)
P < 0.05